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Biomedical subjects

Y Yamaguchi

Publications and source records attributed to Y Yamaguchi.

At least 865 records · Page 48Linked to original sources

Chemical model of reaction cascades induced by activated enzymes or catalysts. Two-step cascades in visual transduction.

A dissipative system is approximated by a nonlinear rate equation: Z congruent to K1Z - K2Z3 (K2 greater than 0), in which the right side is derived from -delta G/delta Z of Taylor's series of the thermodynamic potential given by Gibbs' function G(Tc, Pc) (Z) at about the critical point C(Tc, Pc) of the control variables (parameters) T and P. The stability or instability of the system is treated by the changes in the control parameters. In the case that T not equal to P not equal to 0 in the steady state, Z = 0, and T and P pass the point C, K1 becomes negative. By this change, the G function is convex at Z = 0 and each product is created rapidly with concentration or number of the molecules Z = ([K1]/K2)1/2. This dynamic theory is applied to enzyme cascades. Based on cyclic GMP (cGMP) hypothesis in visual transduction, the cascade hydrolysis of cGMP of vertebrates is analyzed by dividing it into two-step reaction cascades: The initial process is that metarhodopsin II catalyzes the exchange of GDP for GTP by transducin (Gtd) and that GTP-Gtd complex is hydrolyzed to GDP-Gtd complex. In the following cascade cGMP is hydrolyzed with amplification of phosphodiesterase (PDE) activated by the removal of the small inhibitory subunit. The quantity of the hydrolysis of cGMP is estimated as approximately 5 x 10(4-5) molecules per photolyzed rhodopsin semiempirically, and this coincides well with experiments.

3',5'-Cyclic-GMP Phosphodiesterases↗

Complete external ophthalmoplegia in a patient with congenital myopathy without specific features (minimal change myopathy).

An 11-month-old female infant with mild asphyxia at birth had severe generalized muscle hypotonia and weakness, predominantly in the neck flexors, a high-arched palate and a funnel chest from early infancy. Her facial muscles were also markedly involved. In addition, she showed striking non-progressive, complete external ophthalmoplegia and mild ptosis. A muscle biopsy specimen showed non-specific myopathic changes, including mild variation in fiber size, mild type 1 fiber predominance, type 2B fiber deficiency and slightly increased acid phosphatase activity. Complete ophthalmoplegia may thus be seen not only in myotubular myopathy but also in various forms of congenital non-progressive myopathy.

Abnormalities, Multiple↗

Parasympathetic nervous system in patients with Graves' disease determined by R-R interval variations on electrocardiogram.

Little is known about an interrelationship between thyroid dysfunction and parasympathetic nervous system. R-R interval variations on electrocardiogram (ECG) have been considered to be reliable indicator reflecting abnormalities of parasympathetic nervous system. We have attempted to apply this technique in patients with hyperthyroidism. Studies were conducted in 60 healthy subjects and 57 patients with Graves' disease. R-R interval variations were expressed as coefficient of variation on 100 heart rates at the time of resting (CVq) and deep respiration (CVd). A negative correlation between R-R interval variations (CVq, CVd) and ages was observed in healthy subjects. CVq was significantly lower in untreated Graves' disease than in antithyroid drug-treated Graves' disease and control subjects. A similar result also was obtained in CVd. Decreased CVq in untreated patients with Graves' disease was restored by administration of beta blockades, propranolol and metoprolol, but not by administration of alpha blockade, bunazosine. The present investigation suggests that there are hypofunctions in parasympathetic nervous system associated with beta (especially beta one) effects in patients with hyperthyroidism due to Graves' disease.

Adrenergic alpha-Antagonists↗

Establishment of human monoclonal antibody recognizing a new tumor-associated antigen from a patient with small cell lung carcinoma.

Mouse-human heterohybridoma (3H12) producing human antibody was established by fusing P3/X63-Ag-U1 (P3U1) myeloma cells with lymphocytes from a patient of small cell lung carcinoma (SCLC). This monoclonal antibody reacts to lung cancer cells, especially SCLC, but not to adenocarcinoma or squamous cell carcinoma cells. It does not show any reactivities to other tumors or normal cells so far examined. An immunoprecipitation experiment with this antibody revealed that the antigen on SCLC was a single chain moiety of 150 kilodaltons (Kd). Judging from the cell type reactivity and molecular size of the antigen, this monoclonal antibody appears to detect a new tumor-associated antigen on human SCLC.

Animals↗

Renal function in rats with angiotensin II-salt-induced hypertension: effect of thromboxane synthesis inhibition and receptor blockade.

