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Biomedical subjects

Y Sakata

Publications and source records attributed to Y Sakata.

At least 199 records · Page 11Linked to original sources

[Thrombotic complication in the course of aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome; possible involvement of dysplasminogenemia (plasminogen Tochigi) in the pathogenesis of thrombosis].

A 44-year-old Japanese man having aplastic anemia (AA)-paroxyamal nocturnal hemoglobinuria (PNH) syndrome was referred to our hospital because of purpuras due to thrombocytopenia in July 1994. He suffered from pneumonia after admission, complicated with cerebral, splenic, and left renal infarction. Pulmonary infaction was also confirmed by perfusion lung scan. He had a plasma plasminogen (PLG) functional activity of 54.4% with a normal level of PLG antigen. The gel isoelectrofocusing pattern of the plasminogen derived from the patient showed 10 normal bands and 10 additional doublet bands with slightly higher isoelectric points than the normal components. Abnormal PLG is converted by urokinase to an inactive two-chain plasmin molecule. These findings were similar to those of a case with dysplasminogenemia (PLG Tochigi) reported by Aoki et al. He was given warfarin for the prevention of thrombosis in December 1994. As of October 1995, these was no recurrence of thrombosis. The cause of thrombosis in the present case have been the association with PNH, predisposition to PLG Tochigi, or the complication of pneumonia. This is the first report of AA/PNH syndrome associated with dysplasminogenemia.

Adult↗

[Chemotherapy for pancreatic cancer].

Few antitumor agents are effective for advanced pancreatic cancer. 5-fluorouracil, doxorubicin, epirubicin, and mitomycin C were tested as single agents for their respective efficacy against pancreatic cancer. Their response rates were 15, 12, 24 and 24%, respectively. Several trials of combination chemotherapy using mitomycin C, doxorubicin and 5-FU (FAM) were performed, but their response rates did not go exceed those of single agents. Recently, the goal of chemotherapy for pancreatic cancer is thought to be quality of life. Combination of 5-FU and cisplatin or 5-FU, leucovorin and alpha interferon were effective for the prolongation of life with less toxicities. Their median survival times were 7.6 months, and 22 months in PR cases, respectively. CPT-11, gemcitabine, taxotere and BOF-A2 are promising new drugs for their effectiveness and benefits for patients with pancreatic cancer. Combination of mitomycin C, carboquone and 5-FU with angiotensin II was effective in terms of antitumor effect and prolongation of life. Generally, a large number of patients with advanced pancreatic cancer cannot receive chemotherapy because of deterioration in performance status. For them, combination of continuous venous infusion of low-dose 5-FU and low-dose cisplatin could be effective. The majority of patients with pancreatic cancer must await new agents and methodology in the future.

Antineoplastic Combined Chemotherapy Protocols↗

Expression of plasminogen activator inhibitor 2 in the adult and embryonic mouse tissues.

We have studied the expression of plasminogen activator inhibitor 2 (PAI-2) in the adult mouse and during embryonic development using immunohistochemistry and the polymerase-chain reaction. Mouse PAI-2 mRNA was mainly expressed in the skin, bone-marrow, spleen, lung, thymus, and urinary bladder. Immunohistochemical studies suggested that PAI-2 was synthesized in macrophages and epithelial cells such as skin epithelial cells, transitional cells of the urinary bladder, and mesothelial cell of peritoneum and pleura. PAI-2 mRNA and antigen expression was observed only in the skin of 15 day-old mouse embryos. These data suggest that PAI-2 may play a role in protecting the mouse embryo from the protease attack in the amniotic fluid and also in maintaining and/or protecting the structure of various surfaces in the mouse.

Aging↗

[Visiting nurse support for patients wishing to die at home].

Thirty-two (1994) and 55 (1995) patients in the terminal stage of many kinds of cancer were cared for satisfactorily at home by a visiting team of nurses from Niigata Cancer Center Hospital. A prostate cancer patient with multiple bone metastasis was suffering from morphine-resistant intractable pain, and highly dependent on medical care. We continued to take care of him by frequent visitation and psychological assist until he eventually died at home according to his wishes. It is important to create a suitable support team for the continual difficult home care of each terminal patient.

