Showing papers by "Hirosaki University published in 1995"

Molecular features of the CAG repeats and clinical manifestation of Machado—Joseph disease

Abstract: Machado--Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration mapped to chromosome 14q32.1. The CAG expansions of the MJD1 gene was identified as the cause of the disease. We have analyzed 90 MJD individuals from 62 independent MJD families and found that the MJD1 repeat length is inversely correlated with the age of onset (r = -0.87). The MJD chromosomes contained 61-84 repeat units, whereas normal chromosomes displayed 14-34 repeats. In the normal chromosomes, 14 repeat units were the most common and the shortest. In association with the clinical anticipation of the disease, a parent--child analysis showed the unidirectional expansion of CAG repeats and no case of diminution in the affected family. The differences in CAG repeat length between parent and child and between siblings are greater in paternal transmission than in maternal transmission. Detailed analysis revealed that a large degree of expansion was associated with a shorter length of MJD1 gene in paternal transmission. On the other hand, the increments of increase were similar for shorter and longer expansion in maternal transmission. Among the three clinical subtypes, type I of MJD, with dystonia, showed a larger degree of expansion in CAG repeats of the gene and younger ages of onset than the other types.

Reduction in risk of mortality from colorectal cancer by fecal occult blood screening with immunochemical hemagglutination test. A case‐control study

Abstract: Fecal occult blood testing by immunochemical hemagglutination has been shown to be superior to the Hemoccult test, both in sensitivity and in specificity. The test has been widely used as a tool for population screening in Japan, but there has been no study to evaluate the efficacy of screening using this test. A case-control study to evaluate the screening was conducted in study areas where no previous and no other concomitant colorectal cancer screening had been performed. Case series in the study were 193 cases who died of colorectal cancer. Three controls were selected randomly from the list of individuals who were alive at the time of diagnosis of the corresponding case and had been living in the same area as the case, matched by gender and by age. Odds ratios (OR) of dying of colorectal cancer for those screened within 1, 2 and 3 years of case diagnosis vs. those not screened were 0.40 [95% confidence interval (CI) 0.17-0.92], 0.41 (95% CI 0.20-0.82), and 0.48 (95% CI 0.25-0.92), respectively. OR increased towards 1.0 as the duration during which screening histories were compared was extended, and showed similar tendencies when analyzed by number of years since the most recent screening history. These results suggest that colorectal cancer screening by the immunochemical fecal occult blood test would reduce mortality from colorectal cancer.

The influence of fatty liver on insulin clearance and insulin resistance in non-diabetic Japanese subjects.

Abstract: OBJECTIVE : To determine whether fatty liver impairs insulin clearance and contributes to insulin resistance in obese and lean healthy non-diabetic men and women. DESIGN : Cross-sectional, descriptive. SETTING : Medical outpatient clinic ; university hospital. SUBJECTS : Twenty-seven (14 men) non-diabetic obese (Body fat % = 31.5 ± 9.3 ; mean ± s.d.) and 19 (13 men) non-diabetic non-obese (body fat % = 19.0 ± 6.8 ; P < 0.01 vs obese) healthy subjects aged 31-64 without liver disease. MAJOR OUTCOME MEASURES : Liver density relative to the spleen on CT scan (LFS), glucose infusion rate (GIR) and metabolic insulin clearance rate (MIC) during euglycemic hyperinsulinemic clamp ; anthropometric (waist-hip ratio : WHR) and CT-determined (visceral fat area : VFA) measures of fat distribution. RESULTS : Fatty liver was inversely related to MIC (r = -0.39 ; P < 0.01) with a positive correlation with fasting p-insulin (r = 0.39 ; P < 0.01). There were no statistically significant correlations between BMI, body fat % or WHR and MIC. GIR was inversely related to body fat % (r = -0.49 ; P < 0.01), VFA (r = -0.56 ; P < 0.01) and WHR (r = -0.36 ; P < 0.01) in all subjects, with an inverse relationship to fatty liver in men (r = -0.43 ; P < 0.05). CONCLUSION : Increased steatosis of the liver is associated with reduced insulin clearance, contributing to insulin resistance in non-diabetic Japanese men and women.