This study was designed to assess the contribution of thromboxane (Tx) A2 to the pathogenesis of renal dysfunction in rats with angiotensin II (Ang II)-salt hypertension. Hypertension was induced in rats drinking 0.15 mol/l NaCl by infusion of Ang II (125 ng/min, intraperitoneally) for 12 days. Relative to values in water- and saline-drinking rats without Ang II infusion, rats with Ang II-salt hypertension exhibited increased renal vascular resistance, decreased renal blood flow, and increased renal excretion and glomerular synthesis of TxB2. Treatment with an inhibitor of TxA2 synthesis, UK 38,485, had no effect on renal function in normotensive and hypertensive rats. Similarly, the TxA2 and prostaglandin endoperoxide antagonist SQ 29,548 did not affect renal function in normotensive rats. In contrast, in rats with Ang II-salt hypertension of 12 days' duration, SQ 29,548 caused a reduction in renal vascular resistance, allowing for maintenance of renal blood flow in the face of an accompanying reduction in blood pressure. A comparable reduction in renal perfusion pressure, produced by constriction of the abdominal aorta above the renal arteries, was not accompanied by a reduction in renal vascular resistance in Ang II-salt hypertensive rats. Therefore, the SQ 29,548-induced lowering of renal vascular resistance is attributable not to renal blood flow autoregulation, but to blockade of the renal vasoconstrictor actions of TxA2 and/or prostaglandin endoperoxides. This interpretation implies that pressor eicosanoids contribute to increase renal vascular resistance in rats with severe Ang II-salt hypertension.

Angiotensin II↗

Significant prolongation of hamster liver transplant survival in Lewis rats by total-lymphoid irradiation, cyclosporine, and splenectomy.

The effects of total lymphoid irradiation, cyclosporine and splenectomy alone and in combination have been studied in liver transplants from the LVG hamster to the LEW rat. Neither CsA alone, splenectomy alone, nor TLI alone prolonged graft survival. CsA/splenectomy and TLI/CsA produced significant prolongation of graft survival. TLI/CsA/splenectomy prolonged graft survival by over sixfold compared with controls. While CsA alone was ineffective in reducing lymphocytotoxic antidonor antibody, splenectomy alone or CsA/splenectomy did significantly suppress production of antibody. Only very low levels of antibody could be detected in animals treated with TLI/CsA/splenectomy. TLI/CsA/splenectomy has an immunosuppressive effect sufficient to significantly prolong liver graft survival in the LVG hamster to LEW rat combination and may represent a promising treatment protocol in experimental cross-species transplantation.

Animals↗

Parasympathetic nervous system activity in hypothyroidism determined by R-R interval variations on electrocardiogram.

Little is known about the relationship between hypothyroidism and the parasympathetic nervous system. R-R interval variations revealed by electrocardiogram (ECG) are known to be a useful clinical indicator of abnormalities of parasympathetic nervous system activity. Studies were conducted in hypothyroid patients, and significant reductions in R-R interval variations were observed in patients with primary severe hypothyroidism due to Hashimoto's thyroiditis, and in patients with Graves' disease who became severely hypothyroid during antithyroid drug therapy. R-R interval variations were restored to normal levels in both groups of patients after treatment. The present investigation suggests that in marked hypothyroidism there are hypofunctional abnormalities in the parasympathetic nervous system in association with a reduction in the levels of serum T4 and T3.

Adult↗

Evaluation of selective liver denervation methods.

This study compares four methods of hepatic denervation and defines the rate and physiological significance of reinnervation. Five groups of rats were prepared: 10 underwent orthotopic liver transplantation. In nine rats a 90% aqueous phenol solution was applied circumferentially to the portal vein. Thirteen rats underwent microsurgical denervation; 28 received different doses of 6-hydroxydopamine (6-HODA) administered as a single intraportal injection [50 (n = 10), 75 (n = 6), and 100 mg/kg (n = 6)]. Twelve rats were studied as controls. Rats were killed 1, 4, and 8 wk after surgery to determine liver tissue content of norepinephrine (NE). Changes in mean arterial pressure (MAP) in response to hepatic nerve stimulation, which was supramaximum in intensity and frequency, were measured before rats were killed. NE content in controls ranged from 121 to 204 ng/g and MAP increased by 30-38 mmHg after electrical stimulation. At 1, 4, and 8 wk after treatment the liver NE content was less than 1, 2.3, and 20.2 ng/g in the transplant group; less than 1, 2.7, 4.1 ng/g in the phenol group; and 17.2, less than 1, and 3 ng/g in the surgically denervated group. In the 6-HODA group, values were 18.9, 47, and 61.5 ng/g (50 mg/kg); 5.7, 20.2, and 15 ng/g (75 mg/kg); and 7.7, 2.5, and 17.5 ng/g (100 mg/kg). When the level of NE was undetectable, MAP increase after stimulation was 0-18% that of controls. When NE content was 15-23% of normal, MAP increased 49-62% regardless of the denervation technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Drug-induced hypersensitivity nephritis: lymphocyte stimulation testing and renal biopsy in 10 cases.

