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Biomedical subjects

T Yamamura

Publications and source records attributed to T Yamamura.

At least 181 records · Page 10Linked to original sources

[Apolipoprotein E].

Apolipoprotein E (apo E) is one of the apolipoprotein components in very low density lipoproteins (VLDL) and high density lipoproteins (HDL). Apo E binds to low density lipoprotein (LDL) receptors and apo E-specific remnant receptors, and regulates remnant lipoprotein metabolism through these receptors in the liver. In the general population, apo E shows genetic heterogeneity, with three alleles (epsilon 4, epsilon 3, and epsilon 4) which produce apo E isoproteins, apo E4, apo E3, and apo E2, respectively. Apo E2 is defective in its binding to lipoprotein receptors, resulting in the accumulation of lipoprotein remnants in the plasma. Type III hyperlipoproteinemia appears in a few percent of the individuals who are homozygous for apo E2 and the development of hyperlipoproteinemia requires the presence of other genetic or environmental factors. Even heterozygous individuals with apo E2 or apo E4 differ from those with only apo E3 in plasma lipoprotein metabolism. Subjects with an E3/2 phenotype had reduced LDL and increased VLDL levels, and those with an E4/3 phenotype had increased LDL levels in serum. In addition to these common apo E isoproteins, there are several unique mutants of apo E, which are associated with hyperlipoproteinemia and atherosclerosis.

Amino Acid Sequence↗

[Pharmacokinetic studies on continuous intraportal 5-fluorouracil infusion].

Pharmacokinetics of 5-FU administered by continuous intraportal infusion were studied by infusing 5 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg of 5-FU, respectively, into the ileocecal vein for an hour. Blood samples were collected from portal vein, femoral vein and liver, and small intestine specimens were obtained at proper intervals. The rabbits were sacrificed at 120 minutes from the start of 5-FU infusion. The results were as follows: Extremely high concentrations of 5-FU in the portal vein, femoral vein and liver tissue were observed in the 5-FU group infused with 40 mg/kg. This phenomenon was suggested to rely on the effect by which the 5-FU catabolic enzyme, dihydrouracil dehydrogenase, was saturated with a large inflow of 5-FU. FdUMP concentration of the liver was lower than that of the small intestine in all groups. These results suggest that a large dose of 5-FU infusion is effective to increase the FdUMP concentration in the liver with continuous intraportal 5-FU infusion.

Animals↗

Preoperative detection of local extension of carcinoma of the rectum using magnetic resonance imaging.

BACKGROUND: We evaluated the ability of magnetic resonance imaging (MRI) to define local extension of rectal carcinoma. STUDY DESIGN: Thirty-three patients with rectal carcinoma were preoperatively assessed by MRI. RESULTS: When sagittal or coronal images, or both, were added to transverse images as needed, the sensitivity rate was 84.2 percent and the specificity rate was 92.9 percent. False-positive results when using only transverse images were mainly related to slight extramural spread, to an anterior location in the lower rectum (partial volume effect), and to massive extramural spread of the middle rectal tumors. CONCLUSION: Preoperative MRI was helpful to define tumor extension three-dimensionally.

Aged↗

[Regulatory T cell network].

Experimental autoimmune encephalomyelitis (EAE) is induced by myelin-specific autoimmune T cells that are characterized by a limited T cell receptor (TCR) heterogeneity. Recent studies demonstrate that regulatory T cells recognizing EAE-associated idiotopes and ergotope are involved in the auto-regulation of EAE. Anti-idiotypic T cells are rapidly induced after T cell vaccination or TCR peptide immunization, indicating that the anti-TCR response is a recall response and that natural anti-idiotypic network is established in the normal T cell repertoire. Anti-idiotypic T cells are induced not only by vaccination but as the consequence of EAE. In this review, I stress that prevention and treatment of autoimmune disease should aim at the re-organization of anti-idiotypic network.

Animals↗

[The pathogenic mechanism of experimental autoimmune encephalomyelitis and approach for new immunological therapy].

