Search

BACKGROUND: The aims of this study were twofold: (1) to compare the body image and tactile acuity of patients with fibromyalgia and asymptomatic participants, and (2) to investigate the effects of an 8-week exercise-based intervention (aerobic or Pilates exercises) on the body image, tactile acuity, and pain intensity in patients with fibromyalgia. METHODS: A cross-sectional study and a secondary analysis of a randomized controlled trial were carried out, which assessed the following outcomes in 24 patients with fibromyalgia and 24 asymptomatic participants: subjective body image (Drawing Test), tactile acuity (Two-Point Discrimination Test), limb circumference (Cirtometry), and pain (Pain Numerical Rating Scale). After the assessment, the 24 patients with fibromyalgia were randomly allocated to one of the intervention groups: aerobic or Pilates. RESULTS: There was no significant difference in the tactile acuity of the cervical, lumbar, hands, and feet regions between the participants with fibromyalgia and the asymptomatic participants (p > 0.05). However, patients with fibromyalgia showed changes in subjective body image when the drawings were compared to the cirtometry measurements. After the intervention, there was no significant difference between aerobic exercise and Pilates for pain and tactile acuity in the cervical, lumbar, hands, and feet regions of patients with fibromyalgia (p > 0.05). CONCLUSIONS: Patients with fibromyalgia presented altered perception in subjective body image but not on tactile acuity, when compared to asymptomatic participants. In addition, there was no difference between aerobic exercise and Pilates for pain and tactile acuity in these patients.

Background Although clinical practice guidelines recommend pain education as the first-line option for the management of chronic musculoskeletal pain, there is a lack of pain education programmes in healthcare. Thus, digital health programmes can be an effective tool for implementing pain education strategies for public health. This trial will aim to analyse the implementation and effectiveness outcomes of three online pain science education strategies in the Brazilian public health system (SUS) for individuals with chronic musculoskeletal pain. Methods We will conduct a hybrid type III effectiveness-implementation randomised controlled trial with economic evaluation. We will include adult individuals with chronic musculoskeletal pain, recruited from primary healthcare in the city of Guarapuava, Brazil. Individuals will be randomised to three implementation groups receiving a pain science education intervention (EducaDor) but delivered in different modalities: group 1) synchronous online; group 2) asynchronous videos; and group 3) interactive e-book only. Implementation outcomes will include acceptability, appropriateness, feasibility, adoption, fidelity, penetration, sustainability, and costs. We will also assess effectiveness outcomes, such as pain, function, quality of life, sleep, self-efficacy, and adverse effects. Cost-effectiveness and cost-utility analyses will be conducted from the SUS and societal perspectives. The evaluations will be done at baseline, post-intervention (10 weeks), and 6 months. Discussion This study will develop and implement a collaborative intervention model involving primary healthcare professionals, secondary-level healthcare providers, and patients to enhance self-management of chronic pain. In addition to promoting better pain management, this study will also contribute to the field of implementation science in public health by generating important insights and recommendations for future interventions. Trial registration ClinicalTrials.gov (NCT05302180; 03/29/2022).

OBJECTIVE: To explore whether using a single matched or composite outcome might impact the results of previous randomised controlled trials (RCTs) testing exercise for non-specific low back pain (NSLBP). The first objective was to explore whether a single matched outcome generated a greater standardised mean differences (SMD) when compared to the original unmatched primary outcome SMD. The second objective was to explore whether a composite measure, comprised of matched outcomes, generated a greater SMD when compared to the original primary outcome SMD. DESIGN: We conducted exploratory secondary analyses of data. SETTING: Seven RCTs were included, of which two were based in the USA (University research clinic, Veterans Affairs medical centre) and the UK (primary care clinics, nonmedical centres). One each were based in Norway (clinics), Brazil (primary care), and Japan (outpatient clinics). PARTICIPANTS: The first analysis comprised 1) five RCTs (n=1,033) that used an unmatched primary outcome but included (some) matched outcomes as secondary outcomes, and the second analysis comprised 2) four RCTs (n=864) that included multiple matched outcomes by developing composite outcomes. INTERVENTION: Exercise compared to no exercise. MAIN OUTCOME MEASURES: The composite consisted of standardised averaged matched outcomes. All analyses replicated the RCTs' primary outcome analyses. RESULTS: Of five RCTs, three had greater SMDs with matched outcomes (pooled effect SMD 0.30 (95% CI 0.04, 0.56), p=0.02) compared to an unmatched primary outcome (pooled effect SMD 0.19 (95% CI -0.03, 0.40) p=0.09). Of four composite outcome analyses, three RCTs had greater SMDs in the composite outcome (pooled effect SMD 0.28 (95%CI 0.05, 0.51) p=0.02) compared to the primary outcome (pooled effect SMD 0.24 (95%CI -0.04, 0.53) p=0.10). CONCLUSIONS: These exploratory analyses suggest that using an outcome matched to exercise treatment targets in NSLBP RCTs may produce greater SMDs than an unmatched primary outcome. Composite outcomes could offer a meaningful way of investigating superiority of exercise than single domain outcomes.

The aim of this study is to examine the efficacy on healing pressure ulcers (PU) of using a supplement combination containing arginine, glutamine and ß-hydroxy-ß-methylbutyrate, which was given to two elderly patients with renal dysfunction. The PU was surgically opened, decompressed and treated by drugs. A half quantity of the defined dose of the supplement combination, with an enteral nutrition product, was administered to the patients twice a day. This combination improved the PUs, with no effect on renal function. This novel finding may provide a nutritional rationale of arginine, glutamine and ß-hydroxy-ß-methylbutyrate for PUs associated with renal dysfunction.

