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Biomedical subjects

T Saitoh

Publications and source records attributed to T Saitoh.

At least 163 records · Page 9Linked to original sources

Sex-related spatial kin structure in a spring population of grey-sided voles Clethrionomys rufocanus as revealed by mitochondrial and microsatellite DNA analyses.

Polymerase chain reaction-directed mitochondria (mt) and microsatellite DNA analyses were performed to examine the kin structure in a spring population of grey-sided voles Clethrionomys rufocanus in Hokkaido, Japan. The spatial distribution of 81 voles in a trapping grid (about 1 ha) was estimated by using the catch-mark-release method. DNA samples were extracted from the toes clipped for individual identification. Maternal lineages of voles were unequivocally determined by the mtDNA haplotypes, as identified by nucleotide sequencing of the control region. Relatedness between individuals was estimated based on the genotype and allele frequencies at several microsatellite loci. Although the distribution of voles was uniform within the grid, neighbouring females were frequently from the same maternal lineage. Relatedness values between females correlated negatively with geographical distances. Combination of the two molecular markers revealed four clusters of closely related, matrilineal females in the population, whereas no such cluster was apparent in males. The present study first demonstrated a sex-related spatial kin structure in a natural population of the grey-sided vole.

Animals↗

Mutations of the X region of hepatitis B virus and their clinical implications.

Nucleotide (nt) sequences of the X region of more than 130 hepatitis B virus (HBV) isolates were determined and derived from patients with a variety of clinical features. Correlation of nt substitutions with clinicopathological characteristics was attempted. The X region (465nt) is crucial for the replication and expression of HBV because the X protein transactivates the HBV genes and this region contains the core promoter, enhancer II, and two direct repeats. There are several mutational hotspots, some of which seem to relate to immunological epitopes of the X protein. Two kinds of mutations which have important clinical significances were found. One is an 8-nt deletion between nt 1770 and 1777, which truncates 20 amino acids from the carboxyl terminus of the X protein. This deletion leads to the suppression of replication and expression of HBV DNA, resulting in immunoserological marker (HBsAg) negativity. This silent HBV infection is responsible for the majority of non-A to non-E hepatitis. The other mutation substituting T for C (nt 1655), T for A (nt 1764) and A for G (nt 1766) seems to relate to fulminant hepatitis. Further sequencing studies and in vitro mutagenesis experiments will clarify the significance of other mutations of the X region.

Amino Acid Sequence↗

Renal circulation and cellular metabolism during left ventricular assisted circulation: comparison study of pulsatile and nonpulsatile assists.

We examined left ventricular assist during 6 h for an acute myocardial infarction model in pigs. The outflow cannula was placed in the ascending aorta and an inflow cannula in the left atrium. A pump (Pulsatile group: Zeon Medical and Nonpulsatile group: Nikkiso HPM-15) was connected to each cannula. Items measured were the regional blood flow of the cortex and the medulla in the kidney, renal arterial flow, arterial blood ketone body ratio (AKBR), lactate/pyruvic acid, BUN, creatinine and beta 2-microglobulin. After experimental study, the kidneys were removed, and a pathological study was performed. In the pulsatile assisted group, renal cortical blood flow increased but medulla blood flow decreased. On the other hand, in the nonpulsatile assisted group, both regional blood flows decreased. That means that in the pulsatile assisted group intrarenal redistribution improved, rather than in the nonpulsatile assisted group. The results of our study indicated that pulsatile assist produced superior circulation in the kidney, and the microcirculation on the cell level was superior as well in early treatment of acute left heart failure.

Animals↗

Glial cells in Alzheimer's disease: preferential effect of APOE risk on scattered microglia.

