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Biomedical subjects

M Kawamura

Publications and source records attributed to M Kawamura.

At least 775 records · Page 43Linked to original sources

Low-molecular-weight proteinase inhibitor of human epidermis inhibiting papain and trypsin activity.

A low-molecular-weight proteinase inhibitor was isolated from human epidermal extracts by means of ultrafiltration, gel filtration and ion-exchange chromatography. On polyacrylamide gel electrophoresis (PAGE), the isolated fraction exhibited a single band of activity at pH 9.4, and inhibitory activity against papain and trypsin was detected in this band. Using sodium-dodecyl-sulphate PAGE, the molecular mass of the inhibitor was estimated to be 2,200 daltons.

Electrophoresis, Polyacrylamide Gel↗

Recovery from hemialexia.

Hemialexia is believed to be caused by the lesion of the splenium of the corpus callosum. However, no previous reports conclusively demonstrated that the hemialexic had the splenial lesion. A right-handed male with hemialexia who was presumed to have the splenium sectioned for a partial removal of a pineal tumor was examined with magnetic resonance imaging. The sagittal and coronal imagings clearly showed that his splenium was not present. The hemialexic had partially recovered at 9 years after the onset. The patient was 76% correct in Japanese phonogram words and 92% correct in ideogram words in an interfield same-different judgment, that is, judging whether 2 one-letter words, one in the left hemifield and the other in the right, were the same or different. Consequently, the possible mechanism for the recovery is that the transfer of visual word information from the right hemisphere to the left has been partially achieved by commissural fibers other than those of the splenium. Information from phonogram words in the right hemisphere is probably less transferred to the left hemisphere than that from ideogram words. The results also suggested that when the transfer of word information in the right hemisphere to the left is interfered with, the left hemisphere tends to mistake the same pair of words for the different pair.

Adolescent↗

Inhibitory effect of prostaglandin D2 on DNA synthesis in nuclei.

Prostaglandin (PG) D2 treatment inhibited DNA synthesis in isolated nuclei of mastocytoma P-815, 2-E-6 cells. On treatment with PGD2 (10 micrograms/ml), the inhibition was distinct by 8 hrs, and complete after 18 hrs. This effect of PGD2 on DNA synthesis in nuclei was not direct or mediated by cyclic AMP, but was a cell-mediated reaction. The cytoplasmic fractions of PGD2-treated and untreated cells both had stimulatory effects and their potencies were the same except for that of the cytoplasmic fraction of 8 hr-treated cells, which was less than that of the cytoplasmic fraction of untreated cells. On treatment with PGD2, inhibition of DNA synthesis in the nuclei began after 8 hrs, and this inhibition could not be reversed, even by adding the cytoplasmic fraction from untreated cells to the assay system. A nuclear salt extract prepared by adding 0.3 M NaCl to nuclei of cells that had been treated with PGD2 for 18 hrs had a much smaller stimulatory effect on DNA synthesis of salt-treated nuclei than an extract of nuclei from untreated cells. It is suggested that inhibition of cell growth by PGD2 is not mediated by intracellular cyclic AMP, but that PGD2 induces a factor(s) that inhibits nuclear DNA synthesis.

Adenylyl Cyclases↗

The storage form of renin in renin granules from rat kidney cortex.

Renin granules were partially purified from rat kidney cortex, and a storage form of renin in the granules was examined. Renin granules were isolated by discontinuous Percoll density gradient centrifugation followed by continuous Percoll density gradient centrifugation. The partially purified fraction was free from mitochondria and microsomes, as judged by the absence of marker enzymes of these organelles, but contained some lysosomal enzyme activities. The specific renin activity was 0.58 mg angiotensin I/hr/mg protein, 500 times as active as the original homogenate. Immunochemical staining with specific antisera against rat kidney renin revealed that about 10% of the granules recovered in the partially purified fractions were stained strongly. The stored renin was not activated either by acidification or by trypsin treatment, indicating that stored renin was in the fully active form. By sodium dodecyl sulfate gel electrophoresis, the stored renin had two different molecular weights, 38,000 and 36,000, and these molecular weights were not reduced by dithiothreitol or 2-mercaptoethanol, suggesting that these renins are single-chain types as opposed to the two-chain type found in male mouse submaxillary gland. These results suggest that active renins with two different molecular weights may be released from renin granules of juxtaglomerular cells.

Animals↗

Is renin secreted by exocytotic mechanism through mature renin granules from juxtaglomerular cells?