Purpose: To evaluate the dosimetric implications of using VMAT (Volume Modulated Arc Therapy) treatment planning techniques compared to traditional Arc therapy methods for patients undergoing SBRT (Stereotactic Body Radiation Therapy) for early‐stage Non‐Small Cell LungCancer(NSCLC).Methods: Ten NSCLCcancer patients are planned with both VMAT and Arc techniques. The SBRTtreatment plans comparison was quantified by several Dose‐Volume Histogram (DVH) indicators including mean, maximum and minimum doses for GTV, ITV, PTV, OAR (Organs At Risk), and V95 (volume receiving at least 95% of the prescribed dose) for PTV. Results: On average VMAT plans require for treatment delivery 16.6 ± 20.2 % more monitor units (MU) than the traditional Arc plans. The average PTV minimum, maximum and mean doses as a percentage of prescribed dose are 94.5 ± 3.9 %, 114.1 ± 3.3 % and 106.6 ± 1.6 % for VMAT vs 91.6 ± 4.4 %, 119.5 ± 5.3 % and 109.5 ± 2.5 % for the Arc technique. The V95 PTV coverage for VMAT plans range from 99.4 % to 100 % with a mean of 99.7 %, compared with a range of 96.8 % to 100 % with a mean of 99 % for the Arc plans. The maximum dose received by the lungs, spinal cord and chest wall show on average significant increases for Arc plans as opposed to VMAT plans (5.7 ± 6 % increase for lungs, 4.4 ± 9.2 % for cord and 2.4 ± 6.3 % for chest wall ). The average mean doses and minimum doses for the OAR are similar for both techniques. Conclusions: The comparison of VMAT vs Arc plans for SBRT of NSCLC patients is subject to many variables, including GTV and PTV volume sizes, shape and their proximity relative to the OAR.

The treatment for high-grade glioma remains an enigma. The standard treatment using surgery, radiation therapy and chemotherapy for such highly malignant lesions has only yielded modest results, in terms of survival and improving the quality of life of patients. Less than 10% of such patients survive beyond two years. All conventional therapies have failed to increase the survival beyond this extent. There has been a growing interest in the molecular approaches for the treatment of high-grade gliomas which include gene therapy, oncolytic virotherapy, and immunotherapy. These new therapies are in preclinical and investigational stages. They may not substitute the conventional therapies; they may not be the ultimate elixir for this deadly disease. However, in the coming years, they are likely to have synergistic and complimentary roles alongside conventional therapies. Through this paper, we have attempted to highlight the rationale behind gene therapy which can be used for cytotoxic approaches, immunomodulation strategy, and targeted toxin delivery in the tumor cell. We have reviewed current available literature and through this paper focus on reporting such therapeutic options, their potential usage, benefits and limitations.

Introduction: A recent report of EORTC-STBSG phase III randomized trial (2010) describes that regional hyperthermia can improve chemotherapy results for patients with high-risk soft-tissue sarcoma and Krawczyk et al. (PNAS, 2011) have just discovered that mild high temperature can prohibit homologous recombination - a process to repair double strand breaks. The clinical outcomes and laboratory findings support the combination use of hyperthermia therapy (HT) with chemotherapy or radiotherapy. However, uncontrolled heating can cause severe burns of bones and other critical structures. Thus, it is extremely important to quantify heat transport and thermal dose in the human body for safe and accurate HT. Materials and Methods: Custom phantoms were made of materials with relative permittivity equivalent to soft tissue and shapes similar to the patient body with embedded heat reflectors simulating bones and heat exchangers simulating the blood streams. Eight thermistors were placed at various depths to monitor temperature changes during the heating process. The phantoms were heated by microwave surface heaters with adjustable heat power and water bolus. At therapeutic temperatures, thermographs and 3D surfaces at depths of interest were captured using an infrared camera and a 3D camera. Results and Discussion: Initial results without heat exchangers show that spatial temperature distribution varies greatly with the heat power, heating duration, treatment depth, surface shape, bolus thickness, and presence of heat reflectors. Understanding effects of the controllable variables of the heat power, heating duration, and bolus thickness and the intrinsic variables of the body shape, bone, and blood flow on the temporal and spatial temperature distributions in patients would allow us to optimize the heating process and to calculate the effective thermal doses.

Chronic actinic dermatitis (CAD) has distinct clinical features different from polymorphous light eruption (PLE). In order to clarify the difference between CAD and PLE, not only in clinical histories and findings but also in photobiological and histopathological reactions to phototests, we investigated 6 Japanese patients with CAD and performed provocative phototests which are our standardized methods in diagnosing PLE. On provocative phototests in CAD, pruritic papules were reproduced with smaller doses of UVB, at longer hours after irradiation (48-72 h) and they lasted for more days than in patients with PLE. Our study demonstrated that although milder cases of CAD and severe cases of PLE could not be distinguished clearly based on photobiological reactions alone, typical cases of CAD showed completely different provocative phototest results from those of PLE.

