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Biomedical subjects

S Abe

Publications and source records attributed to S Abe.

At least 775 records · Page 43Linked to original sources

Studies on topical antiinflammatory agents. IV. 21-(Alkylthio)acetates and (methylthio)methoxides of corticosteroids.

A series of 21-(alkylthio)acetates and 21-(methylthio)methoxides of corticosteroids were synthesized and examined for vasoconstrictive activities. The activities of seven compounds were equal to or greater than that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV). Among them, betamethasone 21-(methylthio)acetate 17-propanoate (2Ca) was found to have the most potent activity, which is superior to that of BV. A structure-activity relationship study revealed that substitution of the 21-hydroxy group of corticosteroids with the (methylthio)acetate function is a useful approach for obtaining potent activity.

Administration, Topical↗

Cloning and expression of a pili gene of Corynebacterium renale in Escherichia coli.

A plasmid gene library of Corynebacterium renale piliated strain No. 109P+ was prepared in Escherichia coli in order to study the chemical structure of the pili of C. renale. Of 3,000 recombinant clones tested, 5 reacted with anti-pili anti-serum. The gene products of these clones reacted with anti-pili monoclonal antibodies 8/4, 5/2 and B20/3 but lacked the reactivity with 13/4. SDS-PAGE analysis revealed that the expressed protein had a molecular mass of 48 kilodalton and deletion analysis showed that the encoding region for this protein was localized within a 1.4 kilobase gene including a promoter sequence. Immunoelectron microscopy showed that mouse antibodies raised to the expressed protein bound to the entire surface of the pili of C. renale. These results indicate that the cloned gene encodes a major structural protein of C. renale pili.

Animals↗

Modulation of accessory molecules on lung T cells.

Stimulation of T cells via the CD3/TCR complex is associated with the reduced expression of accessory molecules, a phenomenon called modulation. To investigate whether the modulation is implicated in the pathogenic mechanism of pulmonary disease, we determined the MFI of CD3, CD4 and CD8 on lung and blood lymphocytes in ten normal subjects and 54 patients with various pulmonary and extrapulmonary diseases. Although there were no significant differences in MFI of these accessory molecules on lung lymphocytes among the groups, MFI of CD3 on lung lymphocytes was significantly decreased compared with that on blood lymphocytes in all groups, demonstrating the modulation of CD3 on lung lymphocytes. Since it has been shown that T cells whose CD3/TCR is modulated are hyporesponsive to various mitogenic signals, our observation seems to represent another aspect of the mechanism whereby the local pulmonary milieu maintains the autoregulation of immune response.

Adult↗

[Acute toxicity study of cefpirome sulfate in mice and rats].

Acute toxicity of cefpirome sulfate (CPR) was examined in 6-week-old mice and rats and immature (5-day-old) rats. The LD50 values of CPR (mg/kg) were as follows: (1) mice: intravenous, 2420 (95% confidence limits, 2122-2758) for males and 2400 (2181-2640) for females; intraperitoneal, 3850 (3407-4351) for males and 4200 (3889-4536) for females; and oral, 16200 (14781-17755) for males and 18500 (17290-19795) for females. (2) 6-week-old rats: intravenous, 1900 (1784-2023) for males and 2080 (1953-2215) for females; intraperitoneal, 6550 (6179-6943) for males and 5800 (5311-6334) for females; subcutaneous, more than 10000 for both sexes; and oral, more than 8000 for both sexes. (3) 5-day-old rats: subcutaneous, between 1750 and 2500 for males and 2080 (1651-2621) for females. Major changes in general health conditions observed in 6-week-old mice and rats were decreased spontaneous activity, lying prone, tremor, respiratory changes (slow or deep respiration, gasping), clonic or clonic-tonic convulsions. In the 6-week-old rats dosed subcutaneously, vocalization, writhing and cutaneous changes at the injection site (dark reddening or blackening, swelling, exfoliation, depilation, induration) were also observed. In the 5-day-old rats dosed subcutaneously, the changes noted were slow respiration, writhing, cyanosis, and dark reddening and swelling of the skin at the injection site. After administration, transient depression of body weight gain or loss of body weight was observed in the mice and rats except the rats dosed orally. These changes disappeared at 7 days after administration at latest, and all surviving animals showed favorable body weight gain thereafter. Necropsies revealed hemorrhage under meninges in the brain in many of the mice and rats which died. Other findings included subcutaneous changes at the injection site in the 6-week-old and 5-day-old rats dosed subcutaneously (dark reddening, retention of dark red fluid, retention of red, white or dark red gelatinous material) and changes in the peritoneal cavity in the 6-week-old rats dosed intraperitoneally (red or dark red spots on the serous membrane, reddening of adipose tissues).