Hepatitis C virus infection and membranoproliferative glomerulonephritis in Japan.

Abstract: The prevalence of hepatitis C virus (HCV) infection was determined in 146 adult patients with various types of glomerulonephritis and renal diseases monitored between 1990 and 1993. Serum HCV antibody (HCV Ab) was evaluated, and positive cases were tested for HCV RNA by polymerase chain reaction. HCV infection was present in 1 (1.7%) of 58 cases of immunoglobulin A nephropathy, 0 (0%) of 14 cases of lupus nephritis, 0 (0%) of 12 cases of minimal change nephrosis, and 0 (0%) of 28 cases of other renal diseases, which is similar to the 2% prevalence observed in healthy blood donors in Japan. In contrast, HCV Ab was observed in 2 (8.3%) of 24 cases of membranous nephropathy and 6 (60%) of 10 cases of membranoproliferative glomerulonephritis (MPGN) Type I. The prevalence of HCV infection in MPGN patients was significantly higher than the frequency of HCV infection observed in the other patients with renal diseases (P < 0.001). HCV RNA was present in all cases in which HCV Ab was present. The six patients with HCV-MPGN were similar to the four patients with idiopathic MPGN with respect to age, presence of nephrotic syndrome, and renal dysfunction, but had a higher incidence of liver dysfunction, cryoglobulinemia, rheumatoid factor, and hypocomplementemia (low C3). HCV infection is present in a large percentage of patients with MPGN in Japan and clinically may differ slightly from other cases of MPGN.

Endogenous gamma interferon, tumor necrosis factor, and interleukin-6 in Staphylococcus aureus infection in mice.

Abstract: The production and roles of endogenous gamma interferon (IFN-gamma), tumor necrosis factor (TNF), and interleukin-6 (IL-6) in both lethal and nonlethal infections of Staphylococcus aureus were investigated in mice. In the case of nonlethal infection, although no bacteria were detected in the bloodstreams, bacteria that colonized and proliferated persistently for 3 weeks were found in the kidneys. All mice given lethal injections died within 7 days, and large numbers of bacteria were detected in the bloodstreams, spleens, and kidneys. The first peaks of IFN-gamma, TNF, and IL-6 were observed in the bloodstreams and spleens of the mice with nonlethal and lethal infections within 24 h. Thereafter, in the nonlethal cases, IFN-gamma, TNF, and IL-6 peaked again in the spleens and kidneys during the period of maximum growth of bacteria in the kidneys, although only IL-6 was detected in the sera. In contrast, in the case of lethal infection, the titers of IFN-gamma and IL-6 in the sera and TNF in the kidneys peaked before death. Effects of in vivo administration of monoclonal antibodies (MAbs) against IFN-gamma and TNF on the fates of S. aureus-infected mice were studied. In the nonlethal infections, anti-TNF alpha (anti-TNF-alpha) MAb-treated mice, but not anti-IFN-gamma MAb-treated mice, died as a result of worsening infection, suggesting that endogenous TNF plays a protective role in host resistance to S. aureus infection. In the mice that received lethal doses, injection of anti-TNF-alpha MAb accelerated death. However, although injection of anti-IFN-gamma MAb inhibited host resistance of the infected mice early in infection, most of the animals survived the lethal infection by injection of anti-IFN-gamma MAb, suggesting that endogenous IFN-gamma plays a detrimental role in S. aureus infection. Thus, this study demonstrated that IFN-gamma and TNF play different roles in S. aureus infection.

The role of proinflammatory and immunoregulatory cytokines in the pathogenesis of ulcerative colitis.