Gliomas are the most common primary brain tumors,comprising 40-60% of all primary brain tumors.The most frequent types are glioblastoma multiforme, astrocytoma, and oligodendroglioma. Radiation therapy is one of the most important treatment modalities for gliomas, mainly because these tumors are usually localized. The patienti¯s head can be immobilized, allowing for good targeting of the tumor. As a result of technological advances, the range of treatment options using radiation therapy has increased. Photon, electron, neutron and proton radiation beams are all in clinical use. The accuracy of the treatment delivery has also improved, with the development of three-dimensional techniques and image fusion. Our understanding of both the radio sensitivity of gliomas, and the tolerance of normal brain tissue is better, allowing the design of novel fractionation schemes. Radiation is being combined with both local and systemic chemotherapy, offering

The impact of repeated surgical resection on the survivorship of patients with malignant astrocytomas is an issue of some controversy in the medical literature.To clarify this issue through a retrospective analysis of treatment outcomes in a brain tumor clinic.The patient records from the Brain Tumor Clinic at Hahnemann University Hospital for the period 1988 to 2000 were reviewed. From these, 112 cases of glioblastoma multiforme and 50 cases of anaplastic astrocytoma were chosen for analysis.The group of patients with glioblastomas showed a median survival of 415 days. When analyzed as subgroups based on the number of surgical resections, the median survival was 393 days in the group with biopsy only, 380 days in the group with one surgical resection, and 548 days in the group with two or three resections. Using the Kaplan-Meier method to generate survival plots and the log rank test to compare groups, repeat debulking was found to be a significant predictor of survival (P = 0.173). The group of patients with anaplastic astrocytomas showed a median survival of 1,311 days. When analyzed by subgroups, the patients with biopsy only had a median survival of 544 days, those with one debulking 1,589 days and those with two or three debulkings 1,421 days. There was a trend toward increased survival with debulking and the log rank test again showed statistical significance (P = 0.1998).This study indicates that repeated surgical resections offer increased survival for both glioblastomas and anaplastic astrocytomas.

The aim of this study was to explore the roles of toxic shock syndrome toxin-1 (TSST-1) in collagen-induced arthritis (CIA). DBA/1 mice were immunized with type II collagen (CII) and treated with TSST-1. Intraperitoneal and intravenous injections of TSST-1 aggravated CIA, enhancing its incidence and severity. CIA was accompanied by an increase in anti-CII IgG Ab levels. Intraperitoneal administration with TSST-1 enhanced IFN-gamma, TNF-alpha, and IL-4 production in DBA/1 mice. We discovered the mRNA expressions of IFN-gamma, IL-2, TNF-alpha, IL-1beta, and iNOS in spleen cells stimulated with TSST-1 in vitro. However, IL-12 and IL-4 mRNA expression were seen constitutively without stimulation. Only a little increase of IL-12 and IL-4 mRNA expression was seen at 2-3 h after treatment with TSST-1. Our experiments demonstrated that CIA was aggravated by the treatment with TSST-1, which may have induced various proinflammatory cytokines and the production of both Th1 and Th2 cytokines.

Cerebral radionecrosis is a possible complication of brain radiation therapy in patients with primary or metastatic tumors. This retrospective study evaluated the role of Tc-99m hexamethyl propyleneamine oxime (HMPAO) scintigraphy in monitoring the effects of radiation on the brain.Ninety-eight patients (41 female, 57 male) with a mean age of 51 years (range, 16-82 years) underwent 128 sets of single-photon emission computed tomography studies. TI-201 and Tc-99m HMPAO single-photon emission computed tomography studies were performed for tumor localization and evaluation of the effect of radiation on the cerebral cortex. Thirty concomitant neuropsychological tests and 96 anatomic imaging (computed tomography/magnetic resonance imaging) were performed. The average radiation dose was 52 Gy delivered as 1.8 to 2 Gy/fraction. Thirty-two patients received an average dose of 160 mCi of I-125 EGFr concomitantly. The average follow-up period was 34 months. Abnormalities away from the tumor site were interpreted as positive on HMPAO studies, neuropsychological testing, or anatomic imaging; otherwise, they were classified as negative.There were 10/45 (22%) and 75/83 (90%) abnormal HMPAO study results before and after radiation therapy. The HMPAO studies compared with neuropsychological testing showed 3/13 (23%) and 14/17 (82%) concordant abnormalities in addition to tumor site in patients pre- versus postradiation therapy. There was better concordance of HMPAO and anatomic imaging in 22/30 (76%) patients versus 24/67 (36%) patients before radiation therapy. HMPAO imaging after radiation therapy revealed significantly more perfusion abnormalities. There were significant differences between all of the aforementioned parameters. CONCLUSION Tc-99m HMPAO imaging is useful in the evaluation of the effects of radiation therapy on the brain and is highly concordant with neuropsychological testing. It is superior to anatomic studies in identifying radiation-induced changes.

