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Biomedical subjects

M Kihara

Publications and source records attributed to M Kihara.

At least 163 records · Page 9Linked to original sources
PubMed1995

Central diabetes insipidus caused by pituitary metastasis of lung cancer.

Tumor metastasis to the hypophyseal system has rarely been reported with either clinical or radiographic evidence. A 52-year-old woman presented with polydipsia, polyuria, and loss of appetite. She was diagnosed as having diabetes insipidus caused by pituitary micrometatasis of lung adenocarcinoma. After she had been treated with radiation therapy to the pituitary gland, the gland size was reduced as confirmed by magnetic resonance imaging, and her urine volume decreased. However, meningitis carcinomatosa appeared later. This was a rare case of secondary diabetes insipidus due to pituitary metastasis of lung cancer.

Adenocarcinoma↗
PubMed1995

Synthesis and biological evaluation of 3,4-diphenyl-1,2-dihydroisoquinolines as a new tamoxifen analogue.

3,4-Diphenyl-1,2-dihydroisoquinoline derivatives (1) as a new tamoxifen analogue were synthesized with trifluoromethanesulfonic acid from 3,4-diphenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (2), which were prepared by intramolecular Barbier reaction of N-(2-iodobenzyl)phenacylamines. Anti-proliferative activities of 1 and 2, and 3,4-diphenyl-1,2,3,4-tetrahydroisoquinolines (3) prepared by NaBH4 reduction of 1 against human mammary carcinoma MCF-7 cell line and human nasopharyngeal carcinoma KB cell line were evaluated. 1,2-Dihydroisoquinoline (1a) was the most active against MCF-7 cells in the compounds tested and the activity [IC50(micrograms/mL) 0.94] was nearly equipotent to that of tamoxifen. The structure-activity relationships of the compounds 1,2 and 3 were discussed.

Antineoplastic Agents↗
PubMed1995

[Analysis of cause of recent rise in number of foreigners reported to HIV/AIDS surveillance in Japan].

HIV/AIDS surveillance in Japan experienced a sharp and transient rise in 1991-92 in the number of foreign HIV positives but not of AIDS cases, for reasons of which remain unclear. Using the national HIV/AIDS surveillance data base the cause of the increase was studied by comparing the trends of foreign cases diagnosed in 1991-92 with those in 1985-90 in terms of gender, age, nationality, clinical stage, possible route of infection, possible place where the case contracted HIV and the place where the case was identified. Present analysis revealed: (1) In 1991-92 there was a large increase in the number of heterosexually-infected female HIV positive aged below 30 years reported from the areas surrounding Tokyo, of which the majority was of Asia origin. (2) A similar but moderate change was also seen in foreign males infected heterosexually but not in those infected homosexually. These were predominantly of U.S./Europe origin, aged > or = 30 and reported from Tokyo. (3) Although most of the foreign cases reportedly contracted HIV outside of Japan, those infected in Japan began being reported in 1991-1992. These results suggest that change in foreign cases seen in 1991-1992 was not only in number but also in gender, age, nationality, route of infection and geographical distribution. This should be taken into consideration in considering the HIV/AIDS prevention strategy in Japan.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Antihypertensive effects of 2-octynyladenosine (YT-146), a selective adenosine A2 receptor agonist, in Dahl salt-sensitive rats.

The antihypertensive effects of a novel adenosine A2 receptor agonist, 2-octynyl adenosine (YT-146), were evaluated in Dahl salt-sensitive rats. After rats were fed a high-salt (8% NaCl) diet for 2 or 3 weeks, they received oral YT-146 (0.1 or 1.0 mg/kg) or vehicle as a single dose (acute study) or once daily for 10 days (chronic study). In the acute study, tail-cuff blood pressure (BP) and pulse rate (PR) were measured before and 3, 6, and 24 h after administration, and blood samples were collected 3 h after administration. In the chronic study, BP and PR were measured 3 and 24 h after administration and urine was collected for 24 h on day 9. Blood samples were also collected 3 h after administration on day 10. BP was significantly lowered by 1.0 mg/kg of YT-146 in either the acute study (from 184 +/- 3 to 152 +/- 5 mm Hg, P < .01) or the chronic study (from 226 +/- 4 to 201 +/- 2 mm Hg, P < .01), while an increase in PR was not observed (acute study: from 382 +/- 8 to 366 +/- 3 beats/min; chronic study: from 420 +/- 8 to 411 +/- 8 beats/min). YT-146 had no effect on plasma renin activity (PRA), plasma aldosterone, vasopressin (ADH), and atrial natriuretic peptide (ANP) in the acute study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1994

Lung cancer risk of GSTM1 null genotype is dependent on the extent of tobacco smoke exposure.