Reactive glial cells are consistently found in the brain tissue of Alzheimer's disease (AD) patients. Both clustered and scattered glial cells occur in AD brain. A number of clustered microglial cells, but not astrocytes, had a positive correlation with neurite plaque numbers, suggesting that clustered micro-glial cells are uniquely associated with plaques whereas clustered astrocytes may have functions outside the plaques as well. APOE epsilon 4, the major genetic risk factor for AD, had a dose-dependent effect to increase the numbers of scattered microglial cells whereas the APOE risk showed no correlation with any of the clustered glial cells or scattered astrocytes. These findings raise the possibility that the increased levels of scattered, but not clustered, microglial cells are the immediate response to APOE risk and might be primarily involved in AD pathogenesis.

Aged↗

Genetic association of the low-density lipoprotein receptor-related protein gene (LRP), an apolipoprotein E receptor, with late-onset Alzheimer's disease.

The presence of the APOE epsilon 4 allele encoding apolipoprotein E4 (apoE4) is the major genetic risk factor for late-onset Alzheimer's disease (AD). However, the molecular and cellular mechanisms by which APOE epsilon 4 renders AD risk are unclear. In this report, we present genetic evidence that an apoE receptor, LRP, may be associated with the expression of late-onset AD. Using a biallelic genetic marker in exon 3 of LRP, late-onset AD cases markedly differed from the control subjects in the distribution of LRP genotypes, and this difference was highly accentuated among AD cases with positive family history of senile dementia. Furthermore, the numbers of neutritic plaques were significantly altered as a consequence of different LRP genotypes in postmortem AD cases. Taken together, our results implicate the pathophysiology of LRP in the expression of late-onset AD.

Age of Onset↗

Effects of apolipoprotein E on dementia and aging in the Shanghai Survey of Dementia.

We investigated the status of the apolipoprotein E allele in 538 participants in the incidence phase of the ongoing Shanghai Survey of Dementia, including 103 demented subjects, 72 with mild cognitive impairment and 363 cognitively normal. The apo E epsilon 4 allele was present in 10.2% of control subjects and the allelic frequency did not change between ages 60 to 96 years. The apo E epsilon 4 allelic frequency was increased both in those wiht Alzheimer's disease (AD) (25.4%) and those with vascular dementia (VaD) (22.2%), but not in those with other dementing illnesses or the cognitively impaired. All of the subjects homozygous for apo E epsilon 4 were demented, three were diagnosed as having AD, and three met NINDS/AIREN criteria for VaD. The increased apo E epsilon 4 allelic frequency in clinically diagnosed VaD patients suggests that some of the infarcts are secondary to congophilic angiopathy. The adjusted odds ratio of developing AD in this community-derived study for persons with at least one apo E epsilon 4 allele was 4.1 (95% CI: 2.2, 7.7). Thus, the apo E epsilon 4 risk of developing AD in this Chinese cohort is similar to that in western community studies.

Age Factors↗

Reversibly increased lymphocyte response to mitogens in a young man with isolated adrenocorticotropic hormone deficiency.

A 21-year-old man with isolated adrenocorticotropic hormone (ACTH) deficiency complained of loss of consciousness in association with hypoglycemia. Both plasma ACTH and cortisol levels were low and failed to respond to corticotropin-releasing hormone (CRH) stimulation. The patient also showed abnormal findings in hematological examination, such as neutropenia and anemia with lymphocytosis, activity of coagulation factors, and electroencephalography (EEG). Furthermore, mitogen-induced lymphocyte proliferation was increased. After successful replacement therapy with hydrocortisone 15 mg/day, most of these abnormalities including the lymphocyte proliferation were fully restored.

Adrenocorticotropic Hormone↗

Defective neurite extension is caused by a mutation in amyloid beta/A4 (A beta) protein precursor found in familial Alzheimer's disease.