Animals↗

Histopathology of cystic cavities in the cerebral white matter of HTX rats with inherited hydrocephalus.

To investigate the mechanism of cystic cavity formation in the cerebral white matter of the HTX rat, a strain with inherited hydrocephalus, the authors carried out a histopathological study of the brain in pups from birth to postnatal day (P) 26. Cystic cavities were formed in the cerebral white matter on the lateral side of the basal ganglia of all HTX rats with moderate to severe ventricular dilatation and, additionally, in the white matter beneath the paramedian cortex in advanced cases at P10-26. In the initial stage of cyst formation, disarrangement of the ependymal cell layer and spongy alteration of the white matter took place in pups between P1 and P7. The ependymal disarrangement involved disruption and flattening of the ependymal cells, which were often devoid of microvilli, cilia and intercellular junctional complexes. The spongy state was due to expansion of the extracellular space and multiple microcyst formation with fluid accumulation in the early stage, and large cystic cavities in the advanced stage. The cerebrospinal fluid (CSF) in the ventricle communicated with the fluid in the cystic cavities via the disarranged ependymal cell layer. The ependymal damage was more prominent at the lateral wall of the posterior horn than at the anterior horn of the lateral ventricles. These cavities were demarcated by reactive glial cells in the advanced stage. However, the cavities enlarged in accordance with progressive dilatation of the lateral ventricles during postnatal development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Development of GFAP-positive cells and reactive changes associated with cystic lesions in HTX rat brain.

HTX rat, a congenital hydrocephalic strain, develops ventricular dilatation and cystic cavities in the cerebral white matter after birth. To investigate the reactive changes in glial cells around these cavities, immunohistochemical staining for glial fibrillary acidic protein (GFAP), a specific marker protein of astrocytes, and bromodeoxyuridine (BrdU), a thymidine analogue, was carried out on 107 Wistar and HTX rat brains from birth to postnatal day (P) 26. Animals were divided into three groups: Group A, Wistar rats as normal controls; Group B, HTX rats with a normal structure or only mild ventricular dilatation without any lesion in the white matter; and Group C, HTX rats with severe ventricular dilatation and cyst formation in the white matter. Group B rats showed similar development of GFAP-positive (GFAP+) cells to that in Group A rats, both morphologically and quantitatively. On the other hand, Group C rats showed definite structural changes in GFAP+ cells around the cystic cavities from P5. These included enriched cytoplasm and thickened cell processes with increased GFAP expression, and enveloped most cyst walls from P10. However, quantitative examination of the percentage of GFAP+ cells in Group C rats showed a similar developmental profile to those in Group A and B rats. Furthermore, the labeling index of BrdU-positive cells, indicating S-phase cells, in the white matter in Group C rats showed a similar decreasing pattern to that in Group A and B rats from P1 to P26.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Metabolic fate of indometacin farnesil, a prodrug of indomethacin: characteristic biotransformation of indometacin farnesil in rats.

1. Hydrolysis of indometacin farnesil (IMF), a farnesyl ester of indomethacin, was higher in plasma and pancreatic juice than in liver and kidney homogenates of rats. Plasma hydrolytic activity was extremely low in beagle dog, monkey and human. 2. Orally administered 14C-IMF was absorbed mainly via the throacic lymph duct and distributed into tissues such as liver, adrenal and spleen as the unchanged from; the 14C in rat plasma was present mainly as indomethacin released from IMF. 3. The concentration ratios of indomethacin in carrageenin-induced inflamed paw to blood after 14C-IMF administration were significantly greater than those after 14C-indomethacin dosing. 4. These results indicate that absorbed IMF might be transported as the unchanged drug into tissues, including the site of inflammation and then hydrolysed to indomethacin in the tissues.

Animals↗

Small-cell-type poorly differentiated squamous cell carcinoma of the lung. Cytologic, immunohistochemical and nuclear DNA content analysis.

The relationship between the nuclear DNA content, the immunohistochemical findings, the clinical characteristics (tumor volume doubling time and survival) and the cytomorphologic features of small cell poorly differentiated squamous cell carcinoma of the lung was studied in ten cases. There were no significant correlations between the immunohistochemical stainings for neuron-specific enolase and keratin and the clinical characteristics in these cases. The DNA histogram patterns were classified as type I or type II, depending on the degree of dispersion of values. There was no relationship between the immunohistochemical findings and the DNA histogram patterns. Only the DNA histogram patterns were related to some of the clinical characteristics: patients with type II histograms had significantly shorter tumor volume doubling times than did patients with type I histograms. Such information may aid in distinguishing the small cell type of poorly differentiated squamous carcinoma from classic small cell carcinoma of the lung, with which it may be confused.