Recently, homozygous gene deletion of GSTM1, one of the Mu class glutathione S-transferase isozymes, was found to occur in approximately half of the population of various ethnic origins and has been implicated in tobacco-related carcinogenesis. In the present study we evaluated the risk of GSTM1 null genotype for lung cancer in relation to the extent of tobacco smoke exposure in 178 lung cancer patients (157 males, 21 females) and 201 healthy controls (140 males, 61 females), who were all Japanese and current smokers aged < or = 69 at the time of diagnosis. GSTM1 genotype was determined by polymerase chain reaction. We found GSTM1 gene to be lacking in 45.3% of the control population and demonstrated that the null genotype was aggregated a lot more in the squamous and small cell carcinoma groups (63-64%) than the control group but slightly more in the adenocarcinoma group (54.3%). Furthermore, when male patients and controls were analysed in relation to the degrees (< 800, 800-1200 and > or = 1200) of smoking index (sigma (cigarettes smoked per day) x (years of smoking)], the proportion of GSTM1 null genotype was found to increase progressively in the squamous and small cell carcinoma groups from 42-50% (odds ratio 0.8-1.3) in the patients with smoking index < 800 to 72-75% (odds ratio 3.1-3.7) in the patients with smoking index > or = 1200, while it was unrelated in the adenocarcinoma (50-55%, odds ratio 1.2-1.5) and in the control groups (42-48%). These results support the hypothesis that the GSTM1 null genotype is one of the genetic traits for smoking-related lung cancers, the risk of which, however, appears to be dependent on the extent of tobacco smoke exposure.

Aged↗
PubMed1994

Hypoxic effect of exogenous insulin on normal and diabetic peripheral nerve.

Insulin administration can cause or worsen experimental and human diabetic neuropathy ("insulin neuritis"). In this study, we tested the hypothesis that insulin administration impairs tissue oxygenation. We infused insulin under nonhypoglycemic conditions and evaluated its effect on endoneurial oxygen tension, nerve blood flow, and the oxyhemoglobin dissociation curve of peripheral nerve in normal and diabetic rats. Intravenous insulin infusion resulted in a dose-dependent reduction in endoneurial oxygen tension in normal nerves (from 26% at 0.04 U/kg insulin to 55% at 32 U/kg). The nerves of rats with streptozotocin-induced diabetes were resistant, but with control of hyperglycemia this susceptibility to the endoneurial hypoxic effect of insulin returned. The reduction in endoneurial oxygen tension regressed with glycosylated hemoglobin (Y = 53.8-2.7X, where Y = %reduction in endoneurial oxygen tension and X = HbA1; r = 0.87; P = < 0.001). Diabetes or insulin administration resulted in only minimal and physiologically insignificant alterations in the oxygen dissociation curve and 2,3-diphosphoglycerate of sciatic nerve. Instead, insulin administration resulted in a reduction in nerve nutritive blood flow and an increase in arteriovenous shunt flow. When the latter was eliminated by the closure of arteriovenous shunts (infusion of 5-hydroxytryptamine), endoneurial oxygen reverted to normal. These findings indicate a deleterious vasoactive effect of insulin and may explain the development of insulin neuritis.

2,3-Diphosphoglycerate↗
PubMed1994

Slow hemodialysis performed during the day in managing renal failure in critically ill patients.

Slow hemodialysis (HD) was performed for 10 h during the day in 11 critically ill patients with renal failure. The dialysis method was a modification of the pump-driven continuous venovenous HD. A nonsterile bicarbonate-containing hemodialysate was passed into the EVAL membrane dialyzer at a flow rate of 30 ml/min. No patient developed further hemodynamic instability during the treatment. The serum urea level was maintained below 20 mmol/l within 4 days of initiating the treatment. It allowed the patients to rest without interruption at night. This method was safely conducted by general nursing staff under the supervision of nephrologists on duty during the day. This schedule offers an approach to renal replacement therapy for hemodynamically unstable patients without any potential problem in the extracorporeal circulation at night.

