Biomedical subjects
Publications and source records attributed to R Nakano.
Studies on the clinical course of familial ALS suggest that the duration of illness is relatively consistent for each mutation but variable among the different mutations. The authors analyzed the relative amount of mutant compared with normal SOD1 protein in the erythrocytes from 29 patients with ALS with 22 different mutations. Turnover of mutant SOD1 correlated with a shorter disease survival time.
To investigate the characteristic structure of hydatidiform mole, type IV collagen expression was determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type IV collagen with specific monoclonal antibody, and Northern blot analysis was performed to assess expression of messenger ribonucleic acid for the alpha1(IV) chain. In addition, serum levels of type I, III, and IV collagen were measured by RIA. Immunohistochemical staining for type IV collagen revealed stronger staining of the trophoblastic basement membrane in hydatidiform mole than in normal pregnancy. Northern blot analysis revealed that the villous expression of messenger ribonucleic acid for the alpha1(IV) chain was significantly increased in hydatidiform moles compared with normal pregnancy (P < 0.01). Although there were no differences in the serum type I and III collagen levels between hydatidiform mole and normal pregnancy, the type IV collagen level was significantly higher in patients with hydatidiform mole than in normal pregnancy (P < 0.05). These results suggest that type IV collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.
To investigate the characteristic structure of hydatidiform mole, various types of collagen expression were determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type I, III, and VI collagen with specific monoclonal antibodies. Collagens were also extracted from the villous tissues obtained from normal pregnancy and hydatidiform mole by the salt precipitation method. Immunohistochemical staining for type I, III, and VI collagen revealed weak staining of the villous stroma in hydatidiform mole compared with that in normal pregnancy. Both the ratios of type III to type I collagen and the ratios of type V to type I collagen in the villous tissues were significantly decreased (P < 0.05) in molar pregnancy compared with those in normal pregnancy. These results suggest that alterations in the distribution and composition of collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.
Intussusception accounts for almost all cases of intestinal obstruction in children. In contrast, intussusception in adults is relatively rare. An 86-year-old Japanese female with rectal bleeding came to our hospital via ambulance. At first, colonoscopy findings revealed the sigmoid colon cancer. Ultrasonography showed a hypoechoic mass with a multiple concentric ring sign. Computed tomography showed a round fluid-filled cystic structure. Colon contrast studies demonstrated stenosis in the rectosigmoid colon. A laparotomy was performed. The sigmoid colon was intussuscepted to the rectosigmoid colon. We employed both rectosigmoid and sigmoid colon resection. The resected specimen showed that the disease was advanced sigmoid colon cancer with ulcer formation due to an ischemic change. Tumor was 4.5 cm x 2.0 cm in size. The disease was histopathologically diagnosed as advanced sigmoid colon cancer, well-differentiated adenocarcinoma. We report here a case of adult intussusception due to the sigmoid colon cancer.
beta-Lactamases are the principal mechanism of bacterial resistance to beta-lactam antibiotics. In recent years, resistance due to production of beta-lactamases including extended-spectrum beta-lactamses, carbapeneases and AmpC beta-lactamses, has risen at alarming rate in clinical isolates of gram-negative bacteria. AmpC beta-lactamses are classified by whether genes locate on chromosome or plasmid. The purpose of this paper is to address the general mechanism involve in AmpC beta-lactamase production and the clinical importance of the enzymes.
We report a Japanese family with autosomal dominant adult-onset amyotrophic lateral sclerosis (FALS) with onset in the bulbar musculature, clinically benign course, absence of the Cu/Zn superoxide dismutase-1 (SOD 1) gene mutation, and many Bunina bodies, in addition to involvement of the upper and lower motor neurons. The proband was a Japanese woman who was 66 years old at the time of death. Family history disclosed five patients with FALS over three generations. She developed dysarthria at age 57, followed by dysphagia, muscle weakness of the upper extremities, and difficulty in respiration. She could walk without support until her death. The elder sister of the proband developed dysarthria at age 48 and died at age 58. A genetic study of the nephew of the proband showed the absence of a mutation in the SOD 1 gene. Neuropathological examination of the proband disclosed neuronal loss in the upper and lower motor neurons, and numerous Bunina bodies in the lower motor neurons without Lewy body-like inclusions or ubiquitin-immunoreactive neuronal inclusions. No degeneration of the Clarke's column, middle root zone of the posterior column, or posterior spinocerebellar tract was present. Review of the literature revealed that only patients with FALS with a long survival period of over 5 years had pathological findings consistent with FALS with posterior column involvement. This study contributes to the elucidation of the clinicopathological heterogeneity of FALS.