Clonal central nervous system neuronal cells, B103, do not synthesize detectable endogenous APP or APLP. B103 cells transfected with both wild-type (B103/APP) and mutant APP construct (B103/APP delta NL) secreted comparable amounts of soluble forms of APP (sAPP). B103/APP cells produced sAPP and cleaved at amyloid beta/A4 (A beta) 16, the alpha-secretase site, and B103/APP delta NL cells produced sAPP beta cleaved at A beta 1, the beta-secretase site. B103/APP delta NL cells developed fewer neurites than B103/APP cells in a serum-free defined medium. Neurite numbers of parent B103 cells were increased by the 50% conditioned medium (CM) from B103/APP cells but reduced by the CM from B103/APP delta NL cells. Chemically synthesized A beta at concentration levels higher than 1 nM reduced numbers of neurites from B103 or B103/APP delta NL cells. However, A beta at 1-100 nM could not reduce the neurite number of B103/APP cells. The protective activity against A beta's deleterious effect to reduce neurite numbers was attributed to sAPP alpha in the CM. Although sAPP alpha could block the effect of A beta, sAPP beta could not do so under the identical condition, suggesting the importance of the C-terminal 15-amino acid sequence in sAPP alpha. Nevertheless, sAPP alpha's protective activity required the N-terminal sequence around RERMS, previously identified to be the active domain of sAPP beta. The overall effect of APP mutation which overproduced A beta and sAPP beta and underproduced sAPP alpha was a marked decline in the neurotrophic effect of APP. We suggest that the disruption of balance between the detrimental effect of A beta and the trophic effect of sAPP may be important in the pathogenesis of AD caused by this pathogenic APP mutation.

Alzheimer Disease↗

[Postoperative inflammatory responses to gelatin- and collagen-impregnated Dacron grafts and changes of endotoxin].

Between June, 1993 and January, 1995 a gelatin-sealed knitted Dacron (Gelseal) (g-G0, n = 7) and a collagen-sealed knitted Dacron graft (Hemashield) (g-H0, n = 8) were randomly implanted to 15 patients (pts) for replacement of thoracic aorta. We evaluated postoperative inflammatory responses and levels of Toxicolor and Endospecy which are the measurements of endotoxin. Five pts in g-G0 and 3 pts in g-H0 showed that a body temperature (BT) were above 37.5 degrees C on the 7th postoperative day (POD). In three of them (2 in g-G0 and 1 in g-H0), BT above 37.5 degrees C continued until POD 14 due to the bacterial infection. The other causes of elevation of BT were pleural effusion (2), pericardial effusion (1) and unknown origin (2). Patients without evidence of infection (n = 12) were divided into 2 groups (g-G: pts with Gelseal, n = 5, g-H: pts with Hemashield, n = 7). On POD3, postoperative BT in g-H was significantly higher than in g-G. And, on POD7, BT in g-G rose up more than in g-H. However, on POD14, BT decreased to the normal range in both groups. The values of WBC in g-G were slightly higher than in g-H and they became normal after POD7 in both groups. The levels of CRP in g-H were higher than in g-G after POD3 and in both groups they were still high on POD14. In terms of endotoxin., Toxicolor was already above the normal range from POD1 and decreased to the normal range after POD14. However, the level of Endospecy kept within normal range. In conclusion, Toxicolor-reactive substance elevates by using Gelseal and Hemashield. Its substance is not endotoxin. It would not be appropriate to consider that endotoxin is an origin of fever between POD7 and 14.

Aortic Aneurysm, Thoracic↗

[Central sleep apnea syndrome successfully treated with nasal bi-level positive airway pressure and sleep position adjustment].

A 55-year-old obese man was admitted to our hospital because of a severe morning headache. He snored and had recurrent episodes of sleep apnea that began 10 years earlier and had since become much worse. An overnight polysomnographic recording confirmed that he had sleep apnea syndrome, predominantly of the central type. The apneas were more frequent when he lay on his back (apnea index 54.5) than on his side (apnea index 1.2). He was treated with sleep position adjustment and nasal bi-level positive airway pressure, inspiratory positive airway pressure at 5 cmH2O and expiratory positive airway pressure at 2 cmH2O. His snoring, headache, and oxygen desaturation resolved. This case suggests that airway collapse may cause central apnea, and that nasal continuous positive airway pressure, and nasal bi-level positive airway pressure and adjustment of sleep position can be effective in some patients with central-type sleep apnea syndrome.