Aged↗

[The characters of AFP-producing early gastric cancer].

During the last decade, we have experienced 525 cases of gastric cancer. Within these, 195 were early gastric cancer (37.1%). Five and eight year survival rates were 86.9 and 77.2%. There were seven cases of recurrence, all of which were liver metastasis of submucosal cancers. Two combined with pulmonary metastasis. Three of the recurrent cases had serum AFP raised (greater than 20ng/ml) before or after partial gastrectomy. When these gastric specimens were reviewed, AFP positive cells were stained by PAP method. Compared with the AFP negative group of 168 early gastric cancers, invasion of lymphatic and venous vessels of the stomach and incidence of the liver metastasis were significantly higher in the stained group. 1.3 and 4.5 year survival rates of the cases (including ours) of AFP producing early gastric cancer, which had been reported in Japanese literatures, were 76.1, 45.7 and 22.9%, respectively. Liver metastasis was found in 7 of 12 cases (58.3%). It is clear that AFP producing early gastric cancer has the same tendency for liver metastasis as the AFP producing advance gastric cancer does. To prevent its recurrence, early diagnosis by PAP method for specimens with hepatic picture and aggressive adjuvant chemotherapy are mandatory.

Aged↗

[Platelet activation during thrombolysis and percutaneous transluminal coronary angioplasty in the acute phase of myocardial infarction].

To clarify the mechanism of recanalization and reocclusion in thrombolysis and percutaneous transluminal coronary angioplasty (PTCA), the plasma concentrations of beta-thromboglobulin (beta-TG), thromboxane B2 (TXB2) and platelet aggregation adenosine diphosphate (ADP) (2 microM/ml, collagen 2 micrograms/ml) were assessed in 11 normal subjects and in 19 patients with acute myocardial infarction whose infarct-related vessels were recanalized by thrombolysis and/or PTCA. In patients with acute myocardial infarction, the plasma concentrations of beta-TG and TXB2 were significantly higher than those in normal subjects (beta-TG: 128 +/- 132 ng/ml vs 38 +/- 17 ng/ml, TXB2: 131 +/- 154 pg/ml vs 36 +/- 18 pg/ml). Collagen-induced platelet aggregation decreased significantly in patients with acute myocardial infarction; whereas, ADP-induced platelet aggregation showed no significant difference. Infarct-related vessels recanalized by thrombolysis (seven patients: group 1) and PTCA (seven patients: group 2) were patent on the follow-up angiograms. Infarct-related vessels were reoccluded in five patients immediately after PTCA or during the follow-up angiography (group 3). Beta-TG and TXB2 did not change before and after recanalization in groups 1 and 2, but increased significantly after recanalization in group 3 (beta-TG: 155 +/- 185 ng/ml----269 +/- 233 ng/ml, TXB2: 104 +/- 87 pg/ml----169 +/- 91 pg/ml). Platelet aggregation did not differ significantly among the three groups. We concluded that platelets are not activated during thrombolysis and/or PTCA in cases without reocclusion, while platelets are markedly activated during PTCA in cases with reocclusion. Thus, it is suggested that platelet activation plays an important role in the mechanism of reocclusion.

Adenosine Diphosphate↗

Does allopurinol prevent myocardial injury as a result of hypoxia-re-oxygenation in rats?

We made use of the xanthine oxidase inhibitor allopurinol and examined changes related to myocardial injury of the rat heart during hypoxia-re-oxygenation. The rat heart was perfused using the Langendorff method. With low-oxygen perfusion for 60 min in a solution saturated with mixed gases of 95% N2 + 5%O2, contractile tension did not develop and tension development was not restored upon re-oxygenation. During hypoxia, the resting tension increased (4.1 g) in the absence of allopurinol. In the allopurinol-administered group (100 microM), contractile tension did not develop during hypoxia; however, the development of tension was restored (18%) upon re-oxygenation. The elevation of resting tension was less (3.2 g) during hypoxia. All events related to the myocardial injury (inhibition of Na+, K(+)-ATPase activities, generation of malondialdehyde, extracellular leakage of creatine kinase) after low-oxygen perfusion for 60 min and re-oxygenating perfusion for 30 min were mild in the allopurinol treated group, compared with findings in the non-administered group. Tissue ATP at 10 min after low-oxygen perfusion was of a significantly high value in the allopurinol treated group (13.2 mumols/g dry weight), compared with findings in the group not given the drug (8.4 mumol/g dry weight). Sixty minutes after low-oxygen perfusion, tissue ATP in the allopurinol group also remained high, compared with the group not given the drug. Although the intensity of the epicardial NADH fluorescence indicated that the extent of inhibition of aerobic energy production during 10 min of low-oxygen perfusion was the same for both groups, lactate was produced in large quantities in the allopurinol treated group, hence energy generation advanced with glycolysis. These observations suggest that allopurinol prevents myocardial injury as a result of hypoxia-re-oxygenation. In the low-oxygen perfusion period, generation of energy is maintained and improved with glycolysis and there is a reduction in the generation of free radicals and an inhibition in lipid peroxidation.

