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Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 721 records · Page 40Linked to original sources

[A comparative study between the clinical and autoptic findings in cases with malignant tumor in the head and neck].

In 106 autopsies of patients in Kitasato University Hospital from 1974 to 1989, who had died of malignant tumor in the head and neck, the relationship between the clinical diagnosis and its autoptic finding was retrospectively investigated. The result was summarized as follows. 1. Characteristics in 98 cases other than malignant lymphoma: 1) Local recurrence was detected by autopsy in 60 cases (61%) among 98. Discrepancy between clinical diagnosis and autoptic findings was recognized in 10 cases (10%), in whom 4 false positive cases by clinical diagnosis were included and it was considered that the rate was relatively high. 2) The metastatic lymph nodes were demonstrated by autopsy in 50 cases (51%). Discrepancy between clinical diagnosis and autoptic findings was found in 37 (38%), 35 of them were clinically diagnosed to be negative. However, in 35 of them it was considered that the discrepancy had not influenced their fatal courses. 3) Metastases to distant organs were demonstrated by autopsy in 49 (50%). Discrepancy between clinical diagnosis and autoptic findings was found in 39 (40%). 33 of them were clinically diagnosed to be negative. The discrepancy concerned with the causes of death was shown in 5 cases. 2. Characteristics in 8 cases of malignant lymphoma: Discrepancy between clinical diagnosis and autoptic findings of distant metastases was frequently observed but the discrepancy concerned with the causes of death was not shown. There were 2 cases in which side effect of chemotherapy may cause poor prognosis.

Adolescent↗

WF-2421, a new aldose reductase inhibitor produced from a fungus, Humicola grisea.

WF-2421 is a novel aldose reductase inhibitor produced by Humicola grisea. WF-2421 was purified from the culture filtrate by successive ion exchange chromatography and the chemical structure was assigned to be alpha-formamido-5'-(2-formamido-1-hydroxyethyl)- beta,2',6-trihydroxy-3-biphenylpropanoic acid (1) on the basis of spectroscopic evidence. The IC50 value of WF-2421 was 3 x 10(-8) M against partially purified aldose reductase of rabbit lens.

Aldehyde Reductase↗

Studies on WF-3681, a novel aldose reductase inhibitor. IV. Effect of FR-62765, a derivative of WF-3681, on the diabetic neuropathy in rats.

Pharmacokinetic properties of WF-3681 and FR-62765 in rats were examined. FR-62765 showed higher peak concentrations in the plasma and higher concentrations in the sciatic nerve than WF-3681 when each compound was administered orally to rats. We therefore evaluated FR-62765 in rats with diabetic neuropathy. As a result, FR-62765 at 32 mg/kg/day administered for 3 weeks to streptozotocin-induced diabetic rats significantly prevented the accumulation of sorbitol in the sciatic nerve and the reduction of motor nerve conduction velocity in the tail. From these results it was concluded that the aldose reductase inhibitor FR-62765 might be a useful drug for diabetic neuropathy.

Aldehyde Reductase↗

[Kinetics of immune complex deposition and influence of decomplementation on their clearance in cationized antigen induced acute serum sickness].

Using a murine acute serum sickness model caused by cationized bovine gamma-globulin (CBGG), the histological findings, accumulation of CBGG in the organs and the effect of decomplementation for the clearance of immune complex (IC) were investigated. The accumulation of CBGG increased in the lungs in the presence of anti-CBGG antibody 1 hour after injection of CBGG, but did not change in the kidneys. This suggests that CBGG forms IC in situ in the kidneys, and that circulating IC accumulates in the lungs. Decomplementation did not influence the uptake of CBGG immediately after challenge but delayed the clearance of CBGG in the kidneys, lungs, liver and spleen. A beneficial role of the complement system in the clearance of IC even for those formed in situ was recognized. Histological changes, cellular infiltration and microvascular destruction, evoked in the lungs in this experimental model immediately after challenge, were not seen in the kidney, suggesting the different modes of complement activation in these organs.

