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B Introduction: b Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of extranodal large B-cell lymphoma characterized by selective growth of lymphoma cells in the lumina of small vessels. B Conclusions: b In this 5-year, long-term follow-up analysis of the PRIMEUR-IVL study, frontline treatment of CNS-oriented therapy with standard R-CHOP for untreated IVLBCL patients without apparent CNS involvement provided durable response and clinically meaningful results for PFS, OS, and low incidence of secondary CNS involvement with manageable toxicity. FIVE-YEAR RESULTS OF A PHASE 2 STUDY OF CNS-ORIENTED THERAPY WITH R-CHOP FOR UNTREATED INTRAVASCULAR LARGE B-CELL LYMPHOMA: FINAL ANALYSIS OF THE PRIMEUR-IVL STUDY. [Extracted from the article]

Background and Objective T-helper type 17 ( Th17) cells produce interleukin-17 ( IL-17) and help to protect against inflammation and infection in periodontal disease. Furthermore, while follicular dendritic cell-secreted protein ( FDC- SP) may be involved in the inflammation of periodontal tissue, the biological role of FDP- SP in periodontal disease is still unknown. The purpose of the present study was to clarify the expression of IL-17 and FDC- SP in experimental periodontitis in rats. Material and Methods Seven-week-old male Wistar rats were divided into baseline control, sham and test groups. Experimental periodontitis was induced by placing a ligature in the mesiopalatal area, and untreated rats served as a baseline control group. Morphological changes in alveolar bone were investigated 7, 14 and 28 d after treatment. Expression of the Rankl, osteoprotegerin ( Opg) and Il17 genes was analyzed 5 and 7 d after the induction of experimental periodontitis. Results Alveolar bone resorption progressed in the test group for 7 d, but not thereafter. At 5 d after the induction of periodontitis, the Rankl/ Opg mRNA ratio and the expression of IL-17 in the test group were significantly increased compared with the respective values in the baseline control group; however, there were no significant differences between the test and control groups at 7 d. The expression of FDC- SP was significantly decreased in the test group compared with the baseline control group at 5 and 7 d after the induction of periodontitis, and this value had returned to normal levels at 14 and 28 d. Conclusion These results suggest that both IL-17 and FDC- SP could be involved in the inflammatory response, and FDC- SP in the junctional epithelium might play an important role in the Th17 cell-related immune response. [ABSTRACT FROM AUTHOR]

Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell transplantation (allo- SCT) recipients and >50% of cases of severe hyponatremia are caused by the syndrome of inappropriate secretion of antidiuretic hormone ( SIADH). Here, we present a patient with rapidly progressive severe hyponatremia as an initial sign and symptom of human herpesvirus-6-associated post-transplantation acute limbic encephalitis ( HHV-6 PALE) after allo- SCT. A 45-year-old woman with acute lymphoblastic leukemia received unrelated bone marrow transplantation from a one locus-mismatched donor at the DR locus. On day 21, she developed a generalized seizure and loss of consciousness with severe hyponatremia, elevated serum antidiuretic hormone ( ADH), and decreased serum osmolality. A high titer of HHV-6 DNA was detected in cerebrospinal fluid. Treatment with foscarnet sodium and hypertonic saline was started with improvement of neurological condition within several days. Although an elevated serum ADH, low serum osmolality, and high urinary osmolality persisted for 2 months, she had no other recurrent symptoms of encephalitis. Our experience suggests that hyponatremia accompanied by SIADH should be recognized as a prodromal or concomitant manifestation of HHV-6 PALE, and close monitoring of serum sodium levels in high-risk patients for HHV-6 PALE is necessary for immediate diagnosis and treatment initiation. [ABSTRACT FROM AUTHOR]

