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Biomedical subjects

M Usui

Publications and source records attributed to M Usui.

At least 37 records · Page 2Linked to original sources

Serum alpha-subunit levels in patients with pituitary adenomas.

OBJECTIVE: We investigated preoperative and postoperative serum alpha-subunit levels and the alpha-subunit response to TRH in patients with various types of pituitary tumour and correlated the data with histological findings in order to clarify the significance of alpha-subunit measurement in pituitary adenomas. PATIENTS: We examined 59 patients with pituitary tumours (22 with GH cell adenomas, 30 with clinically nonfunctioning adenomas and seven with other tumours) treated at Toranomon Hospital between 1996 and 1998. RESULTS: The basal alpha-subunit level was supranormal in six out of 22 (27%) patients with a GH cell adenoma and in nine out of 30 (30%) patients with a nonfunctioning adenoma. A paradoxical alpha-subunit response to TRH was found in seven out of 22 (32%) patients with a GH cell adenoma. These seven patients also showed a paradoxical GH response to TRH administration. In addition, paradoxical response to TRH was found in eight out of 30 (27%) patients with a clinically nonfunctioning adenoma. In contrast, patients with other types of pituitary tumour showed neither a supranormal alpha-subunit level nor a paradoxical response to TRH. The supranormal alpha-subunit level and the abnormal response to TRH were normalized in both GH cell adenoma and nonfunctioning adenoma patients after successful surgery. Immunohistochemical studies showed alpha-subunit positive cells in 51% of GH cell adenomas or nonfunctioning adenomas and there was a good concordance with the serum alpha-subunit levels in both GH cell adenoma and nonfunctioning adenoma patients. CONCLUSIONS: These findings suggest that supranormal serum alpha-subunit levels are mainly due to hypersecretion by the tumour itself, while the paradoxical alpha-subunit response to TRH is an associated phenomenon in patients with a GH cell adenoma or nonfunctioning adenoma. The alpha-subunit level and the response to TRH may be useful indicators for assessing the operative outcome, especially in nonfunctioning adenoma patients who have no other definite endocrine markers.

Adenoma↗

BCG inoculation and corticosteroid sensitivity.

PURPOSE: This study was conducted to clarify the relationship between Bacille de Calmette-Guérin (BCG) inoculation and corticosteroid sensitivity. METHODS: Lewis and WKAH rats were inoculated with BCG vaccine weekly beginning at six weeks of age. At 15 weeks, spleen cells were cultured with PHA and betamethasone for 24 hours. RNA was extracted and interleukin-2 gene expression was measured using a real-time PCR method. RESULTS: BCG inoculation sensitized Lewis rats, but not WKAH rats, to PPD stimulation. In Lewis rats, IL-2 gene expression increased after BCG inoculation, while betamethasone suppressed IL-2 expression. In WKAH rats, the expression of IL-2 was not affected by repeated BCG inoculations and betamethasone had no effect on BCG-treated rats. CONCLUSION: BCG inoculation may affect steroid sensitivity in some strains of rats.

Animals↗

Effects of calnexin deletion in Saccharomyces cerevisiae on the secretion of glycosylated lysozymes.

Disruption of the calnexin gene in Saccharomyces cerevisiae did not lead to gross effects on the levels of cell growth and secretion of wild-type hen egg white lysozymes (HEWL). To investigate the function of calnexin in relation to the secretion of glycoproteins, we expressed both stable and unstable mutant glycosylated lysozymes in calnexin-disrupted S. cerevisiae. The secreted amounts of stable mutant glycosylated lysozymes (G49N and S91T/G49N) were almost the same in both wild-type and calnexin-disrupted S. cerevisiae. In contrast, the secretion of unstable mutant glycosylated lysozymes (K13D/G49N, C76A/G49N, and D66H/G49N) greatly increased in calnexin-disrupted S. cerevisiae, although their secretion was very low in the wild-type strain. This indicates that calnexin may act in the quality control of glycoproteins. We further investigated the expression level of the mRNA of the molecular chaperones BiP and PDI, which play a major role in the protein folding process in the ER, when glycosylated lysozymes were expressed in wild-type and calnexin-disrupted S. cerevisiae. The mRNA concentrations of BiP and PDI were evidently increased when the glycosylated lysozymes were expressed in calnexin-disrupted S. cerevisiae. This observation indicates that BiP and PDI may be induced by the accumulation of unfolded glycosylated lysozymes due to the deletion of calnexin.

