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Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 649 records · Page 36Linked to original sources

Giant neutrophils derived from tetraploid leukemic clone in an acute myeloblastic leukemia: cytofluorometric study.

Near-tetraploid chromosomes were observed in a patient with acute myeloblastic leukemia with maturation (M2 in FAB classification). Large and morphologically bizarre leukemic cells and giant neutrophils in each maturation stage were observed in both peripheral blood and bone marrow. Cytogenetic studies revealed that the main stem line was 93; XXYY, +9, and DNA cytofluorometry showed that these large leukemic cells and giant neutrophils had 4C DNA content. These findings strongly suggested that these giant neutrophils were derived from leukemic clone with tetraploidy.

Aged↗

Physiological de novo thyroid hormone formation in primary culture of porcine thyroid follicles: adenosine 3',5'-monophosphate alone is sufficient for thyroid hormone formation.

We describe a method of culturing intact porcine thyroid follicles for physiological de novo thyroid hormone formation; the roles of cAMP and protein kinase-C in thyroid hormone formation were also studied. Thyroid follicles were obtained by digesting minced porcine thyroid tissue with 0.04% collagenase and cultured in Coon's Modified Ham's F-12 medium supplemented with 0.5% calf serum, 0.5 mU/ml TSH, other standard hormones, and 3 antibiotics (6H medium). On the fourth day of culture, 6000-8000 follicles/well were plated in 12-well culture dishes. On the sixth day, thyroid hormone formation was carried out by incubating thyroid follicles with 0.5 microM KI in the presence of 6H medium for 2 days in a 5% CO2-95% air incubator at 37 C. To examine the effects of cAMP and protein kinase-C on de novo thyroid hormone formation, follicles were incubated with KI in the presence of 1-2.5 mM (Bu)2cAMP, 10 microM forskolin, 2 microM prostaglandin E2 (PGE2), or 0.5-1 microM 12-O-tetradecanoylphorbol-13-acetate in TSH-free medium for 2 days. The amount of newly formed thyroid hormone was measured by RIA of T3 content in the Pronase digest of thyroid follicular cells. Thyroid follicles cultured in 6H medium had normal polarity of the membrane, determined by electron microscope, and thyroid cAMP was responsive to the alteration of TSH. In this culture system cAMP alone was sufficient to form thyroid hormone. 12-O-Tetradecanoylphorbol-13-acetate, a protein kinase-C stimulator, disrupted thyroid follicles and inhibited cAMP-mediated thyroid hormone formation. The integrity of follicular structure was also required for thyroid hormone formation in this culture system. This study introduces perhaps the most physiological culture system for de novo thyroid hormone formation. Our data provide direct evidence that thyroid hormone formation is linked to cAMP and that the protein kinase-C system acts as an inhibitor of thyroid hormone formation.

Animals↗

Potential neuroleptic agents, N-[(2-pyrrolidinyl)methyl]-2,3-dihydrobenzofuran-7-carboxamide derivatives.

A series of 2,3-dihydrobenzofuran-7-carboxamides, presenting a stabilized intramolecular hydrogen bond, was synthesized and evaluated in pharmacological models for antipsychotic activity. Among them, N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2, 3-dihydrobenzofuran-7-carboxamide (15) showed an atypical neuroleptic profile similar to that of sulpiride (1) and more lipophilic properties than 1. Compound 15 was 11 times more potent in antagonistic activity on apomorphine-induced hyperactivity in mice (ED50 = 30 mg/kg, p.o.) and stronger in potentiation of methamphetamine lethality in rats than 1, while it was as weak in inhibitory activity of apomorphine-induced stereotype in rats (ED50 greater than 500 mg/kg, p.o.) as 1. On the other hand, N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methyl-5-methylthio-2, 3-dihydrobenzofuran-7-carboxamide (30) showed a classical neuroleptic profile with a potency comparable to haloperidol in antagonistic activity on apomorphine-induced hyperactivity in mice (ED50 = 0.65 mg/kg, p.o.). The structure-activity relationships were also discussed.

Animals↗

Hydrogen peroxide inhibits iodide influx and enhances iodide efflux in cultured FRTL-5 rat thyroid cells.

This study describes the effects of hydrogen peroxide on the two iodide transport systems, I influx and I efflux, in the cultured FRTL-5 rat thyroid cells. I influx was measured by the amount of I taken up by the cells during incubation with Na125I and NaI for 7 min, and I efflux was measured by calculating the rate of 125I release from the 125I-loaded cells in the presence and absence of 5 mmol/l H2O2. Exposure to greater than 100 mumol/l H2O2 for 40 min caused a significant inhibition of I influx; the inhibition was reversible and non-competitive with iodide. Thyroid Na+K+ ATPase activity, a major mechanism to drive I influx, decreased by 40% after the cells were exposed to 5 mmol/l H2O2 for 10 min. H2O2 enhanced I efflux only when Ca2+ was present in the medium. The mechanism of an enhanced I efflux by H2O2 appears to be mediated through the elevation of free cytosolic Ca2+ concentration. Our data indicate that H2O2 can affect I transport by inhibiting I influx and enhancing I efflux.