Attitude to Death↗

Effect of staphylokinase concentration of plasminogen activation.

Activation of Glu- and Lys-plasminogen by various concentrations of recombinant staphylokinase (SAK) were studied by the generation of amidolytic activity from the chromogenic substrate S-2251(H-D-Val-Leu-Lys-pNA) and by SDS-PAGE analysis. Surprisingly, excess SAK decreased and fixed the rate of S-2251 hydrolysis in a mixture of Lys-plasminogen and SAK. Since the effect of SAK on S-2251 hydrolysis by plasma was similar, the hydrolysis kinetics by free plasmin and plasmin-SAK complex were studied. Hydrolysis by either enzyme form followed Michaelis-Menten kinetics with a Km of 0.38 mM for plasma and 3.74 mM for SAK-plasmin complex. The catalytic rate constant was 22.7 s-1 for plasmin and 21.0 s-1 for the SAK-plasmin complex. With excess SAK and vigorous removal of plasmin activity from plasminogen, the pre-activation lag period differed greatly between Glu- and Lys-plasminogen. Based on the different substrate specificity of plasmin and plasmin-SAK complex, we analyzed the Glu-plasminogen activation with either catalytic or excess SAK. With excess SAK, almost no Lys-plasminogen was detectable and whole Glu-plasminogen was converted directly to Glu-plasmin, then gradually to Lys-plasmin. In contrast, Lys-plaminogen appeared rapidly with catalytic amount of SAK. These results suggest that inhibition of Glu-plasminogen to Lys-plasminogen to Lys-plasminogen conversion in the plasminogen-SAK complex in the presence of excess SAK prolonged the initial lag phase of activation.

Dose-Response Relationship, Drug↗

Suppression of interleukin-1 beta production in the circumventricular organs in endotoxin-tolerant rabbits.

Interleukin-1 beta (IL-1 beta) production in the brain and the spleen was investigated in rabbits which show febrile tolerance to bacterial endotoxin, lipopolysaccharide (LPS). Febrile tolerance to LPS was induced by daily intravenous (i.v.) injections of LPS (4 micrograms/kg, i.v.) for 5 days. In the LPS-tolerant rabbits, the second phase of the biphasic fever induced by i.v. injection of LPS (4 micrograms/kg) disappeared, although the first phase remained intact. In situ hybridization and immunohistochemical studies revealed that IL-1 beta production was observed in the circumventricular organs, such as the organum vasculosum laminae terminalis (OVLT), subfornical organ (SFO) and area posterema (AP), 1 h after the first exposure to i.v. injection of LPS (4 micrograms/kg) (acute rabbits). In contrast, IL-1 beta production in these circumventricular organs disappeared in the LPS-tolerant rabbits. IL-1 beta production was observed in the spleens of the acute and the LPS-tolerant rabbits after i.v. injections of LPS. The cells which produced IL-1 beta in the spleen following LPS injections were confirmed to be monocytes/macrophages and polymorphonuclear leukocytes by immunohistochemistry in both the acute and the LPS-tolerant rabbits. The LPS-injected acute rabbits showed a significant increase in the number of IL-1 beta-immunoreactive monocytes/macrophages, compared with that in the saline-injected acute rabbits. However, there was no significant difference in immunoreactive cell numbers between the saline-injected acute and LPS-injected tolerant rabbits, or between the LPS-injected acute and the LPS-injected tolerant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Newly synthesized histamine accelerates ornithine decarboxylase activity in rat intestinal mucosa after ischemia-reperfusion.