Calcium-Binding Proteins↗

New diagnostic approach for ocular tuberculosis by ELISA using the cord factor as antigen.

BACKGROUND/AIMS: Diagnosis of ocular tuberculosis is difficult, particularly the retinal vasculitis type, because most cases occur without concurrent active pulmonary tuberculosis. Recently, it has been reported that detection of antibodies against purified cord factor (trehalose-6,6'-dimycolate, TDM), the best studied, most antigenic, and most abundant cell wall component of tubercule bacilli, is very useful for rapid serodiagnosis of pulmonary tuberculosis. In this study, an attempt was made to evaluate whether the detection of anticord factor antibody is also useful for diagnosis of ocular tuberculosis and the necessity of antituberculous therapy for tuberculous retinochoroiditis was discussed. METHODS: Cases consisted of 15 patients with uveitis and retinal vasculitis, nine patients with presumed ocular tuberculosis, three patients with sarcoidosis, and three patients with Behçet's disease. IgG antibodies against purified cord factor prepared from Mycobacterium tuberculosis H37Rv were detected by enzyme linked immunosorbent assay. RESULTS: All cases of clinically presumed ocular tuberculosis were positive, whereas all of the cases of sarcoidosis or Behçet's disease were negative for anticord factor antibodies. When the anticord factor antibody titres were compared on the basis of the presence or absence of previous antituberculosis chemotherapy, the mean anticord factor antibody titre of the untreated group showed a tendency to be higher than in the treated group, but not significantly (p=0.07). CONCLUSIONS: The detection of anticord factor antibody may be useful to support the diagnosis of ocular tuberculosis. Additionally, a positive result for anticord factor antibody may indicate that tubercule bacilli are present in some organ(s) of the patient even in the absence of active systemic disease.

Adult↗

Regression by ACE inhibition of arteriosclerotic changes induced by chronic blockade of NO synthesis in rats.

We previously reported that chronic inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME) induces vascular inflammation at week 1 and produces subsequent arteriosclerosis at week 4 and that cotreatment with an angiotensin-converting enzyme (ACE) inhibitor prevents such changes. In the present study, we tested the hypothesis that treatment with an ACE inhibitor after development of vascular inflammation could inhibit arteriosclerosis in rats. Wistar-Kyoto rats were randomized to four groups: the control group received no drugs, the 4wL-NAME group received L-NAME (100 mg x kg(-1) x day(-1)) for 4 wk, the 1wL + 3wNT group received L-NAME for 1 wk and no treatment for the subsequent 3 wk, and the 1wL + 3wACEI group received L-NAME for 1 wk and the ACE inhibitor imidapril (20 mg x kg(-1) x day(-1)) for the subsequent 3 wk. After 4 wk, we observed significant arteriosclerosis of the coronary artery (medial thickening and fibrosis) and increased cardiac ACE activity in the 1wL + 3wNT group as well as in the 4wL-NAME group, but not in the 1wL + 3wACEI group. In a separate study, we examined apoptosis formation and found that posttreatment with imidapril (20 mg x kg(-1) x day(-1)) or an ANG II AT1-receptor antagonist, CS-866 (5 mg x kg(-1) x day(-1)), induced apoptosis (TdT-mediated nick end-labeling) in monocytes and myofibroblasts appearing in the inflammatory lesions associated with a clear degradation in the heart (DNA electrophoresis). In conclusion, treatment with the ACE inhibitor after 1 wk of L-NAME administration inhibited arteriosclerosis by inducing apoptosis in the cells with inflammatory lesions in this study, suggesting that increased ANG II activity inhibited apoptosis of the cells with inflammatory lesions and thus contributed to the development of arteriosclerosis.

Angiotensin-Converting Enzyme Inhibitors↗

Risk of aneurysm recurrence in patients with clipped cerebral aneurysms: results of long-term follow-up angiography.

