Phase transition in the Zr1-xScxB12 system.
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Biomedical subjects
Publications and source records attributed to K Hamada.
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The role of endothelin in the pathogenesis of cerebral vasospasm after subarachinoid hemorrhage was investigated by evaluating the effect of FR139317, a novel potent ETA receptor antagonist, on the vasospasm in a canine two-hemorrhage model. Intracisternal administration of FR139317 (0.1 mg) significantly reduced the vasoconstriction of the basilar artery at day 7 (control group, n = 6, 61.6 +/- 4.0%, FR139317 treated group, n = 6, 75.9 +/- 1.5% of basal diameter, p < 0.01). In normal anesthetized dogs, the intracisternal administration of FR139317 did not affect the basal diameter of the basilar artery, blood pressure or heart rate. These results suggest that endothelin plays an important role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, and that FR139317 could be a valuable tool for preventing vasospasm after subarachnoid hemorrhage.
In a differential study to distinguish bruises from putrefactive discoloration, glycophorin A, a component of the erythrocyte membrane, was extracted from discolored skins and detected by immunological methods utilizing an anti-glycophorin A serum. Skin samples of 18 bruises, 8 postmortem hypostasises and 7 putrefactive discolorations were removed from 27 bodies in which postmortem intervals ranged from 4 h to 2.5 months. In 13 out of the 18 bruises (72.2%), glycophorin A was detected by the immunological methods. It was noted that glycophorin A was detectable even in a severely putrefied body 10 days after death. In contrast, no glycophorin A was detected in any of the postmortem lividities or the putrefactive discolorations. These results suggest that the absence of glycophorin A does not always indicate a skin discoloration of postmortem origin, but a positive glycophorin A reaction does indicate a skin discoloration due to bruise.
A case of primary mucinous carcinoma originating in the renal pelvis associated with renal lithiasis is reported. The left kidney removed was mostly occupied by mucinous carcinoma with areas of signet ring cell carcinoma. The epithelium covering the pelvis consisted of a single layer of columnar epithelium with scattered goblet cells and mucous glands. A series of careful examinations of the abdominal viscera failed to disclose any other primary lesion. The patient died with multiple peritoneal tumor disseminations eight months after the operation despite additional chemotherapy.
Roxithromycin (10 mg/kg) was administered once-daily for seven or 28 days to mice intragastrically and its effects on cytokine synthesis were studied. Administration of roxithromycin for 28 days resulted in increased synthesis of interleukin (IL)-1 and tumour necrosis factor (TNF-alpha) production by macrophages, and the production of IL-2, IL-4 and interferon gamma by splenocytes. In contrast, 7 day administration of roxithromycin did not affect these parameters. Furthermore, clindamycin treatment did not significantly increase the capacity of host cells to produce cytokines, irrespective of the duration of treatment, when compared with the solvent control receiving 0.9% ethanol solution or the untreated controls. In addition, the supernatant of a 7 day culture of splenocytes with roxithromycin showed suppression of the production of TNF-alpha and prostaglandin E2 by mitogen-stimulated macrophages, and this suppressive activity was impaired by a monoclonal antibody to murine IL-4. Thus, this data suggests that roxithromycin may not only enhance the host defence system through increased cytokine synthesis by host cells, but also exhibit anti-inflammatory activity by including an anti-inflammatory cytokine, IL-4.
