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Biomedical subjects

Y Hara

Publications and source records attributed to Y Hara.

At least 541 records · Page 30Linked to original sources

[Ulcerogenic effect of a GABA derivative, baclofen, in the rat: effect of hypothermia].

The ulcerogenic action of baclofen, a lipophilic derivative of GABA, was studied in the urethane anesthetized rat in relation to body temperature. Baclofen at the doses of 2, 4 and 8 mg/kg, s.c. induced gastric ulceration in a dose-dependent manner in the hypothermic (body temperature: 28-30 degrees C) rat. Duodenal ulcers were also observed in about 80% of the hypothermic animals treated with the highest dose of baclofen. Baclofen, even at 8 mg/kg, s.c., however, failed to induce gastric ulceration in the normothermic (body temperature: 37-38 degrees C) rat. Histamine, at the secretagogue dose causing acid secretion as potently as 8 mg/kg of baclofen, induced gastric ulcers in both the hypothermic and the normothermic rats. These results indicate that the ulcerogenic effect of baclofen is closely related to the thermoregulation mechanism and may provide important clues for clarifying the pathophysiology of gastroduodenal ulcers induced by hypothermic treatments such as water-immersion stress ulcers or cold exposure ulcers.

Animals↗

Effects of GABA antagonists and structural GABA analogues on baclofen stimulated gastric acid secretion in the rat.

The effects of GABA receptor antagonists (bicuculline and phaclofen) and structural GABA-analogues on baclofen stimulated gastric acid secretion were studied in standardized perfused rat stomach preparations. Pretreatment with bicuculline, a GABAA-receptor antagonist, in the doses of 1 and 3 mg/kg, subcutaneously, had no influence on the gastric acid response to baclofen. In addition, phaclofen, a GABAB antagonist, in the doses of 3 to 30 mg/kg, intravenously, was found to have no significant effect on the acid response to baclofen. However, GABA-analogues (MOPS and ABA; 10-30 mg/kg, i.v.) and lipophilic GABA derivatives structurally related to beta-amino acids (APPA and APHA; 30 mg/kg, i.v.) significantly counteracted the secretagogue action of baclofen. Further experiments on APPA action showed that the antisecretory effect of APPA could be overcome by higher doses of baclofen. APPA did not affect bethanechol stimulated acid secretion. These results suggest that the secretagogue action of baclofen is independent to GABAA- and GABAB-receptors and that APPA may interact with baclofen in regulation mechanisms of acid secretion, although further investigations are necessary to define the mode of action of APPA on the GABA-ergic system.

Amino Acids↗

Direct evidence indicating that a GABA-mimetic stimulates acid secretion through central mechanisms.

Acid secretagogue effects of central and peripheral baclofen were compared in the rat. Intravenously (0.1-1.0 mg/kg) and intracerebroventricularly (0.1-1.0 micrograms) administered baclofen augmented acid output to the same degree in a dose-dependent manner. GABA microinjected into the lateral hypothalamus (200 and 400 micrograms) significantly increased acid output. These support the proposal that baclofen stimulates acid secretion through central mechanisms and also the possible role of GABA in central regulation mechanisms of acid secretion.

Anesthesia↗

A cytotoxic antibody produced by allo-skin transplantation in cats.

A high titer of cytotoxic antibody against donor lymphocytes, tentatively designated as anti-F1, was found in one cat who received 3 times of skin allograft from the same donor. The anti-F1 antibody titer was 1:16, and the antibody activity was mostly detected in the IgG fraction. A cross-absorption test using erythrocytes from F1-positive animals revealed that the F1(+) antigen recognized by anti-F1 antibody was expressed on erythrocytes as well as lymphocytes. The frequencies of F1(+) and F1(-) types in 81 healthy cats, involving all the cats used for allo-immunization in the present study, were 30.9 and 69.1%, respectively. Moreover, F1 antigen was considered to be a hereditary antigen from family studies.

Animals↗

Decrease in mitogen-induced lymphocyte proliferative responses in cats infected with feline immunodeficiency virus.

The blastformation tests using concanavalin A and pokeweed mitogen were carried out on peripheral blood lymphocytes obtained from cats infected with feline immunodeficiency virus (FIV). The infected cats included those showing multiple chronic disease, those with a single mild sign, and one with no clinical sign. The infected cats showed significantly lower mitogenic responses of peripheral lymphocytes to both mitogens and lower lymphocyte counts as compared to uninfected healthy cats. These immunologic alterations in the infected cats may be closely related to the development of immunodeficiency-like disorders associated with FIV.

Animals↗

The mechanism for the discrepancy between serum total and free thyroxine values induced by autoantibodies: report on two patients with Graves' disease.