BACKGROUND AND PURPOSE: With many patients living long after microsurgical aneurysm clipping for subarachnoid hemorrhage (SAH) and with the evolution of intravascular procedures as less invasive alternatives, knowledge of the long-term results of clipping is becoming important. METHODS: Of 412 patients who underwent clipping of ruptured or unruptured cerebral aneurysms at our institution between 1976 and 1994 and who survived >3 years after surgery, 225 patients who were in good general condition and younger than 80 years were offered follow-up angiography to detect newly formed aneurysms. Of the 225, 80 patients (35.6%) agreed to undergo angiography. In addition, 32 patients underwent angiography for new medical indications other than SAH. Therefore, 112 patients underwent angiography, representing a total of 140 clipped aneurysms. RESULTS: The mean interval from surgery was 9.3 years for all patients and 9.0 years for the clipped aneurysms (range 3 to 21 years). Four aneurysm regrowths were detected of the 140 (2.9%) clipped aneurysms, representing 3 of 125 completely clipped aneurysms, 1 of 14 incompletely clipped aneurysms, and 0 of 1 aneurysm not studied with postoperative angiography. De novo aneurysms were detected in 9 of 112 (8.0%) patients. The annual rate of de novo aneurysm formation was 0.89%. CONCLUSIONS: This study shows that the annual rate of de novo aneurysm formation is relatively high (0.89%) and that the cumulative risk becomes significant after 9 years. In consideration of the fatality rate of SAH, follow-up angiography may be indicated for patients with clipped aneurysms 9 to 10 years after surgery.

Angiography, Digital Subtraction↗

Radiofrequency ablation at the coronary sinus ostium interrupts the vagal efferent input to the atrioventricular node in the canine heart.

The fat pad at the junction of the inferior vena cava and inferior left atrium is the area of convergence of vagal projections into the atrioventricular node (AVN) region. The present study investigated whether radiofrequency (RF) ablation applied to the area around the coronary sinus (CS) ostium would impair vagal input to the AVN in the canine heart. Twenty-four dogs were anesthetized by sodium pentobarbital and RF energy was delivered at 20W for 5-10s. In the baseline state without vagal stimulation (10Hz, 2ms), the electrophysiological variables did not change significantly after RF ablation. Vagally induced changes in the sinus cycle length and effective refractory period of the right atrium and left ventricle did not differ after RF ablation. However, the effects of vagal stimulation on the AVN function were impaired after RF ablation to the CS area from the ostium to 10mm within the ostium. After ablation was applied to the fast pathway area, the vagally induced changes in the AVN function decreased, but these changes were not affected after RF ablation in the slow pathway area. RF ablation in the vicinity of the CS would attenuate vagal input to the AVN.

Animals↗

Role of nitric oxide in regulation of coronary blood flow in response to increased metabolic demand in dogs with pacing-induced heart failure.

The role of endothelium-derived nitric oxide (NO) in the metabolic control of coronary blood flow (CBF) in heart failure (HF) is poorly understood, so the present study investigated the effects of inhibitors of NO synthesis on the response of CBF to changes in myocardial oxygen consumption (MVO2) in dogs with HF produced by rapid ventricular pacing and in control dogs. The CBF, MVO2, and other hemodynamic parameters were measured in anesthetized animals. Before infusion of Nomega-nitro-L-arginine methyl ester (L-NAME), the increases in CBF and MVO2 during pacing tachycardia were not significantly different between the control and HF dogs. Intracoronary infusion of L-NAME did not alter the responses of CBF or MVO2 to pacing tachycardia in the control dogs, but in the HF dogs, it reduced the CBF response to pacing tachycardia without altering the tachycardia-induced changes in MVO2. Intracoronary infusion of L-arginine reversed the effect of L-NAME. These results suggest that in HF dogs NO contributes to the regulation of CBF in response to an increased metabolic demand.

Animals↗

[An immunopathological study of autoimmune keratitis in nude mice with embryonic rat thymus grafts].

PURPOSE: The purpose of the present study was to examine the keratitis detected in these mice after the xenogeneic thymus gland transplantation. METHODS: The thymus glands were collected from F 344 rat embryos and transplanted under the renal capsules of BALB/c nude mice (rat TG nude mice). Histological and immunohistological examinations and a transfer experiment of keratitis was also conducted. RESULTS: The histological image was characterized by the infiltration of mononuclear cells and neutrophils and the marked angiogenesis. The autoantibodies reacting specifically to corneal epithelial cells and corneal stroma were recognized in the blood. The deposits of immunoglobulins and complements were simultaneously observed in the corneal stroma and around the basement membrane. Corneal lesions of rat TG nude mice were therefore successfully transferred into naive nude mice by host splenic CD 4 positive cells. CONCLUSION: The present study demonstrated that autoimmunity was involved in the development of keratitis in rat TG nude mice and that these mice were the first animal models to develop autoimmune keratitis spontaneously.

