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Biomedical subjects

T Murase

Publications and source records attributed to T Murase.

At least 145 records · Page 8Linked to original sources

Progesterone and the zona pellucida activate different transducing pathways in the sequence of events leading to diacylglycerol generation during mouse sperm acrosomal exocytosis.

We tested the involvement of protein tyrosine kinase and G-protein transducing pathways in the formation of diacylglycerol (DAG) during exocytosis in mouse spermatozoa. In capacitated spermatozoa, stimulation with solubilized zona pellucida (ZP) or progesterone led to the formation of DAG and to exocytosis of the acrosomal granule. Stimulation of DAG formation and exocytosis by ZP were inhibited in a concentration-dependent fashion by pre-exposure to tyrphostin A48, a protein tyrosine kinase inhibitor. These ZP-induced responses were also reduced in a concentration-dependent manner by prior incubation with pertussis toxin, a G-protein (Gi class) inhibitor. On the other hand, generation of DAG and exocytosis triggered by progesterone were inhibited if spermatozoa were preincubated with different concentrations of tyrphostin A48, but were not affected by pre-exposure to pertussis toxin. Progesterone acts on at least two novel surface receptors, one being a gamma-aminobutyric acid (GABA) type A (GABAA)-like receptor. Transducing mechanisms coupled to this receptor were tested directly by stimulating spermatozoa with GABA. Treatment of capacitated spermatozoa with GABA resulted in DAG formation and exocytosis. These responses were not seen when cells were preincubated with tyrphostin A48. Pertussis toxin, however, did not affect the generation of DAG and exocytosis triggered by GABA, in agreement with results obtained using progesterone. Taken together, these results indicate that DAG formation during acrosomal exocytosis is differentially regulated by transducing pathways activated by oocyte-associated agonists.

Acrosome↗

Silver-stained nucleolar organizer regions in the uterine myomatous tumors.

The numbers of silver-stained nucleolar organizer regions (AgNORs) were counted in uterine myomatous tumors, and compared with those in corresponding normal myometria. The mean number of AgNORs in myomatous tumors tended to increase according to the neoplastic changes. The mean number of AgNORs in leiomyosarcoma (6.4 +/- 0.9) was significantly higher than that in cellular leiomyoma (4.5 +/- 0.7, P < 0.01). or leiomyoma (3.0 +/- 0.5, P < 0.001). In the normal myometria, the mean number of AgNORs (3.3 +/- 0.4) in the premenopausal women showed a higher tendency than that in the post-menopausal women (2.4 +/- 0.5). These results therefore suggest that AgNOR counts may be useful for diagnosis of cellular activity in uterine myomatous tumors.

Female↗

Intracerebroventricular injection of adrenomedullin inhibits vasopressin release in conscious rats.

The hypotensive peptide, adrenomedullin (AM), was first isolated from the tissue of human pheochromocytoma. Recently, AM-immunoreactivities have been found in the central nervous system, including the supraoptic and the paraventricular nuclei. In this study, the effect of centrally administered AM on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular injection of AM (1.0 microgram/rat) partially but significantly attenuated the plasma AVP increase induced by hyperosmolality (intraperitoneal (i.p.) injection of hypertonic saline (600 mosmol/kg)) at 30 min after the injection. It also significantly attenuated the plasma AVP increase induced by hypovolemia (i.p. injection of polyethylene glycol) at 30 min after the injection. These results suggest that central AM might play an inhibitory role in both osmo- and baro-regulation of plasma AVP.

Adrenomedullin↗

A novel donor splice site mutation in the glycogen debranching enzyme gene is associated with glycogen storage disease type III.

Analysis of glycogen debranching enzyme (debrancher) cDNA from a patient with glycogen storage disease type III revealed a deletion of 124 base pairs. A donor splice site mutation (IVS G+1 to T) was identified in the patient's debrancher gene, which caused exon skipping of the upstream exon and resulted in a truncated enzyme due to premature termination. Mutational analysis of the patient's family showed that this point mutation was inherited from the father. Southern blot analysis of the patient's genomic DNA showed an additional, unique EcoRI fragment of 5.8 kb, which was inherited from the mother. These results suggested that the patient was a compound heterozygote for the donor splice site mutation, which is the first identified in the debrancher gene, and had a genetic defect relating to an aberrant 5.8-kb EcoRI fragment.

Adult↗

Chronological observation of mouse endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17 beta-estradiol.

Chronological observation of the neoplastic endometrial lesions induced by N-methyl-N-nitrosourea (MNU) and 17 beta-estradiol (E2) were studied. E2 induced cystic glandular hyperplasia, but adenomatous hyperplasia was induced predominantly by MNU. Atypical hyperplasia and adenocarcinoma were induced cooperatively by E2 and MNU, and first found at week 12; the incidence of adenocarcinoma increased in accordance with the week-course. Some atypical hyperplasia might be changed to adenocarcinoma. Mean AgNORs numbers in (pre)neoplastic lesions increased in accordance with neoplastic changes. This model was useful for clarifying histogenesis of human endometrial carcinogenesis.

