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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 631 records · Page 35Linked to original sources
PubMed1988

Heart with circulatory failure secretes and processes atrial natriuretic peptide in a manner different from normal heart.

The role of catecholamine in atrial natriuretic peptide (ANP) secretion and its secretory mechanism in normal humans is not well defined; therefore, we studied the relationship among ANP, catecholamine, and atrial pressures in 25 patients without cardiovascular disease and in 35 patients with chronic congestive heart failure (CHF, 20 in mitral valve disease and 15 in dilated cardiomyopathy). In patients without cardiovascular disease, right atrial pressure at rest showed a positive correlation (r = 0.80, p less than 0.001) with ANP concentration, whereas left atrial pressure did not. The relation narrowed (r = 0.82) when the bicycle ergometer exercise in the supine position was conducted. Neither adrenalin nor noradrenalin significantly correlated with ANP concentration. In patients with mitral valve disease and dilated cardiomyopathy, the significant relations (r = 0.56 p less than 0.001, r = 0.85 p less than 0.001, respectively) between left atrial pressures and ANP concentrations at rest were observed, and following exercise, induced more significant relations. Right atrial pressures did not correlate positively with ANP concentrations. The increments of ANP concentrations induced by exercise load were markedly reduced compared with those of patients without cardiovascular disease. Although concentrations of both noradrenalin and adrenalin in patients with mitral valve disease and dilated cardiomyopathy at rest were much higher than those without cardiovascular disease, only noradrenalin had a highly positive correlation with ANP concentrations (r = 0.88 p less than 0.001, r = 0.78 p less than 0.001, respectively). Furthermore, the circulating ANP molecular weight forms in all patients studied were analyzed by gel chromatography coupled with radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Computed radiographic evaluation of simulated pulmonary nodules. Preliminary results.

We evaluated the capabilities of a computed radiography system (CRS) and a standard radiography system (SRS) in the detection of simulated solitary pulmonary lung nodules of various sizes and contrast. A phantom simulated the pulmonary anatomy, and specially shaped plexiglass disks were externally mounted to simulate solitary pulmonary nodules of different diameters and thicknesses. ROC curves were generated based on the performance of each of the radiologists observing each film set. In this preliminary study, the overall performance for both the CRS and the SRS were comparable in detecting simulated pulmonary nodules.

Humans↗
PubMed1988

The use of a perfluorochemical emulsion as a vascular perfusate in drug absorption.

In-vitro simultaneous luminal and vascular perfusion using the perfluorochemical emulsion, FC-43 emulsion, as a vascular perfusate, was examined for drug absorption in rat jejunum. The intestinal membrane in this system was found to retain its normal barrier functions for drug transport, as evident from the following: (i) stable absorption clearance of tritiated water and salicylic acid at steady-state, (ii) agreement of this clearance with that by in-situ single-pass luminal perfusion, (iii) active transport of D-glucose and its inhibition by phloridzin and (iv) normal glutamate pyruvate transaminase activity in the intestinal mucosa. FC-43 emulsion gave a more normal absorption site blood flow than the usual vascular perfusate containing erythrocytes and albumin in Krebs-Henseleit bicarbonate buffer solution. Consequently, this emulsion was useful for examining the contribution of blood flow resistance toward drug absorption. The rate-limiting steps of absorption of tritiated water, antipyrine and salicylic acid were examined by perfusion using FC-43 emulsion. The absorption of tritiated water was almost completely blood flow-limited and its absorption clearance may possibly be an approximated absorption site blood flow. The contribution of blood flow resistance to total resistance for antipyrine absorption exceeded that for salicylic acid absorption.

Animals↗
PubMed1988

Presynaptic and postsynaptic alpha 2-adrenergic receptors in human cerebral arteries and their alteration after subarachnoid hemorrhage.