The sera from two patients with Graves' disease gave abnormally high serum free T4 values as compared with the total T4 and other hormone values, suggesting the presence of autoantibodies to labelled T4 analogue used in the Amersham free T4 assay kit. The autoantibodies appeared to develop after the initiation of methimazole therapy and disappeared again after the cessation of methimazole. This binding activity to labelled T4 analogue was demonstrated to be in the immunoglobulin G with a kappa light chain isotype in both sera, and was displaced by unlabelled T4 in a dose-dependent manner. The binding of immunoglobulin G purified from these sera to labelled T4 or T4 analogue was found to be almost identical to that of the corresponding serum binding. Since the specific radioactivity of labelled T4 analogue used in the Amersham free T4 assay kit is about 10 times higher than that of the labelled T4 in the Amersham total T4 assay kit, serum free T4 determinations are much more vulnerable to thyroid hormone autoantibodies. Thus, in the presence of autoantibodies, a large discrepancy develops between free T4 and total T4 values.

Adult↗

[Basic studies on glass ceramics. 3. Influence on calcification of osteogenic cells in vitro].

Two established osteogenic cell lines (NY, MC 3 T3-E 1) were used in vitro to determine the biocompatibility of glass ceramics and their effect on initial calcification of osteogenic cells. Morphological study of the cell under the phase-contrast microscopy and histochemical staining were applied as follows. First, glass ceramic granules were placed in 60 mm dishes, and cells were suspended in the dishes in alpha-MEM supplemented with 10% FBS (basic medium) or medium with 50 micrograms/ml of L-ascorbic acid added. After 8 or 14 day of culturing, calcium formation was tested by von-Kossa's staining. Also, alkaline phosphatase staining was performed by the azo-dye method. As controls, cultures in dishes without glass ceramic granules were stained at the same time. The results obtained in the experimental culture were as follows. 1. Phase contrast microscopy showed that contacts with glass ceramics did not cause cellular death or degeneration. 2. In both cell cultures with the glass ceramics the von-Kossa reaction was positive as early as the 8th day. 3. The alkaline phosphatase reaction on the 8th day occurred only in MC 3 T3-E 1. The reaction was localized on fibroblastic cells which proliferated three-dimensionally around glass ceramics, and on small polyhedral cells situated relatively for apart from the ceramics. 4. On the 14th day, the MC 3 T 3-E 1 formed large nodules around the glass ceramics, and they were stained uniformly positive by von-Kossa's method. The alkaline phosphatase-positive cells extended spoke-like forms. 5. In medium with L-ascorbic acid, growth of NY was inhibited, After being cultured for 14 days, abundant von-Kossa positive reaction was found around glass ceramics in both cells. In MC 3 T 3-E1 on the 8th days, the alkaline phosphatase reaction was stronger with glass ceramics than with basic medium only. On the contrary, in the control cultures of both cells there was negative von-Kossa reaction during the culture period. The above results showed that glass ceramic granules have the biocompatibility needed for bone grafts, and they facilitated calcification of MC 3 T 3-E 1 in culture.

Alkaline Phosphatase↗

[Relationship between the anti-hemolysin activity and the structure of catechins and theaflavins].

We examined the corresponding isomers of catechins and theaflavins for anti-hemolysin activities against Staphylococcus aureus alpha-toxin and Vibrio cholerae O1 hemolysin. Catechins and theaflavins showed anti-hemolysin activities in a dose-dependent manner. Among the catechins tested, (-)catechin gallate, (-)epicatechin gallate and (-)epigallocatechin gallate having galloyl groups in their molecules showed more potent anti-hemolysin activities against both toxins. On the other hand, free catechins, i. e. (-)catechin, (-)gallocatechin, (-) epicatechin and (-)epigallocatechin had low anti-hemolysin activities against alpha-toxin. Although (-)catechin or (-)gallocatechin had no effect on cholera hemolysin, (-) epicatechin and (-)epigallocatechin were slightly inhibitory. Among dextrocatechins, (+) epicatechin and (+)epigallocatechin proved to be more effective than (+)catechin and (+) gallocatechin. The anti-hemolysin activities of theaflavins against alpha-toxin and cholera hemolysin were dependent on the number of the galloyl group in their structure. These results suggest that the tertiary structure of the catechin or theaflavin and the active site of hemolysin, that affects the interaction between them, plays an important role in the anti-hemolysin activity.

Biflavonoids↗

[Percutaneous dissolution of uric acid and cystine stones causing acute ureteral obstruction].