Abstract: We investigated the production of proinflammatory cytokines (IL-1 beta, IL-6, IL-8, and TNF-alpha) and immunoregulatory cytokines (IL-2, IFN-gamma, and IL-10) in the colonic mucosa of patients with active ulcerative colitis (UC), inactive UC, and non-inflammatory bowel disease (IBD) colitis by organ culture. The production of proinflammatory cytokines was significantly increased in all the studied groups compared with controls. In active UC, levels of these cytokines, except for IL-1 beta, were markedly increased compared with non-IBD colitis, and the levels were positively correlated with the degree of inflammation. Patients with non-refractory active UC receiving steroids showed levels of IL-1 beta and TNF-beta production similar to those in controls. IL-10 production was also significantly increased in all the studied groups, the value of being the highest in active UC. In contrast, IL-2- and IFN-gamma production was significantly decreased in both active and inactive UC compared with controls, and the values in active UC were inversely correlated with the degree of inflammation. In non-IBD colitis, decreased IL-2 production was observed, but IFN-gamma production did not differ from that in controls. In an experimental study, each of the proinflammatory cytokines was injected into the colonic mucosa of rats. All of these proinflammatory cytokines, except for IL-1 beta induced colonic mucosal damage that showed some histologic features similar to those of UC. These results suggest that the increased production of proinflammatory cytokines, particularly of IL-6 and IL-8, and the decreased production of IL-2- and IFN-gamma, probably downregulated by the enhanced production of IL-10, play an important role in the pathogenesis of UC.

Identity elements of Saccharomyces cerevisiae tRNAHis

Abstract: Recognition of tRNA(His) by Saccharomyces cerevisiae histidyl-tRNA synthetase was studied using in vitro transcripts. Histidine tRNA is unique in possessing an extra nucleotide, G-1, at the 5' end. Mutation studies indicate that this irregular secondary structure at the end of the acceptor stem is important for aminoacylation with histidine, while the requirement of either base of this extra base pair is smaller than that in Escherichia coli. The anticodon was also found to be required for histidylation. The regions involved in histidylation are essentially the same as those in E.coli, whereas the proportion of the contributions of the two portions distant from each other, the anticodon and the end of the acceptor stem, makes a substantial difference between the two systems.

4-5-Day-Period Variation and Low-Level Dry Air Observed in the Equatorial Western Pacific during the TOGA-COARE IOP

Abstract: A significant 4-5-day-period variation was observed in surface and aerological data obtained at the equator, 156E during November 1992. The time-height structure of the variation is determined by use of spectral and composite analysis. The 4-5-day period variation can be basically explained by westward-propagating mixed Rossby-gravity wave disturbances. However, the structure of the circulation was significantly distorted by the presence of a tropical depression. Further, two distinctive events of extremely dry air in the lower troposphere were observed. The vertical profiles of specific humidity as well as the equivalent potential temperature had distinct minima at about the 3 km level. The trajectory analysis revealed that the dry-air parcels were brought from a subtropical area by tropical disturbances, especially by the intense meridional flow associated with 4-5-day period disturbances. These events of dry-air intrusion are detected in the precipitable water data derived from SSM/I satellite imageries and the zonal scale of the intrusion is estimated to be about 1000 km. Convection was strongly suppressed over the dry air, and the latter was maintained to about 4 days due to very weak vertical mixing.

NMDA (NMDAR1) and AMPA-type (GluR2/3) receptor subunits are expressed in the inner ear.

Abstract: Using receptor subunit-specific antibodies, the cellular localization of NMDA and AMPA type glutamate receptor subunits was studied within the rodent (rat, guinea pig) and non-human primate (monkey) inner ear. In the spiral and vestibular ganglion, almost all cells were immunoreactive for the NMDAR1 subunit and the AMPA type receptor subunit GluR2/3. This indicates that both NMDA and non-NMDA type glutamate receptors may be co-distributed in the primary afferent neuronal components, and are possibly involved in neurotransmission in the primary auditory and vestibular systems. This study also indicated the possible localizations of glutamate receptors in the nonneuronal cells in the inner ear, suggesting that some nonneuronal cells may also have the ability to mediate glutamate signalling.