To identify clinical predictive factors for visual outcome in a large series of patients who underwent plaque radiotherapy for uveal melanoma.Clinical factors, including patient data, tumor features, and radiation variables, were analyzed for their impact on visual acuity using Cox proportional hazards regression models.Patients with uveal melanoma and initial visual acuity of 20/100 or better in the affected eye who were treated with plaque radiotherapy between July 1976 and June 1992.Two end points were used to evaluate posttreatment visual acuity: (1) final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and (2) loss of visual acuity (minimal [5 lines Snellen visual acuity] vs moderate [or = 5 lines Snellen visual acuity]).Of 1300 consecutive patients with uveal melanoma treated by plaque radiotherapy, 1106 had a visual acuity of 20/100 or better at the time of treatment. In this group, poor visual acuity was found in 34% at 5 years and 68% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, cobalt isotope, anterior tumor margin posterior to equator, and worse initial visual acuity. Moderate loss of visual acuity of 5 Snellen lines or more was found in 33% at 5 years and 69% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted moderate visual acuity loss included increasing tumor thickness, worse initial visual acuity, notched plaque shape, tumor recurrence, proximity to foveola of less than 5 mm, patient age of 60 years or older, subretinal fluid, and diabetes mellitus or hypertension. When analyzing visual outcome with regard to tumor thickness, ultimate poor visual acuity of 20/200 or worse at 5 years was found in 24% with a small melanoma (or = 3.0 mm), 30% with a medium melanoma (3.1-8.0 mm), and 64% with a large melanoma (8.0 mm). When analyzing visual outcome with regard to tumor proximity to visually important structures, tumors less than 5 mm from the optic disc or foveola demonstrated poor visual acuity in 35% at 5 years, whereas those 5 mm or more from the optic disc and foveola showed poor visual acuity in 25% at 5 years.Ultimate visual acuity after plaque radiotherapy for uveal melanoma depends on many factors, including patient age and general health, initial visual acuity, tumor location and size, subretinal fluid, radioactive isotope, and final tumor control. At 10 years' follow-up, 68% of patients demonstrate poor visual acuity. Visual acuity is most effectively preserved in eyes with small tumors outside a radius of 5 mm from the optic disc and foveola. Arch Ophthalmol. 2000;118:1219-1228

Ubiquitin-conjugating enzymes (Ubc) are involved in ubiquitination of proteins in the protein degradation pathway of eukaryotic cells. Ubc transfers the ubiquitin (Ub) molecules to target proteins by forming a thioester bond between their active site cysteine residue and the C-terminal glycine residue of ubiquitin. Here, we report on the NMR assignment and secondary structure of class I human ubiquitin-conjugating enzyme 2b (HsUbc2b). Chemical shift perturbation studies allowed us to map the contact area and binding interface between ubiquitin and HsUbc2b by1H-15N HSQC NMR spectroscopy. The serine mutant of the active site Cys88 of HsUbc2b was employed to obtain a relatively stable covalent ubiquitin complex of HsUbc2b(C88S). Changes in chemical shifts of amide protons and nitrogen atoms induced by the formation of the covalent complex were measured by preparing two segmentally labeled complexes with either ubiquitin or HsUbc2b(C88S)15N-labeled. In ubiquitin, the interaction is primarily sensed by the C-terminal segment Val70 - Gly76, and residues Lys48 and Gln49. The surface area on ubiquitin, as defined by these residues, overlaps partially with the presumed binding site with ubiquitin-activating enzyme (E1). In HsUbc2b, most of the affected residues cluster in the vicinity of the active site, namely, around the active site Cys88 itself, the second alpha-helix, and the flexible loop which connects helices alpha2 and alpha3 and which is adjacent to the active site. An additional site on HsUbc2b for a weak interaction with ubiquitin could be detected in a titration study where the two proteins were not covalently linked. This site is located on the backside of HsUbc2b opposite to the active site and is part of the beta-sheet. The covalent and non-covalent interaction sites are clearly separated on the HsUbc2b surface, while no such clear-cut segregation of the interaction area was observed on ubiquitin.

The intracellular level of p27(Kip1), a cyclin-dependent kinase (CDK) inhibitory protein, is rapidly reduced at the G1/S transition phase when the cell cycle pause ceases. In this study, we demonstrated that two posttranslational mechanisms were involved in p27(Kip1) breakdown: degradation via the ubiquitin (Ub)-proteasome pathway and proteolytic processing that rapidly eliminates the cyclin-binding domain. We confirmed that p27(Kip1) was ubiquitinated in vitro as well as in vivo. The p27(Kip1) -ubiquitination activity was higher at the G1/S boundary than during the G0/G1 phase, and p27(Kip1) ubiquitination was reduced significantly when the lysine residues at positions 134, 153, and 165 were replaced by arginine, suggesting that these lysine residues are the targets for Ub conjugation. In parallel with its Ub-dependent degradation, p27(Kip1) was processed rapidly at its N terminus, reducing its molecular mass from 27 to 22 kDa, by a ubiquitination-independent but adenosine triphosphate (ATP)-dependent mechanism with higher activity during the S than the G0/G1 phase. This 22-kDa intermediate had no cyclin-binding domain at its N terminus and virtually no CDK2 kinase inhibitory activity. These results suggest that p27(Kip1) is eliminated by two independent mechanisms, ubiquitin-mediated degradation and ubiquitin-independent processing, during progression from the G1 to S phase.

Nedd4 is a ubiquitin-protein ligase containing a calcium/lipid-binding domain, multiple WW domains and a C-terminal Hect domain, which is required for both the ubiquitin transfer and the association with E2 ubiquitin-conjugating enzymes. Nedd4 has been reported to be involved in the selective ubiquitination of some regulatory proteins in transcription and membrane transport.Three mRNA species for human Nedd4 were found to be 6.4-, 7.8- and 9.5-kb in size, and their expression patterns varied among normal tissues and cancer cell lines, indicating the tissue- and cell-specificities of Nedd4 expression. The Nedd4 protein, approximately 120 kDa in weight, was found in the cytoplasm, mainly in the perinuclear region and cytoplasmic periphery, of human cultured cells. Neural differentiation induced not only the down-regulation of Nedd4 but also the localization of the protein to both the cytoplasm and neurites. To identify the ubiquitination pathway that is linked to Nedd4, we demonstrated that specific E2 enzymes, including human Ubc4, UbcH5B, UbcH5C, UbcH6 and UbcH7, could transfer ubiquitin molecules to Nedd4 at the active cysteine residue, whereas E6AP accepted ubiquitins from Ubc4, UbcH5B, UbcH5C and UbcH7. Furthermore, nuclear localization of N-terminal deletion mutant Nedd4 enabled us to investigate the interaction between Nedd4 and E2 enzyme (Ubc4 or UbcH7) in the cell. The simultaneous expression of the full-length Nedd4 and E2 enzyme revealed the both proteins mostly colocalized in the cytoplasmic periphery, while the N-terminal deleted Nedd4 induced the nuclear and perinuclear colocalization with E2 enzyme.Our findings suggested that Nedd4 plays an important role in the cell regulation, including neural differentiation through cooperation with specific E2 ubiquitination pathways.

