Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 271 records · Page 15Linked to original sources

PubMed1994

Role of histamine receptors in intestinal repair after ischemia-reperfusion in rats.

BACKGROUND/AIMS: Previously, we showed that an elevated production of histamine promotes the healing of injured intestinal mucosa after ischemia-reperfusion. The aim of the present study was to determine whether histamine-mediated repair of the intestinal mucosa after ischemia-reperfusion involves the engagement of H1 or H2 receptors. METHODS: The superior mesenteric artery was occluded for 15 minutes followed by reperfusion, and H1- or H2-receptor antagonists were infused intraduodenally. After ischemia-reperfusion, ornithine decarboxylase activity in the jejunal mucosa and lipid transport to mesenteric lymph were examined. RESULTS: In jejunal mucosa, ornithine decarboxylase activity markedly increased at 6 hours after reperfusion and remained elevated at 48 hours. The ischemia-reperfusion-induced increase in ornithine decarboxylase activity was attenuated (in a dose-dependent manner) by an H1-receptor antagonist (chlorpheniramine maleate) but not by an H2 antagonist (cimetidine). Intraperitoneal injection of an H3 antagonist (thioperamide) increased histamine output in mesenteric lymph and stimulated intestinal ornithine decarboxylase activity. Transport of dietary lipid into mesenteric lymph was depressed 24 hours after an ischemic insult, yet it returned to the normal level 48 hours after ischemia-reperfusion. The recovery of the lipid transport normally observed at 48 hours after ischemia-reperfusion was attenuated by the H1 antagonist. CONCLUSIONS: The beneficial effects of histamine on the repair of intestinal mucosa after ischemia-reperfusion results from the engagement and activation of the H1 receptor.

Animals↗

PubMed1994

Mediation of the trophic effects of short-chain fatty acids on the rat jejunum and colon.

BACKGROUND/AIMS: Short-chain fatty acids (SCFAs) are trophic to small intestinal and colonic mucosa. This study determined whether SCFAs infused into the cecum out of continuity stimulated jejunal and colonic cellularity and whether these effects were mediated by the autonomic nervous system and/or enterotrophic hormones. METHODS: To eliminate direct trophic effects of SCFAs in contact with mucosa, 60 rats underwent cecal isolation with placement of an infusion catheter into the proximal cecum, formation of distal cecocutaneous stoma, and restoration of intestinal continuity with ileocolonic anastomosis. Rats underwent cecal denervation or remained normally innervated and received 1 of 3 infusions for 10 days: SCFAs, saline, or no infusion. Twenty-four additional rats were assigned to the same groups but underwent infusion into the proximal colon (in circuit). RESULTS: Cecal infusion of SCFAs into innervated rats increased (P < 0.05) jejunal DNA, villous height, surface area, crypt depth, and gastrin without increasing colonic variables. In denervated rats, SCFAs did not significantly affect these variables. However, direct intracolonic infusions of SCFAs increased (P < 0.05) colonic mucosal DNA and crypt depth. CONCLUSIONS: Jejunotrophic effects of cecally infused SCFAs are mediated afferently by the autonomic nervous system and are associated with increased jejunal gastrin. SCFAs have local trophic effects on the colon.

Animals↗

PubMed1994

A physiological role of brain histamine during energy deficiency.

Histaminergic activation in the rat hypothalamus was investigated under a deficit in energy supply. Fasting of rats for 24 h increased hypothalamic histamine (HA) content. Intraperitoneal (IP) injection of insulin (2 U/kg) increased pargyline-induced accumulation of tele-methylhistamine (t-MH) leaving steady-state HA and t-MH levels unaffected, which implies enhancement of HA turnover rate. The insulin infusion induced hypoglycemia both in rats with and without pargyline pretreatment. Infusion of 2-deoxy-D-glucose (2-DG) into the third cerebroventricle also produced an increase in pargyline-induced accumulation of t-MH and no change in steady-state HA and t-MH levels. The 2-DG infusion induced hyperglycemia. Hypothalamic glycogen content decreased after 24 h starvation, but this decrease was prevented by depletion of HA by alpha-fluoromethylhistidine. Absolute glycogen contents in the cortex were lower than those in the hypothalamus, and were not affected by fasting or depletion of HA. The results indicate that activation of hypothalamic HA in response to glucoprivation may modulate homeostatic control of energy supply in the brain.

