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Objective Solitary extramedullary plasmacytoma (SEP) of the thyroid is rare, and its clinical and pathologic features are not entirely understood. Generally, patients with SEP of the thyroid also present with Hashimoto thyroiditis. We report, for the first time, a case of SEP of the thyroid in a patient with subclinical hyperthyroidism. Methods A 46-year-old woman presented to the emergency department with symptoms consistent with a panic attack. Following a physical examination, neck ultrasonography, and laboratory tests, we determined that the patient was hyperthyroid and possessed a toxic multinodular goiter. The patient elected to undergo a total thyroidectomy to treat the subclinical hyperthyroidism and to remove the nodules. Results SEP diagnosis requires consideration of the systemic spread of multiple myeloma and a combination of immunohistochemical examination, imaging, and other laboratory tests. Upon further examination, we confirmed SEP through the following criteria: the absence of kidney failure or hypercalcemia, a biopsy demonstrating plasma cell histology, a lack of bone or tissue involvement, and low serum myeloma protein concentration. The immunophenotype of the tumor cells further confirmed SEP diagnosis, with positivity for CD138, CD79a, and lambda light chain antibodies and no reactivity toward cyclin D1. Conclusion This case fulfilled the criteria for SEP, and we were able to rule out multiple myeloma. Currently, no standard treatment exists for SEP. Yet, the prognosis remains encouraging. Going forward, SEP of the thyroid should be considered in the differential diagnosis of a patient with subclinical hyperthyroidism and a toxic multinodular goiter.

A 24-year-old male Egyptian complained of cramp-like upper abdominal discomfort and weight loss (3 kg) over 4 weeks. Physical examination merely gave evidence of the weight loss and of a slightly prominent gas-filled abdomen, mild diffuse abdominal tenderness and considerable borborygmus. Radiology of the intestines revealed chronic subileus of the small intestine caused by stenosis of the ileocaecal valve, which was impassable by coloscope. Biopsy suggested schistosomiasis of the ileocaecal valve. Examination of the resected ileocaecum showed a typical signet-ring carcinoma of the ileocaecal valve which had infiltrated all layers but had not metastasised to the regional lymph nodes (pT3, N0, M0). Typical eggs of Schistosoma haematobium were present in the mucosa of the tumour segment and of the neighbouring tissues. It is possible that chronic intestinal schistosomiasis is a potentially precancerous condition, similar to schistosomiasis of the urinary bladder.

The production of vascular endothelial growth factors (VEGF), a major cause of neoangiogenesis, is a prerequisite for tumor growth and invasion. VEGF have also been shown to be important for the formation of osteoclasts. Because giant cell tumors of bone (GCT) are frequently hypervascular and have the ability to recruit macrophages and multinucleated osteoclast-like giant cells, we evaluated the levels of VEGF gene transcript in several of these tumors using Northern blot analyses, semiquantitative reverse transcription polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry. Our results showed that three major isoforms of VEGF (121, 165, and 189) were expressed in all cases of GCT investigated, with isoform 121 transcripts the most abundant. By both FISH and immunohistochemistry, we have shown that VEGF was present in spindle-shaped stromal-like tumor cells, round macrophage-like cells, and osteoclast-like multinucleate giant cells. Moreover, we have shown that the levels of VEGF gene expression but not microvessel density correlated with Enneking's clinical stage of GCT. There were higher levels of VEGF gene expression in stage III GCT than in stage I/II GCT (P [lt ] .0357). In conclusion, our results indicate that overexpression of VEGF may be associated with the advanced stage of the neoplasm. HUM PATHOL 31:804-812.

Giant cell tumor of bone (GCT) is one of a few neoplasms in which the macrophage/osteoclast precursor cells and osteoclast-like giant cells infiltrate the tumor mass. Monocyte chemoattractant protein 1 (MCP-1) is a potent chemotactic factor specific for monocytes. In search of relevant cytokines that may enhance the recruitment of these reactive cells, we evaluated the localization and regulation of MCP-1 mRNA and protein in GCT by using Northern blot analysis, in situ hybridization and immunohistochemistry. We also determined whether conditioned medium obtained from GCT cultures can recruit human peripheral blood monocytes (CD68+) in an in vitro chemotactic assay. Using Northern blot analysis, we detected the specific gene transcript for MCP-1 in all GCT samples tested. In situ hybridization and immunohistochemistry revealed that both MCP-1 gene transcript and protein were consistently present in the cytoplasm of stromal-like tumor cells of GCT. Treatment of mononuclear cells from GCT at third passage with TGF-β1 for 24 h increased the level of MCP-1 mRNA in a dose-dependent manner, with the maximum effect at 1 ng/ml. Conditioned media from GCT cultures promoted the chemotactic migration of CD68+ peripheral monocytes, an activity which was abolished by the addition of MCP-1 antibody to the conditioned medium. Thus, the results of this study suggest that recruitment of CD68+ macrophage-like cells may be due to the production MCP-1 by stromal-like tumor cells. These CD68+ cells may originate from peripheral blood and could have the capability of further differentiating into osteoclasts in the tumor. J. Cell. Biochem. 70:121–129, 1998. © 1998 Wiley-Liss, Inc.