OBJECTIVE: Androgens have paradoxically different effects on hair follicles depending on body site, stimulating beard growth while inducing regression in some areas of the scalp. The mesenchyme derived dermal papilla at the base of the hair follicle regulates many aspects of the growth of follicular epithelium, and is probably the site of androgen action. Since 5 alpha-dihydrotestosterone is considered to be the active intracellular androgen in many target tissues and is required for some androgen-mediated hair growth, such androgen-sensitive cells should contain 5 alpha-reductase. This study was designed to investigate whether cultured human dermal papilla cells contain 5 alpha-reductase and whether the metabolic capacity varies with the body site of the follicle in line with the clinical picture. DESIGN: Testosterone metabolism in cultured dermal papilla cells from androgen sensitive beard follicles was compared with less androgen dependent non-balding scalp follicles. Primary cell cultures were established from follicles of 11 patients with normal hair growth. The cells were grown to confluence in 10-cm Petri dishes and incubated with 5 nM 3H-testosterone in serum-free medium for 2 hours. The cells and the culture medium were collected separately for individual analysis. MEASUREMENTS: Unlabelled carrier and 14C-marker steroids were added to both the cell and medium extracts before separation by thin-layer chromatography. The individual steroid identities were confirmed by recrystallizing up to five times to a constant 3H/14C ratio. RESULTS: Testosterone was taken up by both cell types; significant amounts of 5 alpha-dihydrotestosterone were recovered inside beard cells, but not in scalp cells, whereas androstenedione was identified in both. An unidentified compound was present intracellularly in both cell types, but was not present in the culture medium. 5 alpha-Dihydrotestosterone was present only in the culture medium of beard cells but androstenedione was present in a similar amount in the medium from both cell types. The presence of other steroids could not be confirmed in either the cell extracts or the culture medium. CONCLUSIONS: The production of 5 alpha-dihydrotestosterone by beard cells concurs with the poor beard growth in men with 5 alpha-reductase deficiency, supporting our hypothesis that androgens mediate their effects on the hair follicle via the mesenchyme-derived dermal papilla.
We investigated the yearly changes of the incidence of Pseudomonas aeruginosa (P. aeruginosa) isolated from chronic lower respiratory tract infections (CLRTI), and also performed a clinical study on CLRTI with P. aeruginosa by transtracheal aspiration (TTA) to clarify the recent trend of P. aeruginosa infection in CLRTI and the predisposing clinical factors to the acute exacerbation. The isolation rate of P. aeruginosa among the total isolated bacteria in CLRTI between December 1978 and March 1983 was 8.4%, but it increased to 23.1% between April 1988 and March 1993. In 69 episodes (40 cases) of P. aeruginosa isolated from CLRTI between April 1983 and March 1993, monomicrobial infections of P. aeruginosa were 42 episodes (60.9%) and polymicrobial infections were 27 episodes (39.1%). When the diseases were classified into acute exacerbated and non-exacerbated phases, polymicrobial infections were seen more in the former phase, and the principal organisms detected with P. aeruginosa were Haemophilus influenzae and Streptococcus pneumoniae. In the acute exacerbated cases, predisposing conditions concerning the exacerbation were divided into four patterns: 1. polymicrobial infections with H. influenzae or S. pneumoniae, 2. after acute upper respiratory tract infections due to viral superinfection, 3. early phase from bacterial replacement by P. aeruginosa, 4. immunocompromised states such as adrenal corticosteroid administration or systemic underlying diseases. These results suggest that the importance of P. aeruginosa in CLRTI is increasing year by year and we must pay attention to the fact that P. aeruginosa alone may also cause acute exacerbation in the latter 2 patterns of the condition.
This clinical study involved 35 cases, anaerobic bacteria were detected by TTA (transtracheal aspiration) or percutaneous lung aspiration, or pleural puncture. These cases were treated over the last 8 years in our department. There were 9 empyema, 9 pneumonitis, 5 lung abscess, 1 necrotizing pneumonia and 11 chronic lower airway infection. In 13 cases (37%), anaerobic bacteria alone were detected, whereas both anaerobic and aerobic bacteria were observed in the other 22 cases (63%). Of all bacteria detected. Bacteroids and Peptostreptococcus were the most common. With respect to host factors involved in the pathogenesis of pleural and parenchymal infection, aspiration was though to be a major trigger in only 11 out of the 24 cases (46%). The other 13 cases (54%) showed no evidence of aspiration, indicating that some other triggers was responsible. In further study, these 13 cases were found either to be heavy smokers with Brinkman index of more than 600, or to show sign of chronic lower airway infection. Both conditions were characterized by an inhibition of the mucociliary transport in the lower airway. Therefore, this study suggested that in the case without apparent aspiration the failure of local defense mechanisms in the airway, as a result of heavy smoking and/or chronic lower airway infection are involved in the pathogenesis of anaerobic respiratory infection.