Humans↗

[Conversion of chronic necrotizing pulmonary aspergillosis to invasive pulmonary aspergillosis, and successful treatment with fluconazole].

An 82-year-old man with rheumatoid arthritis was admitted to the hospital because of bloody sputum, appetite loss, and a chest-radiographic abnormality. He had previously been treated with oral steroid therapy. The chest X-ray film showed an infiltrative shadow with airlucency in the right upper lung field. Sputum culture for fungi was negative, but a test for aspergillus antigen in serum was positive. Other clinical findings were also compatible with conversion of chronic necrotizing pulmonary aspergillosis to invasive pulmonary aspergillosis. The patient was successfully treated with a drip infusion of fulconazole. The patients condition was stable for several months, after which he died due to uncontrollable atrial flutter. Mild immunosuppression due to oral steroid therapy probably caused chronic necrotizing pulmonary aspergillosis in this case. The patient's general condition worsened after admission and invasive pulmonary aspergillosis developed. This case taught us that therapy for chronic necrotizing pulmonary aspergillosis should include management of the patient's general condition as well as treatment of the pulmonary lesions.

Aged↗

[Lung lobar volume in patients with chronic interstitial pneumonia].

We measured lung lobar volume by using helical computed tomography (HCT) in 23 patients with idiopathic interstitial pneumonia (IIP), 7 patients with chronic interstitial pneumonia associated with collagen vascular disease (CVD-IP), and 5 healthy volunteers. HCT scanning was done at the maximal inspiratory level and the resting end-expiratory level. To measure lung lobar volume, we traced the lobar margin on HCT images with a digitizer and calculated the lobar volume with a personal computer. The lower lobar volume and several factors influencing it in chronic interstitial pneumonia were studied. At the maximal inspiratory level, the lower lobar volume as a percent of the whole lung volume was 46.8 +/- 4.13% (mean +/- SD) in the volunteers, 39.5 +/- 6.19% in the patients with IIP, and 27.7 +/- 7.86% in the patients with CVD-IP. The lower lobar volumes in the patients were significantly lower than in the volunteers. Patients with IIP in whom autoantibody tests were positive had lower lobar volumes that were very low and were similar to those of patients with CVD-IP. These data suggest that collagen vascular disease may develop in patients with interstitial pneumonia. The patients with IIP who had emphysematous changes on the CT scans had smaller decreases in total lung capacity and lower ratios of forced expiratory volume in one second to forced vital capacity than did those who had no emphysematous changes, those two groups did not differ in the ratio of lower lobar volume to whole lung volume. This suggests that emphysematous change is not factor influencing lower lobar volume in patients with chronic interstitial pneumonia. We conclude that chronic interstitial pneumonia together with very low values for lower lobar volume may be a pulmonary manifestation of collagen vascular disease.

Chronic Disease↗

Eosinophilic gastroenteritis presenting with acute pancreatitis.

We present the findings on a 27-year-old male with eosinophilic gastro-enterocolitis accompanied with acute pancreatitis. Acute pancreatitis may be induced by pancreatic duct obstruction caused by marked swelling of the papillary region of the duodenum due to eosinophil infiltration. After prednisolone treatment, clinical manifestations rapidly improved; the serum amylase decreased and the peripheral eosinophilia was recovered. The serum interleukin-5 (IL-5) level was high at diagnosis and decreased by prednisolone therapy; however, IL-5 was detected by enzyme immunoassay even during clinical remission. These results indicate that eosinophilia is mediated by IL-5, and detectable levels of IL-5 indicate the possibility of relapse.

Acute Disease↗

[Circadian chemotherapy in cancer patients].

Continuous infusion of 5-FU at night was performed for four patients: three had liver metastasis (one with gastric cancer and two with rectal cancer) and one had local recurrence of rectal cancer. The chemotherapy schedule was 400 mg/m2/day 5-FU intraarterial or intravenous infusion from 6:00 p.m. to 6:00 a.m. for five days repeated every 3 weeks. There were one complete response, two partial responses and one with no change. It is expected that the chemotherapy of 5-FU at night will result in a high efficacy and lower toxicity.