Plasminogen activation is observed in the human epidermis during re-epithelialization of epidermal defects. The activation reaction depends on plasminogen activators (PAs) associated with re-epithelializing keratinocytes. PA inhibitor type 2 (PAI-2) is thought to be a major epidermal PA inhibitor in keratinocytes. However, no data are available on the expression of PAI-2 in keratinocytes during epidermal regeneration. We have therefore analysed PAI-2 at the mRNA and protein level in keratinocyte cultures as well as in epidermal lesions in which re-epithelializing keratinocytes were apparent. We found that PAI-2 expression at the mRNA and protein level was negatively correlated with the cell density in regular keratinocyte cultures. In organotypic cocultures, in which the transition from a re-epithelializing to a sedentary phenotype can be studied, PAI-2 was most strongly expressed in early cultures prior to formation of a differentiated epidermis-like structure. We found a strong expression of PAI-2 in keratinocytes that re-epithelialized dermal burn wounds or lesions caused by the autoimmune blistering disease pemphigus vulgaris. Our results suggest that not only PAs, but also a major PA inhibitor, PAI-2, are expressed in keratinocytes that are actively involved in re-epithelialization.

Phosphorescence of low density polyethylene induced by 6 MeV electrons was observed in the temperature region 10–285 K. Decay of phosphorescence at temperatures below γ-relaxation region follows monoexponential equation. Above this transition, for T ⩾ 169 K kinetics can be described by two term relation. At low temperatures phosphorescence life time τ T is temperature independent while at higher ones τ T exhibits strong temperatures dependence. Time resolved emission, spectrum at T = 20 K is presented. Tentative conclusions are postulated.

Tartrate-resistant acid phosphatase (TRACP) and carbonic anhydrase II (CA II) are key enzymes responsible for osteoclastic bone resorption. In this study, we proposed that estrogen loss in postmenopausal osteoporosis may enhance gene expression of TRACP and CA II, and subsequently increase osteoclastic bone resorption. We have, therefore, used the ovariectomized rat model of postmenopausal bone loss to investigate changes at the gene transcriptional level in osteoclastic bone-resorbing enzymes in ovariectomized (OVX) rats, sham ovariectomized (S-OVX) rats, and estrogen-treated ovariectomized (E-OVX) rats. We have demonstrated for the first time that ovariectomy in rats enhances gene expression of TRACP, and CA II. The mRNA levels in OVX were approximately three- and four-fold higher, respectively, than those in S-OVX. Enhancement was observed 1 week after ovariectomy and transcripts remain high during the experimental period of 8 weeks. Administration of 17 beta-estradiol to OVX (E-OVX) reduced gene expression of these osteoclastic bone-resorbing enzymes 18 hours after injection. It appeared that the suppression of the osteoclastic bone-resorbing enzymes by 17 beta-estradiol was most effective during the first 1-2 weeks but the degree of suppression was reduced at 8 weeks after ovariectomy. In conclusion, our results suggest that estrogen prevents bone loss by reducing the mRNA levels of osteoclastic bone-resorbing enzymes in bone tissue.

Distribution function D ( E ) of electrons trapped in irradiated LDPE was calculated on the basis of time resolved absorption spectra recorded at temperatures of 20–250 K. Variation of absorption spectra with time and temperature were observed and discussed in terms of simultaneous decay and relocation of electrons from shallow to deeper traps. Results obtained imply domination of trap limited transport for shallowly trapped electrons. For deeper traps, hopping mechanism is prevailing.