We previously demonstrated that both histamine synthesis (histidine decarboxylase activity) and polyamine synthesis (ornithine decarboxylase activity) increased in the rat intestinal mucosa after ischemia-reperfusion, whereas the relationship between these two factors remains unclear. To elucidate this relationship, we performed the present study. The superior mesenteric artery was occluded for 15 min followed by reperfusion. After ischemia-reperfusion, histidine decarboxylase activity and ornithine decarboxylase activity in the rat jejunal mucosa were measured in a time-dependent manner. Histidine decarboxylase activity increased 1 hr after ischemia-reperfusion, although ornithine decarboxylase activity did not; however, its activity did increase 6 hr after. The increase of ornithine decarboxylase activity was attenuated when the increase of histamine synthesis was suppressed by the inhibition of histidine decarboxylase activity caused by pretreatment with alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase. Pretreatment with H1-receptor antagonist attenuated the increase of ornithine decarboxylase activity after ischemia-reperfusion. These results indicate that the newly synthesized histamine, as indicated by an increase of histidine decarboxylase activity, increases ornithine decarboxylase activity after ischemia-reperfusion of the rat intestinal mucosa.

Animals↗

Effect of TFC-612, a 7-thia prostaglandin E1 derivative, on a peripheral arterial occlusive disease model in rats.

TFC-612, methyl 6-[((1R,2S,3R)-3-hydroxy-2-[(1E,3S,5R)-3-hydroxy-5- methyl-1-nonenyl)-5-oxocyclopentyl]-thio]-hexanoate, inhibited the progression of the lesion in a lauric acid-induced peripheral arterial occlusive model at 1.0 mg/kg p.o. or 1.0 microgram/rat/h s.c. in rats. Aspirin (32 mg/kg, p.o.), an anti-platelet drug, did not suppress the lesion growth. On the other hand, ketanserin (10 mg/kg, p.o.), a 5-HT2 antagonist, also inhibited the progression of the lesion. In vitro, TFC-612 inhibited rat platelet aggregation induced by collagen and ADP with IC50 values of 5.4 ng/mL and 9.5 ng/mL, respectively. Aspirin also inhibited collagen-induced aggregation with an IC50 value of 6.3 micrograms/mL, but not ADP-induced aggregation at 180 micrograms/mL. Ketanserin had no effect on either aggregation at 40 micrograms/mL. In ex vivo experiments, aspirin inhibited platelet aggregation induced by collagen at 10 and 32 mg/kg in rats. However, TFC-612 showed significant inhibition only at 10 mg/kg. TFC-612 and ketanserin increased dermal blood flow in the rat paw at 1.0 microgram/kg i.v. and 100 micrograms/kg i.v., respectively. Aspirin had no effect on blood flow at 3.2 mg/kg i.v. These results suggest that the improvement of microcirculation, in addition to anti-platelet action by TFC-612, contributes to its inhibitory effect in a peripheral arterial occlusive model in rats.

Alprostadil↗

Pregnancy outcome among long-term survivors with acute leukemia.

By means of a mail questionnaire, we evaluated the influence of treatment for acute leukemia on offspring of long-term survivors and determined whether the outcome of pregnancy in patients (or spouses) induced relapse of acute leukemia. In 322 replies from the 445 institutions where a questionnaire was sent, there were 1136 adult long-term survivors. We analyzed the 43 adults who had become pregnant or become a father after postremission therapy. The mean age at the leukemia onset was 26.4 and 21.6 years for males and females. Forty-six normal children (26 boys and 20 girls) were born of long-term survivors including 7 pairs of siblings and a pair of twin sisters. There were no malformed babies. There were five abortions. The average duration until delivery was 79 months after diagnosis, and 49 months after the final postremission therapy. Four of 38 parents of live offspring died (3 relapse, 1 other disease), and the other 34 parents of live offspring were in complete remission at the point of this survey. The adverse effect of treatment on the offspring of long-term survivors could not be clarified in this survey. Additional lifetime follow-up of long-term survivors with acute leukemia and their offspring may be necessary.

Acute Disease↗

Prevention of recurrent bleeding from gastric ulcer with a nonbleeding visible vessel by endoscopic injection of absolute ethanol: a prospective, controlled trial.