Four cases with ureteral obstruction due to uric acid or cystine stones were treated successfully by percutaneous irrigation with sodium bicarbonate or tromethamine-E. These cases underwent percutaneous nephrostomy for the reason of prolonged complete obstruction (case 1), sustained pyelonephritis (case 2) or decreased renal function (case 3 and 4). Two catheters were placed through the nephrostomy tract before irrigation, 6 Fr. ureteral catheter just above the ureteral stone and 10 Fr. pigtail or 12 Fr. Malecot catheter in the renal pelvis. The ureteral stones were markedly reduced in size and passed spontaneously after 6-11 days' duration of irrigation in three cases. In case 2, the remaining stone was removed transurethrally after 14 days' duration of irrigation, and was found to be composed of organic matrix. Percutaneous dissolution is considered to be a safe and reliable method and may be an alternative way of treating uric acid or cystine stone causing acute ureteral obstruction.

Acute Disease↗

[A phase I study of weekly administration of CPT-11 in lung cancer].

A clinical study of weekly administration of CPT-11, a semi-synthetic derivative of Camptothecin, was performed in patients with advanced lung cancer to determine the optimal dose for a weekly single dose schedule. Sixteen out of 19 patients enrolled were evaluable. The starting dose was 50 mg/m2 and gradually escalated to 100, 125 and 150 mg/m2. CPT-11 was given by intravenous infusion for 90 minutes every week. The maximum tolerated dose for this schedule was estimated to be 125 mg/m2. The dose-limiting toxicity was leukopenia with median nadir of 2,900/mm3, median day to nadir of 21, and median day to recovery of 7. Other major toxicity was gastrointestinal upset, but was mild and tolerable. Objective tumor responses were observed in four patients, three with non-small cell carcinoma and one with double cancer (small and non-small cell carcinoma). The responding patients were treated at a dosage of 100 mg/m2 or more. The recommended dose for a phase II study is considered to be 100 mg/m2 iv infusion for a weekly single-dose schedule.

Aged↗

[Clinical usefulness of scintigraphy with 99m technetium phosphates in rhabdomyolysis].

We performed bone scans with 99mTechnetium phosphates in 15 cases of clinically suspected rhabdomyolysis admitted to Chigasaki Tokushukai Hospital. Whole body scans were performed within 5 days from the onset of illness or admission. Accumulation of the radioactivity in the skeletal muscle was revealed in 13 of the 15 cases and the involved muscle groups were visualized vividly. Etiologies of rhabdomyolysis were diverse, ranging from malignant syndrome to sepsis. Myocardial concentration was absent in all of the cases. Renal concentration of the isotope was seen in cases where the degree of rhabdomyolysis was higher and renal impairment was present. We conclude that 99mTechnetium phosphate bone scan is useful in clinically suspected rhabdomyolysis as a diagnostic test and as a test to localize and quantitate the muscular involvement.

Adult↗

Existence of ADP- and KCl-insensitive phosphoenzyme intermediate of Na+,K(+)-ATPase at alkaline Ph.

The Na(+)-ATPase activity of Na+,K(+)-ATPase in the absence of K+ was least dependent on the sodium concentration when the pH was 9.5. Around 40% of the phosphoenzyme formed from ATP in the presence of 0.5 mM MgCl2 at alkaline pH was insensitive to both KCl and ADP. High-Na+ chase reversed this insensitivity, i.e., the phosphoenzyme became sensitive to KCl or ADP. On the other hand, phosphorylation at 0.1 mM MgCl2 instead of 0.5 mM showed at least 95% sensitivity to KCl. These observations suggest that ADP- and KCl-insensitive phosphoenzyme was formed when excess Mg++ was present during phosphorylation at alkaline pH. This phosphoenzyme might be an intermediate in the process of ATP hydrolysis.

Adenosine Diphosphate↗

[Clinical features of uveitis in childhood during the past 20 years].

One hundred and fifty five cases (237 eyes) of children with uveitis were clinically observed in the past 20 years. There was no fluctuation in the number of patients during the period. Concerning the age as the first visit, the smallest group was under 4 years of age and the numbers of patients increased at ages 14 and 15. Chief complaints usually corresponded to the age of the cases. Cases with anterior uveitis accounted for 25% of all cases, intermediate uveitis 12%, posterior uveitis 45% and panuveitis consisted of 17% of all cases, respectively. In the course of treatment, improvement of visual acuity was not statistically significant; the visual prognosis of cases affected under age 7 years was relatively poor. At the time of final observation, the visual acuity of cases, who had first visited during the past 10 years, were better than those who presented during the previous decade. Uveitis had healed or improved in 68% of cases treated in our clinic. As complications, band-shaped keratopathy was seen in 8% of the patients, cataract in 22% and glaucoma in 5%, respectively. Thirty two per cent of the cases received systemic steroid therapy and the average duration was 3.8 months. Fifty two operations were performed in 30 cases (19%), 37 eyes (16%); 16 were cataract operations and 24 were operations for glaucoma.