Animals↗

PubMed1994

Thermoregulation and hypothalamic histamine turnover modulated by interleukin-1 beta in rats.

To clarify the involvement of hypothalamic histamine in thermogenic response provoked by high ambient temperature, or interleukin-1 beta (IL-1 beta), changes in rectal temperature and histamine turnover were investigated. Rectal temperature was maintained normally after exposure to high ambient temperature, but elevated by IL-1 beta. In spite of these different responses of body temperature, hypothalamic histamine turnover was increased in each treatment. The results suggest that hypothalamic histaminergic neurons are activated not only peripherally by high ambient temperature, but also centrally by IL-1 beta as endogenous pyrogen.

Animals↗

PubMed1994

Neuronal glucoprivation enhances hypothalamic histamine turnover in rats.

Histamine (HA) turnover in the rat hypothalamus following insufficient energy supply due to glucoprivation was examined after administration of insulin or 2-deoxy-D-glucose (2-DG). HA turnover was assessed by accumulation of tele-methylhistamine (t-MH), a major metabolite of brain HA, following administration of pargyline. Intraperitoneal injection of 1, 2, and 4 U/kg of insulin, which had no influence on steady-state levels of HA and t-MH, increased pargyline-induced accumulation of t-MH. Accumulation of t-MH due to pargyline was inversely related to the concomitant plasma glucose concentration after different doses of insulin. The level of t-MH accumulated by pargyline did not change compared with that of controls, when a euglycemic condition was maintained or insulin at a dose of 6 mU per rat was infused into the third cerebroventricle. Intracerebroventricular infusion of 24 mumol per rat of 2-DG, which had no influence on steady-state levels of HA and t-MH, increased the level of t-MH enhanced by pargyline. The results indicate that an increase in hypothalamic HA turnover in response to glucoprivation may be involved in homeostatic regulation of energy metabolism in the brain.

Animals↗

PubMed1994

Galactosylsucrose and xylosylfructoside alter digestive tract size and concentrations of cecal organic acids in rats fed diets containing cholesterol and cholic acid.

Influences of galactosylsucrose and xylosylfructoside on body mass gain, the digestive tract mass and concentrations of organic acids such as acetic, propionic, butyric, lactic and succinic acid in the cecum were compared among rats fed a cholesterol-enriched fiber-free diet [cholesterol 6 + cholic acid 1.5 (g/kg)] containing either galactosylsucrose, xylosylfructoside or sucrose (100 g/kg) or the above fiber-free diet without test sugar (control) for 21 d. Body mass gain was greater in rats fed sucrose, but not in rats fed galactosylsucrose or xylosylfructoside, than in control rats. The mass of the small intestine and colon plus rectum was larger in rats fed xylosylfructoside than in control rats. Cecal contents and cecal tissue mass were heavier, water content of cecal contents was higher, and pH and ammonia concentration of cecal contents were lower in rats fed diets containing xylosylfructoside than in control rats. Galactosylsucrose had similar effects, although not all differences were significant. The concentration of hydrogen ion in cecal contents positively correlated to total cecal concentration of measured organic acids and to amount of cecal contents. Total concentration of measured organic acids in cecal contents positively correlated to cecal tissue mass. The estimated contribution of galactosylsucrose, xylosylfructoside and sucrose for body mass deposition were 0.19, -0.29 and 0.51 (g body mass gained/g sugar), respectively.

Ammonia↗

PubMed1994

Six missense mutations associated with type I and type II protein C deficiency and implications obtained from molecular modelling.

The molecular basis of protein C deficiency was studied in three type I and three type II heterozygotes. Three probands showed thrombotic complications. All the exons and intron/exon junctions of the protein C gene were studied using a strategy combining by the polymerase chain reaction (PCR) amplification, single-strand conformational polymorphism (SSCP) analysis, and DNA sequencing of the PCR-amplified fragments. Six missense mutations were identified, including three novel ones. One was located in exon II, in which the initiating translation codon (ATG) encoding for Met at position -42 was replaced by ACG encoding for Thr. The other five were located in exon IX, and included TAC(Tyr399)-->CAC(His), CCG(Pro327)-->CTG(Leu), GAC(Asp359)-->AAC(Asn) in two cases, and GGG(Gly350)-->AGG(Arg). Four of the six missense mutations occurred in CG dinucleotide. Sequence analysis of the other exons excluded additional mutations. By restriction enzyme analysis, co-segregation of the mutation with protein C deficiency was observed in four families. The other two mutations at amino acid positions -42 and 350 were also considered to be associated with protein C deficiency due to the absence of these mutations in 50 normal individuals. A structural model of the protease domain of mutant activated protein C was constructed by the chimeric modelling method, and the resultant model suggested conformational changes due to each missense mutation identified in protein C deficiency. The present data also provide some evidence regarding the genetic heterogeneity of protein C deficiency.