The process of recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced endochondral ossification involves 1) the proliferation and differentiation of mesenchymal cells into chondroblasts and osteoblasts; 2) the production and maturation of cartilage and bone matrix; and 3) the differentiation of circulating osteoclast precursor cells into osteoclasts. Currently the molecular mechanisms of these complex sequential events are unknown. It seemed reasonable to us to assume that communication between cells through soluble mediators during bone induction by rhBMP-2 may play an important role in the sequential differentiation of chondroblasts, osteoblasts, and osteoclasts. We have therefore used a human osteoblast-like initial transfectant cell line (HOBIT) to study the effect of rhBMP-2 on gene expression of interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-beta 1), both of which affect osteogenesis and ostoeclastogenesis. Our results have demonstrated that rhBMP-2 acts on HOBIT cells to stimulate expression of IL-6 and TGF-beta 1 genes and the production of IL-6. Enhancement of gene expression of IL-6 and TGF-beta 1 by rhBMP-2 was both sensitive (half maximal effect at approximately 10 ng/ml) and potent (maximum induction was approximately four and threefold greater than controls, respectively). Time course studies showed that the induction of TGF-beta 1 and IL-6 mRNA occurs within short periods--4 and 8 hours after exposure to rhBMP-2, respectively. Interestingly, these effects, however, were not accompanied by the mitogenic action of rhBMP-2. It suggests that rhBMP-2 enhances IL-6 and TGF-beta 1 production during osteogenesis and at least in part mediates the complex sequential differentiation of chondroblasts, osteoblasts, and osteoclasts during rhBMP-2-induced endochondral ossification.

CA 19-9 is used as a tumour marker of the upper gastrointestinal tract. However, extremely elevated CA 19-9 levels are found also in patients with benign diseases. Cholestasis was present in 97.1 % of patients with high elevated CA 19-9, independent of their primary disease. 50% of patients with non-malignant diseases and increased CA 19-9 levels showed liver cirrhosis, cholecystitis, pancreatitis and/or hepatitis. In 8.8% no explanation was found for the extremely high CA 19-9 level. The results provide evidence of different factors influencing the CA 19-9 level.

The pulse radiolysis of low density polyethylene (LPDE), using optical absorption detection and emission spectroscopy, has been investigated in the temperature range 6–150 K, the experiments being complemented by a study of the photoluminescence. It was found that excitons can be autolocalized at temperatures below 20 K, and this process is strongly dependent on the thermal history of the sample.

The kinetics of the conductivity decay in polyethylene film induced by 6 MeV electron pulses was studied using d.c. conductivity techniques. The influence of external field and radiation dose on the transient current has been examined, and the drift mobility of charge carriers was found to be 3.1 × 10-2 cm2V-1s-1.

Influence of MgO surface coverage with benzene on the mechanism of radiolysis has been investigated. Products of degradation of benzene are mainly produced for low surface coverage, whereas for high surface coverage — oligomeric and polymeric products, such as biphenyl (main product), o-terphenyl and products of their hydrogenation are obtained.

Thioformaldehyde S,S-dioxide (sulfene) has a highly reactive C=S bond. The estimation of the length and strength of this bond depends largely on the quantum chemical approximation selected. In comparison with ab initio schemes, the use of semiempirical MINDO/3, MNDO, AM1, and PM3 schemes involves difficulties related to the parameters for sulfur.

Over the past twenty years intensive research is being focused on deciphering the ability of the mammalian fetus to heal early gestation skin wounds without scar formation. Although this phenomenon remains poorly understood. This review highlights recent experimental studies concerning the cellular, matrix and growth factor components of scarless fetal wound repair.

The luminescence and surface conductivity induced by short electron pulses in polycrystalline MgO has been studied in the temperature range from 77 to 778 K. The origin of main luminescence bands at 450,520 and 600 nm is discussed. The dominant role of F + ( F + s ) centres as a radiative recombination centres is suggested. The kinetics of the luminescence observed at low temperature region from 77 to 293 K can be explained in terms of tunnelling process leading to decay of excess charges.

Laser treatment of the cutaneous vascular lesions gained approbation and well-established position among plastic surgery techniques. Rapidly evolving laser market delivers us modem and safer devices. In the paper we discuss the most common vascular lesions and available lasers used to treat them. Described indications and safety rules might be useful for many specialists for their patient therapy choice.

