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Biomedical subjects

S Matsubara

Publications and source records attributed to S Matsubara.

At least 307 records · Page 17Linked to original sources

Experimental allergic myositis: ultrastructural, histochemical, immunological and immunohistochemical studies.

The quadriceps femoris muscles of experimental allergic myositis, in strain 13 guinea pigs immunised with rabbit myosin B fraction, were subjected to histochemical, immunohistochemical and electron microscopic studies. They demonstrated a variety of degenerative changes of muscle fibres, infiltration of lymphocytes and macrophages along with deposition of immunoglobulin G (IgG) and complement factor 3 on the surface of the muscle fibres. One third of the infiltrating cells were macrophages with acid phosphatase activity in the cytoplasm. The serum IgG of the model had an affinity for the surface of normal guinea pig muscle fibres and for thick filaments and other organelles. Its affinity for the heavy and light chains of myosin, actin, troponin T and for other proteins was shown by the immunoblotting method combined with one- and two-dimensional electrophoreses.

Animals↗

Experimental allergic myositis: strain 13 guinea pig immunised with rabbit myosin B fraction.

Of 32 guinea pigs (Hartley and strain 13), 20 were immunised with whole muscle homogenate, microsome or myosin B fraction of rabbit skeletal muscle with Freund's complete adjuvant (FCA); the purified myosin fraction was also used as an antigen in four animals at a concentration lower than other antigens; four were injected with normal saline and FCA; other four had no injection. Five histological changes, namely necrosis, phagocytosis, central nuclei, inflammation and vacuoles, in the quadriceps femoris muscle were compared by quantitative analysis. The group immunised with myosin B fraction showed necrosis, phagocytosis and inflammation more frequently than those immunised with other preparations (p less than 0.05). The changes were more frequent in the strain 13 than in Hartley (p less than 0.05).

Animals↗

Protective effect of human granulocyte colony-stimulating factor on microbial infection in neutropenic mice.

A purified human granulocyte colony-stimulating factor (hG-CSF) was studied for its protective effect on the induction of neutropenia and enhanced susceptibility to microbial infections in mice receiving cyclophosphamide (CPA). A severe reduction in peripheral blood neutrophils was induced 4 days after injection with 200 mg of CPA per kg although the level normalized rapidly thereafter. When mice were injected subcutaneously once a day with 2.5 micrograms of hG-CSF beginning on the day after CPA injection, the reduction was prevented markedly, even 4 days later. On the other hand, in mice receiving CPA 4 days prior to infection, a weakened resistance to intraperitoneal challenge with a strain of Pseudomonas aeruginosa was induced. This weakened resistance was dose-dependently restored to normal by four daily injections with hG-CSF. A daily dose of 1.0 microgram was required for complete restoration, although hG-CSF did not directly inhibit bacterial growth in vitro. In hG-CSF-treated mice, morphologically mature neutrophils migrated rapidly into the peritoneal cavities where bacteria were inoculated, followed by a rapid elimination of bacteria from the locality as compared with controls. In addition, the same treatment with hG-CSF was able to protect significantly against systemic infections caused by Serratia marcescens, Escherichia coli, Staphylococcus aureus, and Candida albicans. These data show the possibility that prophylactic therapy with hG-CSF may augment the resistance of immunocompromised patients to infections.

Agranulocytosis↗

The significance of activation of reticuloendothelial function on hepatectomy.

The prognosis of patients after massive hepatectomy is poor in certain cases whose hepatic reserve, including reticuloendothelial function, is deteriorated. We administered OK-432 before 70% hepatectomy on rats to activate the reticuloendothelial function and studied its effect on postoperative course. The elevations in plasma endotoxin, GOT and GTP were attenuated, and the deterioration of the complement activity after hepatectomy was greatly improved by OK-432 treatment. The RNA content in the liver was significantly increased by OK-432 administration. These findings suggest that activation of the reticuloendothelial function at the time of massive hepatectomy enhances endotoxin clearance from blood and thereby contributes in lessening the magnitude of hepatic injury, maintaining the serum complement, and improving liver protein synthesis.

Animals↗

Activation of reticuloendothelial function for prevention of endotoxemia after hepatectomy in cirrhotic patients.