Acute Kidney Injury↗
PubMed1994

New norepinephrine potentiators: synthesis and structure-activity relationships of a series of 4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols.

A variety of 1,2,3,4-tetrahydroisoquinolin-4-ols (1-6) were prepared as part of our search for new norepinephrine (NE) potentiators and to clarify the structure-activity relationships. These compounds and some previously prepared compounds were compared with 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ol (PI-OH) (1a) for ability to potentiate NE. The potency, for 2-substitution, was found to be in the order: Me > Et > iso-Pr > H. The compounds substituted by a halogen atom at the para position in the 4-phenyl group of PI-OH showed greater activities than did PI-OH, and the observed order of potency for the substitution was Cl > Br > F > H. The compound (4) methylated at the hydroxy group in PI-OH had greatly diminished activity. Although the desoxy compound (6) of PI-OH potentiated the response to NE at low concentrations, the potentiation was progressively masked by an inhibitory activity as the concentration of 6 was increased. In addition, the 4-cyclohexyl analogue (5) failed to potentiate NE. These results show the importance of the beta-phenylethanolamine skeleton of PI-OH for producing NE potentiation without accompanying inhibitory action. The racemic 4-chlorophenyl analogue (2a) was resolved by HPLC to (R)-(+)-2a and (S)-(-)-2a. The NE-potentiating activity was found to reside exclusively in (R)-(+)-2a, which had the highest activity among compounds tested in this study; the activity ratio was 25 at 3 x 10(-6) M. The antidepressant activity of racemic 2a was evaluated by a forced swimming test.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Synthesis and pharmacological evaluation of phenolic 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols as a new norepinephrine potentiator.

2-Methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline-4-ol(PI-OH) (2a) and its derivatives form a new class of compounds possessing norepinephrine (NE) potentiating activity. As a new series of compounds, the isomeric 4-(4-hydroxyphenyl)- and 4-(3-hydroxyphenyl)-2-methyl-1,2,3,4- tetrahydroisoquinolin-4-ols (3a and 3b), and 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinolin-4-ol (3c) were prepared and their NE potentiating activities were evaluated. The 4-(4-hydroxyphenyl) analogue (3a) had only moderate activity and the 4-(3-hydroxyphenyl) analogue (3b) possessed a slightly higher activity than PI-OH. The 4-(3,4-dihydroxyphenyl) analogue (3c) was the most active compound and the pD2 value was 7.71 +/- 0.06 (activity ratio; 26.9 fold) at a concentration of 3 x 10(-6) M. These results indicate the importance of dihydroxyphenylethanolamine moiety of 3c for the inhibition of NE uptake.

Animals↗
PubMed1994

Pharmacokinetic profiles of intravenous imipenem/cilastatin during slow hemodialysis in critically ill patients.

The pharmacokinetics of imipenem/cilastatin were determined in 7 critically ill patients undergoing slow hemodialysis (HD). All patients were anuric. Following intravenous administration of 500 mg of imipenem/cilastatin, concentrations of the drugs in the serum and dialysate were monitored during slow HD. The elimination phase half-life of imipenem was 3.1 +/- 0.3 h and that of cilastatin was 9.7 +/- 1.2 h. The total body clearance of imipenem and cilastatin was 84.0 +/- 7.2 and 32.2 +/- 2.4 ml/min, respectively. Clearance of imipenem and cilastatin during slow HD was 24.3 +/- 2.4 and 54.3 +/- 3.1%, respectively, of total body clearance. After the 10.5-h session of slow HD, serum concentrations of imipenem and cilastatin were 2.3 +/- 0.4 and 16.0 +/- 1.2 mg/l, respectively. It appears that at least 500 mg of imipenem may be needed as a supplemental dose after a session of slow HD or the application interval should be shortened to maintain a therapeutic concentration.

Aged↗
PubMed1994

[Maintenance hemodialysis in IgD- lambda -type multiple myeloma associated with severe renal failure].