Nifedipine-induced gingival overgrowth is known to be characterized by fibrosis and some degree of inflammation. However, the molecular mechanism of the fibrosis is not fully understood. The purpose of this study was to investigate in vitro the effects of nifedipine and interleukin-1alpha on the molecules involved in fibrosis, namely type I collagen, matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1). Four human gingival fibroblast strains, derived from four healthy volunteers, were cultured in media containing nifedipine (1 microg/ml), with or without interleukin-1alpha (0.05 ng/ml). The mRNAs of type I collagen, MMP-1, and TIMP-1 were measured by reverse transcription-polymerase chain reaction (RT-PCR). The proteins of MMP-1 and TIMP-1 were examined by enzyme-linked immunosorbent assay (ELISA), and the ratios of MMP-1 to TIMP-1 proteins were calculated. The mRNA expression of type I collagen showed no significant change. Both mRNA expression and protein production of MMP-1 were up-regulated by interleukin-1alpha, either alone or in combination with nifedipine, whereas those of TIMP-1 were up-regulated by nifedipine alone or in combination with interleukin-1alpha. The ratio of MMP-1 to TIMP-1 was not changed by nifedipine alone, but it was increased by interleukin-1alpha alone or in combination with nifedipine. However, in two of the four cell strains tested, nifedipine reduced the ratio of MMP-1 to TIMP-1 compared with that for interleukin-1alpha alone. These results suggest that nifedipine may predispose to fibrosis in some individuals in situations where interleukin-1 levels are raised. [ABSTRACT FROM AUTHOR]

Background Although it is thought that both Th1- and Th2-type inflammations are involved in the pathogenesis of atopic dermatitis (AD), it is controversial which immune response is more involved in regulating the clinical severity of AD. We recently found that the squamous cell carcinoma antigens 1 (SCCA1) and SCCA2 are novel biomarkers of bronchial asthma, downstream of IL-4 and IL-13. Objective We examined whether SCCA1 and SCCA2 could also serve as biomarkers of AD, reflecting its Th2-type immune responses, and whether the expression level of SCCA was correlated with clinical severity of AD. Method We compared the expression of SCCA1 and SCCA2 at the mRNA and protein levels in both involved and uninvolved skin of AD patients and in normal control skin. We next analysed induction of SCCA by IL-4 or IL-13 in keratinocytes. Finally, we compared the serum level of SCCA with laboratory parameters reflecting Th2-type inflammation and clinical severity in AD patients. Results SCCA1 and SCCA2 were highly expressed in involved skin of AD patients, compared with their uninvolved skin, at both mRNA and protein levels. SCCA protein was dominantly expressed in suprabasal keratinocytes in the epidermis of AD patients. Either IL-4 or IL-13, but not IFN-γ or TNF, induced production of SCCA in keratinocytes. These result suggest that SCCA is induced in AD skin, probably due to direct actions of IL-4 and/or IL-13 on keratinocytes. Serum levels of SCCA were well correlated with eosinophil numbers and serum lactate dehydrogenase levels, and weakly with serum IgE levels, in AD patients. Furthermore, serum levels of SCCA were strongly correlated with clinical severity. Conclusions Th2-type inflammation dominantly regulates the clinical severity of AD, and SCCA is a relevant biomarker of AD, reflecting both Th2-type inflammation and clinical severity. [ABSTRACT FROM AUTHOR]

The object of the present study was to determine the histopathological guidelines for accurate diagnosis of cases of acute focal demyelinating disease that simulates brain tumors. The surgical pathology of three such cases is assessed. Histopathological keys to the diagnosis of such cases are as follows. First, a pattern of sheets of atypical gemistocytic astrocytes in the white matter that show well-formed processes and that are adequately distanced from each other argues against a diagnosis of neoplasm. Second, uniform distribution of foamy macrophages aligned along axons, with occasional focal collections surrounding blood vessels and in the absence of any associated coagulative necrosis argues against the presence of a tumor. Third, perivascular chronic inflammatory infiltration, especially a mixture of lymphocytes and macrophages, favors the diagnosis of demyelination plaque. In such cases the lymphocytes will be predominantly T cells. Fourth, pleomorphic astrocytic proliferation with a lack of vascular endothelial proliferation should raise the suspicion that the lesion may not be a brain tumor. These diagnostic keys should be followed when diagnosing cases that are suspected to be demyelination processes rather than brain tumors. The presence of demyelination plaque should then be confirmed by imaging modalities such as staining with myelin-and axon-specific stains. [ABSTRACT FROM AUTHOR]

The angiomatous variant of the pleomorphic xantho-astrocytoma (PXA) is a morphological subtype of PXA that is characterized by the presence of large numbers of tiny blood vessels with variable wall thicknesses. A case of an angiomatous variant of PXA occurring in the temporal lobe of a 43-year-old man is presented. The patient had a 20-year history of seizures. Considering the clinical course and intra-operative electro-encephalography findings, it appears that this tumor was the epileptic focus in this patient and that it had been present for 20 years. Histopathologically, various degenerative changes, such as microcystic changes, calcification and hyaline thickening of vessel walls were seen in the tumor. In particular, obvious vascularity in the tumor and secondary vascular degenera-tion should be related to gradual growth and benign clinical course of an angiomatous variant of PXA. [ABSTRACT FROM AUTHOR]