Purpose: To introduce video surfaceimaging guidance in synchronization with 4D cone‐beam CT(CBCT) scans, and in combination with respiration‐ gated or target‐tracked dose delivery to treat mobile tumors, without collaterally damaging nearby critical structures. Methods: The approach uses the concept that the integral of balanced forces over the moving surfaces is directly proportional to the lung volume changes. The respiratory motions, representing the lung volume variations, were measured with the dynamic volume under the moving surfaces of the thorax and abdomen. Sequential surfaceimages on several patients and volunteers were acquired for the feasibility study. Respiratory motions were repeatedly measured on volunteers undertaking a quiet (normal) or a forced (deep) breath. The dynamic volume under the moving surfaces were robustly fitted with a linear trend and a trigonometric wave function that was compared with the fitted curves for target moving trajectories derived from forty 4D‐CBCT scans. Results: A large chest wall superior‐outward movement was the unique characteristic of a forced breath that had doubled the volume variations and elongated the respiration period from quiet breath of ∼4 seconds to >6 seconds. Under a quiet breath, target motion trajectories could be easily described by single sine functions that were consistent with dynamic surface volume modeling except for having different motion amplitudes. The accuracy in synchronization of the real‐time surface motion with respiration motion was within the measurement uncertainty of ∼2 mm. Conclusions: The analytical results with a hypothetical single sine platform allow us to accurately predict internal target motion with use of real‐time video images. Synchronization of dynamic volume with respiratory motion appears applicable for association of 4D medical imaging with 4D videoimaging.

The optimal management of patients with brain tumors requires knowledge of the tumor characteristics upon presentation and the discovery of recurrence after therapy. Thallium-201 (Tl-201) chloride has shown varying uptake in tumors, depending on their viability and the type and degree of malignancy. This study explores the diagnostic potential of thallium imaging in patients with brain tumors.Forty-three Tl-201 single photon emission computed tomographic scintigrams were performed on 40 patients with intracranial neoplasms, nearly equally divided between patients with no prior treatment and patients who had prior treatment and were suspected to have recurrent tumor and/or radiation necrosis. A thallium tumor index was calculated as the ratio of counts for a region of interest drawn in the lesion area and its mirror image in normal brain tissue. A two-tailed Student's t test was performed to compare the thallium index and histopathologic findings.A value of 1.5 for the thallium tumor index allowed for the best correlation between the prediction of malignancy and the histopathologic results. In the pretreatment group, a thallium tumor index greater than 1.5 correlated with high grade malignancy, and less than 1.5 correlated with either a well differentiated astrocytoma or benign cyst. In the posttreatment group, a thallium tumor index greater than 1.5 correlated with recurrent and/or residual malignant tumor.For those patients undergoing initial evaluation, the thallium study can help in the differential diagnosis of an intracranial mass lesion and offers confirmation of results of biopsy. For those patients who already have received treatment, the study can be used to detect recurrent or residual tumor.

A gene whose overexpression can endow Saccharomyces cerevisiae cells with resistance to HM-1 killer toxin was cloned from an S. cerevisiae genomic library. This gene, designated HKR1 (Hansenula mrakii killer toxin-resistant gene 1), contains a 5.4-kb open reading frame. The predicted amino acid sequence of the protein specified by HKR1 indicates that the protein consists of 1,802 amino acids and is very rich in serine and threonine, which could serve as O-glycosylation sites. The protein also contains two hydrophobic domains at the N-terminal end and in the C-terminal half, which could function as a signal peptide and transmembrane domain, respectively. Hkr1p is found to contain an EF hand motif of the calcium-binding consensus sequence in the C-terminal cytoplasmic domain. Thus, Hkr1p is expected to be a calcium-binding, glycosylated type I membrane protein. Southern and Northern (RNA) analyses demonstrated that there is a single copy of the HKR1 gene in the S. cerevisiae genome, and the transcriptional level of HKR1 is extremely low. Gene disruption followed by tetrad analysis showed that HKR1 is an essential gene. Overexpression of the truncated HKR1 encoding the C-terminal half of Hkr1p made the cells more resistant to HM-1 killer toxin than the full-length HKR1 did, demonstrating that the C-terminal half of Hkr1p is essential for overcoming the effect of HM-1 killer toxin. Furthermore, overexpression of HKR1 increased the beta-glucan content in the cell wall without affecting in vitro beta-glucan synthase activity, suggesting that HKR1 regulates beta-glucan synthesis in vivo.