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease mediated by myelin protein-specific CD4 T cells of the Th 1 phenotype and is a major animal model for the study of multiple sclerosis. Here we review current research advancements on the pathogenic mechanism of disease induction, remission and exacervasion. Progresses both in the molecular biology and immunology permit us to make a new strategy of specific therapy for EAE. There are three important strategies to prevent disease; the first is to block the trimolecular complex and associated accessory molecules to stop the T cell activation, the second is to regulate the activated T cells with immunological networking system and the third is to modulate the immunological responses mediated by T cells in the central nervous system.

Animals↗

[New strategies for treatment of multiple sclerosis based on the autoimmune pathogenesis].

Multiple sclerosis (MS) is thought to be an autoimmune disorder, mediated by myelin-specific T cells. Recent studies demonstrate that activated T cells specific for MBP are increased in MS, and that the MBP-specific T cells and T cell infiltrates in MS brains conserve homologous TCR CDR3 motifs. Since the CDR3 motifs are also shared by encephalitogenic T cells inducing EAE, it is likely that therapeutic strategies effective for EAE may be useful for MS. In this review, I discuss the possible application of TCR vaccination, TCR antagonist peptides and oral tolerization. Considering the chronic relapsing features of MS, treatments which are safe and may tighten the immune regulatory networks are recommendable.

Amino Acid Sequence↗

Clinicopathological study of anorectal mucosa in total colectomy with mucosal proctectomy and ileoanal anastomosis.

OBJECTIVE: To find out whether the extent of inflammation of the anorectal mucosa affects the quality of the mucosectomy and postoperative function in patients undergoing total colectomy with mucosal proctectomy and ileoanal anastomosis. DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: 33 patients with ulcerative colitis and 17 with familial adenomatous polyposis. INTERVENTIONS: With the patient in the prone jackknife position, the anorectal columnar mucosa above the dentate line was removed transanally by the forceps coagulation technique. MAIN OUTCOME MEASURES: Score of histological appearance on light microscopy. RESULTS: All the patients with ulcerative colitis had moderate (n = 17, 52%) or severe (n = 16, 48%) inflammation, and their mean histological score was 12 (range 7-16). The patients with polyposis had little or no inflammation, and a mean histological score of 0.4 (range 0-2). The mucosectomy became more difficult as the severity of the inflammation increased, but there were no significant differences between the two groups in operating time, blood loss, or bowel function postoperatively. CONCLUSION: Though mucosectomy is technically more difficult in the presence of severe inflammation, there were no adverse effects on bowel function postoperatively.

Adenomatous Polyposis Coli↗

Effects of daily administration of methamphetamine on multiple active/passive avoidance performance in rats.

The effects of daily methamphetamine (M-Amp) treatment with (2 mg/kg/day, i.p.) were examined on multiple active/passive avoidance performance (MAP) in rats. After avoidance training, the animals were given M-Amp every day; on the days of learning sessions, which were on alternate days, the drug was administered at 15 min before the session. Daily administration of M-Amp produced enhancement of the number of respondings (running) as an excitatory dimension of behavior, disruption of immobilities as an inhibitory dimension, and impairment of successes as a discriminatory dimension, when compared with saline-treated rats. Following M-Amp withdrawal, recovery from these damages of learned behavior was observed, except the deterioration in the discriminative dimension. In conclusion, the MAP paradigm is good for assessing the behavioral effects of M-Amp treatment, making it easy to distinct the behavioral effects of M-Amp into excitatory-inhibitory and discriminative dimensions. It is important to distinguish the behavioral components induced by M-Amp, since the damage of learned avoidance performance consists of different dimensions in the M-Amp-treated rats. Impairment of discriminative behavior appears to demonstrate an attentional deficit, which may explain the behavioral disorderliness in M-Amp abusers who display no disturbance of apparent consciousness. These results are discussed with association of brain monoamine alterations.

Animals↗

T lymphocyte lines and clones selected against synthetic myelin basic protein 82-102 peptide from Japanese multiple sclerosis patients.