Animals↗

[A clinico-pathological study of small renal cell carcinoma].

Between 1960 and 1989, 50 patients with small renal cell carcinoma measuring below 3 cm in diameter were examined. Among them, 31 patients were nephrectomized, but in 19 patients, the renal cell carcinoma was found first at autopsy. The average tumor diameter of the unrecognized ones was smaller than that of nephrectomized patients with the minimum of 0.4 cm. Forty-one patients had clear cell carcinoma, 9 granular cell carcinoma, 40 grade 1 tumor, and 10 grade 2 tumor. The grade 3 tumor was not found in our study. Three out of the 50 patients had distant metastasis at the time of operation or autopsy. Six patients had microscopic tumor thrombi just close to the tumor pseudo-capsule. Two patients had apparent tumor thrombi in the main renal vein. The smallest tumor that showed microscopic tumor thrombi measured 1.5 cm in diameter. The incidence of tumor thrombi was correlated with tumor diameter. The step sections by 4 mm thick of nephrectomized specimens were examined on 16 patients. The daughter tumor was found in two patients. The tumor thrombi had close relationships with the presence of distant metastasis (p less than 0.001) and/or the daughter tumor (p less than 0.01). In conclusion, small renal carcinoma measuring less than 1.5 cm in diameter was considered to be treated by conservative surgery.

Adult↗

Secretion of Aspergillus oryzae alkaline protease in an osmophilic yeast, Zygosaccharomyces rouxii.

To produce Aspergillus oryzae alkaline protease (Alp) in an osmophilic yeast Zygosaccharomyces rouxii, we constructed an expression plasmid consisting of the Z. rouxii glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter, the prepro-Alp cDNA of A. oryzae, the whole sequence of Z. rouxii plasmid pSR1, and the G418 resistant gene. The resulting plasmid, when introduced into Z. rouxii cells, directed the secretion of a large amount (about 300 mg/l) of Alp into the culture medium. The N-terminus and specific activity of the enzyme were identical to those of A. oryzae Alp.

Amino Acid Sequence↗

[A clinical study of complements as a marker of a hepatocellular carcinoma].

Serum complement C3, C4, and C3 proactivator (C3PA) have been evaluated for their diagnostic power in detecting a hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). It was found that serum complement levels were lower in LC patients than in HCC patients and that difference of the serum C4 and C3PA levels between LC patients and HCC patients were statistically significant. In addition, serum C3 PA levels were found to correlate significantly with the serum gamma-GTP levels in HCC patients. Thus, using the cutoff values of C4 and C3PA as the mean values for HCC patients, examination of serum complement levels enabled the detection of 38% of the HCC patients with low AFP levels. These findings suggest that the examination of the serum complements may be a useful a tool for the detection of HCCs in LC patients.

Biomarkers, Tumor↗

[Comparative pharmacokinetics of pipecuronium bromide, pancuronium bromide and vecuronium bromide in anesthetized man].

The pharmacokinetics of pipecuronium bromide was studied in 9 male patients (ASA class 1-2, 20-65 years of age). Following a single intravenous dose of pipecuronium 0.08 mg.kg-1, plasma levels were measured by capillary gas chromatography. Plasma concentration-time curves were evaluated by fitting the data to a bi-exponential equation. The pharmacokinetic parameters of pipecuronium were compared with those of pancuronium (0.08 mg.kg-1) and vecuronium (0.08 mg.kg-1) previously obtained under the same anesthesia (66% N2O, 33% O2 and 1% halothane). With pipecuronium, following pharmacokinetic parameters were obtained; distribution half-life; T1/2 alpha = 3.9 +/- 0.7 min (mean +/- SEM), elimination half-life; T1/2 beta = 102 +/- 12 min, volume of the central compartment; V1 = 95 +/- 13 ml.kg-1, volume of distribution at steady state; Vdss = 264 +/- 41 ml.kg-1, clearance; Cl = 1.8 +/- 0.2 ml.min-1.kg-1. Microconstants of two-compartment open models (k12, k21, k10) were also calculated. Using Mann-Whitney's U-test, these parameters of pipecuronium were compared with those of pancuronium (n = 3) and vecuronium (n = 4). V1 and Vdss of pipecuronium were significantly larger than those of pancuronium (V1; 38 +/- 12 ml.kg-1 and Vdss; 120 +/- 4 ml.kg-1) (both P less than 0.10). Reflecting the larger central volume of pipecuronium, pipecuronium tended to have a larger clearance than that of pancuroniumu (Cl; 1.1 +/- 0.2 ml.min-1.kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Clinical analysis of ascitic fluid in patients with liver cirrhosis and hepatocellular carcinoma].