Adult↗

PubMed1994

[A case of adult Chlamydia pneumoniae pneumonia diagnosed from a culture method].

We diagnosed a 41-year-old female patient to be suffering from Chlamydia pneumoniae (C. pneumoniae) by using PCR and culture methods. She had a prolonged dry cough and slight fever. Her chest roentgenogram showed a segmental infiltration in the middle of the right lung field. We treated her with 400 mg of cefpodoxime proxetil (CPDX-PR) per day. On the 4th day after beginning the treatment with CPDX-PR, she still complained of a productive cough. We changed the treatment by using 300 mg of roxithromycin per day and these symptoms disappeared. To diagnose C. pneumoniae early, PCR, MIF and culture methods are very useful diagnostic tools.

Adult↗

PubMed1994

2-deoxy-D-glucose suppresses food intake through activation of hypothalamic histamine in rats.

The aim of this experiment was to demonstrate whether brain histamine contributes to delayed suppression of food intake after administration of 2-deoxy-D-glucose (2-DG). Food intake decreased significantly for 48 h after infusion of 2-DG into the rat third cerebroventricle. This delayed decrease in food intake was abolished by depletion of neuronal histamine by intraperitoneal pretreatment with alpha-fluoromethylhistidine (160 mumol/rat), a suicide inhibitor of a histamine-synthesizing enzyme. Intracerebroventricular infusion of 24 mumol 2-DG accelerated turnover rate of hypothalamic histamine. These results indicate that the delayed feeding suppression by 2-DG is modulated through histaminergic neurons in the hypothalamus. This histaminergic response may be related, at least in part, to homeostatic control of energy metabolism in the brain.

Animals↗

PubMed1994

Fluorogenic assay of activated factor VII. Plasma factor VIIa levels in relation to arterial cardiovascular diseases in Japanese.

Factor VII (FVII) plays an important role in initiation of the tissue factor-induced coagulation pathway. An increase in FVII coagulant activity (FVIIc) has been proposed as an independent risk factor for coronary artery disease. However, it remains uncertain whether high FVIIc levels are due to an increase in the activation of FVII or an increase in the concentration of FVII mass. We developed a new fluorogenic assay for plasma activated FVII (FVIIa) that used soluble tissue factor. The sensitivity of this assay ranged from 0.2 to 1000 ng FVIIa per milliliter of plasma. Plasma FVIIa levels were measured in 110 healthy subjects and 93 patients with hypertension, diabetes mellitus, and/or cardiovascular disease. The mean plasma FVIIa level in healthy Japanese individuals was 2.5 ng/mL, which was lower than that in Western subjects. Gel filtration analysis showed that most of the circulating FVIIa was in a free form, and binding of FVIIa to tissue factor in plasma was not detected. Aging increased both the FVIIa level and FVII mass, whereas menopause increased mainly the FVII mass. Elderly patients with arterial cardiovascular diseases showed increases in plasma FVIIa levels and FVIIa to FVII antigen (FVII:Ag) ratios. Among the elderly, arterial cardiovascular disease was more common in a high-FVIIa than a low-FVIIa group. Plasma FVIIa levels were not correlated with serum levels of total cholesterol or triglycerides. The FVIIa level and the FVIIa-to-FVII:Ag ratio were positively correlated with fibrinogen level and negatively correlated with body mass index and serum albumin level in the elderly. In conclusion, aging, cardiovascular disease, and malnutrition increased plasma FVIIa levels. FVIIa levels were not correlated with lipid levels or hepatic synthesis, suggesting that FVIIa may be an independent risk factor for cardiovascular disease.

Adolescent↗

PubMed1994

Atypical peritracheobronchial vasculitis and an effective treatment.