Three soluble forms of membrane attack complex inhibitory factor (MACIF or CD59) were prepared using recombinant baculovirus-infected insect cells. They consisted of 70, 77 and 86 amino acids, starting from the amino terminus of naturally occurring CD59, and were designated recombinant (r) CD59 70, 77 and 86, respectively. All three rCD59 lacked a glycosylphosphatidylinositol (GPI) anchor, unlike membrane CD59 which has a GPI anchor at the carboxyl terminus (77th amino acid). Their activities in inhibiting complement activation were assayed with C5b-7 intermediate cells and C8 and C9 components. The inhibitory activity of rCD59 70 was as high as that of rCD59 77 and twice that of rCD59 86. In addition, it was one-fourth and one-hundredth lower than the activities of urine and erythrocyte CD59, respectively. However, when assayed in the presence of human serum at a final concentration of 50% (v/v), the activities of both urine and erythrocyte CD59 were greatly decreased to one-tenth of that of rCD59 70. Purified rCD59 70 molecules were all glycosylated, but rCD59 77 and 86 were mixtures of glycosylated and non-glycosylated molecules. The inhibitory activites of rCD59 77 and 86 were the same for the glycosylated and non-glycosylated forms. These results suggest that the soluble rCD59 provide a means for elucidating the biological roles of CD59. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a study on the ubiquitin-positive pneumocytes which are a marker of cellular injury in non-specific interstitial pneumonia (NSIP).

The therapeutic effect of methylcobalamin (Met-12) on sleep–wake rhythm disorders was examined in a double-blind test. In the test group which was given a large dosage, a higher percentage of improvement was found compared to the control group with a small dosage, although the difference was not significant. The test group inconsistently showed significant improvement in both the sleep–wake cycle parameters and in clinical symptoms. The tendency was for the results to show a beneficial effect of Met-12 on rhythm disorders. However, because the percentage of improvement was low and significant improvement was inconsistent, Met-12 might be considered to have a low therapeutic potency and possible use as a booster for other treatment methods of the disorders. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy of retrograde balloon dilatation for primary pelvi-ureteric junction (PUJ) stenosis (RBDP) in children. Patients and methods Sixteen children (12 boys, four girls; mean age 29 months) with primary PUJ stenosis initially underwent RBDP. A double-pigtail catheter was left in the ureter for 6 weeks to provide drainage. The initial diagnosis of PUJ stenosis and the subsequent post-operative assessment were both made by diuretic renography in almost all patients. All children were followed up for between 9 and 38 months (mean 25) after the procedure. Results RBDP was unsuccessful in nine of 17 renal units. In three of these, failure was caused by inability to pass the catheter through the PUJ or vesico-ureteric junction (VUJ). In six cases, failure was caused by recurrent or persistent stenosis. In eight of 17 renal units, RBDP was successful in relieving the stenosis. The morbidity from the procedure was minimal. Conclusions Long-term follow-up revealed a significant failure rate for RBDP, caused by the inability to pass the catheter through the VUJ or PUJ, or persistent and/or recurrent stenosis. Recurrent stenosis may result from excessive dilatation which traumatizes the PUJ and causes subsequent scarring. Failure to overcome the stenosis is thought to be caused by a large redundant renal pelvis, producing 'kinking' of the upper ureter. In these cases, only reduction pyeloplasty may be successful in relieving the obstruction. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article which discusses the abnormal change and development for the disease identity of restless legs syndrome (RLS) based on the observations of astronauts in zero gravity.

Chinese hamster ovary (CHO) cells are widely used for the industrial production of therapeutic monoclonal antibodies (mAbs). To meet the increasing market demands, high productivity, and quality are required in cell culture. One of the critical attributes of mAbs, from a safety perspective, is mAb fragmentation. However, methods for preventing mAbs fragmentation in CHO cell culture are limited. In this study, we observed that the antibody fragment content increased with increasing titers in fed-batch cultures for all three cell lines expressing recombinant antibodies. Adding copper sulfate to the culture medium further increased the fragment content, suggesting the involvement of reactive oxygen species (ROS) in the fragmentation process. Though antioxidants may be helpful to scavenge ROS, several antioxidants are reported to decrease the productivity of CHO cells. Among the antioxidants examined, we observed that the addition of catechin or (-)-epigallocatechin gallate to the culture medium prevented fragmentation content by about 20% and increased viable cell density and titer by 30% and 10%, respectively. Thus, the addition of catechins or compounds of equivalent function would be beneficial for manufacturing therapeutic mAbs with a balance between high titers and good quality., (© 2024 American Institute of Chemical Engineers.)