Protective effects of soy protein on the peroxidizability of lipoproteins in cerebrovascular diseases.

Abstract: To study the mechanism of dyslipoproteinemia, lipoproteins [very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL)] were isolated from stroke patients and healthy persons by ultracentrifugation. Lipoproteins were dialyzed into copper dichloride solution to study the effects of soycreme administration on lipoprotein peroxidation. Blood was drawn from 15 patients with cerebral thrombosis who were not administered soycreme, 10 patients with cerebral thrombosis who were administered soycreme and 11 healthy persons. The lipoproteins were dialyzed into 5 mol/l copper dichloride solution for various lengths of time, and then lipid constituents in the lipoproteins were measured by thin-layer chromatography. After the dialysis, percentages of cholesteryl ester and triglyceride in various lipoproteins decreased significantly (P < 0.05 or 0.01) in both patient groups and in healthy persons. Spot X1 was found between triglyceride and free fatty acid on the thin-layer chromatography, and spot X2 was located between free fatty acid and free cholesterol after dialysis. Spots X1 and X2 reflect lipoprotein peroxidation. Percentages of these spots were higher in VLDL, LDL and HDL in the patient groups than in the healthy subjects. Soycreme administration suppressed the appearance of spots X1 and X2. Furthermore, blood cholesterol concentrations were reduced by the administration of soy protein. Thus, soy may be useful in the prevention and/or treatment of atherosclerosis.

Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down's syndrome.

Abstract: Summary. Acute megakaryoblastic leukaemia (M7) and transient myeloproliferative disorder in Down's syndrome (TMD) are characterized by rapid growth of abnormal blast cells which express megakaryocytic markers. To clarify properties of the blast cells in M7 and TMD cases, we examined erythroid markers expression in blasts from six cases with M7 and seven cases with TMD in this study. Erythroid-specific mRNAs encoding 7-globin and erythroid 6-aminolevulinate synthase were found to be expressed in blasts from most of these cases, indicating that majorities of the blasts in M7 and TMD cases have erythroid and megakaryocytic phenotypes. We also found that mRNAs encoding GATA-1 and GATA-2 are expressed in all these cases. These results suggest that M7 blasts and TMD blasts correspond to the erythroid/megakaryocytic bipotential progenitor cells.

Inhibition of trazodone metabolism by thioridazine in humans

Abstract: To clarify the involvement of cytochrome P4502D6 (CYP2D6) in the metabolism of trazodone, the effects of coadministration of thioridazine, which is an inhibitor of this isozyme, on plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were studied. The subjects were 11 depressed patients receiving trazodone at bedtime for 1-18 weeks. The dose was 150 mg in 10 patients and 300 mg in one. Thioridazine 40 mg/day was coadministered for 1 week, and blood samplings were performed before and after the coadministration. Thioridazine significantly (p < 0.001) increased plasma concentrations of both trazodone (713 ± 252 vs. 969 ± 370 ng/ml) and m-CPP (61 ± 22 vs. 94 ± 34 ng/ml). The present study thus suggests that CYP2D6 is involved in the metabolism of trazodone.

On a class of small 2-designs over gf(q)

Abstract: A 2 − (v,k,λ;q) design is a pair (V, B) of a v-dimensional vector space V over GF(q) and a collection B of k-dimensional subspaces of V such that each 2-dimensional subspace of V is contained in exactly λ members of B. Assuming transitivity of their automorphism groups on the nonzero vectors of V, we give a classification of nontrivial such designs for v = 7, q = 2,3 with small λ, together with the nonexistence proof of those designs for v ⩽ 6. © 1995 John Wiley & Sons, Inc.