Lesions of port-wine stain (PWS) type are the most commonly occurring vascular malformations of the skin which concerns about 0.3% of the population. These important from aesthetic and psychological points of view capillaries malformations have always been difficult for treatment. Previously applied methods consisting in cryosurgery, dermabrasion, radiation therapy or surgery and skin grafting produced unsatisfactory results. It was only when highly selective lasers were introduced that PWS could be treated effectively and safely. A lot of available lasers and lack of experience of the health care providers result in not always proper qualification of the lesions to the given laser type. The aim of the study was to present a prospective analysis of the efficacy of treatment of PWS vascular malformations by means of KTP 532 nm laser. From January 2003 to May 2005, 155 patients (115 women, 40 men) aged from 2 to 62 years (mean age 18.23) were treated by means of laser at the Plastic Surgery Hospital in Polanica Zdrój, Poland. In the investigated population, the vascular malformation was a component of Sturge-Weber syndrome in 7 patients, Klippel-Trenaunay syndrome--in 2 patients, while in one case it accompanied Recklinghausen disease. The vascular lesions had not been treated before in majority of cases, while in 37 patients the laser therapy was the continuation of other previously attempted treatment, which included excision and skin grafting, argon laser therapy, radiation therapy and pulsed dye laser treatment. The procedures were performed with at least 4-week intervals without, or under local and in children general anaesthesia. Therapeutic efficacy was evaluated independently by 3 surgeons and a photographer on the basis of Subjective Scoring System (SSS) comparing simultaneously shown pictures of the patients taken prior to and after the last procedure. The outcomes of treatment were classified according to a 4-degree scale: excellent outcome--75-100% improvement, with 100% perceived as eradication of the lesion; good--50-74% improvement; fair--25-49% improvement and poor--less than 25% improvement, including no observable improvement. In 81% of the lesions (126 patients) treatment with KTP 532 nm laser produced significant improvement which was found satisfactory by the patient. excellent outcome of treatment was obtained in 49 patients (31%), good in 42 (27%), fair in 35 (23%). However, despite many laser treatments using various energy and pulse duration, there was almost not observable improvement in 19% of the study population (29 patients). The PWS which failed to treatment were most commonly located on the limbs. The results of treatment was poor in 74% of malformations which were located beyond the face and neck (all of them were on the limbs). There was no episodes of scarring or persistent pigmentary changes in any of the patients.1. KTP (532 nm) laser is an effective and safe tool in the management of capillary malformations of PWS type. 2. The treatment is especially effective in adults and in lesions localized to the face and neck area. 3. Port-wine stain localized on the trunk and extremities often appears to be KTP laser resistant.

An investigation has been made of fluorescence lifetimes in low-density polyethylene (LDPE). Samples of material 50 /spl mu/m thick were irradiated in air to various doses between 0 and 1 MGy using an electron accelerator. This caused enhanced and rapid ageing of the LDPE, the behaviour of which was then investigated using a time-correlated single photon counting fluorometer. The results demonstrate that fluorescence is a function of radiation absorbed dose. The greater the dose, the more rapidly does the fluorescence signal decay. This derives from the fact that the structure of the LDPE is changing via crosslinking and oxidation and thus the aged polymer network is unable to vibrate as readily as can unaged pristine material. The results indicate that fluorescence could, in principle, be used as a tool for the condition monitoring of polymer insulation.

The authors show that high-energy electron irradiation of polyethersulphone brings about changes in the behaviour of both its steady-state and time-resolved fluorescence. This is due largely to the degree of crosslinking that takes place within the material, although it is recognised that chain scission also occurs to a certain extent. Thus, fluorescence is demonstrated to be a viable technique for monitoring structural changes in polymers.

Investigations were made of current transients induced in polyimide by pulses of bremsstrahlung radiation. Test specimens, 50 /spl mu/m thick, were mounted in a vacuum chamber that was positioned as the target in the output beam of an electron accelerator. The electron beam was converted to bremsstrahlung via its interaction with a 4 mm thick lead shield placed in front of the test chamber. The test specimens were stressed by direct voltages to give applied fields approaching 10/sup 7/ V/m and the current following a bremsstrahlung pulse was recorded on a fast oscillograph. Experiments were carried out with both fresh material and material irradiated by electrons to various doses, with a maximum of 100 kGy. It was found that there were marked differences in behaviour between fresh and irradiated material. With positive dc polarisation and an unirradiated sample the output current signal showed an initial negative peak followed by a positive one, the amplitudes of the peaks increasing with increasing polarising voltage. The negative peak decreased in amplitude with increasing radiation dose and at 5 kGy had practically disappeared completely. The positive one remained and increased in amplitude with dose and field. The material also demonstrated a diode effect, in that with a negative bias no output signal was observed. Upon reversal of the field, however, a very large positive pulse was evident.