Background: Polymorphous adenocarcinoma is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of polymorphous adenocarcinoma-associated genes, such as PRKD1/2/3, ARID1A, and DDX3X, in a large cohort of Japanese patients with polymorphous adenocarcinoma., Methods: We examined the cases of 36 Japanese patients with salivary gland polymorphous adenocarcinoma and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for polymorphous adenocarcinoma-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations., Results: This study revealed the indolent clinical course of polymorphous adenocarcinoma with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (23.3%). Twenty cases (55.6%) of polymorphous adenocarcinoma (but none of the mimics) exhibited alterations in at least one polymorphous adenocarcinoma-associated gene. Rearrangement of polymorphous adenocarcinoma-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (p = 0.0005), the presence of prominent nucleoli (p = 0.0003), and ARID1A split positivity (p = 0.004) were independent risk factors for disease-free survival., Conclusion: Japanese patients with polymorphous adenocarcinoma showed clinicopathological features similar to those reported in Western countries. This study disclosed that polymorphous adenocarcinoma-associated genetic alterations were common and specific findings in polymorphous adenocarcinomas. The diagnostic role and possible prognostic significance of polymorphous adenocarcinoma-associated genetic alterations in polymorphous adenocarcinomas were suggested., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Visual information in the retina is processed via two pathways: ON and OFF pathways that originate from ON and OFF bipolar cells. The differences in the receptors that mediate signal transmission from photoreceptors imply that the response speed to light signals differs between ON and OFF pathways. We studied the initial optokinetic responses (OKRs) of mice using two-frame motion stimuli presented with interstimulus intervals (ISIs) to understand functional difference of these pathways. When two successive image frames were presented with an ISI, observers often perceived motion in the opposite direction of the actual shift. This directional reversal results from the biphasic nature of the temporal filters in visual systems whose characteristics can be estimated from the dependence on ISIs. We examined the dependence on ISIs in the OKRs of TRPM1 -/- mice, whose ON bipolar cells are dysfunctional, as well as in those of wild-type control mice. Wild type and TRPM1 -/- mice showed comparable OKRs in the veridical direction when no ISI was present. Both types of mice showed OKRs that decreased and eventually reversed as the ISI increased, but with a directional reversal at a shorter ISI in TRPM1 -/- than wild-type mice. In addition, the temporal filters of TRPM1 -/- mice estimated from dependence on ISIs were tuned for higher frequencies, suggesting that compared with wild-type mice, the visual system of TRPM1 -/- mice responds to light signals with faster dynamics. We conclude that the ON and OFF pathways contribute to initial OKRs by providing visual signals processed with different temporal resolutions., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Special AT-rich sequence-binding protein 2 (SATB2)-associated syndrome (SAS) is characterized by alterations of SATB2. Its clinical features include intellectual disability and craniofacial abnormalities, such as cleft palate, dysmorphic features, and dental abnormalities. Here, we describe three previously undiagnosed, unrelated patients with SAS who exhibited dental abnormalities, including multiple odontomas. Although isolated odontomas are common, multiple odontomas are rare. Individuals in families 1 and 3 underwent whole-exome sequencing. Patient 2 and parents underwent targeted amplicon sequencing. On the basis of the hg19/GRCh37 reference and the RefSeq mRNA NM_001172517, respective heterozygous mutations were found and validated in Patients 1, 2, and 3: a splice-site mutation (chr2:g.200137396C > T, c.1741-1G > A), a nonsense mutation (chr2:g.200213750G > A, c.847C > T, p.R283*), and a frame-shift mutations (chr2:g.200188589_200188590del, c.1478_1479del, p.Q493Rfs*19). All mutations occurred de novo. The mutations in Patients 1 and 3 were novel; the mutation in Patient 2 has been described previously. Tooth mesenchymal cells derived from Patient 2 showed diminished SATB2 expression. Multiple odontomas were evident in the patients in this report; however, this has not been recognized previously as a SAS-associated phenotype. We propose that multiple odontomas be considered as an occasional manifestation of SAS., (© 2018 Wiley Periodicals, Inc.)