Eighty-two episodes (77 cases) in which any pathogens were isolated from transtracheal aspiration (TTA) and which satisfied the new clinical criteria of acute bacterial bronchitis were clinically evaluated. Major pathogens isolated from TTA included H. influenzae, S. pneumoniae and B. catarrhalis. Fever developed in 91.5% of the patients. Sputum volume averaged 16.3 +/- 14.9 ml per day. All the patients suffered from coughs, which were so severe as to disturb sleep in 8.5% of the patients. Inflammatory indices included WBC 9738.0 +/- 3158.5/microliter, CRP 10.1 +/- 7.9 mg/dl and ESR 69.0 +/- 38.8 mm/hr on average, PaO2 fell in most cases. Compared to the group of patients with acute bacterial bronchitis from which a single pathogen was isolated, the numbers of elderly patients and smokers were significantly more in the group of multiple pathogens isolated from TTA. Prior episodes related to the development of acute bacterial bronchitis were upper respiratory inflammation in 46.3% and undergoing bronchoscopy in 4.9% of the patients. Antibiotics therapy cured acute bacterial bronchitis in 96.3% of the patients. In spite of treatment, 3 patients developed pneumonia and died.
A healthy-looking 44-year-old female was admitted to our hospital complaining of fever and hemosputum. The chest roentgenogram on admission showed patchy infiltrates of the segment 3 and 8 of the right lung. Laboratory studies showed a leukocyte count of 9700/microliters, erythrocytes sedimentation rate of 55 mm/hour and C reactive protein of 8.7 mg/dl. The arterial PO2 was 71.9 torr while the patient was breathing room air. Transtracheal aspiration was performed on admission, and strains and culture for bacteria, acid fast bacilli, fungi and mycoplasma were negative. Respiratory syncytial virus was isolated from transtracheal aspirates. The RSV complement fixing antibody titers rose from 1:40 to 1:16. She became afebrile on the fourth day after admission and her chest roentgenogram improved gradually. RSV infection should be considered in the differential diagnosis of atypical adult pneumonias.
We studied the effect of erythromycin (EM) on the attachment of Pseudomonas aeruginosa and Neisseria gonorrhoeae to HeLa and HT-177 cell and on cytotoxin production of P. aeruginosa. 1. EM inhibited attachment of these bacteria. 2. EM inhibited manifestation of the pili of these bacteria. 3. EM inhibited production of protein II, the second attachment factor of N. gonorrhoeae. 4. EM inhibited production of 66 K cytotoxin of P. aeruginosa. On the basis of these findings, it was suggested that EM might inhibit infection by repressing manifestation of the attachment factor and production of cytotoxin of the bacteria.
We measured neutrophil's CL (CL-index) in 12 patients of the bacterial pneumonia three times per each case: before, during and after chemotherapy. Before the initiation of chemotherapy. CL-index in the six patients remained higher than that in healthy controls, while the remaining six showed lower levels of CL-index compared to the controls. In the 11 cases, their CL-indexes fell to levels lower than those obtained before treatment. Additionally, in the 11 cases their CL-indexes increased after the termination of chemotherapy. Furthermore, in the nine cases the product of the neutrophil number and CL-index was decreased by chemotherapy, and the decrease in the product correlated with improvement in their clinical conditions.