Animals↗

[Clinical features of epidemic nosocomial keratoconjunctivitis in 41 patients].

PURPOSE: To evaluate the clinical features of nosocomial epidemic keratoconjunctivitis (EKC) occurring in the ophthalmology ward of Tokyo Medical University Hospital. MATERIALS AND METHODS: We studied the symptoms and clinical course of 41 patients who had EKC caused by nosocomial infections in our hospital. We attempted to detect adenovirus antigen and viral DNA from conjunctival swabs and also to isolate the virus. RESULTS: The clinical symptoms of EKC, including postoperative cases, were not severe. In some cases, patients' complaints, for example, increase of lacrimation or appearance of a foreign body sensation, were contributory to diagnosis. Among the 41 patients, 31 out of 34 (91.2%) EKC patients who had undergone ophthalmic surgery had EKC in the operated eye. In cases receiving bilateral operations, EKC occurred first in the initially operated eye. The sensitivity of Adeno-check was 76.9%. Adenovirus type 19 was isolated from conjunctival swabs in 26 cases. CONCLUSIONS: The early diagnosis of EKC is extremely important to prevent the spread of nosocomial infections. Careful observation of operated eyes and close attention to patient complaints may aid in the early detection of EKC.

Adenoviridae Infections↗

[Comparison of detectability of visual field abnormality by frequency doubling technology in primary open-angle glaucoma and normal-tension glaucoma].

PURPOSE: To compare the effectiveness of frequency doubling technology(FDT) in detecting abnormalities in primary open-angle glaucoma(POAG) and normal-tension glaucoma(NTG). SUBJECTS AND METHODS: Twenty-nine POAG patients (29 eyes) and 27 NTG-patients(27 eyes) were studied. All subjects underwent testing with program C-20 of FDT with appropriate corrective lenses. RESULTS: No significant differences were observed between the two groups in mean age, mean deviation(MD), and pattern standard deviation(PSD) measured by the Humphrey Field Analyzer(HFA). The correlation between MD values determined by HFA(x) and FDT(y) is represented by y = 0.60x - 2.7 (r = 0.78, p < 0.01) in the POAG group and y = 0.59x + 0.6 (r = 0.81, p < 0.001) in the NTG group. No significant difference was found in the average PSD between the two groups. In early glaucoma cases (MD > or = -5 dB by HFA), a larger proportion of cases in the POAG group than the NTG group had a lower significance level of MD determined by FDT than by HFA (p < 0.02). At many test points on the temporal periphery in FDT the mean sensitivity was lower in the POAG group than in the NTG group; whereas no significant differences among HFA test points were observed. CONCLUSIONS: FDT detected visual field abnormalities in POAG cases more sensitively than in NTG cases. This finding indicates that the pathogenesis of My-cell damage is different in POAG and NTG.

Glaucoma↗

Immunogenicity of human amniotic membrane in experimental xenotransplantation.

PURPOSE: The immunogenic characterization of amniotic membrane is still unknown. This study was designed to examine the immunogenicity of human amniotic membrane, by using experimental xenotransplantation models. METHODS: Anti-human class I, class II, and Fas ligand monoclonal antibodies were used against cryopreserved amniotic membrane and cell viability tested for cryopreserved amniotic membrane. Amniotic membranes were then transplanted to the limbal area, intracorneal space, and under the kidney capsule. The scores of transparency and neovascularization after transplantation were recorded by slit lamp microscopy. Host cell infiltration was examined by hematoxylin-eosin or immunohistochemical staining. Control grafts were transplanted human cryopreserved skin grafts. RESULTS: Strong class I expression was observed in amniotic epithelium, mesenchymal cells, and fibroblasts in cryopreserved amniotic membrane. Some fibroblast cells unexpectedly expressed class II antigen. Fas ligand-positive cells were also detected in mesenchymal cells of amniotic stroma. Approximately 50% of epithelial cells of amniotic membrane cryopreserved for several months were still viable. In limbal transplantation, although some CD4(+) and CD8(+) T cells surrounded the amniotic graft, the response was mild. In intracorneal transplantation, all grafted amniotic membranes were accepted and clear, without host cell infiltration. In contrast, all skin grafts were rejected within 3 weeks after intracorneal transplantation. In amniotic membrane transplantation under the kidney capsule, extremely few host vessels and cells infiltrated the amniotic membrane; however, more host cells infiltrated the skin tissues under the kidney capsule. CONCLUSIONS: Amniotic membrane seems to be immune-privileged tissue and to contain some immunoregulatory factors, including HLA-G and Fas ligand. The amniotic membrane may be useful to supplement corneal collagen, and it may be applied not only to the ocular surface but also intracorneally.