OBJECTIVE: To identify type VI collagen expression in human ovarian follicles during follicular growth. DESIGN: In vitro experiment. SETTING: Department of Obstetrics and Gynecology, Wakayama Medical College, Japan. PATIENT(S): Regularly cycling women who underwent adnexectomy. INTERVENTION(S): Immunohistochemistry and in situ hybridization for human type VI collagen. MAIN OUTCOME MEASURE(S): Expression of type VI collagen. RESULT(S): Expression of type VI collagen was observed in the theca cell layers during folliculogenesis, whereas no expression of type VI collagen was observed in the granulosa cell layers at the mRNA and protein levels. As the follicles grew, immunostaining for type VI collagen became intense in the theca cell layers, especially the theca externa. In preovulatory follicles, however, weak, fragmented, or discontinuous immunostaining of the theca cell layers was observed. This fragmented or discontinuous immunostaining was evident predominantly in the apical area of preovulatory follicles rather than in the basal area. CONCLUSION(S): Type VI collagen is present in the theca cell layers of follicles during folliculogenesis and plays an important role in interactions between the theca cells and extracellular matrix. These interactions may lead to changes in the shape, proliferation, migration, or differentiation of follicular cells during follicular development, maturation, and ovulation.
To determine the relationship between hypoglycemic activity and body weight gain induced by insulin sensitizers, we compared the effects of thiazolidinedione analogs (troglitazone and pioglitazone) and the oxadiazolidinedione analog (Z)-1,4-bis4[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phen oxy¿but-2-ene (YM440) in diabetic db/db mice. Oral treatment with YM440(100 mg/kg) for 28 days decreased the blood glucose concentration (control v YM440, 418 +/- 12 v243 +/- 44 mg/dL). The hypoglycemic activity of this agent was comparable to that of troglitazone (300 mg/kg) and pioglitazone (100 mg/kg). There were no changes in food intake among the groups. Troglitazone and pioglitazone, but not YM440, significantly increased body weight gain during treatment (control, 7.2 +/- 0.5 g; YM440, 7.5 +/- 0.8 g; troglitazone, 10.9 +/- 0.8 g; and pioglitazone, 14.5 +/- 1.1 g). To further assess whether the increase in body weight by troglitazone or pioglitazone was due to adipogenesis, the weight of intraabdominal fat tissue (epididymal, retroperitoneal, and perirenal) was determined. There were no differences in the total weight of visceral fat between the control and YM440 treatment (3.53 +/- 0.23 and 3.60 +/- 0.16 g). In contrast, troglitazone and pioglitazone significantly increased the fat weight (4.31 +/- 0.13 and 4.66 +/- 0.19 g). Thiazolidinediones are known as ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor responsible for adipogenesis. Troglitazone and pioglitazone activated PPARgamma and increased triglyceride accumulation and mRNA expression of fatty acid-binding protein (FABP) in 3T3-L1 cells. However, YM440 had no effect on these indices for adipocyte differentiation. These results suggest that the mechanism is different for the hypoglycemic action of YM440 versus the thiazolidinediones. YM440 ameliorates hyperglycemia without changing PPARgamma activity, adipocyte differentiation, or fat weight. Thus, YM440 could be a useful hypoglycemic agent for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) without affecting body weight.