The pharmacological properties of FK 739, a new angiotensin II-receptor antagonist, were examined. FK 739 inhibited the specific binding of [125I]-angiotensin II to rat aortic smooth muscle cell membrane with an IC50 value of 8.6 nM, but did not displace the specific binding of [125I]-angiotensin II to bovine cerebellum membrane. In isolated helical strips of rabbit aorta, FK 739 shifted the concentration-response curve of angiotensin II-induced contraction in parallel to the right, and the values of the slope and pA2 were 1.06 and 8.45, respectively. In in vivo studies, oral administration of FK 739 at 10 mg/kg significantly inhibited the angiotensin I-induced pressor response in normotensive rats and dogs, and it caused a fall of mean blood pressure in renal hypertensive rats and dogs. In spontaneously hypertensive rats, FK 739 at 32 and 100 mg/kg significantly decreased the mean blood pressure in a dose-dependent manner. Additionally, we studied whether FK 739 would cause side effects such as dry cough, like other ACE inhibitors did. Oral administration of FK 739 (10 and 32 mg/kg) did not affect the capsaicin-induced bronchial edema. On the other hand, captopril (10 mg/kg) significantly enhanced capsaicin-induced bronchial edema. These results indicate that FK 739 is a potent and competitive antagonist for AT1-type receptors, and suggest that FK 739 might be a safe and useful agent for the treatment of hypertension in clinical trials.
To define the relationship between the immunologic reaction and the pathogenesis of cerebral vasospasm (VS) following experimental subarachnoid hemorrhage (SAH), we examined the effect of a cell mediated immunosuppressive agent, FK-506, isolated from Streptomyces tsukubaensis, by using the canine SAH model. There was a significant vasoconstriction in the basilar artery in the control group after SAH. This constriction, however was not successfully prevented by FK-506 or combination of FK-506 and steroid, since there was no significant difference in the vessel caliber size among these groups. The pathologic approach, accompanied by immunohistochemistry, could not discriminate the differences in the nature of the lesion between the untreated group and FK-506 treated groups, except for slight lymphocytic infiltrations present around the basilar artery of untreated group. Histopathologically, inflammatory reactions consisting of neutrophils, that were not suppressed by FK-506 treatment, were clearly seen around the spastic vessels in the subarachnoid space. Furthermore, several constrictive changes or degenerative alterations were also observed in the spastic vascular wall. Immunohistochemically, the deposition of IgG, IgM and C3 was present in the intima and the luminal side of the smooth muscle layer, and capillary vessels of the brain stem. It is considered that this deposition was caused by increased vascular permeability in VS. On the basis of the above findings that the cell mediated immunosuppressive agent, FK-506 failed to prevent vasoconstriction or pathologic lesions but lymphocytic infiltrations, it is considered that the cell mediated immunopathogenesis may play little role in producing VS following SAH.
In order to clarify the possible role of immunological reaction in the pathogenesis of cerebral vasospasm, the authors examined the prophylactic effect of the immunosuppressant agents FK-506 and cyclosporin A on chronic vasospasm in a canine two-hemorrhage model. While a mean constriction of the basilar artery to 81.0% +/- 4.0% (+/- standard error of the mean) occurred on Day 2 and to 63.8% +/- 3.5% on Day 7 in the untreated group, constriction to 77.9% +/- 3.4% on Day 2 and 62.8% +/- 3.0% on Day 7 was demonstrated in the FK-506-treated group (difference not significant). This tendency was also noted in the cyclosporin A-treated group, with basilar artery constriction to 81.8% +/- 3.7% and 56.3% +/- 2.7%, respectively (difference not significant). The histological changes of the basilar artery, including corrugation of the elastic lamina, detachment of endothelial cells, and vacuolar formation in the smooth-muscle layer were not different in the two treated groups and the one control group. Since these immunosuppressant agents are known to inhibit the release of interleukin-2 (IL-2), the level of IL-2 was examined in the cerebrospinal fluid of patients with cerebral vasospasm. While interleukin-1 gradually increased in level as time passed, the level of IL-2 was consistently low during the course of the study, indicating less participation of IL-2 in the pathogenesis of cerebral vasospasm. This clinical observation matched the experimental results. The authors conclude that cell-mediated immunoreaction, initiated mainly by IL-2, plays little role in the pathogenesis of cerebral vasospasm.