In order to prevent endotoxemia after hepatectomy in cirrhotic patients, we administered OK-432 before and after hepatectomy to activate the reticuloendothelial function and studied its effect on postoperative endotoxemia. In the cirrhotic group without OK-432 administration (7 patients), the value of endotoxin increased significantly after hepatectomy, compared to the cirrhotic group which received OK-432 administration (5 patients) and the non-cirrhotic group (12 patients), and the endotoxin level was still higher than the preoperative value even on the 14th day. On the other hand, the cirrhotic group with OK-432 administration and the non-cirrhotic group showed minimal increases of endotoxin levels at the first day, which returned to the preoperative values at the third day. Base on these findings, it is suggested that activation of the reticuloendothelial function bears substantial significance as one of the therapeutic modalities for prevention of endotoxemia after hepatectomy in cirrhotic patients.

Biological Products↗

[Ultracytochemical localization of cyclic 3',5'-nucleotide phosphodiesterase activity in human term placenta].

Reports have so far accumulated suggesting that cyclic nucleotide may play an important role in the regulation of placental function. Cyclic 3',5'-nucleotide phosphodiesterase (PDE) is the enzyme which degrades cyclic nucleotide to nucleotide monophosphate. The presence of this enzyme in the human placenta has been speculated on biochemical grounds, but direct cytochemical evidence has been lacking. Therefore, ultracytochemical localization of PDE activity was demonstrated in the human term placenta directly by electron microscopical enzymecytochemistry. Both cyclic AMP PDE and cyclic GMP PDE activity was observed on the syncytiotrophoblast, but subcellular localization differed in detail. Cyclic AMP PDE activity was positive both on the microvillous membrane and on the basal plasma membrane, while cyclic GMP PDE activity was confined to the microvillous membrane of the syncytiotrophoblast. These observations suggest that the syncytiotrophoblast may play an important role in cyclic nucleotide metabolism and that PDE may regulate nascent cyclic nucleotide in the syncytiotrophoblast.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Ultracytochemical localization of adenylate cyclase and guanylate cyclase activities in human term placenta].

Reports have so far accumulated suggesting that cyclic nucleotide may play an important role in the regulation of placental function, including fetal growth. However, only biochemical data are available on the localization of adenylate cyclase (AC) and guanylate cyclase (GC) and direct histochemical evidence is lacking. Therefore, to understand the cyclic nucleotide metabolism in human term placenta, ultracytochemical localization of AC and GC activity was studied. The AC activity was mainly positive on the basal plasma membrane of syncytiotrophoblast and on the pinocytotic vesicle of fetal capillary endothelial cell. GC activity was observed to be strong on the plasma membrane of microvilli of syncytiotrophoblast. All the cytochemical control studies confirmed the specificities of each enzyme activity. These observations suggest that syncytiotrophoblast may play an important role in cyclic nucleotide metabolism and that AC may receive information from fetal circulation, whereas GC may receive regulation from maternal circulation.

Adenylyl Cyclases↗

[Ultracytochemical localization of Ca++ATPase activity in human term amniotic epithelial cell].

In the human amniotic epithelial cell, intracellular Ca++ is known to play an important role in the initiation of parturition. Ca++ATPase is estimated to act on the regulation of the intracellular Ca++ concentration in amniotic epithelial cell. Therefore, to understand the Ca++ metabolism in human term amniotic epithelial cell, ultracytochemical localization of Ca++ATPase activity was investigated. At the same time, the ultracytochemical localization of Ca++ATPase was also compared with other phosphatases to confirm the specificity. Ca++ATPase activity was found to be positive on lateral plasma membrane of amniotic epithelial cell. The activity was strong at a 10mM Ca++ concentration. The activity was also found to be positive on the plasma membrane when 10mM Mg++ was used instead of Ca++. Acid phosphatase activity was positive on the lysosome of the amniotic epithelial cell. The other phosphatase activities appeared negative. These observations suggest that in the amniotic epithelial cell, Ca++ metabolism is active and the Ca++, entering into the cytoplasm, may flow out through the lateral membrane of the amniotic epithelial cell.

Amnion↗

[Cytochemical study of the electronmicroscopical localization of Ca++ATPase activity in the human trophoblast].

