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Biomedical subjects

H Kuroda

Publications and source records attributed to H Kuroda.

At least 235 records · Page 13Linked to original sources

Study of 16,16-dimethyl prostaglandin E2 for prevention of stress ulcer after hepatectomy of experimental cirrhotic liver and its influence on hepatic regeneration.

The influence of 16,16-dimethyl prostaglandin E2 (16,16-dm PGE2; an agent used for the prevention of stress ulcer after hepatectomy of the cirrhotic liver) on liver regeneration after hepatectomy was studied in rats. The following results were obtained. Ulceration after the stress of 6 h of water immersion was markedly suppressed in rats treated with 30 r/kg of 16,16-dmPGE2 as compared with the untreated controls. In animals that received hepatectomy alone, the gastric pH and gastric mucosal blood flow showed significant reduction from the preoperative levels. In animals that received hepatectomy plus 16,16-dmPGE2 treatment the postoperative reduction in the gastric pH and gastric mucosal blood flow was suppressed, suggesting the effectiveness of 16,16-dmPGE2 treatment in the prevention of stress ulcer after hepatectomy of the cirrhotic liver. The 3H-thymidine uptake percentage and thymidine activity 24 h after hepatectomy and the DNA content 30 h after hepatectomy were significantly higher in animals treated with 16,16-dmPGE2 than in the untreated controls. In animals that were treated intraperitoneally with 50 mg/kg of indomethacin 6 h before hepatectomy the mitotic index 30 h after hepatectomy was markedly lower than that in untreated controls. This indomethacin-induced reduction in the mitotic index tended to be normalized by treatment with 16,16-dmPGE2. These results suggest that 16,16-dmPGE2 treatment effectively prevents stress ulcer and favorably affects hepatic regeneration after hepatectomy of the cirrhotic liver.

Animals↗

[Effects of dopamine on stress ulcer].

Preventive effect of dopamine on stress ulcer formation was investigated in rats. Dopamine 1-10 micrograms/kg/min suppressed the elevation of ulcer index significantly after water immersion and restraint stress in a dose-dependent fashion, however ulcer indices of 25 micrograms/kg/min of dopamine were higher than 10 micrograms/kg/min. Dopamine 1-10 micrograms/kg/min suppressed the decrease of gastric mucosal blood flow, gastric mucosal prostaglandin E2 content and gastric transmucosal potential difference during stress loading in a dose-dependent manner, although the suppression of them in 25 micrograms/kg/min of dopamine was smaller than in 10 micrograms/kg/min also. Dopamine suppressed the increase of gastric acid secretion and gastric motility during stress loading in a dose-dependent fashion up to 25 micrograms/kg/min. These results indicates that dopamine suppresses the formation of stress ulcer by increasing defensive factors and decreasing aggressive factors.

Animals↗

[Surgical and preoperative treatment of soft tissue sarcoma].

Preoperative therapy effects, resected margin and local radicality were investigated in 40 cases of soft tissue sarcoma in which preoperative therapy (mainly radiation therapy) had been given. The results indicated that there was no effect upon prognosis due to postponement of surgery in order to perform preoperative treatment. In cases in which radiation therapy was used for preoperative treatment, even when a surgical margin resulted with in a tumor, no recurrence was found. However, histologically there was concern that some portion of the living tumor cell in marginal area of the tumor might have remained. Thus, at the present stage in cases having undergone initial treatment, radiation limited to the specific area of the resected margin causing non-curative margin should be given. If combined with preoperative radiation therapy, surgical intervention involving "wide margin" can be considered radical. On the other hand, cases having undergone surgery before and receiving preoperative therapy that show good response nevertheless show numerous recurrences. These recurrences, however, invariably occur outside of the irradiated area, and may be attributed to the fact that tumor cell dissemination from the earlier surgery was not within the radiation field. Hence, it was considered that the area for radiation in the case of a recurrence should extend well beyond the scar area.

Combined Modality Therapy↗

[Extended direct anastomosis for coarctation of the aorta and interruption of the aortic arch].