The nature of alpha-adrenergic receptors in human cerebral arteries was characterized, and alteration of these receptors after subarachnoid hemorrhage was examined using a radioligand binding assay. Norepinephrine content of control arteries was also analyzed and compared with that of arteries after subarachnoid hemorrhage. Norepinephrine content in human cerebral arteries in cases of subarachnoid hemorrhage was about 5% of the control group. Specific binding of [3H]yohimbine, a selective alpha 2-antagonist, to cerebral arteries of the control group indicated two classes of binding sites: high-affinity sites with KD of 0.5 nM and Bmax of 18 fmol/mg protein and low-affinity sites with KD of 29 nM and Bmax of 248 fmol/mg protein. In cerebral arteries obtained from the subarachnoid hemorrhage group, [3H]yohimbine binding sites were of a single class with KD of 53 nM and Bmax of 456 fmol/mg protein. These results suggest that sympathetic denervation and subsequent alterations in alpha 2-adrenergic receptors occurred after subarachnoid hemorrhage in human cerebral arteries. These changes in sympathetic innervation to cerebral arteries were considered to be one of the antecedents of delayed vasospasm after subarachnoid hemorrhage.

Adult↗
PubMed1988

Parathyroid hormone degradation by chymotrypsin-like endopeptidase in the opossum kidney cell.

Cathepsin-D has been previously reported to cleave intact PTH into PTH-(1-34) and -(35-84) in membranous fractions of rat and bovine kidney. Whether PTH degradation occurs by intact kidney cells, however, has not been examined in detail. We have, therefore, examined this possibility using an opossum kidney (OK) cell line which possesses the characteristics of proximal renal tubules and responds to PTH. PTH radioimmunoreactivity recovered in trichloroacetic acid-soluble products and in fractions eluted from reverse phase HPLC was measured using an antibody directed to the midregion and C-terminus of PTH. In this study, intact OK cells, but not extracellular enzymes, cleaved human (h) PTH-(1-84) into three discrete fragments which were released into the medium in a time- and temperature-dependent fashion. Half-maximal velocity of PTH-degrading activity (PTHDA) was observed at 9 nM hPTH-(1-84). A 1000-fold molar excess of PTH antagonists [hPTH-(3-34) and [Tyr34]hPTH-(7-34)amide] markedly inhibited PTHDA, whereas ACTH, glucagon, or big gastrin did not suppress it, suggesting an involvement of the PTH receptor in PTHDA. This PTHDA was strongly inhibited by phenylmethylsulfonylfluoride and chymostatin, but not by trypsin inhibitor, elastatinal, or inhibitors of aspartic, cysteine, or metalloproteinases, suggesting that it is due to a seryl chymotrypsin-like endopeptidase. Analysis of chymotrypsin-digested products of hPTH-(1-84) eluted from HPLC exhibited five fragments detected by UV absorbance (210 nm), three of which were measurable by PTH RIA, and each corresponded to the three PTH fragments produced by OK cells. All three fragments were predominantly suppressed in the presence of chymostatin, suggesting that chymotrypsin-like activity is solely responsible for PTHDA in intact OK cells. To further explore the cleavage sites of PTH by chymotrypsin, amino acid analysis of chymotrypsin-cleaved products was performed. The results strongly support the conclusion that a chymotrypsin-like enzyme in OK cells cleaved the hormone between residues 23-24, and 34-35 to produce, at least, hPTH-(24-84) and -(35-84). Lysosomal blockers (chloroquine, ammonium chloride, or monensin) did not affect this PTHDA. Our present study indicates that chymotrypsin-like endopeptidase, but not other endopeptidase or lysosomal enzymes, is responsible for the limited hydrolysis of PTH by intact OK cells.

Amino Acids↗
PubMed1988

Relationship among thyrotropin (TSH), thyroid stimulating immunoglobulins, and results of triiodothyronine (T3) suppression test in patients with Graves' disease.

To investigate the relationship between TSH and abnormal thyroid stimulator(s) in patients with hyperthyroid Graves' disease in whom normal thyroid hormone levels in the serum were maintained by antithyroid drug therapy and in patients with euthyroid Graves' disease, determinations were made of the TSH concentration, action of thyroid stimulating immunoglobulins (TSAb and TBII), and T3 suppression. Out of thirty-three patients with hyperthyroid Graves' disease, twelve patients with subnormal TSH levels were all non-suppressible according to the T3 suppression test results and the detectability of TSAb and/or TBII was as high as 75%. In three out of five patients with euthyroid Graves' disease, the serum TSH level was subnormal. All three showed non-suppressibility in the T3 suppression test and positive action of either TSAb or TBII. One of them became clinically thyrotoxic when the TSAb activity was further increased and TBII became positive, and was therefore diagnosed as having hyperthyroid Graves' disease. The present findings suggest that there are still abnormal thyroid stimulator(s) in patients with hyperthyroid Graves' disease who have low TSH, even if their thyroid hormone concentrations remain normal. Moreover, it is likely that some of the patients with euthyroid Graves' disease are actually in a state of subclinical hyperthyroidism because of the presence of abnormal thyroid stimulator(s).