BACKGROUND/AIMS: The initial abnormalities of renal sodium handling in cirrhosis remain unclear. The aim of this study was to characterize sodium metabolism in preascitic cirrhosis. METHODS: Ten patients with preascitic cirrhosis and ten controls were studied. All subjects ate a diet providing 120 mmol sodium during an equilibration period lasting 5 days and the study day. On the study day, after remaining in bed, plasma levels of atrial natriuretic peptide, brain natriuretic peptide, renin activity, aldosterone, noradrenaline, and cyclic guanosine monophosphate were measured at 7 am. Thereafter, they were instructed to maintain an upright posture until dinner and the measurements were repeated at 9 am and 6 pm. After having dinner, all subjects were asked to remain in bed and the measurements were repeated at 11 pm. To measure renal sodium and cyclic guanosine monophosphate excretion, 24-h urine collections were performed, starting from 7 pm on the day before the experimental day. RESULTS: Plasma levels of atrial natriuretic peptide, brain natriuretic peptide and cyclic guanosine monophosphate in patients with preascitic cirrhosis were significantly elevated compared with those in controls at every sampling time (p=0.03 or less, p= 0.04 or less, and p=0.01 or less). In contrast, plasma renin activities at every sampling time were significantly lower in patients than in controls (p= 0.04 or less). Plasma aldosterone and noradrenaline levels were not significantly different at every sampling time in the two groups. No significant differences in daily renal sodium excretion were found. However, urinary cyclic guanosine monophosphate excretion was significantly higher in patients than in controls (p<0.01). CONCLUSIONS: The initial abnormalities of sodium metabolism in cirrhosis might be characterized by blunted renal responsiveness to natriuretic peptides. The results of the study also provide indirect evidence that the impairment is mainly located at postreceptor levels of signal transduction pathway to the peptides, if the activation of antinatriuretic factors other than renin-angiotensin or sympathoadrenergic systems does not play a role.
For the learning of a finite state machine (FSM) by a recurrent neural network (RNN), we think about how to train an RNN so as to stably mimic an FSM even for sequences having a long length. First, we consider the relationship between the stable behavior and the internal representation of states, that is, clusters of the internal units' outputs. As for this relationship, we prove that an RNN can get the stable cluster transitions when a neuron activation parameter is larger than a certain finite value micro0. Secondly, to acquire the stable behavior, we regard the internal representation for the stable behavior as prior knowledge. This produces a new target function of learning with internal representation term. We derive a Bayesian style method to estimate coefficients of the terms in the function, corresponding to hyperparameters. Finally, experiments show that RNNs readily acquire stable behavior by using our proposed method.
Efficient expression of the dye-decolorizing peroxidase, DyP, from Geotrichum candidum Dec 1 in Aspergillus oryzae M-2-3 was achieved by fusing mature cDNA encoding dyp with the A. oryzae alpha-amylase promoter (amyB). The activity yield of the purified recombinant DyP (rDyP) was 42-fold compared with that of the purified native DyP from Dec 1. No exogenous heme was necessary for the expression of rDyP in A. oryzae. From the N-terminal amino acid sequence analyses of native DyP and rDyP, the absence of a histidine residue in both DyPs, which was considered to be important for heme binding of DyP, was confirmed. These results suggest that rDyP without a typical heme-binding region produced by A. oryzae exhibits a function similar to that of native DyP.
We present a split-and-merge expectation-maximization (SMEM) algorithm to overcome the local maxima problem in parameter estimation of finite mixture models. In the case of mixture models, local maxima often involve having too many components of a mixture model in one part of the space and too few in another, widely separated part of the space. To escape from such configurations, we repeatedly perform simultaneous split-and-merge operations using a new criterion for efficiently selecting the split-and-merge candidates. We apply the proposed algorithm to the training of gaussian mixtures and mixtures of factor analyzers using synthetic and real data and show the effectiveness of using the split-and-merge operations to improve the likelihood of both the training data and of held-out test data. We also show the practical usefulness of the proposed algorithm by applying it to image compression and pattern recognition problems.
This article compares three penalty terms with respect to the efficiency of supervised learning, by using first- and second-order off-line learning algorithms and a first-order on-line algorithm. Our experiments showed that for a reasonably adequate penalty factor, the combination of the squared penalty term and the second-order learning algorithm drastically improves the convergence performance in comparison to the other combinations, at the same time bringing about excellent generalization performance. Moreover, in order to understand how differently each penalty term works, a function surface evaluation is described. Finally, we show how cross validation can be applied to find an optimal penalty factor.