Animals↗

[The relationship between complement C3 receptors (CR1, CR3) on polymorphonuclear leukocytes and complement fragments during hemodialysis].

The expression of complement receptor type 1 (CR1) and type 3 (CR3) on polymorphonuclear leukocytes (PMNs) and generation of complement fragments, C3a, C5a, C4d, iC3b and Bb, were studied in patients during hemodialysis using cuprammonium rayon (Cu) membranes. Furthermore, the relation between the expression of CR1 and CR3 on PMNs from healthy donors and complement fragments was investigated. The expression of CR1 and CR3 on PMNs increased during hemodialysis. Plasma C3a, C5a and iC3b levels increased in the first 15 minutes and then decreased at 120 minutes of dialysis. But plasma Bb level remained high until the end of hemodialysis. Purified Bb had no effect on the expression of CR1 and CR3 on PMNs, but C5a augmented those expression in vitro. Nafamostat mesilate, an artificial proteinase inhibitor, inhibited augmentation of complement receptors on PMNs in concentration dependent fashion. C5a generated through the activation of complement was thought to take an important role in the increased expression of CR1 and CR3 on PMNs.

Aged↗

[Complement fragments in patients with bronchial asthma].

In this study, we investigated the pharmacological reactions induced by ibudilast to the complement system with the aim of clarifying the functional relation of the complement system to allergic reactions and pathology in patients with bronchial asthma. Complement hemolytic activities (CH50 and ACH50), complement profile, anaphylatoxins (C3a and C5a) and complement fragments (Bb, iC3b and C4d) were measured in 20 patients with bronchial asthma. One of antiasthmatic activities induced by ibudilast was concluded to be brought about though inactivation of the alternative complement pathway working on type III allergic reaction. Ibudilast increased the complement fragment Bb in the patients' plasma with the fairly controlled bronchial asthma. This increase in circulating Bb was suspected to be a result of inactivation of intermediate complement complexes, for example C3b.Bb.P, because the amounts in plasma of C3 and C5 showed no changes, while those of factor, B, P, H and I were decreased by ibudilast administration in patients with fairly controlled bronchial asthma. This antiasthmatic ability of ibudilast was restrained in those patients whose peripheral leukocytopenia was advanced before ibudilast administration, and in those whom ibudilast did not provoke an increase in the plasma level of iC3b, or did not prevent the serum level of C5 from increasing. In those unfairly controlled cases, enough anaphylatoxins, especially C5a might be produced to make the margination of peripheral neutrophils to the lung and increase CR3 on neutrophils binding with iC3b.

Adult↗

[Antitumor activity of T-506, a novel synthetic FUDR derivative, on murine colon cancer and its hepatic metastasis].

T-506 is a novel synthetic FUDR derivative which releases FUDR slowly in vivo. We studied antitumor activity of T-506 by i.v. injection against mouse colon cancer, colon 26. When T-506 was administrated to mice daily, from day 1 through day 10, or every 3 days, on days 1, 4, 7, and 11, after s.c. inoculation of the tumor, the survival period was expanded significantly. The subcutaneous tumor growth was also inhibited according to the dose levels. Then, we compared the therapeutic effects on the experimental hepatic metastasis of colon 26 between T-506, 5'-DFUR and UFT at each maximal tolerable dose; that is, T-506 (0.074 m mole/kg/day; i.v. on days 1, 4, 7, and 10), 5'-DFUR (1.0 m mole/kg/day; P. O. from day 1 to 7), UFT (0.1 m mole/kg/day; P. O. from day 1 to 7). T-506 and 5'-DFUR suppressed completely the metastases of 5 of 6 (83.3%) mice and 6 of 7 (85.7%), respectively. UFT did not show a significant inhibitory effect. However, since the loss of body weight was more marked in T-506 than in the other two drugs, the side effect was thought to be a serious problem. These data suggested that if the side effect could be overcome, T-506 would be useful clinically for the treatment of gastrointestinal cancers or hepatic metastases.