We report an interesting case of vasculitis in which the inflammatory lesion was limited to the peritracheobronchus. This case showed positive antineutrophil cytoplasmic antibodies, diffuse peritracheobronchial swelling, and vasculitis in its histology. Steroid therapy was effective for both roentgenological and serological findings. Although the biopsy specimen shows only inflammation and does not satisfy the WHO criteria of Wegener's granulomatosis (WG), a possible diagnosis of WG should not be disregarded.

Autoantibodies↗

PubMed1994

Reinnervation of allografted pancreatic islets in the rat liver.

Rat pancreatic islets were allografted in the liver and were studied morphologically in order to evaluate possible reinnervation. Islets isolated from rat pancreas were allotransplanted in the liver of streptozocin-induced diabetic rats via the portal vein. Electron microscopy revealed nerve endings with synaptic vesicles in the transplanted islets 100 days after transplantation, whereas axons in the islets appeared to degenerate several hours after isolation and prior to transplantation. These findings suggest that the nerve endings observed in the transplanted islets regenerate from nerves that innervate the recipient's liver. The tissue specimens were also investigated immunohistochemically using antityrosine hydroxylase antibody, and histochemically by the modified Karnovsky and Roots' method for visualizing acetylcholinesterase. Some nerve endings in the transplanted islets reacted positively to antityrosine hydroxylase antibody. Acetylcholinesterase was visualized in other nerves. These results indicate that norepinephrine- and acetylcholinesterase-containing nerves may reinnervate the transplanted islets.

Acetylcholinesterase↗

PubMed1994

Remarkable elevation of interleukin 6 and interleukin 8 levels in the bone marrow serum of patients with rheumatoid arthritis.

OBJECTIVE: Characteristic cellular changes have previously been reported in the bone marrow of patients with rheumatoid arthritis (RA). We investigated the levels of various cytokines in RA bone marrow. METHODS: We studied 25 patients with RA (22 women and 3 men) and 10 trauma patients (7 women and 3 men) as non-RA controls. Twelve kinds of cytokines [interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor, tumor necrosis factor (TNF)-alpha, and TNF-beta] were assayed by ELISA in iliac bone marrow serum (BMS), tibial BMS, and peripheral blood serum. RESULTS: Markedly elevated levels of IL-6 and IL-8 were detected in iliac BMS, and much lower levels were found in tibial bone marrow and peripheral blood serum. The levels of IL-6 and IL-8 in iliac BMS showed a close relationship to the extent of synovial proliferation. CONCLUSION: Iliac bone marrow may be an important site for the production or accumulation of IL-6 and IL-8 in RA, and these cytokines may influence synovial proliferation in patients with polyarthritis.

Adult↗

PubMed1994

[Hyperlucent lung].

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Diagnosis, Differential↗

PubMed1994

Three missense mutations in the protein C heavy chain causing type I and type II protein C deficiency.

We have studied the molecular basis of protein C deficiency in three families with a history of thromboembolic disease. An approximately 50% reduction in both functional and immunologic levels of protein C was detected in the plasma from two unrelated patients, designated protein C Osaka 1 and protein C Osaka 2. An approximately 50% reduction in functional level but normal immunologic level of protein C was detected in plasma from a third patient, designated protein C Osaka 3. DNA sequencing of the amplified DNA revealed one missense mutation in each case. Additional mutations in the coding sequence were excluded by DNA sequencing of all protein C exons. We identified a C-to-T change at nucleotide number 6,218 of the protein C gene in protein C Osaka 1. This results in the amino acid substitution of Arg-169 by Trp at the alpha-thrombin cleavage site. In protein C Osaka 2, a G-to-A change at nucleotide number 8,807 was identified leading to the amino acid substitution of Met-364 by Ile in the protease domain. This substitution may impair the synthesis or stability of protein C Osaka 2. In protein C Osaka 3, a G-to-C change at nucleotide number 8,868 was identified. This results in substitution of Gly-385 by Arg in the protease domain. Based on these, it was concluded that Arg-169-to-Trp mutation and Met-364-to-Ile mutation cause type I protein C deficiency and Gly-385-to-Arg mutation causes type II deficiency.

Adult↗

PubMed1993

Aminoglucose-induced feeding suppression is regulated by hypothalamic neuronal histamine in rats.