The pathomorphological and clinical findings were investigated in 10 cases of drug-induced hypersensitivity nephritis. Hypersensitivity due to drugs was strongly suggested by the lymphocyte stimulation test in all patients. The offending drugs included penicillin, cephem derivatives, nonsteroidal anti-inflammatory drugs, and minocycline. All patients developed acute renal failure shortly after administration of regular doses of the drugs. Allergic symptoms plus a raised level of serum IgE or eosinophilia were seen in 7 patients. The remaining 3 patients receiving nonsteroidal anti-inflammatory drugs had no allergic symptoms, but developed severe proteinuria. Eight patients without severe glomerular damage recovered after withdrawal of the offending drugs and temporal dialysis and/or steroid therapy. Renal biopsies revealed tubulitis and tubular epithelial degeneration with interstitial edema as the common characteristic findings. Granulomatous lesions were occasionally observed. Multinucleated giant cells found in the granulomas were positive for LN-3 which is compatible with HLA-DR antigen. The glomeruli appeared normal, except in 2 cases in whom crescentic glomerulonephritis and thrombotic microangiopathy were seen. Our study suggests that the lymphocyte stimulation test and renal biopsy are the most useful means to confirm the diagnosis and provides further evidence for the participation of cell-mediated immunity in the pathogenesis of drug-induced hypersensitivity nephritis.

Acute Kidney Injury↗

Purification and characterization of a major glycoprotein in rat liver lysosomal membrane.

A major lysosomal membrane glycoprotein (LGP107) which has an apparent molecular weight (Mr) of 107 kilodaltons (kDa) was purified from rat liver by a simple method with a yield of 1 mg/87 g wet weight of liver. The purification procedures include; preparation of tritosomal membranes of triton-filled lysosomes (tritosomes), extraction of tritosomal membranes by Lubrol PX, wheat germ agglutinin (WGA)-Sepharose affinity chromatography, and monoclonal antibody-Sepharose affinity chromatography. The quantitative immunoblot analysis indicated that LGP107 represents 6.2% of the total protein of tritosomal membranes. The isoelectric point of the purified glycoprotein was 2.7, and it moved toward neutral pH after sialidase treatment, with its molecular weight decreased by about 10 kDa. LGP107 contained 52% carbohydrates, and the carbohydrate moiety was compared of Fuc, Man, Gal, GlcNAc and sialic acid in a molar ratio of 7.2:68.2:40.6:63.0:32.3, respectively, indicating that LGP107 was highly glycosylated with N-linked complex-type olgosaccharide chains. Out of the N-linked glycans released from the glycoprotein by hydrazinolysis/N-reacetylation, about 70% was sialylated. Anion exchange and reverse-phase high performance liquid chromatography analysis on the structure of N-glycans revealed that a disialyl biantennary form is a major component in the oligosaccharide chains of LGP107.

Animals↗

A survey of sudden death among school children in Osaka Prefecture.

For 2 years, from January 1985 to December 1986, we carried out a thorough investigation of sudden death or apparent sudden death in a population between 5 and 19 years of age in Osaka Prefecture. Sudden death (unexpected death caused by intrinsic factors within 24 h after the onset of symptoms) occurred in 62 boys and 30 girls, with an annual sudden death rate of 3.0 per 100,000 for boys and 1.5 per 100,000 for girls. Of these 92 deaths, 64 occurred among school children (elementary or high school students), and it was these that were subjected to further analyses. Of the school children deaths, 29.7% seemed to be apparent sudden cardiac death (based on circumstances immediately before death, although there was no definite evidence for sudden cardiac death), and 29.7% were sudden death clearly attributable to underlying heart diseases (hence, sudden cardiac death in the usual meaning of this term accounted for about 60% of the 64 sudden deaths). In addition, 17.2% of the 64 cases were sudden death from bronchial asthma. Analysis of seasonal variation in the incidence of sudden death showed that apparent sudden cardiac death frequently occurred in summer, while sudden death clearly attributable to underlying cardiac diseases often took place in winter, sudden death from bronchial asthma occurred chiefly in summer and fall. Of the total number of sudden deaths, death occurred during exercise in 29.7%, and during sleep in 18.8% of individuals. The percentage of sudden deaths occurring during school hours was as low as 23.4% (15/64). Analysis of the physical condition of the 64 sudden death cases immediately before death disclosed the presence of respiratory infection in 10.9%, fatigue in 21.9%, lack of sleep in 4.7% and other conditions in 4.7%. Thus, the percentage of sudden deaths which occurred under ordinary physical conditions was 57.8% (37/64), of which 14 deaths (21.9% of the total) were associated with exercise.