This "Ask the Experts" column addresses two concerns related to use of Depo-Provera. The first question relates to the clinical significance of frequent urination. Two of the three experts assert that frequent urination in a Depo-Provera user is unlikely to be related to method use; urinary tract infection and diabetes are more probable causes. The third notes that hypoestrogenicity could be a factor and suggests examination of the vagina for atrophy, which could cause the tissue around the urethra to become atrophic. The second question addresses techniques for confirming menopause in Depo-Provera users. The experts concur that measurement of follicle-stimulating hormone in perimenopausal Depo-Provera users lacks predictive value. Recommended, instead, is continuation of Depo-Provera with supplemental estrogen until the woman is in her mid-50s. At that time, conventional hormone replacement therapy can be initiated.

This article presents insights on the efficacy of oral contraceptives (OCs) in women who smoke. It presents opinions of three Contraceptive Technology Update board members, namely, Dr. Michael Rosenberg, Dr. Andrew Kaunitz, and Susan Wysocki. Two lines support that the anti-estrogenic effect of smoking reduces the effectiveness of OCs. First, several studies indicate that spotting and bleeding were more frequent in smokers. Smoking reduces estrogen levels in the body; hence smokers experience irregular bleeding with the pill. This is the reason why smokers are at a higher risk of developing osteoporosis in the later years. Breakthrough bleeding also demonstrates higher OC failure rates among smokers. A single study on the efficacy of OCs in smokers revealed a highly diminished effectiveness of the pill in this group. Second, laboratory analysis indicates that estrogen increases the catabolism of estrogen, providing a rationale for these observed effects. The use of low-dose pills in smokers is guided by safety concerns since smoking enhances the development of thrombosis. A balance of the safety and efficacy risks is necessary especially with the increasing use of low-dose OCs.

A complementary DNA (cDNA) encoding the rat homologue of receptor activator of NF-kappaB ligand/osteoprotegerin ligand/osteoclast differentiation factor/tumor necrosis factor (TNF)-related activation-induced cytokine (RANKL/OPGL/ODF/TRANCE) was cloned and sequenced from tibias of ovariectomized (OVX) rats. The predicted amino acid sequence of rat RANKL (rRANKL) has 84% and 96% identity to that of human and mouse RANKL, respectively, and 35% and 37% similarity to that of human and mouse TNF-related apoptosis-inducing ligand (TRAIL), respectively. RANKL transcripts were expressed abundantly in the thymus and bone tissues of OVX rats. rRANKL has a single hydrophobic region between residues 53 and 69, which is most likely to serve as a transmembrane domain. The long C-terminal region containing beta-sheet-forming sequences of the TNF-like core is considered the extracellular region. Three truncated domains within the TNF-like core region were expressed as glutathione S-transferase (GST) fusion proteins and investigated for their ability to induce osteoclastogenesis. The results showed that GST-rRANKL (aa160-318) containing the full TNF-like core region had the highest capability to induce the formation of osteoclast-like cells from RAW264.7 cells. GST-rRANKL (aa239-318 and aa160-268) had lesser degrees of osteoclast inductivity. Furthermore, the GST-rRANKL (aa160-318) is capable of (1) inducing osteoclast formation from rat spleen cells in the presence of macrophage colony-stimulating factor (M-CSF), (2) stimulating mature rat osteoclast polarization and bone resorption ex vivo, and (3) inducing systemic hypercalcemia in vivo; thus the full TNF-like core region of rRANKL is an important regulator of calcium homeostasis and osteoclastic function.

Giant cell tumor of bone (GCT) is one of a few neoplasms in which the macrophage/osteoclast precursor cells and osteoclast-like giant cells infiltrate the tumor mass. Monocyte chemoattractant protein 1 (MCP-1) is a potent chemotactic factor specific for monocytes. In search of relevant cytokines that may enhance the recruitment of these reactive cells, we evaluated the localization and regulation of MCP-1 mRNA and protein in GCT by using Northern blot analysis, in situ hybridization and immunohistochemistry. We also determined whether conditioned medium obtained from GCT cultures can recruit human peripheral blood monocytes (CD68+) in an in vitro chemotactic assay. Using Northern blot analysis, we detected the specific gene transcript for MCP-1 in all GCT samples tested. In situ hybridization and immunohistochemistry revealed that both MCP-1 gene transcript and protein were consistently present in the cytoplasm of stromal-like tumor cells of GCT. Treatment of mononuclear cells from GCT at third passage with TGF-beta1 for 24 h increased the level of MCP-1 mRNA in a dose-dependent manner, with the maximum effect at 1 ng/ml. Conditioned media from GCT cultures promoted the chemotactic migration of CD68+ peripheral monocytes, an activity which was abolished by the addition of MCP-1 antibody to the conditioned medium. Thus, the results of this study suggest that recruitment of CD68+ macrophage-like cells may be due to the production MCP-1 by stromal-like tumor cells. These CD68+ cells may originate from peripheral blood and could have the capability of further differentiating into osteoclasts in the tumor.

