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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 631 records · Page 35Linked to original sources
PubMed1997

Suppression of plasma cholesteryl ester transfer protein activity in acute hyperinsulinemia and effect of plasma nonesterified fatty acid.

Cholesteryl ester transfer protein (CETP) is a major determinant of the plasma high-density lipoprotein cholesterol (HDL-C) level and plays an important role in the reverse cholesterol transport system. The purpose of this study was to determine the effect of acute hyperinsulinemia on plasma CETP activity in normal subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). Hyperinsulinemia was achieved using the hyperinsulinemic-euglycemic clamp. CETP activity was determined as the transfer of radiolabeled cholesterol in HDL3 to acceptor lipoprotein. Mean plasma CETP activity during an insulin infusion in both subject groups was significantly decreased compared with the mean basal activity. Suppression of plasma CETP activity in the NIDDM patients was significantly less than in the normal subjects (-4.2% +/- 7.9% v -9.6% +/- 6.4%, P < .02). Regression analysis showed that this suppression was correlated with plasma nonesterified fatty acid (NEFA) levels after the clamp and with the magnitude of the NEFA decrease (r = .318, P < .02 and r = .292, P < .05, respectively). The data suggest that acute hyperinsulinemia reduces plasma CETP activity through a decrease in plasma NEFA.

Adult↗
PubMed1997

Loss of H19 imprinting and up-regulation of H19 and SNRPN in a case with malignant mixed Müllerian tumor of the uterus.

In several human cancers, it has been recently reported that abnormally altered status of genomic imprinting is related to oncogenesis. In this study, we investigated the expression of three imprinted genes in a case with malignant mixed Müllerian tumor of the uterus (MMMT). In the tumor, expression of H19 showed marked upregulation (6.3-fold) with biallelic expression compared with that in the corresponding normal myometrium. The 5'-promoter region of H19 was hypomethylated in the tumor, whereas it was hemimethylated in the myometrium. Expression of the small nuclear ribonucleoprotein polypeptide N gene (SNRPN) was also upregulated by 1.9-fold. However, the insulin-like growth factor II gene (IGF2) was expressed at low levels in both myometrium and MMMT. The overexpression of H19 is caused by reactivation of the repressed allele of H19 due to demethylation of CpG islands within its 5'-promoter region. Whether upregulation of SNRPN is caused by its biallelic expression remains undetermined because restriction fragment length polymorphisms (RFLP) sites were not informative in SNRPN and IGF2. In conclusion, H19 and SNRPN may play significant roles in the tumorigenesis of MMMT and H19 may have tumor-promoting activity in addition to its known tumor-suppressing activity, probably depending on the tissue and the local milieu.

Autoantigens↗
PubMed1997

Postnatal ontogeny of the thyrotropin-releasing hormone receptor messenger ribonucleic acids in the rat forebrain.

Postnatal developmental change of the thyrotropin-releasing hormone receptors (TRHR) in the rat forebrain was investigated using TRH binding assays and Northern blot analyses from postnatal day 8 to the age of 2 years. TRH binding assays, with [3H]MeHisTRH as the radioactive ligand, demonstrated that the binding capacity in the forebrain was lowest at postnatal day 8 and increased to a maximum level at postnatal day 20. The TRH binding significantly decreased to adult levels between days 20 and 35, and no significant change was observed thereafter. Northern blot analysis, with a 32P-labeled TRHR cRNA probe, revealed that expression of the TRHR gene in the forebrain was not detectable on day 8 after birth, whereas apparent gene expression could be detected in the anterior pituitary. In contrast to the binding capacities, TRHR mRNA levels were very low until postnatal day 20, and increased significantly between days 20 and 35. No significant alteration in mRNA levels was observed after day 35. These results indicated that: (1) TRH binding capacities in the forebrain increased to a maximum levels between the second and third postnatal week and thereafter decreased to adult level, (2) the levels of TRHR mRNA and the TRH-binding capacities did not correlate in that period, suggesting that the TRHR number in the immature forebrain might be regulated by a posttranscriptional mechanism, and (3) expression of the TRHR gene in the forebrain and pituitary seemed to be regulated differentially during development.