Between March, 1986 and May, 1988, extended direct anastomosis was performed for coarctation of the aorta (CoA) (5 infants) and interruption of the aortic arch (IAA) (3 infants). The aortic arch was hypoplastic in 3 patients. The incision was made in the inferior aspect of the aortic arch proximal to the origin of the carotid or brachiocephalic artery, which was then anastomosed to the descending aorta. Pulmonary artery banding was placed in 4 patients with associated complex cardiac anomalies. Aortic cross-clamp time was 19-54 minutes (mean 41 minutes). Pressure gradient between upper and lower extremity was 0-10 mmHg (mean 4 mmHg). There were no operative deaths and no neurologic complications. The peak flow velocity at the site of aortic reconstruction measured by Doppler echocardiographic study after surgery was 1.2-2.5 m/sec (mean 1.7 m/sec). This procedure has the advantages of leaving the subclavian artery intact and no aortic shelf tissue. And it can be applied in IAA or CoA with hypoplastic aortic arch.

Aorta, Thoracic↗

[Clinical effect of LM-001, prostaglandin synthetic inhibitor, on pain from urinary tract stone and vesical urgency after operation of the bladder or prostate].

Clinical effect of LM-001, a prostaglandin synthetic inhibitor developed from a drug delivery system, was evaluated in 54 patients with pain from urinary tract stones (stone pain) and 32 with vesical urgency after an operation on bladder or prostate. LM-001, felbinac ethyl incorporated in lipid microsphere, wes intravenously administered at the onset of stone pain or vesical urgency. Of 54 with stones and 32 with urgency, 53 and 29 were eligible for response, respectively. The symptoms improved or disappeared in some cases just after the administration and in the majority of patients within 15 minutes, in 49 of 53 patients with stone pain. Further, the effectiveness lasted over 24 hours in 26 of the 49 responding to this agent. On one hand, improvement or disappearance of vesical urgency was recognized in 25 of 29 patients, and the effectiveness was observed shortly after injection in 16 and lasted over 24 hours in 13 cases. Toxicities of this drug were investigated in 54 patients with stone pain and 32 with urinary urgency. Side effects consisted of pain at the injection site in 4, a slight fall of blood pressure in 1, slight visual disturbance in 1, body heat sensation in 1, leukocytosis in 3 and elevation of alkaline phosphatase in 1. These symptoms were transient and disappeared without use of any agent. LM-001 is concluded to be a useful drug for controlling stone pain and vesical urgency since an immediate effect, long durability and high response rates were obtained without severe side

Adolescent↗

Structure-activity relationship of endothelin: importance of charged groups.

Endothelin (ET)-related peptides including ET-1 (1-39) were synthesized, and their constricting activity in rat pulmonary artery rings and pressor activity in unanesthetized rat were measured to elucidate their structure-activity relationship. The vasoconstrictor activities of ET-2, ET-3 and sarafotoxin S6b were one-half, one-60th and one-third that of ET-1, respectively. Such differences in biological activities should mainly arise from sequence heterogeneity at the N-terminal portion, especially at positions 4 to 7. All of the blocked ETs at the amino or carboxyl termini showed greatly decreased activities. A monocyclic analog, in which Cys3 and Cys11 were replaced by Ala, showed one-third the activity of ET-1; however, its deamino dicarba analog was almost completely inactive. Significant activities were retained even with replacement of amino acids at positions Ser4, Ser5, Leu6, Met7, Lys9, Tyr13, and Trp21 by Ala, Ala, Gly, Met(0), Leu, Phe, and Tyr or Phe, respectively. On the other hand, replacement of Asp8, Glu10 and Phe14 by Asn, Gln and Ala, respectively, resulted in complete loss of the biological activity. These results indicated that two disulfide bonds in ET molecule were not essential for the expression of vasoconstricting activity. Both terminal amino and carboxyl groups, carboxyl groups of Asp8 and Glu10, and the aromatic group of Phe14 seemed to be contributing, more or less, to the expression of the biological activities.

Animals↗

Differential susceptibility of HLA class II antigens induced by gamma-interferon in human neuroblastoma cell lines.