Adolescent↗
PubMed1988

Clinical response to busramustine (KM-2210) in chronic lymphocytic leukemia: a pilot evaluation of estrogen receptor in relation to its therapeutic effect.

Busramustine (KM-2210), the benzoate of a 17 beta-estradiol-chlorambucil conjugate, was administered to 11 patients with chronic lymphocytic leukemia (CLL) which included eight cases of B-cell CLL and three cases of T-cell CLL. Four patients had received prior chemotherapy. Busramustine was given orally at an initial daily dose of 50-100 mg continuously, and the dose was modified according to hematological improvement. Two cases of B-cell CLL achieved clinical complete responses, six cases including two of T-cell CLL and four of B-cell CLL achieved partial responses and one case of B-cell CLL achieved improvement. The partial and complete response rate was 72.7%. Four patients showed estrogen receptor activity of CLL cells ranging from 3.5 to 57.5 fmol/mg cytosol protein, but there seemed to be no correlation between the estrogen receptor activity of the CLL cells and the therapeutic effects of busramustine. Toxic effects included diarrhea (2/11) and estrogen-related symptoms including breast pain (4/11), genital bleeding (2/5), gynecomastia (2/6) and loss of libido (2/6). The findings of this preliminary study suggest that busramustine is effective in the treatment of CLL, irrespective of the presence of the estrogen receptor.

Adult↗
PubMed1988

Veno-occlusive disease of the liver in a patient with allergic granulomatous angiitis.

A 45-yr-old woman, with asthma and skin erythema, was diagnosed as having allergic granulomatous angiitis. Leukocytosis accompanied by hypereosinophilia and characteristic histological findings of skin lesions also were present. Upon laparoscopy and liver biopsy, the liver showed a congestive appearance and, histologically, showed thickening of the central vein walls, as well as narrowing of the lumens with collagenous fibers, and pericentral hemorrhage with hepatocyte degeneration. A diagnosis of veno-occlusive disease of the liver was made. This is the first report on a case of veno-occlusive disease of the liver occurring in association with allergic granulomatous angiitis.

Female↗
PubMed1987

Ventricular myocytes from neonatal rats are more responsive to dexamethasone than atrial myocytes in synthesis of atrial natriuretic peptide.

Using the primary culture of neonatal rat ventricular myocytes, synthesis and secretion of rat atrial natriuretic peptide (rANP) were studied. Ventricular myocytes in culture, although contained less amounts of cellular immunoreactive (IR)-rANP, secreted substantial amounts of IR-rANP at a rate comparable to that of atrial myocytes. Dexamethasone markedly stimulated synthesis and secretion of IR-rANP by cultured ventricular myocytes in a dose-dependent manner (10(-10)-10(-6) M), of which effect was far more potent than that in atrial myocytes. Testosterone and triiodothyronine also stimulated synthesis and secretion of ventricular IR-rANP to the extent comparable to that of atrial IR-rANP. The present study suggests that tissue-dependent difference in glucocorticoids sensitivity plays an important role in the regulation of developmental ANP gene expression in mammalian heart.

Age Factors↗
PubMed1987

Role of atrial natriuretic polypeptides for exaggerated natriuresis in essential hypertension.