The monoclonal antibody anti-epidermal growth factor receptor (EGFr) antibody-425, against the epidermal growth factor receptor, has the potential to bind specifically to gliomas and not normal brain tissue. A prospective study was conducted (1986-1988) to evaluate the use of Indium-111 (111In)-labeled anti-EGFr-425 in the localization of gliomas before radioimmunotherapy with Iodine-125 (125I)-labeled anti-EGFr-425.Twenty-eight patients with intracranial neoplasms were injected intravenously with an average dose of 2.2 mCi 111In-labeled anti-EGFr-425. Planar and single-photon emission computed tomography scans were performed after 48 and 72 hours. Control studies also were performed in two cases with 111In-labeled Co 17-1A (an antibody to colorectal cancer) and in one case with unlabeled 111In chloride.The immunoscintigraphic findings were generally in good agreement with computerized tomographic findings. The definitive diagnosis was established by biopsy findings: 23 gliomas (1 Grade I, 5 Grade II, 6 Grade III, and 11 Grade IV), 1 meningioma, and 4 metastatic lesions. The localization of gliomas with 111In-labeled anti-EGF-425 had a sensitivity of 0.96, a specificity of 0.60 and an accuracy of 0.90.Immunoscintigraphy with 111-In labeled anti-EGFr-425 can be useful in the management of malignant gliomas, especially before radioimmunotherapy with 125I-labeled anti-EGFr-425.

A vibration diagnostic system has been developed for the main steam turbine of a 375MW fossil power plant. The diagnostic system continuously monitors the shaft vibration of the main steam turbine as well as various process data. Also, the system uses an Al expert system to diagnose the cause of vibration owing to the turbine failure or malfunctions as they occur or tend to occur.

Purpose: For an IGRT prostate cancertreatment using CT simulation and Cone‐beam CT(CBCT), bone‐based automated matching and target‐ volume‐based manual matching are compared with each other to comprehend their characteristics and any major difference. Methods: 20 patients of prostate or prostate/seminal vesicletreatment were selected. All of the patients were treated with XVI‐guided VMAT or IMRT. Each patient has his cone‐beam CTimages in the database. The patient's daily shift information of both manual matching and automated matching was taken from XVI. Then, five patients' data that have the largest deviation between two methods were chosen, and were analyzed by Pinnacle3: the shift information from the manual and automated matching was applied to the plan, and then prostate as GTV and critical organs of the rectum and bladder were contoured. Based on the composite plan, the dose on each organ was computed for both manual and automated matching. Results: PTV from each treatment plan with margin of 5 mm all around except for 3‐mm margin in posterior direction turned out to be wide enough to cover the whole prostate for both manual and automated matching. After aligning each patient's skin‐marking and laser, IGRT suggests 0.5 to 2 cm shifts from the aligned position in posterior/anterior and superior/inferior directions. In spite of the full coverage of GTV, the rectum and bladder received doses significantly different from the two matching approaches. Conclusion: The current margin for PTV seems to work properly so that both GTVs from manual matching and automated matching are fully covered. For IGRT, skin‐marking alignment becomes less important based on the matching data. Importantly, we found bone‐based matching and target‐based matching could result considerable difference in V90 of the rectum and bladder.

Twenty-six patients (20 females, 6 males) with localized tumors of the pelvis, including 3 primary advanced (PRIM), 7 persistent (PERS), 10 recurrent (REC), and 6 metastatic (MET) tumors, were treated with a combination of low-dose rate (LDR) iridium 192 interstitial radiotherapy (IRT), interstitial 915 MHz microwave hyperthermia (IHT), and external beam radiotherapy (RT). Histological diagnoses were squamous cell carcinoma in 13 (50%), adenocarcinoma in 12 (46%) and soft tissue sarcoma in 1 (4%) lesion. Tumor sites were cervix in 8 (31%), colorectum in 6 (23%), vagina in 4 (15%), anus in 3 (12%), ovary in 2 (8%), and other sites in 3 (12%) lesions. IHT was administered immediately before iridium 192 was placed and after its removal for 45-60 minutes at 41-44 degrees C. On December 31, 1991 median follow-up was 25 months (mean: 23 months; range: 5-65 months). At 3 months follow-up (FU), complete remission (CR) occurred in 17 (65%), partial remission (PR) in 7 (27%), and no change or progressive disease (NC/PD), in 2 (8%) lesions. At 12 months FU, in 16 of 21 patients (76%) local control (LC) was achieved, with 1 (5%) patient exhibiting a slow tumor regression. After combined IRT-IHT locoregional relapse or tumor regrowth occurred in 8/26 (31%): 5 (19%) outside and 3 (12%), inside the previously treated volume; relapses occurred within 8-30 (mean: 18) months of follow-up. Factors influencing initial (3 months FU) and long-term tumor response (12 months FU) included tumor class, tumor volume, total radiation dose, and thermal parameters with "good quality of heating" (TQ 41 degrees C > or = 75%) and high minimum tumor temperature (Tmin(av) > or = 41 degrees C). Treatment toxicity was acceptable: whereas 8 (31%) patients experienced acute side effects, which subsided within weeks, 7 (27%) developed long-term complications. Thermal damage was associated with IHT treatments exceeding maximum average temperatures of > or = 44 degrees C and maximum peak temperatures of > or = 45 degrees C.

Malignancies localized in the pelvis are characterized by an increasing incidence and a high mortality due to local tumor progression. In 1990 the cancer facts and figures of the American Cancer Society indicated an estimated 45 000 new cases of and 7600 deaths from rectal cancer, 46 500 new cases of and 10000 deaths from uterine (cervix uteri and corpus/endometrium) cancer, 49 000 new cases of and 9700 deaths from bladder cancer, and 106000 new cases of and 30000 deaths from prostate cancer (American Cancer Society 1990).