Aging↗
PubMed1997

Effect of smoking on the prevalence of albuminuria in Japanese men with non-insulin-dependent diabetes mellitus.

Smoking is a risk factor for diabetic nephropathy in patients with IDDM and potentially those with NIDDM. We investigated the relationship between renal involvement and cigarette smoking in 148 men with NIDDM. The presence of renal involvement was assessed by determining the overnight urinary albumin/creatinine ratio (mg/g, ACR). The patients were divided into three groups, normo-, micro-, and macroalbuminuria, based on the ACR (< 30, 30-300, and 300 < or = mg/g, respectively). The incidence of micro-/macroalbuminuria in 81 smokers was significantly higher than that in 21 ex-smokers (stopped smoking at least 10 years prior to the study) or 40 non-smokers (53.1, 33.3, and 20.0%, respectively). The prevalence of smoking in the groups of patients with normo-, micro-, and macroalbuminuria were 45, 73, and 76%, respectively. The relative risk (odds ratio) for the prevalence of micro-/macroalbuminuria associated with smoking was 4.5 (95% CI, 1.9-11.6, P < 0.001) in smokers and was 2.0 (not significant) in ex-smokers. Our results indicate that stricter counselling about the importance of quitting smoking will be necessary in patients with NIDDM to protect against the development of diabetic nephropathy.

Aged↗
PubMed1997

Differential regulation of type-1 and type-2alpha corticotropin-releasing hormone receptor mRNA in the hypothalamic paraventricular nucleus of the rat.

Novel corticotropin-releasing hormone receptor (CRHR), designated type-2alpha CRHR (CRHR-2alpha), was recently cloned and functionally characterized. In situ hybridization study revealed that CRHR-2alpha mRNA had a distinct distribution from type-1 CRHR (CRHR-1) mRNA in the rat brain. Interestingly, CRHR-2alpha mRNA showed a relatively high expression in the hypothalamic paraventricular nucleus (PVN) even under unstressful condition. This may reflect the important role of CRHR-2alpha in the autoregulation of CRH secretion in the PVN. To determine the regulation of CRHR-2alpha mRNA expression in the PVN, we examined the alteration of CRHR-2alpha mRNA levels in the PVN in rats with lipopolysaccharide (LPS) injection, corticosterone (CORT) administration or adrenalectomy and compared with that of CRHR-1 mRNA, using in situ hybridization histochemistry. I.p. LPS injection (50 microg) induced a significant increase in PVN CRHR-1 mRNA at 3 and 6 h whereas CORT administration (10 mg/day for 12 days) or adrenalectomy (sacrificed 7 days after surgery) decreased CRHR-1 mRNA levels in the PVN. These alterations in PVN CRHR-1 mRNA are consistent with previous reports. In contrast, CRHR-2alpha mRNA levels in the PVN were not altered by any of these treatments. These results indicate that CRHR-1 and CRHR-2alpha mRNA are differentially regulated in the PVN. Further study will be necessary to elucidate the CRHR-2alpha function in the PVN.

Animals↗
PubMed1997

Cutaneous and neurologic disease associated with HTLV-I infection.

Human T-lymphotropic virus type I (HTLV-I) is the etiologic agent of HTLV-I associated myelopathy (HAM)/tropical spastic paresis (TSP), and adult T-cell leukemia/lymphoma (ATLL). ATLL has been associated with HTLV-I in the southeastern United States. However, to our knowledge, no case reports of HAM/TSP in association with ATLL occurring in the United States have been described. We describe a 40-year-old black woman with a 10-year history of recalcitrant psoriasiform eruption and erythrodermic flares. Medical history is additionally significant for a 2-year history of HTLV-I-associated myelopathy and lower extremity spastic paresis. Polymerase chain reaction with Southern blot analysis was used to detect HTLV-I proviral genome from frozen skin biopsy specimens and peripheral blood mononuclear cells.

Adult↗
PubMed1997

Neonatal lupus erythematosus: analysis of HLA class II alleles in mothers and siblings from seven Japanese families.