Five neuroblastoma cell lines have been examined for the induction of HLA class II antigens by a recombinant gamma-interferon. The expression of HLA-DR and -DP was induced on up to 80% of cells in two of five neuroblastoma cell lines examined (KP-N-SI and KP-N-RT). Low expression of HLA-DR and -DP was induced on the SK-N-DZ line in the presence of recombinant gamma-interferon for 10 days. In contrast HLA-DQ was not induced on any of five neuroblastoma cell lines studied. HLA-DR and -DP antigen induction was reversible, falling to nondetectable levels when interferon was removed from the culture medium. The reinduction of interferon to the culture medium again induced HLA-DR and -DP antigen expression in a fashion similar to that originally observed. These results were confirmed by Northern blot analysis using a probe to HLA-DR alpha mRNA. Recombinant interferon appears to induce HLA class II expression at the level of gene transcription or posttranscription. The results also indicate that HLA-DR, -DP, and -DQ antigens are independently regulated. Treatment of neuroblastoma cell lines with gamma-interferon results in the induction of a differentiated phenotype. Although the cytokine gamma-interferon induces neurofilament expression in some of the cell lines, this was not the case for all lines studied. Thus no correlation could be established between the morphological differentiation and either HLA class II or neurofilament expression. In addition, no correlation between response to recombinant interferon and N-myc amplification was noted. The biological significance of HLA class II expression on neuroblastoma cell lines by gamma-interferon may be related to the differentiation stage of neuroblastoma cells or may enable gamma-interferon-treated neuroblastoma cells to be recognized by cytotoxic T-cells.

Dose-Response Relationship, Drug↗

Differentiation of germ cells in seminiferous tubules transplanted to testes of germ cell-deficient mice of W/Wv and Sl/Sld genotypes.

(WB X C57BL/6)F1-W/Wv (hereafter, WBB6F1-W/Wv) mice and (WC X C57BL/6)F1-Sl/Sld (hereafter, WCB6F1-Sl/Sld) mice are sterile due to the deficient spermatogenesis in the testes. The cause of deficient spermatogenesis in WBB6F1-W/Wv mice is considered to be a defect in germ cells themselves, whereas that in WCB6F1-Sl/Sld mice is considered to be a defect in tissue environment necessary for differentiation of germ cells. Seminiferous tubules isolated from cryptorchid testes of C57BL/6- +/+ mice were transplanted into the testes of WBB6F1-W/Wv and WCB6F1-Sl/Sld mice to clarify that the extratubular environment of these mice was intact or not. Type A spermatogonia in the transplanted tubules normally differentiated into spermatids, suggesting that the extratubular environment is intact in both WBB6F1-W/Wv and WCB6F1-Sl/Sld mice.

Animals↗

Endoscope assisted terminal esophago-proximal gastrectomy for the treatment of esophageal varices in portal hypertension--late results and an analysis of the mechanisms of recurrence.

Endoscopic assistance during terminal esophago-proximal gastrectomy (TEPG) was performed in 86 patients with portal hypertension to confirm the complete disappearance of esophageal varices and eradicate any remnants. The utility of endoscope assisted surgery (EAS), and the mechanisms of recurrent varices were thereby analyzed. Some postoperative recurrence is unavoidable after direct attack surgery as portal hypertension is often still present. Nevertheless, satisfactory disappearance was maintained in 56 cases (65 per cent) from 2 months to 9 years of follow up. Recurrent varices were observed in the other 30 cases, the causes presumably being: atrophy of the liver in 15 cases, thrombus formation in the portal vein in 10 cases, and various other causes in 5 cases; indicating increased resistance on the portal blood flow as a uniform mechanism. The episodes of rebleeding due to recurrent varices or staple ulceration in 8 cases were successfully treated by endoscopic injection sclerotherapy and medication. Actual proof of the disappearance of varices through EAS and an analysis of the mechanisms of recurrence are essential for improving the surgical techniques and treatment in cases of recurrent esophageal varices.