Adolescent↗

Atherosclerosis mouse model induced by a high-cholesterol diet supplemented with beta-aminopropionitrile: effects of various anti-atherosclerotic agents on the biochemical parameters.

A mouse model of atherosclerosis was produced by feeding a 1.5% cholesterol diet with 0.4% beta-aminopropionitrile (BAPN) fumarate, a chemical lathyrogen, for 10 weeks, and the pharmacological sensitivity and specificity of this model were evaluated biochemically with various hypolipidemic drugs and calcium antagonists. Histological findings on this model showed typical angiolathyrism with foam cells in the media of the thoracic aorta. Uniform and marked accumulation of cholesterol, notably esterified cholesterol, in the aorta was observed, although it was much less in mice receiving a high-cholesterol diet or BAPN alone. The reduction in elastin contents in the aorta was a characteristic feature of this model. Clofibrate, cetaben and elastase tended to prevent the increase of cholesterol contents in the aorta, together with their significant hypocholesterolemic effects. Nifedipine, diltiazem and verapamil showed a slight preventive effect on the cholesterol accumulation and on the reduction of elastin content in the aorta without a cholesterol lowering effect in the serum. MgCl2 was more effective than other calcium antagonists and even had a hypocholesterolemic effect. The results indicate that this mouse atherosclerosis model may be usable for primary drug evaluation.

4-Aminobenzoic Acid↗

Studies on the T3 suppression test with reference to the thyroidal 123I uptake in Graves' disease: comparison of 24-hour and 3-hour uptake.

Eighty-three patients with Graves' disease had been treated with methylmercaptoimidazole (MMI). They were prescribed a maintenance dose of antithyroid drug (MMI, 5 mg/day) at the time of a T3 suppression test. The 3-hour and 24-hour thyroidal 123I uptake after T3 administration (75 micrograms/day, 2 weeks) were measured (post T3 uptake). In 38 patients whose post T3 uptake was below 35% in post T3 24-hour uptake, treatment was stopped. The T3 suppression test was then repeated 1 and 3 months later. During a one-year follow up, 26 remained well, while 12 relapsed within 6 to 12 months. We have observed a good correlation between 3-hour uptake and 24-hour uptake of 123I after T3 administration (r = 0.847, p less than 0.001). In 38 patients who showed positive T3 suppression, most patients with MMI withdrawal produced a marked overshoot of post T3 3-hour and 24-hour uptake at one month. Retrospective analysis indicated that there was no significant difference in circulating thyroid hormone levels between remission and relapse groups. The present study provides evidence that 3-hour uptake values are able to be substituted for 24-hour uptake values during a T3 suppression test. In addition, overshoot of thyroidal uptake after antithyroid drug withdrawal was observed in 3-hour values, similar to 24-hour values.

Female↗

Changes in thyroid volume during antithyroid drug therapy for Graves' disease and its relationship to TSH receptor antibodies, TSH and thyroglobulin.

Changes in thyroid volume during antithyroid drug therapy for Graves' disease compared with circulating thyroid parameters were evaluated. One hundred and forty-four patients with Graves' disease were treated with methimazole. Thyroid volume was measured by ultrasonography (thyroid volume = pi abc/6, where a is length, b width, and c depth). Serum TSH, TSH-binding inhibitory immunoglobulins, thyroid-stimulating antibodies, thyroglobulin, antimicrosomal antibodies, and antithyroglobulin antibodies were also measured. In the whole group of patients, thyroid volume correlated significantly with thyroglobulin (p less than 0.01) and TSH-binding inhibitory immunoglobulins (p less than 0.01), but not with TSH, antimicrosomal antibodies, and antithyroglobulin antibodies. Furthermore, a positive correlation was found between thyroglobulin and TSH-binding inhibitory immunoglobulins (p less than 0.01). In 11 patients the mean thyroid volume decreased significantly after one year of therapy (p less than 0.01), associated with decreasing levels of serum TSH-binding inhibitory immunoglobulins. Ten patients experienced transient hypothyroidism with an overdose of methimazole, and the mean thyroid volume increased significantly (p less than 0.01) with increasing serum TSH levels. In conclusion, it is suggested that TSH receptor antibodies may have a thyroid growth-stimulating effect. In addition, circulating thyroglobulin levels reflect thyroid volume in Graves' disease.