Mature renin granules were isolated by the combination of discontinuous and continuous Percoll density gradient centrifugation. Stored renin in the renin granules was found to consist of isoelectrically seven different forms. The seven different isoelectric points (pIs) were 5.6, 5.35, 5.2, 5.0, 4.8, 4.6 and 4.4. Approximately 70% of the stored renin as the total enzymatic activities from all isoelectric peaks was found in a peak which pI corresponded to be 5.35. Renin secreted from isolated glomeruli was also focused into seven peaks possessing identical values. However, the distribution pattern of renin peaks was quite different from that of stored renin. In the secreted renin, peaks of 5.35 (pI) and 5.2 (pI) showed high renin activity and each had approximately 30% of released renin as the total recovered. These results indicate multiple forms of renin are stored and secreted by rat kidney. As the distribution pattern of enzymatic activities in renin peaks between stored renin and secreted renin are different, it is probable that renin may not secreted through mature renin granules by exocytotic mechanism.

Animals↗

Relapsing process in FAB subtypes of adult acute leukemia and its relationship to treatment regimens.

The relapsing process in the bone marrow was studied in those 77 patients with adult acute leukemia, diagnosed according to the FAB classification who achieved complete remission (CR) and then received intermittent multi-drug intensification treatment. Relapse occurred in most of the patients who exhibited Auer rods or Ph1 chromosomes in the bone marrow, or in whom blasts increased to 8% or more, but some patients remained in CR by subsequent treatment, that is, relapsing process was reversible. With our conventional treatment, the relapse or relapsing process occurred in most of the patients with L1, L2 and M1 subtypes within 6 months and was irreversible. It occurred mainly between 5 and 13 months in those with M2, M3 and M5 and was reversible in some cases. Patients with M4 subtype received intensified treatment due to the difficulty of achieving remission; relapse was seen in only 3 of 7 cases. To prevent relapse and attain a potential cure, the treatment should be intensive before the relapsing process with adequate supporting care. In view of the above-mentioned observations, our new treatment protocols for acute leukemia were designed to be more intensive than those conventionally employed, and to be discontinued within approximately 10 months in lymphoblastic leukemia and approximately 8 months in myeloid leukemia.

Adult↗

Maternal plasma concentrations of catecholamines and cyclic nucleotides during labor and following delivery.

In plasma obtained from seven mothers before, during, and after normal labor and delivery, catecholamine and cyclic nucleotide concentrations were investigated. Dopamine concentration showed a significant elevation on admission to hospital in labor and there were marked increases in norepinephrine and epinephrine concentrations during labor at 10 cm cervical dilatation and immediately after delivery, respectively. No significant change in dopa, cAMP, or cGMP was found during the experimental period. However, since the van Beaumont quotient (J.Appl. Physiol. 34, 102-106) for cAMP did not follow the reduction in plasma volume, the concentration appeared to rise during labor. Positive correlations were observed between epinephrine on one hand, and heart rate and systolic blood pressure on the other, as well as between norepinephrine and cAMP, respectively, during labor. The diminution of epinephrine on the fourth day postpartum might reflect a reduction of emotional stress concomitant with labor. cAMP was found to be quickly cleared from the bloodstream within 2 hours after delivery. These results suggest that plasma concentrations of epinephrine and cAMP, especially epinephrine, are indices of maternal psychological and physiological stress during labor and following delivery.

Adult↗

Intracellular action of renin, angiotensin production and release.

The enzyme renin has been purified and characterized by structural analysis. Pure renin protein was used to produce a specific antibody to renin, which was useful in demonstrating the presence of a specific renin in many tissues other than kidney. In these cells angiotensins I and II and angiotensin converting enzyme were found to coexist with renin by immunohistochemical studies and by the direct determination with cultured cells. Studies with these cells indicated the local production of renin, angiotensinogen and angiotensins in these cells. Angiotensin II produced in the cultured cells was secreted to the outside of the cells while more than 95% renin remained within the cells. Secretion of angiotensin II from the angiotensin producing cells was demonstrated with perfused mesenteric artery. The secretion was stimulated by the adrenergic beta-agonist isoproterenol in a dose-dependent manner and specifically inhibited by a beta 2-antagonist. Angiotensin II secreted from the vascular bed by the beta 2-adrenoceptor stimulation acts locally to facilitate norepinephrine release. These studies demonstrate local production and secretion of angiotensin II and define its physiological role.

