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Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 361 records · Page 20Linked to original sources

[Clinical evaluation of platelet antagonists on the ex vivo inhibitory effects of platelet aggregation].

It is necessary in clinical to establish the effects of new substances for the primary and secondary prevention of thrombotic illnesses. We measured maximum aggregation after addition of collagen (F.C. 1.7 micrograms/ml) or ADP (F.C. 1.7 mumol/l) in 41 patients without drug treatment, 91 with ticlopidine, 22 with aspirin (ASA); 82-750 mg, 13 with ASA 81 mg, 20 with ticlopidine 100 mg and ASA 81 mg, 13 with cilostazol, 25 with flurbiprofen, 19 with nifedipine and evaluated the ex vivo effect of platelet antagonists. ASA inhibited remarkably collagen-induced platelet aggregation compared with other drugs, but there was significant (p less than 0.01 for 0.5 mumol/l ADP; p less than 0.02 for 1.0 mumol/l ADP) increase of primary aggregation induced by low dose of ADP in 14 healthy volunteers. While ticlopidine only significantly reduced ADP-induced platelet aggregation and we couldn't find dose dependency of ticlopidine (100-300 mg/day) on inhibitory effects of ADP or collagen-induced platelet aggregation. Our results indicate that the administration of one tablet of aspirin for pediatrics (aspirin 81 mg/tab) together with ticlopidine 100 mg is suitable for reduction of platelet aggregation.

Adenosine Diphosphate↗

[Experimental study on the maintenance of sufficient hepatic circulation with arterial blood during the temporary occlusion of the hilar hepatic circulation].

This study was performed to clarify the lowest limit of the blood flow volume to maintain the normal energy metabolism in the liver of mongrel dogs under the condition of total hilar clamping when the hepatic circulation was supplied only through the extracorporeal catheter bypass from the artery to the hepatic portal vein in flow control. The proper hepatic artery was ligated. The levels of adenosine triphosphate and total adenine nucleotide in the liver tissue were maintained as in the same level as the pre-bypass value during 120 minutes of this procedure even though the rate of bypass flow varied between 25% to 100% of normal total hepatic blood flow. When the bypass flow decreased below 10% of the normal flow, the hepatic energy metabolism was observed broken and the anaerobic glycolysis progressed within 30 minutes. Regional hepatic blood flow measured by the hydrogen clearance method was decreased slightly in the 25%-bypass flow and extremely in the 10%-flow after 30 minutes of the bypass. The lowest limit of the arterial blood inflow volume to maintain the hepatic function was confirmed to be in the range between 10% and 25% of the normal total hepatic blood flow volume.

Adenine Nucleotides↗

Retroperitoneal schwannoma mimicking lymph node metastasis of seminoma.

We report a case of retroperitoneal schwannoma mimicking lymph node metastasis. A 32-year-old man presented with an intrascrotal mass, and underwent radical orchiectomy. Histological examination revealed a typical seminoma of the testis. Systemic work-up for staging demonstrated a retroperitoneal mass, which was located in the supra-hilar inter-aortocaval region. Under the diagnosis of retroperitoneal metastasis of the seminoma, he underwent three courses of cisplatin, vinblastine, and bleomycin (PVB) therapy. Persistence of the tumor after the chemotherapy led to retroperitoneal lymphadenectomy, histological examination then revealing a benign schwannoma. The location of the tumor and its unresponsiveness to chemotherapy might be useful indicators for differentiating lymph node metastasis of seminoma from primary tumors of other origin.

Adult↗

Hypothalamic neuronal histamine modulates ad libitum feeding by rats.

Manipulating histamine endogenously, its effects on brain functions were assessed in rats. alpha-Fluoromethylhistidine (FMH), an inhibitor of histamine synthesis, elicited feeding (P less than 0.01) after intra-third cerebroventricular infusion at the early light phase when hypothalamic histamine was normally highest. No periprandial drinking was observed. The effect of FMH was attenuated, and thioperamide, an antagonist of auto-inhibitory effects on both histamine synthesis and release at presynaptic H3-receptor, conversely suppressed food intake (P less than 0.05), when these probes were carried out during the minimum histamine level early in the dark period. Bilateral microinfusion of FMH into the ventromedial hypothalamus (VMH) and the paraventricular nucleus (PVN) selectively induced feeding, but the infusion into the remaining sites of the hypothalamus had no effect. These data show that neuronal histamine plays a physiological role in feeding suppression through the VMH and the PVN in the rat.