Adolescent↗

[Effects of anti-androgens on sexual function. Double-blind comparative studies on allylestrenol and chlormadinone acetate Part I: Nocturnal penile tumescence monitoring].

Allylestrenol (ALE) and chlormadinone acetate (CMA) were administered to patients with prostatomegaly by the double-blind method, and the effects of these antiandrogens on their sexual function were objectively compared. Each agent was orally administered to 58 patients in a dosage of 50 mg/day for 12 consecutive weeks. For the objective evaluation of the sexual function, nocturnal penil tumescence (NPT) was measured using an erectometer. For the subjective evaluation the conventional interview method was employed. The levels of hormones relating to sexual function were also determined. A decrease in NPT was noted in both the ALE and CMA groups, but the degree of the decrease was significantly smaller in the ALE group than in the CMA group (p less than 0.001). The results of the interview, revealed a large between the two drug groups; in the CMA group, marked worsening for all items. In the determination of hormones, levels of luteinizing hormone, follicle stimulating hormone, testosterone and estradiol were decreased in both drug groups, while the prolactin level was increased in both groups. The changes in the testosterone, estradiol and prolactin levels in the CMA group were significantly dominant compared with those in the ALE group. In addition, drop-out cases due to a decrease in the sexual function numbered 7 (12.1%) in the CMA group, while there were no such drop-out cases in the ALE group; the difference in the drop-out rate was thus significant. In conclusion, ALE's effects on the sexual function were concluded to be smaller than those of CMA.

Aged↗

[Effects of anti-androgens on sexual function. Double-blind comparative studies on allylestrenol and chlormadinone acetate. Part II: Self-assessment questionnaire method].

Allylestrenol (ALE) and chlormadinone acetate (CMA) were administered to patients with prostatomegaly by the double-blind method, and a self-assessment questionnaire method developed by the authors was used to study the influence of these two antiandrogens on their sexual function. Each test drug was orally administered to 58 patients, in a daily dosage of 50 mg for 12 consecutive weeks. The questionnaires consisted of 6 categories each consisting of 5 questions, or 30 questions in total. The 6 categories were "sexual desire," "erectile capacity" and "ejaculation," which relate to the sexual function, and "living environment (including the frequency of sex)," "dysuria" and "dummy (personality)." Each question was graded into 0-10 points, and each patient was requested to circle the number which best described his status. The scores were compiled and statistically analyzed. Many patients were senile. Evaluable answers were obtained for 99 (85.3%) of the 116 patients. Factor analysis based on the preadministration scores confirmed the contents of the questionnaires to be appropriate for the objectives of the present study. Multiple regression analysis revealed a high correlation between the self-assessment scores and objective data (nocturnal penile tumescence values; NPT values) when dropout cases due to a decrease in the sexual function and non-replying cases were excluded. The self-assessment questionnaire method was concluded to be as useful an objective test method as the NPT measurement for examining the sexual function. Aggravation of the "frequency of urination during night" was conspicuous in the CMA group, and there was a significant difference (p less than 0.05) in this parameter between the two groups. Except for this parameter, dysuria was improved in both administration groups, and there was no significant difference in the efficacy of the two drugs. Both drugs tended to suppress overall sexual function, but the suppression was less severe in the ALE group. Especially the suppression was significantly (p less than 0.05) lower in the ALE group regarding the 3 parameters of "contact sexual arousal," "contact erection" and "morning erection", which are included in the category of "sexual desire" or "erectile capacity." Also, suppression of "frequency of sex" and "intensity of sexual desire" tended to be lower in the ALE group at a level of significance of p less than 0.1. Regarding questions in the category of "ejaculation," the incidence of non-replies was high in both groups, but its rate was higher in the CMA group.

Adult↗

[Mass screening of prostate in Shiribeshi area in Hokkaido--incidence and clinical symptoms of benign prostatic hypertrophy and prostatic carcinoma].

A prostate mass screening was performed in 6 towns in Shiribeshi area in Hokkaido Prefecture on 384 males who were over 50 years old. The screening included digital palpation, uroflowmetry, blood sampling for tumor markers, questionnaire for voiding disturbances and transrectal sonography. Prostatic carcinoma was found in 9 (2.3%) of 384 males. An incidence of benign prostatic hypertrophy was 15.6% in 384 males. Atypical hyperplasia was found in 4 among 35 biopsied cases. Incidence of voiding disturbance such as retardation, prolongation and nocturia significantly increased with age as well as prostate size.

Aged↗