We have investigated the function of the C-terminal and the third intracellular domains of the ETA receptor by expressing truncated and mutated ETA receptors in COS-7 and CHO cells. All the C-terminal truncated ETA receptors were produced at a similar expression level and were detected in the cell membrane using indirect immunostaining. The sizes of the truncated ETA receptors were decreased in proportion to the molecular mass of the truncated amino acid sequence. When the ligand binding activities were determined for various truncated ETA receptors, it was found that more than eight amino acid residues at the proximal cytoplasmic tail of the ETA receptor were required for ET-1 binding. In addition, the deletion of 16 C-terminal amino acid residues from the third intracellular loop severely decreased the ligand binding activity. It seems that deletion of these cytoplasmic domains of the ETA receptor influences the three-dimensional structure of the ligand binding site located in the extracellular domains. The ETA receptor required more than 13 amino acid residues in the proximity of C-terminal cytoplasmic tail and 10 amino acid residues in the C-terminal region of the third intracellular loop to induce the ET-1 dependent increase in intracellular calcium concentration. Both regions are possibly coupled with G-protein to transmit the ET-1 signal.

e16511 Background: Pelvic lymph node dissection (LND) requirement to adequately stage endometrial cancer has been subject of debate. We conducted an outcome analysis of clinical stage I endometrioid endometrial adenocarcinoma (EEA) patients who underwent surgery with tailored LND and adjuvant therapy (radiation (RT) or chemotherapy) between 1997 and 2008. Methods: Retrospective chart review was performed at our institution. All patients underwent exploratory laparotomy, cytology, total abdominal hysterectomy and bilateral salpingoophorectomy. Pelvic and para-aortic LND was perforned in high-risk patients when technically possible. Cox proportional hazards and the Kaplan Meier method were used for data analysis. Results: 119 patients (stage I 92, II 11, III 15, and IV 1) were identified. Median BMI was 34 and 81% had significant co-morbidities. 50% underwent para-aortic LND (median 4 nodes) and 25% underwent pelvic LND (median 15 nodes), of whom 8% and 10% were positive, respectively. Postoperative complications occurred in 22%. 26% received RT. With a mean follow-up of 20 months, 5-year progression-free survival (PFS) and overall survival (OS) was 71% and 84%. The OS for stage I and IIIC was 88% and 83%, respectively. OS for patients with or without LND was not statistically different ( 73% vs.82%). 12 (10%) recurrences were noted, 8 of which were hematological (HF) with a 5-year HF probability of 21%. On multivariate analysis only myometrial invasion > 50% was independent risk factor for HF. Patients receiving RT showed a trend toward decreased in local recurrences ( 0% vs.30% p = 0.1) but no improvement in OS. Conclusions: In patients with EEA, a tailored approach to LND and adjuvant therapy results in good outcome, but many still have therapy-associated adverse events. Although no difference was found in OS between patients who underwent LND and those who did not, similar survival for patients with stages I and IIIC suggests that therapy directed by the knowledge of nodal status may have an impact on survival. No significant financial relationships to disclose.

Eight patients suffering from papulovesicular light eruption (PVLE) were phototested for reproduction of skin lesions with FL20SE and FL20BLB. Of the 8 patients, 50.0% developed typical lesions of PVLE at the test site by provocative phototesting with FL20SE (3 daily exposure of 2MED). In these patients, similar lesions were induced by the provocative test with FL20BLB for 2 consecutive days without filter, but no eruptions were induced when a sharp cut filter UV-35 was used. In conclusion, it is important to consider not only UVB but also the border spectrum between UVB and UVA (320-340 nm) as the action spectrum of PVLE.

The 5' and 3' ends of the lux mRNA of Vibrio harveyi, which extends over 8 kilobases, have been mapped, and two new genes, luxG and luxH, were identified at the 3' end of the lux operon. Both S1 nuclease and primer extension mapping demonstrated that the start site for the lux mRNA was 26 bases before the initiation codon of the first gene, luxC. The promoter region contained a typical -10 but not a recognizable -35 consensus sequence. By using S1 nuclease mapping the mRNA was found to be induced in a cell density- and arginine-dependent manner. The DNA downstream of the five known V. harveyi lux genes, luxCDABE, was sequenced and found to contain coding regions for two new genes, designated luxG and luxH, followed by a classical rho-independent termination signal for RNA polymerase. luxG codes for a protein of 233 amino acids with a molecular weight of 26,108, and luxH codes for a protein of 230 amino acids with a molecular weight of 25,326. The termination signal is active in vivo as demonstrated by 3' S1 nuclease mapping, confirming that the two genes are part of the V. harveyi lux operon. Comparison of the luxG amino acid sequence with coding regions immediately downstream from luxE in other luminescent bacteria has demonstrated that this gene may be a common component of the luminescent systems in different marine bacteria.

681 Background: Differentiating primary breast tumors that are prone to develop metastasis (Group-I) from those that are not (Group-II) is critical to design appropriate treatments. Previously we isolated several metastasis associated DNA sequences (MADSs) and recently published that MADS-IX and -XI are informative in more than 60% of cases by PCR screening. Our previous attempts to supplement the PCR method with Fluorescence In Situ hybridization (FISH) for screening MADS-IX on primary tumor tissue sections were not consistent due to overlapping of cells and unclear cellular margins. Here we present our results with MADS-IX as a FISH probe in distinguishing the Group-I and Group-II primary breast tumors by screening tumor cell touch preparations. Methods: The DNA samples from primary and metastatic tumor cells isolated from 12 breast carcinoma patients had been compared with the matching normal cell DNA by the Representational Difference Analysis (RDA) and isolated 15 MADSs. Tumor cells were isolated by ...