Adenocarcinoma↗

Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3.

The VLDL receptor, a newly identified lipoprotein receptor, recognizes apoE containing lipoproteins. The human VLDL receptor was overexpressed in 1d1A-7, a mutant Chinese hamster ovary cells lacking LDL receptors. Each VLDL obtained from a normolipidemic subject with two epsilon3 or epsilon2 alleles similarly competed for the binding of radiolabeled rabbit beta-VLDL to the VLDL receptors. The anti-apoE monoclonal antibody 1D7, which inhibited binding of apoE3 to the LDL receptors, failed to compete for the binding of VLDL (apoE3 or apoE2) to the VLDL receptors. Results indicate that the binding site of apoE on the VLDL receptor may differ from its binding site on the LDL receptor.

Animals↗

Lipoprotein(a) is an independent risk factor for multiple cerebral infarctions.

In an attempt to ascertain whether Lp(a) is a risk factor for multiple cerebral infarctions (MCI), we have studied 83 patients with proven MCI and 39 subjects without MCI by computed tomography (CT). Seventy-one patients with non-insulin-dependent diabetes mellitus (NIDDM) were included: 52 with and 19 without MCI. Serum Lp(a) levels were significantly higher in patients with MCI than in subjects without MCI. There were no differences in serum Lp(a) levels between NIDDM and non-diabetic patients with MCI. The logistic regression analysis revealed that Lp(a) and hypertension were independent risk factors for the cerebral event. The current study demonstrated that Lp(a) and hypertension are significant risk factors for multiple cerebral infarctions.

Aged↗

The mechanical properties of the heel pad in elderly adults.

The shock absorbing characteristics of the heel pad in vivo were examined in two groups of active elderly individuals whose ages ranged between 60 and 67 years (n = 10) and between 71 and 86 years (n = 10). For comparative purposes, young adults (n = 10) aged between 17 and 30 years were also examined. A free-fall impact testing device which consisted of an instrumented shaft (mass 5 kg), accelerometer and position detection transducer was used to obtain deceleration and deformation of the heel during impact. The data were obtained from impact velocities of 0.57 m.s-1 (slow) and 0.94 m.s-1 (fast). Peak values of the deceleration and deformation, as well as the time to these peaks from onset of impact, and energy absorption were evaluated. At the slow impact velocity, no age effect was found for the parameters examined except for the energy absorption. At the fast impact velocity, there was higher peak deceleration and smaller deformation for the elderly than for the younger adults. The energy absorbed was less for the elderly than for the younger adults. It was concluded that the capacity for shock absorbency of the heel pad declines with age.

Adolescent↗

A novel missense mutation (Asn5-->Ile) in lecithin: cholesterol acyltransferase (LCAT) gene in a Japanese patient with LCAT deficiency.

We identified a novel missense mutation in the lecithin:cholesterol acyltransferase gene in a new case of lecithin:cholesterol acyltransferase (LCAT) deficiency. The patient was a 64-year-old diabetic Japanese male who showed an extremely low level of serum high-density lipoprotein-cholesterol, corneal opacities, anemia, and proteinuria. Both the patient's LCAT activity and mass were markedly low. DNA sequence analysis of the LCAT gene showed an A-to-T transition at base 97 in exon 1, and predicted a change in asparagine to isoleucine at the 5th amino acid of the protein. Restriction analysis of polymerase chain reaction-amplified DNA using Ase I showed that the patient was homozygous for this mutation. Our results suggested that asparagine 5 was an important amino acid and substitution with isoleucine caused marked reduction of LCAT activity and mass, resulting in LCAT deficiency.

Amino Acid Sequence↗

Association between HLA and islet cell antibodies in diabetic patients with a mitochondrial DNA mutation at base pair 3243.

Islet cell antibodies (ICA), autoantibodies to glutamic acid decarboxylase (GAD) and HLA genotypes were examined in 31 patients with diabetes and a mitochondrial gene mutation located at base pair 3243 (mtDNA 3243 mutation). ICA was detected in 42% (13/31) of these patients compared to 0 of 90 among healthy control subjects. The ICA showed a "non-restricted" pattern of staining in all 13 ICA-positive patients. In a sensitive radioligand assay only 2 of 31 (6%) diabetic patients with the mutation were positive for both GAD65 autoantibodies and ICA, while the remaining 29 patients were GAD65 antibody negative. The ICA-positive patients had an increased frequency of the HLA-DQA1*0301 allele compared to control subjects (p < 0.05). Of the diabetic patients with the mutation 45% (14/31) had progressive clinical course of beta-cell failure. These results indicate that patients with an mtDNA 3243 mutation may develop islet autoimmunity associated with ICA and GAD autoantibodies. We hypothesize that the presence of HLA-DQA1*0301 in individuals with the mtDNA 3243 mutation increases the risk for diabetes and associated autoantibodies against islet cell antigens.