To investigate the clinical significance of ascitic fluid in patients with a malignancy, an abdominal paracentesis to evaluate the ascitic fluid was performed in 10 patients with a hepatocellular carcinoma (HCC) and in 7 patients with liver cirrhosis (LC). The AFP levels in the ascitic fluid and in the serum of the HCC patients was found be significantly higher than that of the LC patients. In addition, the ratio of albumin/total protein in ascitic fluid was also higher in the HCC patients. However, no significant findings were uncovered with regard to the concentration of lipid in ascitic fluid, in either type of patient although 2 HCC patients were found to have a very high concentration of total cholesterol. The cytological findings provided no reliable marker because of significant number of false negatives in the HCC patients. Also, there was no significant difference between the fibronectin levels in the ascitic fluid of either type of patients. This finding differs from previous studies, and suggests that the fibronectin levels in the ascitic fluid may not be a useful marker in determining a malignancy.

Aged↗

[Anesthetic management of hypothyroid patients for coronary artery bypass grafting].

Six hypothyroid patients with ischemic heart disease underwent coronary artery bypass grafting (CABG). Three of them were in euthyroid state by preoperative thyroid supplementation. Although remaining three who had not received preoperative supplementation were in overt hypothyroid state at CABG, their intra- and postoperative courses were satisfactory without any complications. We, therefore, found no benefit from preoperative thyroid supplementation. Serum TSH levels in hypothyroid patients were suppressed for more than three days postoperatively despite concomitant low FT3 and FT4 concentrations. The inhibition of TSH secretion could have been produced by therapeutic dose of dopamine which had been infused from intraoperative through postoperative period. Postoperative thyroid replacement should be initiated as soon as possible in hypothyroid patients to counteract the low FT4 concentration that could be prolonged and aggravated by the infusion of dopamine.

Aged↗

[Diclonal gammopathy (IgG kappa, IgA lambda) with nephrotic syndrome terminating into IgA lambda myeloma after three years--report of a case].

A 43-year-old man was admitted to our hospital because of legs edema and periorbital edema in Dec. 1983. Laboratory findings showed massive proteinuria (3.7 g/day), Bence Jones protein (BJP) in urine, and hypoproteinemia. Peripheral blood examinations were normal and a bone marrow aspiration showed hypocellularity with slight increase of monocytes and plasma cells. Serum immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda). Serum IgG was 1,690 mg/dl, IgA 379 mg/dl and IgM 160 mg/dl. No remarkable findings were obtained in bone survey, Ga-scintigraphy and rectal biopsy, and a diagnosis of diclonal gammopathy with nephrotic syndrome was made. In Aug. 1986, serum IgA started to increase rapidly with concomitant decrease IgG. He died of pneumonia due to pancytopenia in Dec. 1986, when serum IgG was 450 mg/dl, IgA 1,014 mg/dl, and IgM less than 39 mg/dl. Immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda) in serum and BEP (kappa, lambda), IgG (kappa) and IgA (lambda) in urine. An autopsy showed massive infiltration of myeloma cells which were positive for lambda light chain in bone marrow, suggesting a development of myeloma from a diclonal gammopathy in about 3 years.

Adult↗

[The effects of renin, angiotensin II, antidiuretic hormone (ADH) and alpha-atrial natriuretic peptide (alpha-ANP) on renal dysfunction induced by IPPV with PEEP].

We investigated the effects of hormonal changes on decreased urine output induced by IPPV with PEEP in 8 dogs anesthetized with nitrous oxide-oxygen-pentobarbital. The decreased urine output could be attributed to the hemodynamic changes as previously reported. The results of this investigation suggest that renin, angiotensin II and ADH do not have significant influences on the decreased urine output. However, the decrease in alpha-ANP which might have been caused by the compression of the atria and the decrease of venous return induced by IPPV with PEEP, may be the cause of the decrease in urine output.

Angiotensin II↗

[A clinical study of serum erythropoietin concentrations in patients with liver cirrhosis and hepatocellular carcinomas].