Allopurinol↗

[A case of primary pulmonary hypertension with high venous thromboxane B2 concentration].

A 30-year-old male was admitted because of dyspnea, which had started three years before the admission. Chest roentgenogram showed prominence of the proximal pulmonary arteries and diminished vascularity of the peripheral pulmonary arteries. Electrocardiogram showed right axis deviation and right ventricular hypertrophy. Right heart catheterization revealed a markedly elevated pulmonary arterial pressure and pulmonary vascular resistance with normal capillary wedge pressure. Oximetry showed no evidence of intracardiac shunt. Perfusion lung scan revealed nonsegmental, patchy defects in both lungs. Pulmonary arteriography showed no evidence of pulmonary thromboembolism. From the above findings, primary pulmonary hypertension was diagnosed. Nifedipine, ISDN, prazosin, and captopril were administered to evaluate the short term-effect of he vasodilators. Nifedipine was found to be the most effective. The venous thromboxane B2 level was high. After oxygen therapy, venous thromboxane B2 level fell within the normal range following improvement of arterial oxygenation and decrease in venous FDP level. Hemodynamic changes induced by ice-water hand immersion showed marked increase in the mean pulmonary arterial pressure and total pulmonary arterial resistance. These results suggested that chemical mediators such as thromboxane, and pulmonary arterial vasospasm were involved in the pathogenesis.

Adult↗

[A case of elderly (83-year-old) woman with possible left atrial myxoma].

A 78-year-old woman with exertional dyspnea (Hugh-Jones Grade III) and dry cough was admitted to our hospital in April, 1983. She had marked cardiac cachexia and a loss of body weight due to long term heart failure. On physical examination a systolic ejection murmur and a diastolic rumbling murmur were heard without the opening snap sound. Chest radiography revealed pleural effusion and cardiomegaly. M-mode and two dimensional echocardiography demonstrated abnormal echoes in the left atrium, the density being 22.7 Hounsfield Unit. Radionuclide angiography and magnetic resonance imaging (MRI) provided similar findings. No other mass lesion existed in the other chambers. Based on these findings, the mass was diagnosed as a left atrial myxoma. She has been well except for periodic congestive heart failure, for about five years since her discharge. The course of her ailment is interesting because her treatment is mainly symptomatic.

Aged↗

Procedures for plasma prostaglandins assay from bronchial asthmatic patients using 9-anthryldiazomethane-HPLC method.

We report here an efficient method for simultaneous and quantitative determinations of plasma prostaglandins (PGs) from asthmatic patients using 9-anthryldiazomethane-reversed-phase high performance liquid chromatography (HPLC). Detection and simultaneous quantitation of 20 pg PGE1, PGE2, PGF2 alpha and 100 pg 6-keto PGF1 alpha, thromboxane B2 (TXB2) was possible by the present method. Preliminary studies showed that plasma TXB2 levels from stable asthmatic patients were elevated compared with normal healthy subjects, suggesting pathophysiologic implications regarding PGs and TXB2 in asthma may be elicited by the present HPLC method.

Anthracenes↗

[The serial changes of antibody production, macrophage migration inhibition test (MIT) and histopathologic examination in an experimental hypersensitivity pneumonitis in rabbits].

We developed a hypersensitivity pneumonitis model by sensitizing rabbits intratracheally (IT) twice after two subcutaneous sensitizations (SS), and investigated the serial changes in the production of antibody against micropolyspora faeni (Mf), macrophage migration inhibition test (MIT), and histopathologic features. On the third day after the last IT, the proportions of neutrophils in bronchoalveolar lavage fluid (BALF) increased. The antibody levels of Mf specific-antigen in BALF decreased transiently, but those in serum began to increase. The number of AFC in spleen increased rapidly. Histopathologic examination revealed alveolitis and prominent acute pneumonia. On the seventh day after the last IT, the proportion of lymphocytes in BALF, the antibody levels of Mf specific-antigen in BALF, the number of AFC in BALF, and the percent inhibition of MIT were highest. Histopathologic features were characterized by the formation of prominent epithelioid granulomas. On the fourteenth day after the last IT, these features returned to the state of untreated group. These results indicate that the lesions in this HP model are formed by both type III and type IV immune reactions (Coombs-Gall). It was concluded that the seventh day after the last IT was most appropriate for the study of pathophysiology of human HP.

Actinomycetales↗