Animals↗

Enhancement of bradykinin-induced prostacyclin synthesis in porcine aortic endothelial cells by pertussis toxin. Possible implication of lipocortin I.

Bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells was enhanced by pretreatment of the cells with pertussis toxin or islet-activating protein (IAP) for 5 hr or longer. Although ADP-ribosylation of a protein with a molecular weight of 41-42 kD in the cell membranes was completed by 3 hr after the addition of IAP into the incubation medium, there was good correlation between enhancement of bradykinin-induced prostacyclin synthesis and ADP-ribosylation of the IAP substrate over a wide range of IAP concentrations. Furthermore, even if IAP was removed from the incubation medium at 3 hr, bradykinin-induced prostaglandin synthesis at 24 hr was still potentiated. Cycloheximide and actinomycin D enhanced bradykinin-induced prostacyclin synthesis and apparently blocked the effect of IAP. Since this result suggested the involvement of an inhibitor protein(s) of prostacyclin synthesis in the IAP effect, we studied the effect of IAP on the level of lipocortin I which is known to inhibit phospholipase A2. Western and Northern blot analyses revealed that IAP decreased the amounts of protein and mRNA of lipocortin I. These results suggest that the enhancement of bradykinin-induced prostacyclin synthesis by IAP is associated with a decrease in the level of lipocortin I.

Adenosine Diphosphate Ribose↗

Synthesis and NMR study of ribo-oligonucleotides forming a hammerhead-type RNA enzyme system.

We designed a hammerhead-type ribozyme system which consists of three RNA fragments and synthesized the component and related ribo-oligonucleotides by the solid-phase phosphoramidite method using o-nitrobenzyl groups for 2'-hydroxyl protection. Improved conditions for photolytic removal of the o-nitrobenzyl groups are described. Imino proton NMR spectra of the ribozyme complex were measured. The resonances for the hydrogen-bonded imino protons were assigned by comparison with the spectra of model complexes which contain the base sequences of one or two of the stem regions. The results suggest that the complex indeed forms a hammerhead structure and the loop regions take an ordered conformation in the absence of magnesium ions.

Base Composition↗

Interaction of lipocortin I with peripheral-type benzodiazepine binding sites.

Recombinant rat lipocortin I increased [3H]PK 11195 binding to porcine aortic smooth muscle membranes, whereas a polyclonal anti-rat lipocortin I antiserum decreased both basal and lipocortin I-enhanced [3H]PK 11195 binding. The results suggest the possibility of lipocortin I being involved in the function of peripheral-type benzodiazepine binding sites.

Animals↗

Studies on the structure and stabilizing factor of the CUUCGG hairpin RNA using chemically synthesized oligonucleotides.

A tridecaribonucleotide, r-UGAGCUUCGGCUC, and two analogues r(UGAGC)d(UUCG)r(GCUC) and r-UGAGCUUCIGCUC, which form a hairpin structure with a four-base-paired stem and a UUCG loop, were synthesized by the solid-phase phosphoramidite method. Properties of these three oligomers and d-TGAGCTTCGGCTC, the DNA analogue, were studied by UV, CD and NMR spectroscopy. The melting temperature (Tm) data suggest that the 2'-hydroxy1 groups and the 2-amino group of guanosine in the loop (9G) stabilize the CUUCGG hairpin which is known to have an unusually high Tm. NMR studies show that this 9G takes a syn conformation and the phosphodiester backbone has a turn at 9G-10G which is a junction of the stem and loop.

Base Sequence↗

The role of a conserved guanosine residue in the hammerhead-type RNA enzyme.