BACKGROUND: Neonatal lupus erythematosus (NLE) is a syndrome characterized by dermatitis and congenital heart block. The disease is mostly associated with transplacental passage of maternal anti-Ro(SS-A) or anti-La(SS-B) antibodies. Maternal HLA-DR3 and DQ2 alleles are associated with NLE in white and North American black populations. OBJECTIVE: We sought evidence of a potential genetic disposition to NLE in mothers with a relatively homogeneous ethnic background. METHODS: Class II human major histocompatibility complex HLA-DRB1, DQA1, DQB1, and DPB1 alleles were determined by polymerase chain reaction-restriction fragment length polymorphism in anti-Ro(SS-A)-positive mothers as well as in infants from seven Japanese families with siblings concordant or discordant for disease expression of NLE. RESULTS: All seven mothers had two or three DQ alleles of DQA1 and DQB1 possessing specific amino acid residues, which are reportedly associated with anti-Ro(SS-A) autoantibody response in white and black populations. There was no class II HLA profile that distinguished disease manifestations of NLE in infants. CONCLUSION: The HLA class II allele associations with anti-Ro(SS-A) autoantibodies that have been noted in other ethnic groups were also found in Japanese anti-Ro(SS-A)-positive mothers whose infants had NLE, suggesting shared susceptibility factors across racial barriers in maternal predisposition to Ro(SS-A) autoimmune response.

Disease Susceptibility↗
PubMed1997

The relationship between orthostatic dizziness and hypotension in male medical students.

We carried out a questionnaire survey regarding symptoms of orthostatic dysregulation (OD) and administered the Schellong test (orthostatic test) to 123 normal male medical students aged 21-29 years to investigate the relationship between orthostatic dizziness and hypotension. OD was identified in 15 (12.2%) of the subjects based on the questionnaire results. Orthostatic dizziness was noted in 40.7% of the subjects (50/123). The occurrence of orthostatic dizziness was most significantly related to systolic pressure decrease during the procedure for the Schellong test. These results suggest that the testing procedure introduced by Schellong can be useful, and clinically applicable to the assessment of orthostatic dizziness, since it presents the advantage of being simple enough to carry out in clinical practice.

Adult↗
PubMed1997

Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1.

Most of the cerebellar Purkinje cells (PCs) of an adult animal are innervated individually by a single climbing fiber (CF) that forms strong excitatory synapses with the PCs. This one-to-one relationship between a PC and a CF is a consequence of a developmentally regulated regression of the innervation of PCs by CFs. We found that, in mice deficient in the type 1 metabotropic glutamate receptor (mGluR1), the regression of supernumerary CFs ceases by the end of the second postnatal week, which is about one week earlier than in normal mice. Consequently, about one third of PCs in the mGluR1 mutant mice are innervated by multiple CFs in adulthood. We conclude that the regression of CFs normally occurs in two developmental phases and that mGluR1 plays a crucial role in the second phase.

Aging↗
PubMed1997

Apoptotic pocket-like structures of the bulge of the terminal hair follicles of the human scalp.

Terminal hair follicles of the human scalp of all ages showed apoptotic pocket-like structures in the outer root sheath of the bulge area at anagen, but not telogen phase. The occurrence of these hole structures was roughly estimated in 15% of anagen terminal hair follicles of the human scalp. The size of these apoptotic pockets was variable, ranging from pin hole-like spaces to larger structures filled with homogeneous black materials. These unusual variations were often co-localized with apoptotic degenerations and exclusively present in the presumptive bulge of anagen terminal hair follicles where arrector pili muscles were seen in the vicinity. In fact, these vacuolated structures tended to be present on the side where the major part of the arrector pili muscles anchored.

Aged↗
PubMed1997

The most primitive vertebrates with jaws possess highly polymorphic MHC class I genes comparable to those of humans.

We report the isolation and extensive analysis of highly polymorphic MHC class I genes from sharks (Triakis scyllia), which belong to the most primitive vertebrate group with jaws, the cartilaginous fish. Predicted complete peptide-binding domains showed retention of the critical amino acid residues that would interact with antigenic peptide termini and revealed extensive allelic polymorphisms comparable to those of classic human MHC class I molecules. Mosaic structures were apparent in these domains, suggesting recombinational mechanisms to create allelic diversity. The present study demonstrates the establishment of the basic strategy for antigen-presentation employed by MHC class I molecules and documents complete divergence of two polymorphic MHC classes at a phylogenetically primitive stage of vertebrate evolution.