We performed a prospective, randomized trial to assess the efficacy of endoscopic injection therapy with absolute ethanol in preventing recurrent bleeding in patients with nonbleeding visible vessels in gastric ulcers. During the period of 1990 to 1993, 62 patients who bled were found to have gastric ulcers with nonbleeding visible vessels; all of them were enrolled for this trial. The 62 patients were randomly divided into two groups, which were comparable at entry. In group I (33 patients), we performed endoscopic injection therapy with absolute ethanol. In group II (29 patients), we sprayed the ulcers with 0.1% epinephrine and thrombin. Endoscopic injection therapy with ethanol was performed at the second endoscopy in the patients in both groups who had recurrent bleeding. Among the 33 patients in group I, 4 patients (12.1%) rebled after the initial ethanol injection therapy, whereas 10 of 29 patients (34.5%) rebled in the control group (p < .05). No patients in group I required surgical intervention, and ultimate hemostasis was achieved in all 33 group I patients (100%), indicating that endoscopic ethanol injection therapy achieves ultimate hemostasis and prevents recurrent bleeding in patients with gastric ulcers and nonbleeding visible vessels.

Epinephrine↗

Eradication of Helicobacter pylori with lansoprazole and clarithromycin in gastric ulcer patients.

This study attempted to determine the efficacy of lansoprazole plus clarithromycin therapy in the eradication of Helicobacter pylori in gastric ulcer patients. The influence of H. pylori eradication on healing and relapse of ulcers was also studied. Thirty-nine patients received either lansoprazole 30 mg daily for 8 weeks (group 1) or clarithromycin 200 mg twice daily for 2 weeks and lansoprazole 30 mg daily for 8 weeks (group 2). Before treatment, H. pylori status was evaluated by a rapid urease test and histologic examination. H. pylori clearance and eradication were evaluated by a rapid urease test, polymerase chain reaction, and a [13C]urea breath test. Clearance of H. pylori was 0% in group 1 and was 33% in group 2. Eradication of H. pylori was 0% in group 1 and 21% in group 2. Although all five ulcers were healed in patients with H. pylori eradication, ulcers were not healed in the five patients without eradication. Relapse of ulcer was observed in three patients in whom eradication had failed. In this study, for H. pylori-positive gastric ulcer patients, better results were obtained when lansoprazole plus clarithromycin therapy was used, and H. pylori eradication was achieved.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Evaluation of latex agglutination test for alpha-fetoprotein in diagnosing rupture of fetal membranes.

To assess the utility of a latex agglutination test for alpha-fetoprotein in vaginal fluid for diagnosing rupture of the fetal membranes, we tested 91 pregnant women, including 32 with an established rupture, 19 with no evidence of rupture and 40 with a suspected rupture. Results were compared with those of the pH indicator and the fern tests. The latex agglutination test had better sensitivity, specificity, or both, than the pH indicator and the fern tests. We conclude that the latex agglutination test is more accurate than either the pH indicator or the fern test for diagnosing premature rupture of fetal membranes.

Adult↗

Catheter-related infections by Hansenula anomala in children.

During August and September, 1992, we experienced 4 cases of Hansenula anomala (H. anomala, synonym Pichia anomala) fungemia in immunocompromised patients. Two patients had been suffering from a malignant disease, 3 of them had received broad-spectrum antibiotics and a central venous catheter (CVC) had been inserted in all of them. H. anomala was isolated as the sole pathogen from all 4 patients. Three of them responded favorably to fluconazole after withdrawal of the catheter, but one failed. H. anomala should be considered as a possible cause of catheter-related infections.

Catheterization, Central Venous↗

[Renal cell carcinoma with regional lymph node metastasis].