We have designed a hammerhead-type RNA system which consists of three RNA fragments for normal and modified complexes which contain a non-cleavable substrate with 2'-O-methylcytidine and a guanosine-to-inosine replaced enzyme. Examination of the RNA-cleaving activity and conformational properties of the complexes suggests that the 2-amino group of a conserved guanosine residue in the loop region plays an important role for maintaining both the activity and loop conformation.

Base Sequence↗

The role of lipocortin I in macrophage-mediated immunosuppression in tumor-bearing mice.

The soluble mediators and/or mechanisms involved in immunosuppression in tumor-bearing hosts are not well characterized, although macrophages have long been recognized as major participants. We have investigated the role of lipocortin I, a phospholipid-binding protein, in macrophage-mediated immunosuppression in tumor-bearing mice. Proliferation of splenic lymphocytes in response to the mitogens (PHA, Con A, LPS, and PWM) was severely suppressed in tumor (Sqc-NH-1 carcinoma)-bearing mice. This immunosuppression was associated with a decrease in T and B lymphocytes and an increase in macrophages in these spleens. Mac-2+ macrophages were found only in spleens from tumor-bearing mice. Splenic macrophages from tumor-bearing, but not normal, mice were responsible for this immunosuppression, as revealed by negative and positive selection experiments. The levels of lipocortin I mRNA expression were markedly increased in peripheral blood cells from tumor-bearing mice as compared with those from normal mice. Lipocortin I mRNA was strongly induced in splenic mononuclear cells from tumor-bearing mice. Furthermore, these cells displayed increased expression of lipocortin I protein, as judged by Western blot analysis with polyclonal anti-lipocortin I serum. Some nonimmune organs such as the heart, submaxillary gland, muscle, and bladder also displayed increased levels of lipocortin I mRNA expression in tumor-bearing mice. Mac-2+ macrophages among the splenic mononuclear cells in tumor-bearing mice expressed lipocortin I mRNA, as judged by negative and positive selection experiments. Most of these Mac-2+ macrophages also had Mac-1 and Mac-3 Ag. Lipocortin I protein was increased in the serum of tumor-bearing mice as compared with normal mice. The culture supernatants of splenic cells from tumor-bearing mice suppressed the mitogenic responses of splenic cells from normal mice, and addition of anti-lipocortin I antiserum inhibited this suppression. Furthermore, recombinant mouse lipocortin I suppressed mitogenic responses of splenic cells from normal mice. In summary, Mac-2+ macrophage-derived lipocortin I was largely involved in immunosuppression in tumor-bearing mice.

Animals↗

Hypothalamic histamine modulates adaptive behavior of rats at high environmental temperature.

Histamine content in the rat hypothalamus was lower at 4 degrees C and higher at 31 degrees C compared to that at 21 degrees C. Pretreatment with alpha-fluoromethylhistidine, a 'suicide' inhibitor of histamine decarboxylase, attenuated both the increased level of hypothalamic histamine and rat adaptive behavior at 31 degrees C. Increase of histamine content in the hypothalamus appears to be an important factor contributing to rat adaptive behavior to high environmental temperature.

Adaptation, Physiological↗

Constitutive expression of interleukin-7 mRNA and production of IL-7 by a cloned murine thymic stromal cell line.

Mouse interleukin-7 (IL-7) cDNA was cloned from mouse thymic stromal cell clone MRL 104.8a using a polymerase chain reaction (PCR) technique and expressed in COS-7 cells. The resulting recombinant interleukin-7 (rIL-7) supported the proliferation of mouse antigen-specific helper T cell (Th) clone 9-16 in the absence of IL-2 and antigen as well as mouse pre-B cell line DW34. It was also found that high levels of the mRNA for IL-7 were constitutively expressed in the MRL104.8a cells, and a potent amount of IL-7 was produced in its culture supernatant. These results provide the evidence for constitutive expression of IL-7 mRNA and for production of IL-7 by thymic stromal cells that have a critical role in intrathymic T cell development. The results are discussed in the context of the functional and molecular relationship between IL-7 and the previously described cytokines produced by thymic stromal cells.