Ca++ATPase is one of the most important regulatory systems that maintain the intracellular Ca++ concentration, which is essential to many cellular functions. The presence of Ca++ATPase in the human placenta has been speculated on biochemical grounds, but direct histochemical evidence has been lacking. Therefore, ultracytochemical localization of Ca++ATPase on trophoblastic cells of the human placenta was investigated by using the lead citrate method. Strong Ca++ATPase activity on the microvillous membrane and weak activity on the basal plasma membrane of the syncytiotrophoblast were observed. This distribution of Ca++ATPase was in good agreement with biochemical speculations. These results suggested that the syncytiotrophoblast might play an important role in the Ca++ metabolism in the human placenta.

Calcium↗

[Desipramine-induced down regulation of beta-adrenergic receptors: effects of noradrenergic and serotonergic neuronal activities and of alpha 2-adrenergic receptor mediated mechanisms].

The mechanisms of antidepressant (desipramine)-induced down regulation of beta-adrenergic receptors were investigated. The number of beta-adrenergic receptors in rat cerebral cortex was increased by the destruction of norepinephrine (NE) neurons with 6-hydroxydopamine or DSP-4 pretreatments. Desipramine (DMI)-induced down regulation of beta-receptors was completely prevented by these procedures, whereas the destruction of serotonin (5-HT) neurons neither changed the receptor number nor prevented the DMI-induced down regulation. The number of beta-adrenergic receptors showed a decrease within 3 days by treatment of DMI plus (+) mianserin or yohimbine which promotes NE and 5-HT release from nerve endings through presynaptic alpha 2-adrenergic antagonism. Another alpha 2-adrenergic antagonist (-)mianserin, which promotes only 5-HT release, also accelerated the down regulation induced by DMI, but this acceleration was not prevented by the destruction of 5-HT neurons. Combination of DMI with 5-HT releasing agent methiothepin (5-HT autoreceptor antagonist) did not accelerate beta-receptor down regulation. These results suggest that 1) NE availability in the synaptic cleft plays a significant role in the regulation of beta-receptor number, but 2) postsynaptic alpha 2-adrenergic mechanisms also seem to contribute to the regulation, whereas 3) 5-HT neurons have no significant effect on the process.

Animals↗

Recent trends in different histological types of lung cancer in Tokyo based on pathological autopsy records.

The recently increasing trend of lung cancer mortality in Japan was qualitatively analyzed. As the percentages of cases undergoing pathological autopsies in Tokyo were thirty for males and twenty-six for females during the period from 1979 to 1983, the histologically classified death rates in Tokyo could be estimated by combining the reported cases of death from lung cancer with the proportion of these of known histological type. The results indicated an increase in adenocarcinoma, and a decrease in squamous-cell carcinoma, except for the older age-group of men. The latter result suggested that the results were affected by the decreasing proportion of smokers and by the improvement in cigarette quality. The increase in small-cell and large-cell carcinoma, and the decrease in undifferentiated carcinomas, could be explained by problems associated with differing diagnostic standards. However, when these three different types of carcinoma were considered as a single type, the death rate was shown to be increased except in younger age-groups of women.

Adenocarcinoma↗

[Endotoxemia after surgery in digestive diseases].

The blood level of endotoxin after operations in patients with digestive diseases, mainly liver cirrhosis and obstructive jaundice, and the complications most likely related to the presence of endotoxemia were investigated. Twenty-seven patients without either liver cirrhosis or obstructive jaundice showed a minimal elevation of the endotoxin level in blood, as shown by 6.1 +/- 3.9 pg/ml at the first postoperative day and there was only one anastomotic leakage. On the other hand, 18 patients with liver cirrhosis showed a notable and persistent endotoxemia after surgery. The cirrhotic patients who especially underwent splenectomy and hepatectomy showed marked elevations of endotoxin level at the first postoperative day, with values of 151.0 +/- 46.1 pg/ml and 101.3 +/- 36.2 pg/ml, respectively, and one of these patients died of hepatic failure. Thirteen patients with obstructive jaundice developed endotoxemia evidenced by the value of 21.6 +/- 4.8 pg/ml at the first day after surgery. Among these patients, two had gastrointestinal bleeding and one developed DIC. The markedly high and persistent levels of endotoxin in patients with liver cirrhosis or obstructive jaundice may be possibly related with the development of MOF.

Cholestasis↗

Radionuclide lymphoscintigraphy performed on the mastectomized chest wall.