Gene diagnosis of viroids: comparison of return-PAGE and hybridization using DIG-labeled DNA and RNA probes for practical diagnosis of hop stunt, citrus exocortis and apple scar skin viroids in their natural host plants

Abstract: Return-PAGE was reliable for diagnosis of HSVd in hop, CEVd in citron and ASSVd in apple, but was not reliable for HSVd in grapevine and citron, and ASSVd in pear, because of their low concentration. A disadvantage of return-PAGE was possible appearance of double or triple bands in case of mix-infecting samples such as hop or citron. Although DIG-labeled DNA probe was 2.5 to 25 times more sensitive than return-PAGE, the practical reliability of this method was not so superior to return-PAGE. DIG-labeled RNA probe was the most sensitive of the three methods examined in this experiment, which was 25-125 times and 100-625 times more sensitive than DIG-DNA probe and return-PAGE, respectively. Furthermore, DIG-RNA probe was sensitive enough to detect HSVd in grapevine, a symptomless host of the pathogen, although negative sample was emphasized to be re-examined by the other sensitive method such as cucumber bioassay or RT-PCR. DIG-RNA probe, however, is not sensitive enough to detect HSVd in citrus and ASSVd in pear. Based on the results obtained in this experiment, we proposed appropriate amounts of plant tissues for the successful diagnosis of the three viroids.

Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine.

Abstract: Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were studied in 43 depressed patients (19 males, 24 females) receiving trazodone 150 mg at bedtime for 1-3 weeks. Sixteen cases were smokers, and 19 cases were also receiving various benzodiazepines. The means (and ranges) of plasma concentrations of trazodone and mCPP, and the mCPP/trazodone ratio were 619 (251-1059) ng/ml, 59 (32-139) ng/ml and 0.100 (0.044-0.219), respectively. Smokers had significantly (p < 0.05) lower plasma concentrations of trazodone and higher mCPP/trazodone ratios than non-smokers. Age, sex and co-administration of benzodiazepines did not affect any plasma concentrations or the mCPP/trazodone ratio. In 11 cases where the dose was increased to 300 mg, neither plasma concentration/dose ratios nor the mCPP/trazodone ratio changed significantly. The present study thus suggests that : (1) there is a large interindividual variation in the metabolism of trazodone ; (2) smoking enhances the metabolism, but age, sex and co-administration of benzodiazepines do not affect it ; (3) trazodone and mCPP have linear kinetics.

Pathogenesis of Rhodococcus equi infection in mice: Roles of virulence plasmids and granulomagenic activity of bacteria

Abstract: Virulence of Rhocococcus equi ATCC 33701 and its plasmid-cured derivative ATCC 33701P− was compared in BALB/c and C3H/HeJ mice in terms of bacterial growth kinetics and histological changes in the liver, spleen and lungs, and humoral immune responses. Injection with a sublethal dose of 106 ATCC 33701 in mice resulted in microabscess formation after rapid multiplication in the liver and spleen by day 4, and then the bacteria were gradually eliminated with the formation of granuloma and the production of specific antibodies against 15- to 17-kDa antigens of the virulent bacteria. By contrast, ATCC 33701P− was avirulent as shown by early elimination of viable bacteria and no evidence of net multiplication in the organs. Histopathological changes consisted of only slight, transient infiltration of neutrophils and macrophages in the liver. Although live ATCC 33701P− did not evoke any humoral or histological responses in the mice, a large inoculum (108) of killed ATCC 33701 and ATCC 33701P− resulted in the formation of granuloma in the liver and accelerated extramedullary hemopoiesis in the spleen. These results suggest that the pathogenesis of R. equi infection involves at least two important virulence determinants, both of which play critical roles in the disease: one is the virulence plasmid, which is required for R. equi to resist and grow within host cells; and the other is the granulomagenic activity that is related to the lipids and nature of the cell wall of the species, which induces the characteistic pathological changes.