Adult↗

Neuropeptide FF reduces food intake in rats.

The effect of neuropeptide FF (NPFF), a mammalian FMRFamide-like peptide with antiopioid activity, on food intake was investigated in food-deprived rat. The ICV administration of NPFF (5 or 10 micrograms/rat) reduced food intake during the first 60 min after administration. ICV injection of naloxone (10 or 100 micrograms/rat), an opioid antagonist, also decreased food intake. However, the combination of NPFF and naloxone showed no additivity in the anorexigenic effect, suggesting that NPFF and naloxone reduced food intake by the common mechanism. These results indicate that NPFF may function as an endogenous anorexigenic peptide with anitiopioid function.

Animals↗

Osmoregulation of plasma vasopressin in diabetes mellitus with sustained hyperglycemia.

We studied osmoregulation of plasma vasopressin in 5 patients with newly diagnosed diabetes mellitus. All patients showed typical symptoms of uncontrolled diabetes mellitus such as marked hyperglycemia, polyuria, and polydipsia, but did not have advanced diabetic complications. Vasopressin release was studied using 5% hypertonic saline infusion test twice: before treatment when the patient was hyperglycemic, and after treatment 1 to 2 months later when the patient was euglycemic. Plasma vasopressin was measured by a sensitive and specific radioimmunoassay. The mean basal plasma vasopressin value in the patients was significantly higher in the hyperglycemic compared with the euglycemic state (3.75 +/- 0.70 vs 1.18 +/- 0.46 pmol/l, respectively; P < 0.05). The relationship of plasma vasopressin with serum sodium, but not plasma osmolality, during hyperglycemia showed an apparent hypersecretion of vasopressin. In both cases, the sensitivity of the vasopressin response to osmotic stimuli was significantly decreased. During euglycemia, the sensitivity of vasopressin secretion to either sodium or osmolality was almost normal, although a slight rise in the osmostat was observed compared with normal subjects. Together, we found that the positive correlation of vasopressin with sodium or osmolality is maintained but significantly altered in patients with untreated diabetes mellitus. Especially noteworthy is the lowered threshold and decreased sensitivity of osmotically-induced vasopressin secretion during hyperglycemia, which may be caused by multiple factors such as diabetes-associated hypovolemia, osmogenic effects of glucose and other osmoles, depletion of the pool of vasopressin available for release, and the metabolic derangement of osmoreceptor/magnocellular neurons.

Adult↗

Hypertriglyceridemia, but not hypercholesterolemia, is associated with the alterations of fibrinolytic system.

Derangements of the blood coagulation-fibrinolytic system are thought to be associated with the development of cardiovascular disease. Previous studies have identified the alterations in patients with advanced atherosclerosis, however, studies on subjects without apparent cardiovascular complications are scarce. To evaluate the potential risk of thrombosis, we examined the serum lipid levels and fibrinolytic parameters in 54 subjects of different types of primary hyperlipoproteinemia (HL) and 18 normolipidemic controls. Plasma tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen levels were significantly higher in type IV HL than in the controls. Serum triglyceride concentrations were correlated with t-PA (r = 0.537, p < 0.01) and PAI-1 (r = 0.249, p < 0.05) antigen levels, while serum cholesterol levels did not. The current study demonstrated that hypertriglyceridemia, but not hypercholesterolemia, is associated with the alterations of fibrinolytic system.

Adult↗

Grip posture and forces during holding cylindrical objects with circular grips.

Individual finger position and external grip forces were investigated while subjects held cylindrical objects from above using circular precision grips. Healthy females (n = 11) and males (n = 15) lifted cylindrical objects of various weights (0.5, 1.0 and 2.0 kg), and varied diameters (5.0, 7.5 and 10.0 cm) using the 5-finger grip mode. The effects of 4-, 3- and 2-finger grip modes in the circular grip were also investigated. Individual finger position was nearly constant for all weights and for diameters of 5.0 and 7.5 cm. The mean angular positions for the index, middle, ring and little fingers relative to the thumb were 98 degrees, 145 degrees, 181 degrees, and 236 degrees, respectively. At the 10-cm diameter, the index and middle finger positions increased, while the ring and little finger positions decreased. There were no differences in individual finger position with regard to gender, hand dimension, or hand strength. Total grip force increased with weight, and at diameters greater or lesser than 7.5 cm. Total grip force also increased as the number of fingers used for grasping decreased. Although the contribution of the individual fingers to the total grip force changed with weight and diameter, the thumb contribution always exceeded 38% followed by the ring and little fingers, which contributed approximately 18-23% for all weights and diameters. The contribution of the index finger was always smallest (> or = 11%). There was no gender difference for any of the grip force variables. The effects of hand dimension and hand strength on the individual finger grip forces were subtle.