A follow up study of 20 cases of renal cell carcinoma with regional lymph node metastasis at the department of urology in Niigata Cancer Center Hospital from 1979 to 1993 is presented. During this period, we treated 249 patients with renal cell carcinoma with or without lymph node metastasis. Lymph node metastasis could be estimated in 188 out of 249 patients. Histologically, lymph node metastasis was classified as pN1 in 8 cases, pN2 in 7 cases, and pN3 in 5 cases. The 3- and 5-year survival rates of 20 patients with lymph node metastasis were 45.0% and 16.4%, respectively. Nine of the 20 cases had no distant metastasis and 11 cases had distant metastasis. Three of the 9 patients with distant metastasis had no recurrence. Two of these 3 patients are still alive after 10 years and 3 years and 1 patient died because of acute heart failure. These 3 patients had pN1 metastasis smaller than 1 cm lymph node. Four of the 11 patients with distant metastasis had more than a two-year survival. However, 3 patients died due to renal cell carcinoma although primary and metastatic regions were resected and IFN with chemotherapy were given. Only one patient is still alive without recurrence after 3 years. This case detected as right renal cell carcinoma with pN2 metastasis and bilateral pulmonary metastasis was treated with radical nephrectomy with regional lymph node dissection and administered Methotrexate, VP16 and CisPlatinum chemotherapy and IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Definition of early renal cell carcinoma--from the study of pathological and clinical findings according to tumor size].

In this study we tried to define the term "early renal cell carcinoma" from the study of pathological and clinical findings of renal cell carcinoma according to tumor size. During the 33 years from 1961 to 1993, 288 patients with renal cell carcinoma were treated in Niigata Cancer Center Hospital. In 250 of the 288 cases, tumor size was measurable. The average tumor size was 6.9 +/- 3.4 cm (from 1.5 cm to 17 cm). First we divided renal cell carcinoma into four group according to tumor size; under 2.5 cm (n = 32), 2.5-5 cm (n = 67), 5-10 cm (n = 108) and over 10 cm (n = 43). The 5-year survival rate was 89.2, 71.4, 54.3 and 33.2% respectively. The survival rate for tumors under 5 cm in size was significantly higher than that for tumors over 5 cm in size (p < 0.01). Then the tumors under 5 cm were analyzed for every centimeter in tumor size. The survival rate was 89.9% for tumors under 2 cm (n = 22), 94.1% for 2-3 cm (n = 18), 85.2% for 3-4 cm (n = 25) and 61.8% for 4-5 cm (n = 32). None of the patients with tumors under 3 cm died of renal cell carcinoma. One patient with distant metastasis and another patient with regional lymph node metastasis were found among the patients with tumors under 3 cm in size but these two patients are now free from the disease. Recurrence was not found in the patients with tumors under 3 cm in size. There was little vein involvement in the cases under 3 cm (2/37). From these findings, we define the early renal cell carcinoma as the cases in which the tumor is under 3 cm in size and without distant or lymph node metastasis.

Adult↗

[Pharmacokinetic, bacteriological and clinical studies of SY5555 in the pediatric field].