A 52-year-old man was admitted to our hospital because of oliguric renal failure. The patient was well until four weeks earlier, when he developed nausea and anorexia. The urea nitrogen was 179 mg/dl, creatinine 29.2 mg/dl, uric acid 19.0 mg/dl and potassium 8.6 mEq/1. Hemodialysis was started immediately after admission. Bone marrow aspiration showed atypical plasma cell infiltration consistent with multiple myeloma. The immunoelectrophoresis revealed urinary lambda -type Bence Jones protein and serum IgD- lambda -type M protein. The findings of renal biopsy study were consistent with myeloma kidney. On the fourth hospital day, administration of prednisolone 40 mg and melphalan 2 mg was started. The patient also underwent double filtration plasma-pheresis (DFPP). Serum IgD level was decreased from 950 to 113 mg/dl. After a course of chemotherapy, however, he developed severe leukopenia and was complicated with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This complication was successfully treated with imipenem/cilastation and vancomycin combined with granulocyte colony stimulating factor (G-CSF). The patient was discharged and returned to work on maintenance hemodialysis. Fifteen months after the presentation, he manifested progressive peripheral nerve disturbances. Three months later, the patient died--not from renal failure, but from ventricular arrhythmia. The application of maintenance dialysis therapy to myelomatosis has until now been questioned. The present case, however, suggests that aggressive treatment consisting of chronic dialysis therapy as well as chemotherapy and plasma exchange should be administered even in patients with established renal failure.

Humans↗
PubMed1993

Increased risk of lung cancer in Japanese smokers with class mu glutathione S-transferase gene deficiency.

Japanese lung cancer patients (n = 121) and community controls (n = 201), both with current smoking history and aged < or = 69, were compared for the rates of class mu glutathione S-transferase (GSTmu) negative genotype detected by polymerase chain reaction. The prevalence of the GSTmu negative genotype was 45.3% in the community control group and 68.4%, 69.2%, 54.3% and 72.7% in the squamous cell carcinoma, small cell carcinoma, adenocarcinoma and other primary lung cancer groups, respectively. Odds ratios adjusted for age, sex composition and smoking index by multiple logistic regression analysis were 2.71 (1.23-5.99), 2.72 (1.11-6.66), 1.33 (0.68-2.60), and 3.27 (0.83-12.81), respectively. These results suggest that smokers with a GSTmu negative genotype are at higher risk for bronchial carcinoma than smokers with positive genotype.

Adult↗
PubMed1993

Comparison of directly stimulated with axon-reflex-mediated sudomotor responses in human subjects and in patients with diabetes.

The muscarinic receptors of human eccrine sweat gland may be directly stimulated by iontophoresis of acetylcholine (direct response; DIR) and indirectly via nicotinic receptors and an axon "reflex" (AXR). Using a specially designed multicompartmental sweat cell and dual sudorometers, we were able to simultaneously record the evoked DIR and AXR responses. On a second day, we repeated the experiment under identical ambient and stimulus conditions but instead obtained silastic imprints of DIR and AXR for morphometry. Studies were done on 24 controls (mean +/- SD = 47.6 +/- 15.1 years) and 23 diabetic subjects (mean +/- SD = 49.6 +/- 16.3 years). In control subjects, sudorometric DIR recordings were consistently larger than AXR. There was no difference in sweat droplet density by sex, but the size of droplets was larger in males. In diabetic patients 3 of 23 had absent AXR but preserved DIR, suggesting that failure of AXR preceded DIR in patients with neuropathy. Patients with mild neuropathy had an overrepresentation of large diameter droplets in the silastic imprints of both DIR and AXR, while patients with severe neuropathy had a markedly reduced density and small diameter droplets.

Acetylcholine↗
PubMed1993

The influence of dose of microspheres on nerve blood flow, electrophysiology, and fiber degeneration of rat peripheral nerve.

Microsphere embolization of peripheral nerve results in a variable degree of ischemic fiber degeneration. To enhance the utility of the model, we evaluated the relationship between dose of microspheres to the supplying arteries of the sciatic-tibial nerve to nerve blood flow (NBF), electrophysiology, morphology, and behavioral changes. There was considerable variability in the effect of embolization on nerve pathology in individual nerves. However, the dose of microspheres regressed with the degree of hindlimb paresis, reduction in NBF, degree of fiber pathology, and ischemic conduction failure of the tibial nerve, evaluated at day 7. All nerves with severe (grade 4) fiber degeneration had flows of < 3 mL x 100 g-1 x min-1. We conclude that it is possible to predict with a high degree of accuracy the severity of fiber degeneration by the degree of NBF reduction and by the electrophysiologic abnormalities.

Action Potentials↗