Adult↗

An epidemiological study of Salmonella enteritidis by pulsed-field gel electrophoresis (PFGE): several PFGE patterns observed in isolates from a food poisoning outbreak.

An epidemiological analysis of Salmonella enteritidis from a food poisoning was done using pulsed-field gel electrophoresis (PFGE) of BlnI- or XbaI-digested fragments of chromosomal DNA of isolates. S. enteritidis isolates obtained from 19 patients had identical PFGE patterns. Therefore, a strain giving the same pattern was considered to be the causative agent of this outbreak. In addition, four isolates that had different BlnI-digested PFGE patterns were obtained from three patients, suggesting that the observed variations in PFGE patterns might occur as the result of some point mutations of chromosomal DNA during growth or from the existence of several S. enteritidis strains from various sources. Subsequent PFGE analysis of continuously subcultured strains supported the former possibility. These observations indicate that PFGE analysis on multiple numbers of colonies from each patient are necessary for the epidemiologic investigation of S. enteritidis.

DNA, Bacterial↗

A new murine lymphocytotoxic monoclonal antibody recognizing HLA-A2, -A28 and -A9.

Monoclonal antibodies recognizing polymorphic as well as monomorphic epitopes on HLA antigens are important tools for understanding the immunobiology of HLA molecules. We immunized BALB/c mice with a HLA-A2 transfectant and screened for hybridomas which reacted with a HLA-A2 transfectant but not with a HLA-B75 transfectant. After subcloning by limiting dilution four times, a hybridoma secreting a monoclonal antibody (mAb) (IgG 2a, kappa) designated 1-145 was established. 1-145 reacted with Epstein-Barr virus transformed B lymphoblastoid cell lines (B cell lines) which expressed HLA-A2, -A28, -A23 and -A24. The titer of 1-145 in culture supernatant against HLA-A2 and -A28 antigens was similar and the titer against HLA-A23 was lower. 1-145 reacted with cells expressing HLA-A24 but the titer against HLA-A24 antigens was even lower than that against HLA-A23 antigens. The HLA-A24 antigens on the peripheral blood lymphocytes were not detected by 1-145 possibly due to the lower expression compared to the B cell lines. These differences of the titers were reflected to microlymphocytotoxicity assay in which 1-145 culture supernatant lysed all PBLs expressing HLA-A2,-A28 and -A23 but did not lyse PBLs expressing HLA-A24. Published deduced amino acid sequence data of HLA class 1 molecules indicate that Lys in position 127 may be critical for 1-145 binding.

Amino Acid Sequence↗

Adverse events associated with MMR vaccines in Japan.

The largest nationwide active surveillance of four Measles-Mumps-Rubella (MMR) vaccines was conducted in Japan. A total of 1255 pediatricians actively participated in the study, which comprised 8.6% of all members of the Japanese Pediatric Society. The total number of registered recipients of MMR vaccines was 38 203. They were arbitrarily given one of the MMR vaccines produced by three makers (Takeda, Osaka city, Kitasato Minato-ku. Tokyo and Biken Suita city, Japan) or the standard MMR vaccine made of designated strains (Kitasato's measles-AIK-C, Biken's mumps-Urabe Am9 and Takeda's rubella-To336) produced by Takeda, Kitasato and Biken and were observed for 35 days. The rates of virologically confirmed aseptic meningitis per 10,000 recipients were 16.6, 11.6, 3.2 and 0 for the standard MMR, Takeda MMR, Kitasato MMR and Biken MMR vaccines, respectively. The incidence of convulsions between 15 and 35 days was the highest with the standard MMR vaccine and the incidence of fever associated with vomiting occurring between 15 and 35 days (symptoms relevant to aseptic meningitis) were also the highest with the standard MMR vaccine. The incidence of parotid swelling was the lowest with Takeda MMR vaccine. This surveillance revealed that incidences of aseptic meningitis after administration of the standard MMR vaccine and of Biken MMR vaccine were different. This posed questions about the manufacturing consistency of the Urabe Am9 mumps virus vaccines. On the other hand, the National Institute of Health found that the biological characteristics of the Urabe Am9 mumps virus contained in the standard MMR vaccine and in the Biken MMR vaccine were different. The Biken Company reported that the mumps vaccine in the standard MMR vaccine was a mixture of two Urabe Am9 mumps vaccine bulks; one identical to that contained in the Biken MMR vaccine and the other produced by a different manufacturing process.

Child↗