Current transients induced in low density polyethylene (LDPE) are studied. The mobility of holes has been found to be 2.7/spl times/10/sup -6/ m/sup 2/ V/sup -1/ s/sup -1/ below the glassy transition point T/sub g/ of LDPE and 6.3/spl times/10/sup -6/ m/sup 2/ V/sup -1/ s/sup -1/ above it. Conductivity activation energy has been defined as 0.013 eV below T/sub g/ and 0.029 eV above it. Memory effect with anomalous reverse current flow was found in the sample coated with semitransparent Au electrodes for UV flash excitation. The occurrence of micro-discharges during thermally stimulated discharge current (TSDC) recording, in a previously electron beam treated sample is reported.

Splenic cysts cannot be summarized in one entity but open a wide field of aetiopathogenetic factors. The most common types of splenic cysts in central Europe are of epithelial or traumatic origin. Since ultrasound is widely used, the incidence of splenic cysts increased to about 1%. Rarely, splenic cysts give specific symptoms. Giant cysts cause unspecific abdominal pain, sometimes even organ displacement, possibly leading to a decreased function of related organs. In case of rupture, splenic cysts may become life-threatening. We present a patient suffering a giant splenic cyst and give an overview of diagnostic and therapeutic aspects of splenic cysts.

This presentation deals with the influence of ionising radiation on charge transport in polymeric films. A most important aspect of this phenomenon is the development of radiation resistant insulators with good electrical and mechanical properties for use in atomic and fusion power engineering. Other significant reasons for carrying out research on radiation effects in dielectrics are connected with space technology and high-ohmic passivation materials processing. In particular the connection between the different kinds of radiation damage and the mechanism of charge transport has received much of our attention. (3 pages)

Although giant cell tumor of bone (GCT) is generally considered to be an uncommon benign neoplasm, it can pursue an aggressive course with local recurrence and metastasis. Attempts to predict the biological behavior of GCT with histopathological parameters, however, have not been successful. The urokinase-type plasminogen activation system has been implicated in tumor invasion and metastasis and abnormalities of the components of this system have been found in several malignancies. In this study we postulated that the urokinase-type plasminogen activation system associated with bone destruction and local invasion is present in GCT. We therefore evaluated the mRNA levels for urokinase-type plasminogen activator (u-PA), urokinase-type plasminogen activator receptor (u-PAR), and plasminogen activator inhibitor type 1 (PAI-1) by using Northern blot analysis and in situ hybridization in four cases of GCT and spindle-shaped mononuclear cells at the 35th passage from a GCT. Our results showed that giant cell tumors of bone contained variable levels of u-PA, u-PAR, and PAI-1 mRNA, respectively, 2.3, 1.4, and 3.2 kb in size. In situ hybridization showed that u-PA, u-PAR, and PAI-1 mRNA were expressed in both the mononuclear cells and the osteoclast-like giant cells; the signal for u-PA mRNA in the spindle-shaped mononuclear cells was more intense than that in the osteoclast-like multinuclear giant cells. Some spherical mononuclear cells (macrophage-like cells) expressed high levels of PAI-1 mRNA in comparison with the spindle-shaped mononuclear cells. In addition, the 35th passaged spindle-shaped mononuclear cells were used to study the gene expression of u-PA during cell proliferation. The results showed that the level of u-PA mRNA increases after adding 10% fetal calf serum to quiescent cells. The induction was maximal at 16 hours and remained high during 48 hours of treatment. In conclusion, even though osteoclast-like cells are ultimately responsible for the bone resorption of GCT, the mononuclear neoplastic cells of GCT may also be involved in degradation of the extracellular matrix during invasive growth by facilitating the urokinase plasminogen activation system. In addition, our observation of upregulation of u-PA mRNA in spindle-shaped mononuclear cells after serum stimulation indicated that u-PA production may be linked to tumor growth.