Central mechanisms involved in feeding suppression produced by 1-deoxy-D-glucosamine (1-DGlcN) and 1-deoxy-N-acetylglucosamine (1-DGlcNAc) are unclear. To clarify the mechanisms, we investigated the role of hypothalamic neuronal histamine (HA) in feeding suppression induced by 1-DGlcN and 1-DGlcNAc in rats. Food intake was suppressed for 3 days after a single infusion of 24 mumol 1-DGlcN into the third cerebroventricle (i.c.v.). Depletion of presynaptic HA due to intraperitoneal infusion (i.p.) of alpha-fluoromethylhistidine (FMH), a specific inhibitor of the HA synthesizing enzyme histidine decarboxylase (HDC), abolished feeding suppression completely. Blockade of postsynaptic H1-receptors by i.p. injection of 26 mumol chlorpheniramine also abolished the suppression. Oral administration of 2.4 mmol 1-DGlcNAc suppressed food intake. However, depletion of neuronal HA due to FMH did not affect the suppression. I.c.v. infusion of 24 mumol 1-DGlcN increased turnover rate of HA at 1 h after the infusion. Hypothalamic HA concentration, but not that of tele-methylhistamine (t-MH), increased at 24 h after i.c.v. infusion of 1-DGlcN, which suggests a correlation between HA concentration and the behavioral response. These results indicate that 1-DGlcN, but not 1-DGlcNAc, modulates feeding suppression through HA neurons in the hypothalamus. Differences in mechanisms of feeding suppression by these aminoglucoses may depend on the principal sites of action in the brain and/or peripheral organs.

Acetylglucosamine↗

PubMed1993

Neuronal histamine in the hypothalamus suppresses food intake in rats.

Using probes to manipulate hypothalamic neuronal histamine, we report here that changes in neuronal histamine modulate physiological feeding behavior in rats. Infusion of alpha-fluoromethylhistidine (FMH), a "suicide" inhibitor of histidine decarboxylase (HDC), into the third cerebroventricle induced feeding in the early light phase when the histamine synthesis was most accelerated. FMH at an optimum 2.24 mumol dose elicited feeding in 100% of rats. Treatment of FMH specifically and selectively decreased concentration of histamine without affecting concentrations of catecholamines in the hypothalamus. Immediately before the dark phase, when the histamine synthesis was normally lower, FMH infusion did not affect feeding-related parameters such as meal size, meal duration or latency to eat. Conversely, thioperamide, which facilitates both synthesis and release of neuronal histamine by blocking presynaptic autoinhibitory H3 receptors, significantly decreased food intake after infusion of a 100-nmol dose into the third cerebroventricle. The effect of thioperamide was abolished with i.p. injection of 26 mumol/kg chlorpheniramine, an H1antagonist. FMH at 224 nmol was microinfused bilaterally into the feeding-related nuclei in the hypothalamus. The ventromedial nucleus (VMH) and the paraventricular nucleus (PVN), but not the lateral hypothalamus, the dorsomedial hypothalamus or the preoptic anterior hypothalamus were identified as the active sites for the modulation. Neuronal histamine may convey suppressive signals of food intake through H1 receptors in the VMH and the PVN with diurnal fluctuation.

Animals↗

PubMed1993

Study of natural lipocortin I. A potent mediator for macrophage-mediated immunosuppression in tumor-bearing mice.

We previously reported a possible role of lipocortin I secreted from Mac-1+, -2+ macrophages in immunosuppression in tumor-bearing mice. In this study, we purified natural lipocortin I from the spleens of tumor-bearing mice and compared its immunosuppressive activity with recombinant lipocortin I produced by Escherichia coli. The culture supernatants of splenic macrophages from tumor-bearing mice suppressed the mitogenic responses in splenic lymphocytes. The culture supernatants contained higher levels of lipocortin I, but not PGE2, which was considered as a major immunosuppressive factor. Anti-lipocortin I antiserum neutralized these inhibitory activities. Natural lipocortin I purified from the spleens of tumor-bearing mice showed a potent suppressive activity, which was > or = 200 times higher than that of recombinant mouse lipocortin I at protein level. Alkaline phosphatase treatment of natural lipocortin I decreased immunosuppressive activity to the level of recombinant lipocortin I. N-glycosidase F treatment failed to decrease the immunosuppressive activities. These results suggest that the protein modification of lipocortin I, possibly phosphorylation but not glycosylation, is critical for the potent immunosuppressive activity in tumor-bearing mice.

Animals↗