Eighteen patients with essential hypertension were separated into 2 groups, renin-unresponsive and renin-responsive, on the basis of their plasma renin response when challenged by furosemide and upright posture. The response to acute infusion of hypertonic saline solution (1.4% saline solution at a rate of 0.3 ml/min/kg over 60 minutes) was then studied. In the renin-unresponsive group, peak rate of fractional excretion of sodium and peak urine flow after saline loading were 7.6 +/- 0.7% and 476 +/- 34 ml/hour, respectively, and peak value of atrial natriuretic polypeptides (ANP) was 784 +/- 140 pg/ml. In the renin-responsive group, the values were 3.1 +/- 0.4%, 194 +/- 29 ml/hour and 115 +/- 33 pg/ml. Both fractional excretion of sodium, urine flow and ANP response were significantly higher (p less than 0.01) in the renin-unresponsive group. Moreover, a highly significant relation (r = 0.82, p less than 0.01) was observed between fractional excretion of sodium and ANP levels in all hypertensive patients. The degree of saline-induced natriuresis was not related to blood pressure, heart rate, endogenous creatinine clearance, antidiuretic hormone or preexisting level of aldosterone. Plasma renin activity changed little in either group during saline infusion, but tended to be higher at all times in the renin-responsive patients. The present findings suggest that the enhanced secretion of ANP is an important determinant for exaggerated natriuresis observed in patients with renin-unresponsive hypertension.

Adult↗
PubMed1987

Immunological properties of myosin light-chain kinases.

We have studied the immunological and structural properties of myosin light-chain kinases. Immunological studies were performed with affinity-purified antibodies to turkey gizzard smooth-muscle myosin light-chain kinase. Immunoprecipitation experiments demonstrated that avian smooth muscles contain a myosin light-chain kinase of Mr 130,000, whereas the enzyme immunoprecipitated from canine smooth muscles tested has an Mr of 150,000. These antibodies do not react with cardiac- or skeletal-muscle myosin light-chain kinases. Experiments performed with myosin light-chain kinases purified from turkey gizzards (Mr 130,000), bovine tracheal smooth muscle (Mr 160,000) and human platelets (Mr 100,000) demonstrated the following: the primary structures of the turkey gizzard and bovine tracheal enzymes appear to be quite different, based on one-dimensional peptide maps; only one-third as many antibodies bind to the bovine tracheal enzyme as compared to the turkey gizzard enzyme; the antibody:myosin light-chain kinase ratios for half-maximal inhibition of all three enzymes are similar. Based on these data, we conclude that myosin light-chain kinases constitute an immunologically and structurally heterogeneous group of enzymes that have certain catalytic and regulatory properties in common.

Amino Acid Sequence↗
PubMed1987

Effects of steroid and thyroid hormones on synthesis of atrial natriuretic peptide by cultured atrial myocytes of rat.

The in vitro effects of various steroid and thyroid hormones on synthesis of rat atrial natriuretic peptide (rANP) were studied using new-born rat atrial myocytes in culture. Dexamethasone, testosterone and triiodothyronine markedly stimulated both synthesis and secretion of immunoreactive (IR)-rANP with the same peak after 4-day-culture. Dexamethasone and testosterone dose-dependently (10(-7)-10(-6) M) stimulated synthesis of IR-rANP and were the most potent among various steroids tested. Triiodothyronine (T3) also stimulated synthesis of IR-rANP in a dose-dependent manner (10(-8)-10(-7) M), of which effect was more potent than that of tetraiodothyronine, whereas reverse T3 was ineffective. The present study clearly shows that glucocorticoids, androgens and thyroid hormones directly stimulate synthesis of ANP by atrial myocytes and suggests that ANP may play a potential role in mediating and/or modulating the biological effects by these hormones in the cardiovascular system.

Adrenal Cortex Hormones↗
PubMed1987

Papillary-cystic neoplasm of the pancreas with multiple hepatic metastases: a case report.

We report a case of papillary-cystic neoplasm (PCN) of the pancreas in a 42-yr-old woman. Because of complication with multiple hepatic metastases, the patient could not receive radical operation, and was treated palliatively. The right hepatic tumors decreased in volume by an average of 28% (range: 13-54%) following intra-arterial infusion of doxorubicin and gelatine sponge--i.e. chemoembolization therapy. On the other hand, the left lobe tumor increased by 15% in volume following intra-arterial infusion of doxorubicin alone without selective embolization. A subsequent systemic combination chemotherapy (combinations of 5-fluorouracil, doxorubicin and mitomycin-C) was less effective for both the primary and metastatic sites of PCN of the pancreas. Intra-arterial chemoembolization proved useful--as expected--as a palliative measure. Papillary-cystic neoplasm of the pancreas accompanied by hepatic metastasis is very rare. We present herein its clinical behavior and response to the above treatment as documented by CT scan.

Adult↗