Lymphatic flow in the anterior chest wall of 64 patients who underwent surgery for breast carcinoma was studies on images of lymphoscintigraphy using 99mTc-rhenium colloid. Scintigraphic images taken 4 hours after the intradermal injection of radionuclides along both sides of the surgical wound frequently made it possible to visualize the contralateral axillary lymph nodes. In particular, among 20 patients with local chest wall recurrence after the mastectomy, the contralateral axillary nodes were demonstrated in 13. Stimulated lymphatic flow seems to be manifested around the site of local recurrence over the chest wall. On the precise analysis of lymphographic images, faint lymphatic drainages were occasionally identified up to the contralateral axillary lymph nodes at various levels of the anterior chest wall. It is essential that the radiation field be made large towards the area including the downstream of the lymphatic flow. Additionally, accumulation of radionuclides in the lymph nodes appeared to be slowly impaired by the postoperative irradiation after the completion of radiotherapy.

Adult↗

Calcification in glioblastoma multiforme of the cervical spinal cord.

A patient having glioblastoma accompanied with calcification in the cervical spinal cord is presented. A calcifying lesion, detected on preoperative x-ray computed tomograms, was histologically confirmed as calcified areas in the tumor tissue. We discuss the difficulty in differentiating glioblastomas containing calcified masses from benign tumors with areas of calcification and present our hypothesis regarding the cause of calcification in the tumor tissue.

Adult↗

Occurrence of cytochrome P-450 with prostaglandin omega-hydroxylase activity in rabbit placental microsomes.

The microsomes of placenta and uterus from pregnant rabbits have been found to catalyze the omega-hydroxylation of PGE1, PGE2, PGF2 alpha, and PGA1 as well as the omega- and (omega-1)-hydroxylation of palmitate and myristate in the presence of NADPH. These activities were greatly inhibited by carbon monoxide, indicating the involvement of cytochrome P-450. The apparent Km for PGE1 was 2.38 microM and 2.1 microM with the placental and uterus microsomes, respectively. Cytochrome P-450 has been solubilized with 1% cholate from the placental microsomes, and partially purified by chromatography on 6-amino-n-hexyl Sepharose 4B, DEAE-Sephadex A-50 and hydroxylapatite columns. The partially purified cytochrome P-450 efficiently catalyzed the omega-hydroxylation of various prostaglandins such as PGE1, PGE2, PGF2 alpha, PGD2, and PGA1 in a reconstituted system containing NADPH-cytochrome P-450 reductase, cytochrome b5, and phosphatidylcholine. The reconstituted system also hydroxylated palmitate and myristate at the omega- and (omega-1)-position, but could not hydroxylate laurate. These catalytic properties resemble those of a new form of cytochrome P-450 highly purified from the lung microsomes of progesterone-treated rabbits (Yamamoto, S., Kusunose, E., Ogita, K., Kaku, M., Ichihara, K., and Kusunose, M. (1984) J. Biochem. 96, 593-603). This type of cytochrome P-450, viz., cytochrome P-450 with high prostaglandin omega-hydroxylase activity may play a role in the regulation of prostaglandin levels in pregnancy.

Animals↗

A comparative study of dose distribution of a high-energy electron beam and chromosome aberration frequencies.

Electron beam therapy is usually employed for the treatment of tumours located at or near the surface of the body, because the electron beam gives a high dose near the surface, but falls off rapidly with increasing depth beyond the level of the 80% depth dose. Isodose curves for radiotherapy have been obtained using physical methods, but have rarely been investigated on the basis of living human cells. In the present study, lymphocyte chromosome analysis was employed as a biological dosemeter for comparison with the isodose curve measured physically. The peripheral blood was exposed to a 14 MeV electron beam in a plastic tube set in a specially made test-tube stand immersed in a water tank. The chromosome aberration frequencies induced by irradiation of about 95% of peak dose at a depth of 31 mm were found to be higher in value than those induced at a depth of 17 mm where the peak dose had been determined physically. Three gray of irradiation given to whole blood in the presence of contrast medium gave rise to a slight enhancement of radiation-induced chromosome aberration frequencies in the lymphocytes exposed at a depth of 17 mm, but a slight decrease at 31 mm.

Chromosome Aberrations↗