We have measured the serum erythropoietin concentrations in 14 patients with liver cirrhosis and in 14 patients with a hepatocellular carcinoma. Among these patients, 2 with liver cirrhosis (14.3%) and 7 with a hepatocellular carcinoma (50.0%) were found to have raised serum erythropoietin concentrations, ranging up to 40 mU/ml. Negative correlations were found between erythropoietin and the RBC, and the Hb and Ht in the cases with liver cirrhosis. In contrast, a positive correlation which was not significant was found only between the erythropoietin and the RBC in cases involving a hepatocellular carcinoma. This has suggested that the relationship between the erythropoietin and the RBC in cases of a hepatocellular carcinoma differs from the relationship seen under the usual physiological circumstances of those with liver cirrhosis.

Aged↗

[The effects of dopamine and/or dibutyryl cyclic AMP on renal dysfunction induced by IPPV with PEEP in dogs].

We investigated the effects of dopamine (Dop) and/or dibutyryl cyclic AMP (DBcAMP) on renal dysfunction induced by IPPV with PEEP in 32 anesthetized dogs. Blood pressure, pulse rate, creatinine clearance and free water clearance were not significantly altered during the experiment. On the other hand, cardiac index (CI), renal blood flow (RBF), urine output and fractional sodium excretion (FENa) were all decreased significantly by PEEP. Dop and/or DBcAMP improved urine output and FENa irrespective of decreased CI and RBF by PEEP. The increase of urine output could be attributed to the decrease of the water reabsorption in the proximal renal tubule by the drugs. The simultaneous infusion of Dop and DBcAMP was more effective for renal dysfunction caused by PEEP than individual administration of each drug.

Animals↗

[Large granular lymphocyte leukemia containing oligoclonal EB viral DNA].

A 32-year-old female was admitted to our hospital because of abdominal fullness, jaundice and pretibial edema in November, 1987. Leukocyte count of peripheral blood showed 13300/microliters with 84% leukemic cells and bone marrow was normocellular with 63.6% leukemic cells. Leukemic cells had azurophilic large granules with basophilic cytoplasm and positive for CD 2, OKIa 1, NKH-1 and negative for CD 3, CD 4, CD 8, CD 16. T cell receptor (TCR) genes for beta, gamma and delta chain and immunoglobulin heavy chain gene were in germ line configuration. These cells also had natural killer (NK) activity and antibody dependent cell mediated cytotoxicity (ADCC) activity. These observations suggested that they were derived from NK cell lineage. It is often difficult to demonstrate their clonalities in lymphoproliferative disorder of granular lymphocytes (LDGL). In the present case, the analysis of EBV genome using termini probe demonstrated polyclonal bands, while we found constant chromosome abnormalities; 47 XX, +3. From these observations, this case was considered to have several clones, and one of which could be detected by chromosome analysis. The analysis of EBV genome using termini probe may be useful to demonstrate their clonalities in LDGL in addition to conventional chromosome analysis.

Adult↗

Intrarenal reflux and nephropathy.

Using anti-Tamm-Horsfall protein (THP) immunohistochemical study was performed to analyse the relationship between intrarenal reflux and induced nephropathy in surgically resected kidney tissues including hydronephrosis, renal calculi and trauma. With the increase of the histological grade of hydronephrosis intrarenal reflux was observed in two ways. Extra-tubular efflux of THP was seen to correlate with mononuclear and lymphocytic interstitial inflammation with the initiation by cellular immune response. The reflux of THP was also observed in the Bowman's space, but this did not seem to result in glomerular lesions including adhesion and/or sclerosis.

Antibodies, Monoclonal↗

[Clinical evaluation of the combination of carumonam and fosfomycin in the treatment of complicated urinary tract infection].

Carumonam (CRMN), the first monobactam antibiotic in Japan, has excellent activity against gram-negative bacteria and is useful in the treatment of urinary tract infections. However, it may be insufficient in the treatment of complicated urinary tract infections because of the increase in isolation of gram-positive bacteria, and it may be necessary to co-administer antibiotics active against gram-positive organisms to achieve a broader spectrum of coverage in connection with severe infections. The combination of CRMN and fosfomycin (FOM) was evaluated for its effectiveness and safety at the Department of Urology, Yamagata University Hospital and 7 affiliated hospitals. Clinical efficacy was assessed on 64 patients with complicated urinary tract infection according to the Criteria for Clinical Evaluation of Antimicrobial Agents in UTI (3rd. ed.) recommended by the Japan UTI Committee. Clinical efficacy was evaluated as excellent in 16, moderate in 32, poor in 16, with an overall clinical effectiveness rate of 75.0%, which is superior compared with CRMN alone. Of the total of 92 bacterial strains isolated, 66 (71.7%) were eradicated. Subjective adverse reaction was seen in 1 patient (1.4%), as nausea and anorexia. Slight increases in serum GOT and GPT ware recorded in 5 patients (7.1%). These findings disappeared after the termination of administration without treatment. The combination of CRMN and FOM might therefore be useful in the treatment of complicated urinary tract infections.

Adult↗