Background and Objective: T-helper type 17 (Th17) cells produce interleukin-17 (IL-17) and help to protect against inflammation and infection in periodontal disease. Furthermore, while follicular dendritic cell-secreted protein (FDC-SP) may be involved in the inflammation of periodontal tissue, the biological role of FDP-SP in periodontal disease is still unknown. The purpose of the present study was to clarify the expression of IL-17 and FDC-SP in experimental periodontitis in rats., Material and Methods: Seven-week-old male Wistar rats were divided into baseline control, sham and test groups. Experimental periodontitis was induced by placing a ligature in the mesiopalatal area, and untreated rats served as a baseline control group. Morphological changes in alveolar bone were investigated 7, 14 and 28 d after treatment. Expression of the Rankl, osteoprotegerin (Opg) and Il17 genes was analyzed 5 and 7 d after the induction of experimental periodontitis., Results: Alveolar bone resorption progressed in the test group for 7 d, but not thereafter. At 5 d after the induction of periodontitis, the Rankl/Opg mRNA ratio and the expression of IL-17 in the test group were significantly increased compared with the respective values in the baseline control group; however, there were no significant differences between the test and control groups at 7 d. The expression of FDC-SP was significantly decreased in the test group compared with the baseline control group at 5 and 7 d after the induction of periodontitis, and this value had returned to normal levels at 14 and 28 d., Conclusion: These results suggest that both IL-17 and FDC-SP could be involved in the inflammatory response, and FDC-SP in the junctional epithelium might play an important role in the Th17 cell-related immune response., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the mouse retina, there are two distinct groups of direction-selective ganglion cells, ON and ON-OFF, that detect movement of visual images. To understand the roles of these cells in controlling eye movements, we studied the optokinetic responses (OKRs) of mutant mice with dysfunctional ON-bipolar cells that have a functional obstruction of transmission to ON direction-selective ganglion cells. Experiments were carried out to examine the initial and late phases of OKRs. The initial phase was examined by measurement of eye velocity using stimuli of sinusoidal grating patterns of various spatiotemporal frequencies that moved for 0.5 s. The mutant mice showed significant initial OKRs, although the range of spatiotemporal frequencies that elicited these OKRs was limited and the response magnitude was weaker than that in wild-type mice. To examine the late phase of the OKRs, the same visual patterns were moved for 30 s to induce alternating slow and quick eye movements (optokinetic nystagmus) and the slow-phase eye velocity was measured. Wild-type mice showed significant late OKRs with a stimulus in an appropriate range of spatiotemporal frequencies (0.0625-0.25 cycles/°, 0.75-3.0 Hz, 3-48°/s), but mutant mice did not show late OKRs in response to the same visual stimuli. The results suggest that two groups of direction-selective ganglion cells play different roles in OKRs: ON direction-selective ganglion cells contribute to both initial and late OKRs, whereas ON-OFF direction-selective ganglion cells contribute to OKRs only transiently., (© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

A new antithrombogenic stent using ion beam surface modification nanotechnology was evaluated. The ion stent is being developed to inhibit acute and chronic stent-related thrombosis. Thirty self-expanding mesh stents were fabricated from Ti-Ni metal wires with a dimension of 4 mm (diameter) x 25 mm (length) x 0.15 mm (thickness). Twenty stents were coated with type I collagen and irradiated with a He(+) ion beam at an energy of 150 keV with fluences of 1 x 10(14) ions/cm(2) (ion stent group). Ten stents had no treatment (non-ion stent group). The self-expanding stents were implanted into the right and left peripheral femoral arteries of 15 beagle dogs (vessel diameter approximately 3 mm) via a 6Fr catheter under fluoroscopic guidance. Heparin (100 units/kg) was administered intravenously before implantation. Following stent implantation, no antiplatelet or anticoagulant drugs were administered. The 1-month patency rate for the non-ion stent group was 10% (1/10), and for the ion stent group it was 80% (16/20) with no anticoagulant or antiplatelet drugs given after stent implantation (P = 0.0004 by Fisher's exact test). Ten stents remain patent after 2 years in vivo with no anticoagulant or antiplatelet drugs. These results indicate that He(+) ion-implanted collagen-coated Ti-Ni self-expanding stents have excellent antithrombogenicity and biocompatibility. This ion stent is promising for coronary and cerebral stent applications.