Adolescent↗

[Clinical evaluation of serum S100ao protein in patients with urogenital diseases and healthy volunteers].

We investigated the clinical significance of the serum S100ao protein in patients with urogenital diseases. The serum levels of S100ao protein were measured in 179 patients with urogenital diseases and 180 healthy volunteers. The mean value of S100ao protein in serum from healthy volunteers was 203 +/- 107 pg/ml (Mean +/- SD). Therefore, the cut-off level was set to 524 pg/ml (Mean +/- 3SD). The levels of S100ao protein in serum were significantly higher in men than in women (P less than 0.05). The levels of S100ao protein in serum were significantly high in the patients in their fifties and sixties compared with the other patients (P less than 0.01). When serum levels exceeding the cut-off level were considered to be positive, the percentages of positivity in each disease were as follows: renal cell carcinoma; 38.7%, bladder tumor; 9.1%, prostatic carcinoma; 12.5%, testicular tumor; 0%, benign prostatic hypertrophy; 7.4%, urolithiasis; 7.1% and chronic renal failure; 100%. The levels of S100ao protein in serum were significantly correlated with those of BUN, serum creatinine and endogenous creatinine clearance, respectively. S100ao protein in serum was increased immediately after operation and returned to the normal range within one to two weeks after operation. As described above, the level of S100ao protein in serum was affected by renal function, operative procedures and age. However, the positive rate of S100ao protein was so high in patients with renal cell carcinoma that serum S100ao protein might be a valuable tumor marker in those patients.

Adult↗

[Fournier's gangrene: a case report].

A 40-year-old male was admitted complaining of high grade fever, pain, redness and swelling of the right scrotum, right perineum and right flank region. He had no apparent history of previous infection or diabetes mellitus. At the time of admission, the scrotum was partly necrotic with repulsive feculent pus discharge and there was crepitus on palpation of involved areas. Culture of purulent discharge yielded the growth of anaerobic organisms. Surgical drainage was performed immediately and debridement of necrotic tissue in the involved areas was often repeated. At the same time, the patient received antibiotic therapy that included agents effective against anaerobic bacteria. However, the scrotal skin developed gangrene and the right testis hung suspended with cord exposed. This testis was intact. The scrotal skin defect was cured using a skin graft, after the infection had been brought under control.

Adult↗

Expression of active alpha-3 subunit of rat brain Na+,K+-ATPase from the messenger RNA injected into Xenopus oocytes.

Cloned cDNA encoding the so-far uncharacterized alpha-3 subunit of rat brain Na+,K+-ATPase (Hara et al. (1987) J. Biochem. 102, 43-58, Shull et al. (1986) Biochemistry 25, 8125-8132) was incorporated into a vector carrying the SP6 promoter. The mRNA produced in vitro was injected into Xenopus oocytes with the mRNA encoding the Na+,K+-ATPase beta subunit of Torpedo electroplax. Increased Na+,K+-ATPase activity in the oocyte membrane was observed. This newly expressed activity was inhibited by ouabain (Ki = 1.5 x 10(-7) M), suggesting that the alpha-3 subunit of rat brain Na+,K+-ATPase is a highly ouabain-sensitive catalytic subunit.

Animals↗

Directional immobilization of sodium- and potassium-activated ATPase to expose its cytoplasmic part to the liquid phase on microtiter plates by wheat germ agglutinin.

A convenient method for highly efficient and directional immobilization of intact sodium- and potassium-activated ATPase (Na,K-ATPase) using wheat germ agglutinin linked on microtiter plates was developed. Wheat germ agglutinin, which bound tightly to the beta-subunit of Na,K-ATPase and had no effect on the Na,K-ATPase activity, the potassium-activated p-nitrophenylphosphatase activity, or the inhibitory action of ouabain, was covalently linked to microtiter plates and used as an immobilizer of the enzyme. The amount of Na,K-ATPase coupled to microtiter plates in this immobilizing system was more than 10-fold greater than that used in the direct immobilizing system (O. Urayama, M. Nakao, H. Nagamune, and H. Sugiyama, (1984) Anal. Biochem. 141, 194-198). Also in this system, the cytoplasmic domain of Na,K-ATPase was exposed to the liquid phase. This technique was useful for investigating the reactivities of monoclonal antibody specific for the cytoplasmic domain of the enzyme. Moreover, because this technique was used successfully in the immobilization of periodic acid--Schiff positive staining glycoprotein 1 prepared from human erythrocytes and human alpha 2-macroglobulin, the technique should also be useful for other membrane or secreted proteins that possess N-linked sugar chains containing bisecting N-acetylglucosamine or a high amount of sialic acid.

Animals↗