Adult↗

Serum beta-2-microglobulin in patients with multiple myeloma treated with alpha interferon.

In ten patients with multiple myeloma (MM), serum beta-2-microglobulin (B2M) levels were monitored in order to clarify the influence of alpha interferon (IFN) administration. Despite decreases in M-protein and the absence of renal dysfunction, the levels of serum B2M were sustained above those prior to melphalan-prednisolone and IFN therapy in seven patients with MM for six months. Serum B2M did not increase in ten patients with MM treated only by melphalan-prednisolone. Furthermore, serum B2M levels in a patient who achieved a complete response were sustained above her prior level and returned to normal after cession of IFN therapy. Our study suggests that the serum B2M level is increased by treatment with IFN, and does not prove the condition of the disease.

Adolescent↗

Interaction between the two signal transduction systems of the histamine H2 receptor: desensitizing and sensitizing effects of histamine stimulation on histamine-dependent cAMP production in Chinese hamster ovary cells.

The histamine H2 receptor is a member of the family of G-protein-coupled receptors and is linked to the activation of adenylate cyclase phospholipase C (PLC). In this study we examined the effects of protein kinase C (PKC) activation in Chinese hamster ovary (CHO) cells stably expressing canine histamine H2 receptors. Pretreatment with 100 nM phorbol 12-myristate 13-acetate at 37 degrees C for 15 min led to significant potentiation of histamine-dependent and forskolin-dependent cAMP production, whereas the biologically inactive phorbol ester, 4 alpha-phorbol 12, 13-didecanoate, was without effect. These potentiating effects were abolished by preincubation with 0.5 microM bisindolylmaleimide, a PKC inhibitor. Thus the activation of PKCs seems to be involved in the potentiation of cAMP production by acting on a post-receptor mechanism. Preincubation of a CHO cell line, CHO-H2R, with 10 microM histamine for 30 min had two effects. Maximal histamine-dependent cAMP production and forskolin-dependent cAMP production were potentiated by 36% and 105.2% respectively. The other effect was a desensitization of the histamine-dependent adenylate cyclase response as demonstrated by a three-fold increase in EC50. Administration of 0.5 microM bisindolylmaleimide before preincubation of CHO-H2R with 10 microM histamine did not alter the desensitizing effect on cAMP production, but did abolish the sensitizing effect. Preincubation of CHO-H2R cells with 10 nM histamine resulted in moderate potentiation, which was also abolished by bisindolylmaleimide, but not in desensitization of the histamine-dependent cAMP production. Thus these results suggest that preincubation with histamine had a sensitizing effect on cAMP production mediated by PLC and PKC activation, as well as a desensitizing effect on the H2 receptor. The former effect is dependent on the intensity of PLC and PKC signals delivered by H2 receptors. The latter effect requires a higher concentration of histamine.

Animals↗

A gradient from stable to cyclic populations of Clethrionomys rufocanus in Hokkaido, Japan.

A total of 31 years of abundance data from 90 populations of the grey-sided vole (Clethrionomys rufocanus) in northern Hokkaido (Japan) were analysed with respect to population dynamic characteristics. Both non-periodic and multi-annually periodic fluctuations occur among the studied populations. The length of the period varies from 2 to 5 years. The dynamics appear approximately linear on a logarithmic scale, and a log-linear stochastic difference model with one time-lag is found to recreate the periodograms of the time series. The deterministic (log-linear) component of these models determines the periodicity while stochasticity sustains the cycles. The dynamics of the Hokkaidian vole populations are found to vary clinally from the western coast eastwards and towards the interior of the study area. This gradient corresponds superficially to the latitudinal gradient seen in microtine populations in Fennoscandia. However, under close scrutiny, these gradients differ greatly: the Hokkaidian gradient is caused by a cline in delayed density dependence. Statistical delayed density dependence is more negative towards the east and the interior.

Animals↗