Alleles↗
PubMed1997

How did the primordial T cell receptor and MHC molecules function initially?

Two genes, designated Trsc-UAA and Trsc-UBA, which encode highly polymorphic major histocompatibility complex (MHC) class I molecules in the shark Triakis scyllia were isolated. The identification of these genes indicates that the classical MHC class I was already established at the level of elasmobranchs during animal evolution. At the emergence of the MHC/T cell receptor recognition system, the number of genes for T cell receptors (TCR) must have been just one. In this brief review, the way in which a small number of TCR could have recognized MHC-oligopeptide complexes initially, based on recent progress in the phylogenetic analysis of the immune systems in primitive vertebrates, is discussed.

Animals↗
PubMed1997

The relationship between psychosomatic factors and orthostatic dysregulation in young men.

We carried out a questionnaire survey regarding symptoms of orthostatic dysregulation and administered the Japanese Edition of the Cornell Medical Index-Health Questionnaire (JCMI) and the Yatabe-Guilford Personality Test (Y-G test) to 151 male medical students (mean age, 24.6 yr). Orthostatic dysregulation was identified in 19 (12.5%) of the subjects based on the questionnaire results. The percentage classed as types III (possible neurotic) and IV (probable neurotic) according to the health questionnaire was 47.3% in the 19 with orthostatic dysregulation and 8.9% in the controls (n = 78). The percentage classed as types B and E, suggestive of emotional or psychological disturbance according to the personality test, was 42.1% in those with orthostatic dysregulation and 8.9% in the controls. These differences were significant (P < 0.01). These results suggest that psychosomatic factors influence the occurrence of orthostatic dysregulation in young men.

Abdominal Pain↗
PubMed1997

CD4 regulates the efficiency of an endogenous superantigen-induced clonal deletion of TCRV beta 11+ cells in the periphery.

Peripheral T-cell antigen receptor V beta (TCRV beta) repertoire is influenced by clonal deletion both in the thymus and periphery. Developing thymocytes expressing certain TCRV beta are deleted by endogenous superantigens presented on major histocompatibility complex (MHC) molecules in the thymus. Likewise, mature T cells bearing particular TCRV beta chains can be clonally deleted by superantigens in the periphery. The efficiency with which T cells expressing particular V beta subunits are deleted differs depending upon which coreceptor is expressed. Indeed, while deletion of V beta 11+ splenic T cells in CBA/J (Mls-1, a I-E, + MTV 9+) mice is quite efficient for CD4+ spleen T cells, it is much less efficient for CD8+ splenic T cells. If the difference in the efficiency of deletion is due solely to the coreceptor expressed, then a transgene encoding CD4 should increase the efficiency with which CD8+ cells are deleted. To address this question, we have produced CD4 transgenic (TG) mice that express physiologic levels of CD4 on all thymocytes and peripheral CD8 T cells. CD4 molecules expressed on CD8+ splenic T cells were associated with P56lck tyrosine kinase, and were functional as evidenced by their ability to facilitate class II alloreactivity. Furthermore, we found that ectopic expression of TG CD4 molecules on CD8+ cells was able to affect the efficiency of deletion in response to superantigen stimulation. In particular, deletion of TCRV beta 11+ T cells was much less efficient for CD8+ than for CD4+ T-cell subpopulations in (CBA/J x B6) F1 mice. However, expression of the CD4 transgene on CD8+ splenic T cells from these mice increased the efficiency of deletion in the CD8+ V beta 11 T cells. Interestingly, this effect was not observed in a mature CD8+ thymocyte subpopulation. The results in this report demonstrate that CD4 molecules are involved in peripheral deletion of TCRV beta 11+ T cells in (CBA/J x B6) F1 mice, and that the TCRV beta repertoire can be altered by ectopic expression of CD4 on all T-lineage cells.

Animals↗