Amnion↗

New genome type of adenovirus serotype 19 causing nosocomial infections of epidemic keratoconjunctivitis in Japan.

Twelve strains of adenovirus serotype 19, isolated from cases of epidemic keratoconjunctivitis in Japan in 1992, 1993, 1997, and 1998, were analyzed by DNA restriction analysis, using restriction endonucleases BamHI, BglI, BglII, EcoRI, HindIII, KpnI, PstI, SacI, SalI, SmaI, and XhoI. Among these 11 restriction endonucleases, EcoRI, PstI, SacI, and SmaI were discriminative enzymes, showing restriction patterns different from those reported previously for the prototype and the variant 19a. This new genome type was isolated in 1997 and 1998, when an increase of epidemic keratoconjunctivitis cases caused by adenovirus serotype 19 was observed for both sporadic and nosocomial infections. Strains from 1992 and 1993 showed restriction patterns similar to those of the worldwide reported variant 19a for all enzymes used. The changes detected in strains from 1997 and 1998 could be the reason for the recent epidemic.

Adenovirus Infections, Human↗

[A case of cerebellar glioblastoma with massive cerebellar hemorrhage].

A case is reported of glioblastoma multiforme (GM) of the cerebellum associated with an intracerebellar hemorrhage. A 54-year-old male was admitted to our hospital with sudden onset of headache and nausea. CT scan showed right intracerebellar hemorrhage. The patient received conservative therapy and was discharged without any neurological deficits. However a second cerebellar hemorrhage attacked him ten days after discharge. His level of consciousness deteriorating, he underwent suboccipital craniectomy and the hematoma with the surrounding elastic tissues was excised. There were no findings suggesting hemorrhage within the tumor on the preoperative neuroimagings, but histological examination confirmed GM with massive hemorrhage. To our knowledge, only 2 cases of cerebellar GM with massive hemorrhage have been reported in the literature. Our case indicates cerebellar GM should be taken into account as a possible cause of cerebellar hemorrhage.

Cerebellar Diseases↗

[Bone metabolism and angiogenesis].

Bone metabolism is regulated not only by the nutrition supplied by vessel but also by the signals from the cells in vascular tissues. Identification of such signaling molecules has been the major issue in the field of research on the relationship between bone and vasculatures. This review touches on the recent findings on the expression and functions of such signaling molecules including VEGF, MMP and non-collagenous bone matrix proteins.

English Abstract↗

[The meaning of phosphate in bone formation].

Bone formation requires phosphate to calcify the osteoid produced by osteoblasts, Pit-1, a natrium-phosphate cotransporter, is expressed in osteoblasts and its expression levels are regulated developmentally and also by hormones and cytokines. Another type of phosphate transporter is expressed in osteoclasts and its function is required for bone resumption. These observations suggest that phosphate transport into the bone cells may play a role in regulation of bone formation and resorption in vivo and in the pathological situation in patients with bone diseases.

English Abstract↗

Negative regulation of BMP/Smad signaling by Tob in osteoblasts.

Bone morphogenetic protein (BMP) controls osteoblast proliferation and differentiation through Smad proteins. Here we show that Tob, a member of the emerging family of antiproliferative proteins, is a negative regulator of BMP/Smad signaling in osteoblasts. Mice carrying a targeted deletion of the tob gene have a greater bone mass resulting from increased numbers of osteoblasts. Orthotopic bone formation in response to BMP2 is elevated in tob-deficient mice. Overproduction of Tob represses BMP2-induced, Smad-mediated transcriptional activation. Finally, Tob associates with receptor-regulated Smads (Smad1, 5, and 8) and colocalizes with these Smads in the nuclear bodies upon BMP2 stimulation. The results indicate that Tob negatively regulates osteoblast proliferation and differentiation by suppressing the activity of the receptor-regulated Smad proteins.

Alleles↗