Anastomosis, Surgical↗

Isolation of an auxin-regulated gene cDNA expressed during the transition from G0 to S phase in tobacco mesophyll protoplasts.

A cDNA clone for an auxin-regulated gene was isolated from a tobacco mesophyll protoplast cDNA library by differential screening. Nucleotide, sequence analysis showed that the deduced product of the gene, which we have designated par, is hydrophilic and is composed of 220 amino acids. No significant homology to other known proteins was detected. The mRNA of the par gene is approximately 900 bases long and its accumulation was detected in cultured mesophyll protoplasts as early as 30 min after the addition of 2,4-dichlorophenoxyacetic acid to the culture medium. The par mRNA was not detected in leaves or freshly prepared protoplasts or in protoplasts in the absence of 2,4-dichlorophenoxyacetic acid. Expression of the par gene was detected at a low level in actively dividing BY-2 tobacco suspension culture cells. The conspicuous accumulation of par mRNA before the initiation of DNA synthesis in tobacco mesophyll protoplasts suggests that the par gene product could play a role in the initiation of meristematic activity in differentiated mesophyll cells.

Amino Acid Sequence↗

Synthesis of endothelin-1 analogues, endothelin-3, and sarafotoxin S6b: structure-activity relationships.

Two disulfide analogues (types A and B) of endothelin-3 (ET-3; formerly, rat ET), sarafotoxin S6b, and apamin, were synthesized to determine their disulfide structures as in the case of endothelin-1 (ET-1; formerly human and porcine ET). The disulfide structures of ET-3 and sarafotoxin S6b were found to be identical with that of ET-1 (type A) but distinct from that of apamin (type B). The vasoconstricting activities of ET-3 and sarafotoxin S6b were about one-60th and one-third that of ET-1, respectively. Such different biological potencies between endothelins and sarafotoxin S6b could be largely attributed to the sequence heterogeneity at the N-terminal portion. ET-1 analogues were also synthesized to clarify the structure-activity relationships. The opening of any disulfide bond in the ET-1 molecule extremely decreased the activity, while oxidation of the Met residue did not alter it. Amidation of the terminal COOH group and extension of the Lys-Arg sequence to the N-terminus led to 16- and 540-fold decreases in activity, respectively. Removal of the C-terminal Trp residue resulted in complete loss of the activity. The other disulfide analogues (type B and C) of ET-1 showed markedly lower activity than the parent molecule (type A). These results indicated the importance of the whole molecule with the proper double cyclic structure for determining its active conformation.

Amino Acid Sequence↗

Clinicopathological study of livers from brain-dead patients treated with a combination of vasopressin and epinephrine.

Studies were made on the pathological lesions and biochemical indices of the livers of 22 patients in whom normal hemodynamics was maintained for 0-48 days after brain death by administration of vasopressin and epinephrine. Thirty-one specimens of liver tissues were obtained by percutaneous biopsy or at autopsy. The degrees of central venous congestion, central fibrosis, focal fibrosis, fatty metamorphosis, piecemeal necrosis, periportal fibrosis, and intrahepatic cholangitis in livers on various days after brain death were compared with those on the day of brain death (day 0). Central venous congestion was extensive on days 0-4, significantly less on days 5-14, and then again extensive on days 15-48. Central fibrosis and focal fibrosis showed no remarkable change during the 48-day period. Fatty metamorphosis, piecemeal necrosis, and periportal fibrosis showed no significant changes until day 16, but spread extensively on days 40-48. Intrahepatic cholangitis was scarcely observed on day 0 but began to increase after day 3, and spread extensively after day 5. The level of serum glutamic pyruvic transaminase did not increase in most patients until day 15. The mean value of prothrombin activity also did not decrease until day 15. However, the mean value of serum alkaline phosphatase increased gradually after day 3, and was correlated with cholangitis. The present study showed that during prolonged hemodynamic maintenance of brain-dead patients, pathological lesions did not spread or diminished and that biochemical indices did not become worse, or improved, in the first 2 weeks, except for increases in cholangitis and the serum alkaline phosphatase level.

Adult↗