Angiotensin II↗

[A chemotherapy regimen including CDDP in patients with bronchogenic carcinoma--a comparison between bronchial artery infusion and intravenous administration].

Forty patients with lung cancer were treated using two methods. One was transbronchial artery infusion (BAI) of CDDP and the other was intravenous administration of CDDP with VDS, ACNU or etoposide. There was no difference in response rate between the two groups. The response rate was higher in patients with squamous cell carcinoma compared to these with adenocarcinoma. Compared with the combination group, BAI patients had fewer adverse effects, such as myelosuppression, alopecia, nausea and vomiting. Thus, it was concluded that CDDP is very effective for patients with lung cancer and that CDDP administered by BAI is useful for hilar-type squamous cell carcinoma.

Aged↗

[Study on the use of cefotiam in neonates].

Pharmacokinetic and clinical studies were carried out regarding the use of cefotiam (CTM) in the treatment of infections in newborn infants. Absorption and excretion: CTM was administered by bolus intravenous injection at a dose of 20 mg/kg to 9 newborns ranging in age from 1 to 28 days (gestational age, 34-40 weeks; birth weight, 2,000-3,380 g) and 6 infants aged 30 to 87 days (gestational age, 33 approximately 40 weeks; birth weight, 2,100-3,600 g) and its serum concentration and urinary excretion were determined. In the newborns, mean serum concentrations were 43.3 micrograms/ml at 1/4 hour, 36.7 microgram/ml at 1/2 hour, 27.8 micrograms/ml at 1 hour, 17.7 micrograms/ml at 2 hours, 8.8 micrograms/ml at 4 hours and 4.8 micrograms/ml at 6 hours, and in the infants, they were 44.5 micrograms/ml, 31.2 micrograms/ml, 19.1 micrograms/ml, 7.6 micrograms/ml, 2.2 micrograms/ml and 0.7 micrograms/ml at the above sampling times, respectively. Mean half-lives were 1.92 hours for the newborns and 0.96 hour for the infants, and mean urinary recoveries within 6 hours were 41.2% and 50.1% for the newborns and the infants, respectively. Taking individual differences into account, serum peak levels (at 1/4 hour) in newborns were very similar to each other irrespective of age (days after birth), and did not appear to be greatly different from those in infants. Half-lives, however, became shorter with aging, and the half-life of the serum CTM level in infants of about 1 month old should be close to those in young children or school-age children. From these observations, it is suggested to establish a standard regimen in which CTM is administered at a dose of 20 mg/kg once or twice a day to newborns within 3 days after birth, twice or 3 times a day to those aged 4 to 7 days, and 3 or 4 times a day to those aged 8 days or older. Clinical study: The CTM was administered to 11 patients with acute pneumonia, 2 patients each with suspected septicemia and with bullous impetigo, 1 patient with purulent lymphadenitis, 3 patients with idiopathic respiratory distress syndrome and 1 patient with pneumothorax, and its clinical effect was investigated. Excellent responses were observed in 12 of the 15 evaluated cases,good responses in 2, and a poor response in 1, thus an overall clinical effectiveness was 93.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

Localization of components of the renin-angiotensin system within the kidney.

Evidence accumulates that intrarenal angiotensin II (AngII) plays important roles in the regulation of renal functions. To determine the mechanism and site of the intrarenal formation of AngII, we employed histochemical and cell biological methods. Immunohistochemical studies have revealed the coexistence of renin and AngII in juxtaglomerular (JG) cells, and electron microscopic studies and subcellular organelle fractionation have demonstrated the colocalization of renin and angiotensin in renin granules. The mechanism of this AngII accumulation has been investigated. Immunoreactive angiotensin I (AngI) appeared slowly in JG cells after prolonged administration of angiotensin-converting enzyme (ACE) inhibitors. Cloned and cultured renin-containing cells derived from rat kidney were also found to contain renin, ACE, and AngI and AngII. The subcellular fractionation of renin granules from rat kidney homogenate demonstrated AngI and AngII in the renin granule fractions. These findings suggest the formation of both angiotensins in JG cells. To study the release of AngII, we determined the presence of the angiotensins in renal lymph. Renin was found in renal lymph at a high concentration. Both AngI and AngII were also present in renal lymph in moderate concentrations. It is possible that AngII in the interstitial fluid may play a role in the regulation of renal functions. From these results it has been concluded that AngII is formed in JG cells in the kidney and is secreted with renin into interstitial fluid and plasma, and that AngII formed in the kidney cells may participate in various renal functions.

Angiotensin II↗