Animals↗

Evidence for feeding elicited through antihistaminergic effects of tricyclic antidepressants in the rat hypothalamus.

We studied central mechanisms of antidepressants that affect feeding behavior in rats. The tricyclic compounds amitriptyline, doxepin and imipramine significantly induced feeding after their infusion into the third cerebral ventricle in the light phase, but the tricyclic, desipramine, and the dicyclic zimelidine, did not. Drinking was not affected by any compound tested. The relative order of potency in eliciting feeding was: amitriptyline and doxepin greater than imipramine greater than desipramine and zimelidine. To clarify the involvement of neuronal histamine in antidepressant-induced feeding, alpha-fluoromethylhistidine (FMH), a "suicide" inhibitor of histidine decarboxylase, was intraperitoneally administered before infusion of amitriptyline. FMH attenuated the amitriptyline's effect. Bilateral microinfusion of amitriptyline into the ventromedial hypothalamus or the paraventricular nucleus verfied that these are loci for the modulation of feeding by amitriptyline. In the lateral hypothalamus, amitriptyline was less effective. These findings indicate that tricyclic antidepressants directly facilitate feeding, which is, at least in part, mediated by histamine in the hypothalamus.

Amitriptyline↗

Primary transitional cell carcinoma of prostate: case with lymph node metastasis eradicated by neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) therapy.

A case of transitional cell carcinoma of the periurethral prostatic ducts received neoadjuvant chemotherapy consisting of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC), which eradicated pelvic lymph node metastasis, followed by cystoprostatectomy. M-VAC therapy may be indicated for metastatic transitional cell carcinoma of the periurethral prostatic ducts.

Antineoplastic Combined Chemotherapy Protocols↗

Serotype-related antigen of Trichosporon cutaneum in the induction of summer-type hypersensitivity pneumonitis: correlation between serotype of inhalation challenge-positive antigen and that of the isolates from patients' homes.

Inhalation challenge with the culture filtrate-antigens prepared from two strains of different serotype of Trichosporon cutaneum (TIMM 1573, serotype I; TIMM 1318, serotype II) was performed on patients with summer-type hypersensitivity pneumonitis and asymptomatic seropositive family members. Of the 17 patients, 12 were strongly positive, four were mildly so, and one was negative. Interestingly, of the 16 inhalation challenge-positive patients, four reacted to both serotypes I and II, five to serotype I only, and seven to serotype II only. There was a good correlation between the serotype inhalation challenge-positive antigen and that of T. cutaneum isolated from the homes of two patients' homes. A strain of T. cutaneum demonstrating a new serotype was isolated from the homes of two patients, one of whom was negative to both serotypes I and II. Specific antibody activity, lymphocyte proliferative response, and skin reaction to the antigens were also positive, but these findings were not useful to discriminate the inhalation challenge-positive from the inhalation challenge-negative antigen. Neither of the two asymptomatic family members responded. These results indicate that inhalation challenge in patients with summer-type hypersensitivity pneumonitis is provoked by the serotype-related antigen of T. cutaneum, reflecting the sensitization of these patients in their homes.

Alveolitis, Extrinsic Allergic↗

Structural and stereoisomeric specificity of serum-borne sugar acids related to feeding control by rats.

Specificity of chemical structures and stereoisomers among serum-borne short-chain organic acids in rats were assessed for their effects on feeding behavior and humoral factors by infusion into the rat third cerebroventricle. Infusion of glyceric acid (1.0 mumol), 3,4-dihydroxybutanoic acid gamma-lactone (3,4-DB) or 3,4,5-trihydroxypentanoic acid gamma-lactone (2.50 mumol) immediately before the dark phase decreased food intake for, at most, 24 h. These acids did not significantly affect drinking or ambulation. Initial feeding, not necessarily accompanied by periprandial drinking, was induced after infusion of 2,4-dihydroxybutanoic acid gamma-lactone, 2,4,5-trihydroxypentanoic acid gamma-lactone (2,4,5-TP) or exogenous 2,4,5,6-tetrahydroxyhexanoic acid gamma-lactone (2.50 mumol) in the light phase. Of these acids, 3,4-DB most potently suppressed and 2,4,5-TP most potently enhanced feeding. Of these, the 2S,4S-isomer and the 3S-isomer were the most potent of 2,4,5-TP and 3,4-DB, respectively. Only the 2S,4S-isomer of 2,4,5-TP induced hypoglycemia with hyperinsulinemia, whereas opposite effects were produced by the 3S-isomer of 3,4-DB. The results indicate that the positions of the hydroxyl groups on 4-butanolide and the S- and S,S-stereoisomers are important in modulating food intake through the hypothalamus.