The histamine H2-receptor antagonistic activity and antisecretory effects of KU-1257 (N-ethyl-N'-[3-[3-(piperidinomethyl) phenoxy]propyl]urea, CAS 120958-90-9) were studied. The Ki values of KU-1257, roxatidine acetate, famotidine and cimetidine for the inhibition of [3H]-tiotidine binding to guinea-pig cerebral cortex were 0.040, 0.13, 0.016 and 0.40 mumol/l, respectively. The KB values of KU-1257, roxatidine acetate, famotidine and cimetidine for the antagonism against histamine-induced positive chronotropic response of isolated guinea-pig right atrium were 0.041, 0.14, 0.031 and 0.51 mumol/l, respectively. In pylorus-ligated rats, KU-1257, roxatidine acetate and famotidine inhibited gastric acid secretion with respective intraduodenal ID50 values of 12.3, 18.5 and 0.45 mg/kg. In dogs with Heidenhain pouch, the ID50 values of KU-1257 for the inhibition of acid output stimulated by histamine, tetragastrin and meat meal were 0.08, 0.39 and 0.15 mg/kg p.o., respectively. KU-1257 was 2-3 times more potent than roxatidine acetate regardless of secretagogues and twice less than famotidine in meat meal stimulation. These results indicate that KU-1257 is a potent and competitive histamine H2-receptor antagonist.
The effects of KU-1257 (N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl]urea, CAS 120958-90-9) on gastric lesions and duodenal ulcers in rats were compared with those of various antiulcer drugs. KU-1257 prevented the formation of gastric lesions induced by necrotizing agents. The ID50 values against 0.6 N HCl-induced gastric lesions were 18.6 mg/kg, p.o. and 6.0 mg/kg, i.p. The ID50 values against absolute ethanol- and 1% NH3-induced gastric lesions were 12.4 and 9.2 mg/kg, p.o., respectively. Roxatidine acetate, troxipide and teprenone at doses of 100-200 mg/kg p.o. also significantly prevented the formation of gastric lesions by these necrotizing agents. Cimetidine, ranitidine and famotidine had no protective effect against these gastric lesions even at a dose of 200 mg/kg p.o. KU-1257, roxatidine acetate and famotidine inhibited acetylsalicylic acid- and water-immersion stress-induced gastric lesions. KU-1257, roxatidine acetate and famotidine inhibited mepirizole-induced duodenal ulcers, but not troxipide and teprenone. These results suggest that KU-1257 is more potent in the mucosal protective action than troxipide, teprenone, roxatidine acetate and other histamine H2-receptor antagonists.
Healing-promoting actions of KU-1257 (N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl]urea, CAS 120958-90-9) were investigated in chronic gastric and duodenal ulcer models induced by acetic acid in rats and the effects were compared with those of famotidine and roxatidine acetate by gross or histological evaluation. KU-1257 markedly promoted the well-balanced healing of gastric ulcer at oral doses of 10-50 mg/kg x 2/day, as evidenced by the reduction of ulcer, regeneration of mucosa and proliferation of connective tissue. KU-1257 caused an increase in gastric mucus secretion in the regenerated mucosa around the gastric ulcers. Famotidine and roxatidine acetate failed to promote the healing of gastric ulcers even at 100 mg/kg x 2/day p.o. KU-1257 also significantly accelerated the healing of acetic acid-induced duodenal ulcers as well as famotidine and roxatidine acetate. These results indicate that KU-1257 is characterized by a potent promoting action on the healing of chronic ulcers, suggesting that the increase in gastric mucus secretion might be associated with the antiulcer actions of KU-1257 in part.