Carbonic anhydrase II (CA II), an enzyme catalyzing the interconversion of CO2 and water to HCO3- and protons, has a key role in osteoclastic bone resorption, but little is known of the regulation of CA II gene expression by calcitonin. Analysis of mRNA in osteoclasts has been difficult because of the problems of obtaining sufficient number of purified osteoclasts from bone. In this study, however, we have investigated the regulation of CA II mRNA in rat osteoclasts and their putative mononuclear precursors by using in situ hybridization. We have found that the CA II gene is expressed at high levels in osteoclasts and what are probably their maturing mononuclear precursors. Measurement of CA II mRNA in cultured osteoclasts and their putative mononuclear precursor cells by cytophotometry provided evidence that calcitonin, a direct inhibitor of mammalian osteoclast activity, reduces the levels of CA II mRNA in a dose dependent manner; maximum reduction was observed at a concentration of 100 pM of calcitonin. In addition, calcitonin reduced the number of CA II mRNA-positive mononuclear precursor cells. The results also suggest that expression of the CA II gene is a feature of cells committed to the osteoclast lineage.

The fluorescent Dye H33342 (H342) is a bis-benzimidazole used for intravital fluorescent staining. In this report, we found that H342 completely abolished histone 2a mRNA but had no effect on alkaline phosphatase gene expression and protein synthesis in UMR 106-01 rat osteoblast-like cells. The complete loss of histone 2a mRNA occurred after only 20 min of treatment with H342. This effect is unlikely to be a result of inhibition of DNA synthesis, which was only partly suppressed. The mechanism of the action of H342 on histone 2a mRNA is presently unknown. © 1993 Wiley-Liss, Inc.

The acquired thrombocytopenia is part of a large number of diseases caused by a variety of different factors. Besides the classical failure of bone marrow proliferation respectively the replacement of the bone marrow with malignant cells, there are immunological disorders and many substances which may cause thrombocytopenia. The diagnosis of an "idiopathic thrombocytopenia" is sometimes posed even at the end of intensive diagnostic efforts. Possibly a benign neoplasia is also to cause a massive decrease of thrombocytes. We observed preoperatively in one patient with extensive stenosis of the sigma, caused by an inflammatory tumor a thrombocytopenia with a level under 50,000/ml. A normalization in thrombocyte blood counts appeared spontaneously after tumor resection.

Carbonic anhydrase II (CA II) plays an important role during osteoclastic bone resorption. Biochemical investigations of gene expression of CA II, however, have been hampered by difficulty in obtaining sufficient numbers of purified osteoclasts. In this study, we describe a nonradioactive, digoxigenin-labeled cDNA in situ hybridization technique capable of determining the pattern of CA II gene expression in human osteoclast-like cells (OC-like cells) at the single-cell level. The results showed that CA II mRNA was located in the cytoplasm of both imprinted and cultured OC-like cells from a giant cell tumor of bone. On the other hand, no evidence of CA II mRNA was found in either the mononuclear cells (tumor cells) of giant cell tumor of bone or osteosarcoma cells. There is a significant correlation between in situ hybridization and northern blot analysis for CA II mRNA in both the giant cell tumor of bone and the osteosarcoma. Our results also indicated that quantitation of in situ hybridization can be achieved by computed cytophotometry.

The importance of the involvement of nurse practitioners not only in the passage of laws regulating their practices, but also in the interpretation of the law is illustrated by 2 cases. The first case in February, 1991, involved the Drug Enforcement Administration's (DEA) proposal to prevent NPs from directly obtaining a DEA number for drug prescriptions. Affiliated practitioners could only provide services through a physician. 428 persons replied to the proposed regulation in the Federal Register, of which 419 were opposed. The objections were to the impact on access to health care, the problems with physician liability, the confusion created in sites with multiple collaborating physicians, and the difficulty of tracing abuses. Without the full weight of the law in a final ruling, the DEA proceeded to deny DEA numbers to NPs. Congress passed legislation which prevented the DEA from issuing regulations that interfered with access to health care. Questions were raised about whether the DEA was trying to set policy, when the law clearly stipulated who was authorized to prescribe controlled substances. The DEA withdrew the proposed regulation on April 24, 1992. Regulations which give qualified mid-level practitioners their own DEA numbers will be forthcoming soon for comment. The second case involved the Department of Health and Human Services, which published regulations known as the "Gag Rule" in 1987. This gag rule prohibited all providers in family planning clinics funded by Title X of the Public Health Service Act from counseling pregnant women about abortion. The final ruling was made in January, 1988, with a memo of guidance that suggested that a woman would not be prevented from obtaining complete medical information. Court cases (Rust vs. Sullivan, for example) supported the regulations. Medical and nursing groups were outraged at the interference, since 85% of services were performed by nurse clinicians. Further damage was done when the Deputy Assistant Secretary for Population Affairs indicated that nurses were not fully trained to provide pregnancy counseling. Court cases (NFPRHA/NANPRH vs. Sullivan and PPFA vs. Sullivan) argued that the regulations changed the law on who could counsel clients without providing an opportunity for publication of opinions in the Federal Register. The answer to the request for the injunction is pending along with legislation to overturn the gag rule.