Animals↗

Importance of serotype-related antigen in the induction of experimental hypersensitivity pneumonitis by Trichosporon cutaneum in rabbits. Correlation between granulomatous alveolitis and cellular and humoral immune responses to polysaccharide-rich antigen.

We evaluated the immunopathogenic properties of Trichosporon cutaneum, a major etiologic agent of Japanese summer-type hypersensitivity pneumonitis (HP). When the culture filtrate antigen of T. cutaneum was chromatographed on DEAE-cellulose, two peaks of polysaccharide, fractions A and B, were obtained. Fraction B was highly reactive to the specific IgG and IgA antibodies in the serum and bronchoalveolar lavage fluid samples obtained from sensitized rabbits, whereas fraction A was mainly reactive to the IgG antibodies. When the rabbits sensitized by intratracheal injection with the particulate antigen of T. cutaneum were challenged intratracheally by these antigenic fractions, fraction B induced granulomatous alveolitis, but fraction A induced alveolitis rather than granuloma. Lymphocytes of the mediastinal lymph nodes responded prominently to fraction B, but less to fraction A, as assessed by proliferative response. Each of the fractions B obtained from two strains of different serotypes (TIMM 1573, serotype I and TIMM 1318, serotype II) was reactive in enzyme-linked immunosorbent assay to the serum samples from the rabbits sensitized with homologous antigen, but far less to that from the rabbits sensitized with heterologous antigen, that is, the antigenic specificity of fraction B was related to the serotype of T. cutaneum. Fractionation by gel filtration on Sepharose CL-4B revealed that the molecular weight of the antigenic components in fraction B was larger than 1,000,000 and that the components consisted mainly of polysaccharide.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗

[Statistical evaluation of determinants of progression of superficial bladder cancer by proportional hazards model].

To evaluate clinical and pathological factors present at the initial consultation which affect disease progression, we reviewed data from 223 patients with superficial bladder cancer (pTa and pT1) who were initially treated at Nagoya University Hospital between January 1973 and December 1987. The factors included in the present analysis were age, sex, symptoms, interval between initial symptoms and first consultation, location of tumor, size, number, endoscopic shape, histological pattern of growth, grade and stage. The median duration of the follow-up after initial treatment was 46 months. Of the 223 patients, 17 died: 8 (3.6%) of bladder cancer and the remaining 9 (4.0%) of unrelated causes. Disease progression developed in 12 patients (5.4%): muscle invasion of the bladder wall in 11 and lung metastasis in one. The interval between initial treatment and progression ranged from 4 to 108 months, with a median of 11.5 months. Of the 12 patients, 9 (75%) had disease progression within 2 years. Progression was significantly associated with poor prognosis (p less than 0.001): the 5-year actuarial survival rates were 47.1% and 92.8% in patients with and without progression, respectively. Univariate analysis by Cox's proportional hazards model demonstrated that characteristics such as irritative bladder symptoms, higher-grade tumors, invasion into lamina propria, and nonpapillary growth seen at initial consultation were significantly related to disease progression. Cox's proportional hazards model produced hazard ratios of 10.2 in irritative bladder symptoms (yes vs. no), 6.3 in histological grade (grade 3 vs. grades 0-2), 4.9 in stage (pT1 vs. pTa), and 4.7 in pattern of growth (papillary vs. nonpapillary).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