Pharmacokinetic, bacteriological and clinical studies on SY5555, a new oral penem, were carried out, and the following results were obtained. 1. MICs were determined for 6 drugs, SY5555, clavulanic acid/amoxicillin (CVA/AMPC), cefaclor (CCL), cefotiam (CTM), cefpodoxime (CPDX), cefdinir (CFDN) against 20 strains of bacteria isolated from patients who were subsequently treated with SY5555. MICs of SY5555 for Gram-positive cocci ranged from 0.05 to 0.10 microgram/ml against 10 strains of Staphylococcus aureus. The MIC was < or = 0.025 microgram/ml against one strain of Streptococcus pyogenes, and MICs were from < or = 0.025 to 0.39 microgram/ml against Streptococcus pneumoniae. These MIC values were equivalent or superior to those of the other 5 drugs. MICs of SY5555 for Gram-negative bacilli were 0.39 and 6.25 micrograms/ml against Haemophilus influenzae, and these values were equivalent to those of the other drugs, except CPDX. The MIC of SY5555 was 0.39 microgram/ml against 2 strains of Escherichia coli, and this value was equivalent or superior to those of CVA/AMPC and CCL, similar or inferior to those of CPDX and CFDN, and inferior to that of CTM. The MICs of several drugs were determined for 10 strains of Bordetella pertussis and 30 strains of Campylobacter jejuni isolated from patients before this clinical study. The MICs of SY5555 against the 10 strains of B. pertussis were compared with those of 7 drugs, CCL, CTM, CPDX, ampicillin (ABPC), piperacillin (PIPC), imipenem (IPM) and erythromycin (EM). The MIC of SY5555 was 0.78 microgram/ml against all of the strains. This value was superior to those of CCL, CTM and CPDX, similar or inferior to that of IPM and inferior to those of PIPC and EM. The MICs of SY5555 against the 30 strains of C. jejuni were compared with those of 7 drugs. CCL, CTM, CPDX, CFDN, ABPC, IPM and EM, and the MIC of SY5555 was < or = 0.025 microgram/ml or 0.05 microgram/ml and these values were equivalent or superior to those of the 7 reference drugs. 2. SY5555 dry syrup was administered orally at 30 min. after meals, to a total of 5 patients, at doses of 5.0 and 10.0 mg/kg to 2 patients each and at a dose of 15.0 mg/kg to one patient and the plasma concentrations were determined. Peak concentrations were detected 1 to 3 hours after administration in all patients and the peak concentrations were 0.93 and 1.21 micrograms/ml at the 5.0 mg/kg dose, 2.85 and 5.49 micrograms/ml at the 10.0 mg/kg dose and 5.79 micrograms/ml at the 15.0 mg/kg dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

[Clinical and pathological studies of renal cell carcinoma with vein involvement].

To clarify the meaning of vein involvement, the clinical and pathological findings of the patients with renal cell carcinoma were examined. Out of 288 patients treated for renal cell carcinoma-from 1961 to 1993 at Niigata Cancer Center Hospital, 238 patients were examined for vein involvement. Tumor stages were evaluated according to the general rules for clinical and pathological studies on renal cell carcinoma (2nd edition). In 154 patients, the stage was pV0, in 41 pV1a, in 23 pV1b and in 20 pV2. The 5-year survival rate was 72.2% in pV0, 60.1% in pV1a, 51.9% in pV1b and 30.0% in pV2. Histological findings as grade, tumor size, regional lymph node metastasis and distant metastasis were proportional to vein involvement. The difference in the survival rate and histological findings of primary tumor between pV1a and pV1b group was small but the difference between pV0 and pV1a was significant. Therefore, the histological and clinical studies of the cases with pV1a must be done carefully. The 5-year survival rate of the patients with pV2 and without distant metastasis was 50.0%. However, the prognosis of the patients with pV2 and with distant metastasis was poor. Therefore aggressive treatment was not recommended for these patients.

Aged↗

[The evaluation of surgical management for metastatic lesions of renal cell carcinoma].

The clinical experience with 29 renal cell carcinoma patients who underwent resection of their metastatic lesions was reviewed. Fourteen patients had no metastatic lesions when nephrectomy was performed initially (initial M0 group) and 15 patients already had detected metastases at diagnosis of their renal tumors (initial M1 group). The final point of follow-up was May 31, 1994. Eighteen patients (M0 9, M1 9) were curatively resected and 11 (M0 5, M1 6) underwent non-curative resection. In the curatively resected group, 7 patients (3 lung, 2 adrenal gland, 1 brain, 1 bone metastasis) were alive with no recurrence followed from 50 to 174 months. Eight died from tumor recurrences, 1 was alive with tumor recurrence and 2 died from other diseases. The 3-year and 5-year survival rates in the curatively resected group (16 patients, excluding 2 who died from other diseases) were 87.5% and 61.9%, respectively, according to the Kaplan-Meier method. On the other hand, the 3-year and 5-year survival rate in the non-curatively resected group were 36.4% and 27.3%, respectively. Between the curatively resected group and non-curatively resected group, a significant difference was shown concerning the survival rate (3 year: P = 0.0018, 5 year: P = 0.003, generalized Wilcoxon method). We concluded that curative resection was the most important prognostic factor in the treatment of metastatic lesions.

Aged↗