Urticaria is often associated with perivascular infiltration of leukocytes into the lesions. Although mast cell-derived chemical mediators are considered to play crucial roles in the infiltration of leukocytes as well as in the dermal edema, other mechanisms for the leukocyte infiltration have not been well defined. This study revealed that approximately 25% of the cases of chronic idiopathic urticaria in whom wheals had continued for more than 12 h had deposition of immuno-components in the lesions, although histological examination of the lesions did not show leukocytoclastic vasculitis. In these lesions with deposition of immuno-components, both neutrophils and eosinophils had infiltrated at a constant ratio (approximately 2:1), whereas, in the lesions without deposition, a variable population of leukocytes was seen. This result suggests that activation of complements occurs in the lesions of a considerable percentage of patients with chronic idiopathic urticaria and that the complement fragments influence the infiltration patterns of polymorphonuclear leukocytes.

Carotenodermia may arise from excessive dietary intake of carotene containing foods. We reported a 22-year-old woman who had eaten excessive amount of carotene-rich seaweed to lose weight. Her skin color changed to orange-yellow, and her serum beta-carotene was 573 micrograms/dl. After stopping the ingestion of seaweed, her skin color returned to normal.

A miniaturized Gyro centrifugal pump has been developed to be incorporated into a totally implantable artificial heart. The Gyro PI (permanently implantable) model is a pivot bearing supported centrifugal pump with a priming volume of 20 ml. With the miniaturized actuator, the pump-actuator package has a height of 53 mm, a diameter of 65 mm, and a displacement volume of 145 ml. To evaluate the hemocompatibility and efficiency of the Gyro PI pump system, a plastic prototype (Gyro PI-601) was implanted into a bovine model as a left or right ventricular assist device (LVAD or RVAD), bypassing from the left ventricular apex to the descending aorta or from the right ventricular infundibulum to the main pulmonary artery. The calves were anticoagulated with heparin to maintain activated clotting times from 150 to 200 s. Four calves were supported for 23, 24, and 50 days in the LVAD studies, and 40 days in the RVAD study. The first calf died due to intrathoracic bleeding associated with sepsis. The second calf was euthanized for a low flow rate less than 2 L/min due to an obstructed inflow with growing pannus. The third and fourth calves were euthanized as scheduled. Renal and hepatic functions remained normal, and plasma free hemoglobin values were less than 8 mg/dL throughout the experiments. The fourth case showed flow rates of 4.83 +/- 0.57 L/min, input power of 6.16 +/- 0.49 W, and the inside temperature of the actuator of 43.5 +/- 0.52 degrees C. The pumps implanted in the fourth calf demonstrated no thrombus formation at the autopsy. These in vivo experiments revealed that the Gyro PI pump can provide adequate flow as an easily implantable, efficient, antithrombogenic, and nonhemolytic centrifugal LVAD or RVAD with miniaturized actuators.

We investigated the genetic control of immunoglobulin production and the delayed-type hypersensitivity (DTH) response produced by an HIV-specific DNA vaccine using several strains of mice. Murine antigen-specific immunoglobulin production was determined by ELISA. The DTH response was assessed in terms of the footpad swelling reaction. All strains of mice, except for B10.RIII and B10.T(6R), exhibited strong immunoglobulin production and footpad swelling in response to the DNA vaccine. In vitro treatment of lymphoid cells with monoclonal antibodies showed that the footpad swelling response was mediated by CD4+8- and Ia- T cells. However, CD8+ T cells did not suppress footpad swelling. There was no difference in the induction of HIV-specific immunoglobulin production or DTH response induced by the DNA vaccine among the strains, suggesting that HIV-specific DNA vaccine is useful for immunizing various populations against HIV-1.

Leprosy is a rare entity in Japan, but remains quite common in developing countries. We report two sisters with leprosy from Brazil but currently working in Japan who presented to our clinic. The younger sister was infected with the BB type with HLA-A2, A24, B51, Bw52, DR2, DRw8, DRw52, DQw1, and DQw3. The elder sister had the TT type with HLA-A2, A31, B51, Cw3, DRw6, DRw8, DRw52, DQw1, and DQw3. Immunohistochemical findings revealed that CD4+, 4B4+ helper/inducer T-cells were dominant in the granulomas of both cases. Bacilli were not detectable in the biopsy specimens. However, Mycobacterium leprae-specific DNA fragments were found in their peripheral blood and biopsy specimens by polymerase chain reaction.