A cDNA fragment coding for human c-myc was inserted into the genome of the baculovirus Autographa californica nuclear polyhedrosis virus adjacent to the strong polyhedrin promoter. Insect cells infected with the recombinant virus produced significant amounts of c-myc protein, which constituted the major phosphoprotein component in these cells. By immunoprecipitation and immunoblot analysis, two proteins of 61 and 64 kilodaltons were detected with c-myc-specific antisera. The insect-derived proteins were compared with recombinant human c-myc-encoded proteins synthesized in Escherichia coli and Saccharomyces cerevisiae cells. The c-myc gene product was found predominantly in the nucleus by subcellular fractionation of infected insect cells.

SUMMARY An infant boy born to a mother with systemic lupus erythematosus developed multiple morphea and annular erythematous lesions. The annular lesions appeared on his face, back, chest and extremities one month after birth and faded within 7 months. The sclerotic lesions progressed until the age of 6 months and remain on his back, chest, right cheek, the nape of the neck and left shoulder at the age of 3 years. Histological findings in the sclerotic lesions were consistent with scleroderma. Serological tests, performed at 14 months of age, were within normal limits. The mother developed acute SLE and died of cardio-renal failure 8 months after the delivery. It is highly probable that maternal factors transferred through the placenta caused the sclerotic lesions in the infant.

Latex particles were covalently linked to the 5'-proximal region of oligo(dT)30. The resultant oligo(dT)30-Latex was tested for its hybridizability to poly(A) containing mRNA. Several advantages were noted as compared to the conventional oligo(dT)30-cellulose column chromatography; (1) a highly efficient (approximately 95%) hybridization occurs in a short reaction period (10min), (2) more than 95% of poly(A) mRNA can be recovered from oligo(dT)30-Latex by a simple heating followed by brief centrifugation, (3) multiple samples can be handled simultaneously and moreover, (4) the poly(A)-mRNA on the oligo(dT)30-Latex can be directly transcribed by AMV reverse transcriptase to form the cDNA. These properties of oligo(dT)30-Latex promise an excellent reagent for nucleic acid technology.

Thirty patients suffering from polymorphous light eruption (PLE), selected by criteria pointing to UVB sensitivity, were phototested for reproduction of skin lesions. Twenty-seven patients (90.0%) had symptoms compatible with or very similar to papulovesicular light eruption (PVLE). Of the 30 patients, 56.7% developed typical lesion of PLE at the test site by provocative phototesting with UVB. Eruptions of the immediate onset type were apt to be reproduced by multiple repeated irradiation, but those of the delayed onset type were reproduced by a single high-dose exposure. In addition, pruritus at the test site seen in all patients was thought to be an important diagnostic symptom. It was obvious that UVB played an etiological role in PLE, including PVLE.

Sib patients with xeroderma pigmentosum (XP), XP90TO (42 years old, male) and XP92TO (40 years old, female, were assigned to group F by the complementation analysis in hybridized heterodikaryons. The XP90TO and XP92TO fibroblasts exhibited the typical XPF characteristics of a threefold higher sensitivity to the lethal effect of 254 nm UV and a reduced level of 12% unscheduled DNA synthesis (UDS) compared with normal cells. Clinically, both patients manifested moderate to severe acute sun sensitivity by age 8, pigmented freckles by age 10 and skin malignancies at higher ages (6 basaliomas at 42 years in XP90TO; 1 basalioma at 41 years in XP92TO). Despite the still currently sun-sensitive state, the patients showed normal minimal erythema dose (MED) at monochromatic wavelengths of 290, 300 and 305 nm but abnormally delayed peaking of erythema reaction at 48 h after exposure. After irradiation with more than 3 MED, XP92TO showed a long persistence of induced erythema for at least 7 days. A review of the 16 reported XPF patients indicated mild skin manifestations, no neurological abnormalities, and more delayed skin carcinogenesis at a lower frequency than that in XPA patients. In addition, we have collected clinical information from Japanese XP patients in rare complementation groups D and E and reviewed their clinical and photobiological characteristics.

mRNA from human HL-60 cells was used to prepare a cDNA library, from which two full-length clones that encompass the complete c-myc coding region were isolated. One clone, pM1-11, contains all three exons of human c-myc. The second clone, pM4-10, represents a relatively rare transcript that initiated in the first intron and includes the coding exons 2 and 3. The cDNA insert in pM1-11 was used to express the human c-myc protein in both prokaryotic and eukaryotic cells. Insertion of the coding sequences in exons 2 and 3 into the appropriate expression vectors yielded detectable c-myc protein in Escherichia coli lacking the Lon protease and in Saccharomyces cerevisiae upon induction. The protein produced in E. coli has an apparent size of 60 kDa and appears to be unmodified, as it is identical in size to the protein synthesized in an in vitro system. In contrast, yeast cells synthesize two myc proteins, of 60 kDa and 62 kDa. The difference in apparent molecular mass between the two proteins appears to be due, in part, to phosphorylation. Subcellular fractionation of yeast cells showed that the c-myc phosphoprotein is located predominantly in the nuclear fraction.