The Norplant (Huhtamaki Oy/Leiras Pharmaceuticals, Turku, Finland) contraceptive system is a safe, highly effective, reversible method of hormonal contraception. The system consists of six flexible match-size implants that are implanted in the inner aspect of the upper arm. This sustained-release system delivers the progestin levonorgestrel at levels sufficient to prevent pregnancy for as long as 5 years. Norplant is a convenient, easy-to-use method. Adequate counseling of potential users and appropriate selection of patient users are important determinants of patient satisfaction with Norplant.The Norplant implant is described: the release rates and serum levels of levonorgestrel, the mode of action, the indications and contraindications, the effectiveness, incidence of ectopic pregnancy related to Norplant use, metabolic effects, advantages and disadvantages, insertion, the role of counseling, and management of side effects (menstrual bleeding changes, headache, weight changes, mastalgia, and acne), continuation rates and reasons for termination, and removal. Norplant is currently the most effective method of contraception. Counseling is important in order to provide women with as much information for informed consent and to increase awareness and interest in Norplant. In a clinical trial in California, 95% expressed a high level of satisfaction upon implant removal and 71% desired Norplant again; 91% recommended Norplant to friends. 82% reported the side effect of menstrual change; 66% reported 2 or more side effects. Clinical development is ongoing for other sustained release contraceptives. Norplant was developed by the International Committee for Contraceptive Research of the Population Council, and manufactured by Huhtamaki Oy/Leiras Pharmaceuticals in Turku, Finland. Clinical trials have been conducted since 1975. 20 nations have approved its use, and more than 1.5 million women use it. Silastic rubber tubing encapsulates 6 capsules of 36 mg/capsule crystalline levonorgestrel, a strong progestin. Implantation is done just under the skin in a fan shape; levonorgestrel is released at 80 mcg/day for 6 months, and 30-35 mcg/day for the remainder of use. The mode of action is not completely understood, but the assumption is that it is similar to the progestin-only pills. The mechanisms that alter fertility are 1) the change in hypothalamic-pituitary level to inhibit midcycle luteinizing hormone surge, while follicle stimulating hormone and estradiol levels remain within the normal range, 2) the thickening of the cervical mucus which prevents the entry of sperm into the upper genital tract, and 3) the suppression of the estrogen-induced cyclical maturation of the endometrium. It is not an abortifacient. Contraindications are few, but include active thrombophlebitis, undiagnosed abnormal genital bleeding, known or suspected pregnancy, benign or malignant liver tumors, and known or suspected breast cancer of progestin-dependent neoplasms.

The association between the frequency of manifest infectious diseases and cancer risk was investigated in a case-control study at Heidelberg, FRG. A total of 255 cases with carcinomas of the stomach, colon, rectum, breast, and ovary, as well as 255 population controls and 230 hospital controls were interviewed using a standard questionnaire. Controls were matched to the cases for age, sex, and region of residence at the time of the interview. A history of common colds or gastroenteric influenza prior to the interview was found to be associated with a decreased cancer risk. Thus the odds ratios for "three or more common colds per year (on average)" versus "no common cold within the last 5 years prior to the interview" were 0.18 (95% CI = 0.05-0.69) and 0.23 (95% CI = 0.06-0.89) relative to population controls and hospital controls, respectively. There was no apparent relationship between childhood infections or other diseases reported in the earlier history, and cancer risk. While the findings are supported by previous studies and fit well into the results of other fields of cancer research, a conclusive interpretation and biological explanation cannot yet be given.