As has been indicated in experimental autoimmune encephalomyelitis (EAE), the application of synthetic peptides for the selection of T cell lines may provide new insights into the pathogenesis of multiple sclerosis (MS). We report here on T cell lines/clones generated from peripheral blood of MS patients against an immunodominant myelin basic protein (MBP) peptide 82-102. This study demonstrates that the selection of T cell lines against the MBP peptide is much more efficient than against whole MBP in generating a large panel of T cell lines/clones, and therefore provides a powerful strategy for studying autoimmune T cell repertoire in individual subjects. The peptide-selected lines and clones recognized MBP 82-102, shorter peptides MBP 89-101, 89-100 and guinea pig whole MBP mainly in the context of HLA-DR, but did not cross-recognize virus-derived peptides homologous to MBP 82-102. Seven out of ten clones were found to recognize MBP 82-102 in the absence of autologous antigen presenting cells (APC), and in three of the seven clones, specificity for MBP 82-102 could be demonstrated only in the absence of APC because of their strong reactivity against autologous APC. Two-color flow cytometry revealed that the clones were heterogeneous with regard to expression of CD4 and CD8 molecules. Overall, the clones selected by the peptide were rather heterogeneous in phenotype and function compared with those selected by whole MBP.

Adult↗

Low-density lipoprotein receptor mutation that deletes exons 2 and 3 by Alu-Alu recombination.

A deletion mutant in the low density lipoprotein receptor gene of a Japanese patient with heterozygous familial hypercholesterolemia was analyzed. Genomic Southern blotting showed abnormal size restriction fragments with BamHI (7.8 kb), EcoRI (3.8 kb), BglII (17 kb), KpnI (> 23 kb), EcoRV (13 kb), and XbaI (14 kb). The abnormal EcoRI fragment, 3.8 kb, was cloned into lambda phage vector, and the deleted region of 10 kb including exons 2 and 3 was identified. The nucleotide sequence around the deletion joint was determined. The sequence of the eight nucleotides in the deletion-joint region of the mutant gene was identical to the corresponding sequences of both introns 1 and 3 of the normal gene. The deletion seemed to occur by an unequal recombination between the Alu-like sequences in the same direction in introns 1 and 3.

Base Sequence↗

Influence of hypoxic and hypercapnic acidosis on brain water content after forebrain ischemia in the rat.

OBJECTIVE: To determine whether hypoxia or hypercapnia superimposed on ischemia affects brain water content after ischemia. DESIGN: Prospective, randomized, controlled trial. SUBJECTS: Thirty-one male Wistar rats. INTERVENTIONS: The rats were assigned randomly into one of six groups: a) control; b) ischemia; c) ischemia combined with hypoxia; d) ischemia combined with hypercapnia; e) hypoxia; f) hypercapnia. Forebrain ischemia was induced for 5 mins by clamping both carotid arteries and inducing exsanguination. Either hypoxia or hypercapnia was induced until the arterial pH decreased to 7.0. The rats were decapitated after the protocol. MEASUREMENTS AND MAIN RESULTS: After the decapitation, the specific gravities of the neocortex, caudatoputamen, hippocampus, cerebellum, and midbrain were measured using a variable-density bromobenzene-kerosene column technique as an index of brain swelling. The specific gravities of the hippocampus and the neocortex were significantly lower in the ischemic group than in the control group. Specific gravities of the caudatoputamen and neocortex in the ischemia plus hypercapnia group, and specific gravities of the caudatoputamen, neocortex, and hippocampus in the ischemia plus hypercapnia group, were significantly lower than in the ischemia group. CONCLUSIONS: Cerebral water content increases more when ischemia is accompanied by hypoxia or hypercapnia than after ischemia alone. Hypoxic and/or hypercapnic acidosis during the periresuscitation period may be one of the causes of brain swelling after the resuscitation of patients after an anoxic-ischemic insult.

Acidosis, Respiratory↗

End-tidal CO2 changes under constant cardiac output during cardiopulmonary resuscitation.