Effects of Dietary Fiber on Gastrointestinal Transit Time, Fecal Properties and Fat Absorption in Rats

Abstract: The gastrointestinal transit time of food was determined by x-ray fluoroscopy using barium sulfate in rats fed with diets of various dietary fiber contents, and the effects of dietary fiber on the transit time, properties of feces, and fat absorption were examined. In 4- and 16-month-old rats fed with the diet for 3 and 15 month, respectively, the transit time of the cecum and colon in those receiving 20 and 40% wheat bran diets was shortened compared with that in the 0% group. The fecal pellet number and volume increased as the wheat bran content of the diet increased. In another experiments, the daily total fat excretion was found to be the greatest in rats receiving 15% pectin diet, followed by rats receiving 15% cellulose and non-fiber diets, respectively. These results suggest that shortening of the transit time through the cecum and colon with increase of fecal volume and suppression of fat absorption all participate in the mechanism of the inhibitory action of wheat bran on carcinogenesis and on the development of diverticulum of the large intestine.

Successful Treatment of Dark-colored Epidermal Nevus with Ruby Laser

Abstract: The pulsed ruby laser has a selective thermolytic effect. Recently, it has been available for the treatment of superficial pigmented disorders. We studied 5 cases of epidermal nevus treated with the pulsed ruby laser. In comparison with the usual methods including electrocautery, cryotherapy and skin abrasion, ruby laser therapy is an excellent tool due to technological ease and rapid improvement. Depigmentation after treatment in 2 cases was the only side effect of this therapy. Bose cases had a dark pigmentation of the skin. Despite of the risk of discoloration, the ruby laser is one of the most effective tools for therapy of pigmented epidermal nevus.

Antiepileptic Agents and Birth Defects

Abstract: An association exists between maternal use of antiepileptic drugs (AEDs) during pregnancy and birth defects in offspring. The overall malformation rate is 11.1% in offspring of AED-treated epileptic mothers, while it is 5.7% in the offspring of untreated epileptic mothers and 4.8% in those of the general population. Cardiovascular defects, facial cleftings and skeletal anomalies are the most frequently occurring AED-associated malformations. No firm patterns of specific AEDs inducing particular birth defects have been established. Nevertheless, neural tube defects may be specific malformations in infants exposed to both valproic acid (sodium valproate) and/or carbamazepine. Several minor anomalies are influenced by genetic factors. From prospective studies a number of primary risk factors for increased incidences of congenital malformations in the offspring of epileptic mothers receiving AEDs have been identified. These include high drug dosage, high serum drug concentration, the use of AEDs with high teratogenicity potency [primidone > valproic acid > phenytoin > carbamazepine > phenobarbital (phenobarbitone)] and AED polypharmacy (especially combinations of valproic acid and carbamazepine, and phenytoin and/or carbamazepine with or without barbiturates). The mechanism of teratogenicity of AEDs is still being investigated, but it is postulated that epoxide intermediates and other toxic metabolites of AEDs might be involved. In addition, the folate deficiency and impaired folate metabolism caused by AEDs may contribute to the teratogenicity of these drugs. To prevent birth defects, the use of the lowest effective AED dosage and a change from polypharmacy to monotherapy are recommended before conception. A decrease in serum AED concentrations during pregnancy does not in itself justify an increase in drug dosage. The high risk of neural tube defects in offspring exposed to valproic acid (or carbamazepine) warrants prenatal examination in pregnant women receiving this drug, such as ultrasound and amniotic fluid α-fetoprotein investigations. To reduce the risk of this malformation, replacement of conventional formulations of valproic acid with controlled release formulations and the use of folate supplementation are recommended.

Temperature Dependence of the Linewidth of the First-Order Raman Spectrum for SnO2 Crystal

Abstract: The first-order Raman spectrum of the A 1g mode in SnO 2 crystal was measured in the temperature range of 300–973 K and the linewidths at these temperatures were obtained. The temperature dependence of the linewidths was analyzed using the phonon dispersion curves based on the shell model, and the results showed that it may have been caused provably by the cubic anharmonic term in crystal potential energy.