We report a case of struma ovarii with hyperthyroidism and elevated serum concentrations of type IV collagen and laminin. Circulating levels of type IV collagen and laminin were measured using specific radioimmunoassays (RIAs) for 7S collagen and the P-1 fragment of laminin, and the basement membrane components in the tumor were investigated by immunohistochemical analysis. Strong immunohistochemical staining specific for type IV collagen and for laminin was observed to be localized in the follicular walls. The serum levels of these antigens, as determined by RIA, were very high before removal of the tumor but decreased rapidly postoperatively. The present findings suggest that struma ovarii produces large amounts of type IV collagen and laminin. In addition, elevated levels of thyroid hormones might enhance the turnover of the basement membrane in various tissues.
To investigate the role of insulin receptor substrate (IRS)-2 in vivo, we generated IRS-2-deficient mice by gene targeting. Although homozygous IRS-2-deficient mice (IRS-2-/- mice) had a body weight similar to wild-type mice, they progressively developed type 2 diabetes at 10 weeks. IRS-2-/- mice showed insulin resistance and a defect in the insulin-stimulated signaling pathway in liver but not in skeletal muscle. Despite insulin resistance, the amount of beta-cells was reduced to 83% of that in wild-type mice, which was in marked contrast to the 85% increase in the amount of beta-cells in IRS-1-deficient mice (IRS-1-/- mice) to compensate for insulin resistance. Thus, IRS-2 plays a crucial role in the regulation of beta-cell mass. On the other hand, insulin secretion by the same number of cells in response to glucose measured ex vivo was significantly increased in IRS-2-/- mice compared with wild-type mice but was decreased in IRS-1-/- mice. These results suggest that IRS-1 and IRS-2 may play different roles in the regulation of beta-cell mass and the function of individual beta-cells.
We monitored the cryptococcus count in the cerebrospinal fluid(CSF) using the filter technique in two cases of serious cryptococcal meningitis during the course of treatment with antifungal agents. Lumbar puncture was performed once a week, and 1 ml of CSF was filtered through a Millipore filter(5.0-micron pore for cells), followed by staining of the filters with Alcian blue. All of the cryptococci on the filter were counted under a light microscope at a magnification of x 100. More than 500/ml and 2,000/ml of cryptococci were still observed in the CFS in Cases 1 and 2, respectively, in whom CFS cultures for Cryptococcus neoformans became negative after 4 weeks of treatment. Even though the treatment with antifungal agents were continued in these cases, cryptococci could still be observed for 5 weeks and 60 weeks on the filter preparations of Cases 1 and 2, respectively, after the CSF cultures became negative. The cryptococcal antigen could also be detected in the CSF during the positive filter preparations in these cases. At autopsy in Case 2, patchy lepromeningeal inflammatory lesions with the characteristic capsules of cryptococci were observed in the subarachnoid space. These observations suggest that cryptococci, which persisted in the CSF despite the negative cultures, were responsible for the lesions in the subarachnoid space and protracted clinical course in the two cases of cryptococcal meningitis.
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The susceptibilities of 24 Helicobacter pylori isolates, which were originated from clinical materials, to 5 beta-lactam antibiotics [benzylpenicillin (PCG), ampicillin (ABPC), cephalothin (CET), ceftazidime (CAZ), cefotiam (CTM) and imipenem (IPM)], two macrolides [clarithromycin (CAM) and rokitamycin (RKM)], two aminoglycosides [amikacin (AMK) and gentamicin (GM)], two new quinolones [ciprofloxacin (CPFX) and levofloxacin (LVFX)], two tetracycline [tetracycline (TC) and minocycline (MINO)], rifampicin (RIF) and chloramphenicol (CP) were tested. All of the isolates showed similar susceptibilities against beta-lactam antibiotics. However, MICs of CTM and CAZ were two- to four-fold higher than those of PCG, ABPC, CET and IPM, MICs of rokitamycin for the tested strains were higher than those of clarithromycin. MICs of CPFX and LVFX showed two-modal distributions. The first peak of distributions was observed between 0.06 to 0.5 microgram/ml and second one was between 4 to 16 micrograms/ml. These distributions suggested that MIC values of 4 to 16 micrograms/ml could result from the expression of a resistance mechanism. In addition, some of H. pylori strains were observed drug resistances between CP and AMK, new quinolones and AMK respectively. From the molecular epidemiological study, cryptic plasmids were detected from the 3 isolates among 24 strains tested.