OBJECTIVES: To evaluate a) whether end-tidal CO2 values change under constant cardiac output during cardiopulmonary resuscitation (CPR), and b) what factors are responsible for the change. DESIGN: A cohort study. SETTING: University research laboratory. SUBJECTS: Nine mongrel dogs. INTERVENTIONS: Ventricular fibrillation was electrically induced. After 2 mins, open-chest cardiac massage was initiated to maintain cardiac output at 0.2 L/min (23% of baseline cardiac output) by the measurement of blood flow with an electromagnetic flow probe on the ascending aorta. The cardiac massage was kept constant until 50 mins after the induction of ventricular fibrillation. MEASUREMENTS AND MAIN RESULTS: Before and during ventricular fibrillation, end-tidal CO2, minute volume of alveolar ventilation, and CO2 excretion were continuously monitored. Blood gases and oxygen saturation values were also measured in arterial and the mixed venous blood samples. CO2 content was calculated. After induction of ventricular fibrillation, end-tidal CO2 decreased and thereafter continued to increase until the end of the experiment. Two mechanisms may have contributed to the early reduction in end-tidal CO2. One mechanism is a further decrease in CO2 excretion compared with the reduction in alveolar ventilation and the other is an increase in alveolar deadspace (estimated from the increase in the difference between PaCO2 and end-tidal CO2). The subsequent increase in end-tidal CO2 was mainly due to a change in CO2 excretion. There are two hypotheses concerning the subsequent increase in CO2 excretion: the increase in pulmonary capillary blood flow (estimated from the change in the arteriovenous CO2 content gradient) and the increase in CO2 production itself. CONCLUSIONS: End-tidal CO2 changes under constant cardiac output during CPR. When end-tidal CO2 is used to estimate the effectiveness of the cardiac massage, this type of change must be recognized.

Animals↗

Ultrastructural study of extramammary Paget's disease--histologically showing transition from bowenoid pattern to Paget's disease pattern.

Histological, immunohistochemical, and ultrastructural studies were performed on two cases of histologically unusual extramammary Paget's disease. Histologically, the central area of the lesions showed a bowenoid pattern, and the peripheral area showed typical extramammary Paget's disease. The transition zone showed an intermediate pattern. All these areas were positive for CEA and EMA, and negative for S-100 protein. Ultrastructurally, in the intermediate pattern, the tumour cells had abundant cytoplasmic glycogen, and the widened intercellular spaces contained numerous glycogen particles, which were probably secreted by the tumour cells. It is well known that eccrine glands, but not apocrine glands, secrete glycogen particles. Therefore, the present findings suggest that some cases of extramammary Paget's disease are a proliferation of germinative cells with eccrine gland differentiation.

Aged↗

Retinal dopamine and its metabolite contents in zitter rats and spontaneously epileptic rats.

In order to investigate the relationship between visual dysfunction and retinal DA metabolism in zitter rats and spontaneously epileptic rats (SER), we measured the amounts of retinal dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillate (HVA). DA, DOPAC and HVA contents were markedly decreased in zitter rats as compared with the controls, Kyo:Wistar or Sprague-Dawley rats. In contrast, in SER, retinal DA and its metabolite contents were not significantly different from those of Kyo:Wistar rats. SER showed higher levels of DA and its metabolites in comparison with Sprague-Dawley rats. Thus, it is suggested that the debilitation of retinal DA synthesis is at least partly related to the visual dysfunction observed in zitter rats, but not that of SER.

3,4-Dihydroxyphenylacetic Acid↗

Protein tyrosine kinase in colorectal adenoma.

To determine whether protein tyrosine kinase (PTK) could be utilized as a biological indicator of colonic tumorigenesis, we examined the PTK activity in the cytosolic and particulate fractions of homogenates from 25 adenomas (polyps) and from adjacent normal mucosa. The particulate fraction PTK activity in the colorectal adenomas was significantly higher than in the normal mucosa. The adenomas were then analyzed according to size, histological type (tubular and tubulovillous), and degree of dysplasia (mild, moderate and severe). The average particulate fraction PTK activity ratio (adenoma/normal mucosa) of tubulovillous adenomas or adenomas with moderate to severe dysplasia was significantly elevated in comparison with that of tubular adenomas or adenomas with mild dysplasia. The particulate PTK activity ratio increased significantly with increasing adenoma size, while the cytosolic ratio did not. The cytosolic PTK activity ratio in tubulovillous adenomas or adenomas with severe dysplasia decreased significantly with increasing size. These findings suggest that colonic carcinogenesis might be associated with alterations in the cellular level of PTK activity and that the PTK activity ratio (adenoma/normal mucosa) in the particulate and/or cytosolic fractions may possibly correlate with the risk of malignant transformation.

Adenoma↗