Animals↗

[Correlations between blood pressure, left ventricular hypertrophy, and left ventricular diastolic function in hypertensive patients].

We examined the relationship of hypertension to left ventricular hypertrophy (LVH) and left ventricular diastolic function by ambulatory blood pressure monitoring device and echocardiography. We studied 36 untreated hypertensive non-diabetic patients (16 males and 20 females) whose casual systolic blood pressure (CSBP) and/or diastolic blood pressure (CDBP) were higher than 140 mmHg and 90 mmHg, respectively. All patients were less than 65 years of age without organic heart disease. Resting systolic and diastolic blood pressures (RSBP, RDBP) were measured after lying in a supine position for 30 min by the auscultatory method. Ambulatory blood pressure was measured every 30 or 60 min for 24 hours by Colin ABPM 630, and the mean 24-hour ambulatory systolic and diastolic blood pressures (ASBP, ADBP) and the systolic and diastolic hyperbaric indices (SHI, DHI) were obtained. The left ventricular mass index (LVMI) was obtained as an indicator of LVH by M-mode echocardiography. The ratio of peak velocity of mitral inflow caused by atrial contraction to that of rapid inflow (A/R) was obtained as an indicator of the LV diastolic function by Doppler echocardiography. The coefficients of correlation between BP and the LVMI, and the A/R were determined. There were significant positive correlations between the LVMI and ASBP (r = 0.51, p < 0.005), the SHI (r = 0.49, p < 0.005), CSBP (r = 0.47, p < 0.01) and RSBP (r = 0.41, p < 0.05), however, there were no significant correlations between the LVMI and ADBP, the DHI, CDBP, RDBP and age. There were significant positive correlations between the A/R and ADBP (r = 0.44, p < 0.01), age (r = 0.40, p < 0.02), CSBP (r = 0.38, p < 0.05) and RDBP (r = 0.38, p < 0.05), however, no significant correlations between the A/R and ASBP, the SHI, DHI, RSBP and CDBP. Only a weak correlation was observed in all subjects between the LVMI and A/R, which was slightly improved by use of > 90 mmHg CSBP readings (r = 0.32). It was concluded that LVH is related mainly to continuous systolic hypertension, and that LV diastolic dysfunction is related mainly to continuous diastolic hypertension. Therefore, it was suggested that LVH and LV diastolic dysfunction in hypertensive patients are caused by different mechanisms.

Adult↗

[Percutaneous transvenous mitral commissurotomy in managing rheumatic mitral stenosis].

From April 1987 to October 1989, 32 patients with mitral stenosis (MS) were treated, of whom percutaneous transvenous mitral commissurotomy (PTMC) was performed in 14. PTMC was indicated by the surgeons in 5 patients including 1) 2 patients who refused reoperation, 2) one with early gastric cancer, 3) one with severe hyperthyroidism and cardiac cachexia, and 4) one with acute renal failure and aortic stenosis. In the other 9 patients, PTMC was indicated by the cardiologists, because it is less invasive. Thirteen patients underwent open mitral commissurotomy (OMC) and 5 patients were treated with mitral valve replacement (MVR). PTMC group: Symptoms were alleviated in 10 of 14. The mitral valve areas (MVA) changed from 1.03 +/- 0.47 cm2 to 1.90 +/- 0.67 cm2 (p < 0.001), and the mean pressure gradient between the left atrium and left ventricle decreased from 10.2 +/- 3.6 mmHg to 4.9 +/- 1.7 mmHg (p < 0.001). No significant mitral valve regurgitation (MR) was induced by PTMC. OMC group: Symptomatic improvement was observed in all patients. The MVA changed from 1.54 +/- 0.46 cm2 to 3.06 +/- 1.34 cm2 (p < 0.001) and the mean left atrial pressures were reduced from 17.6 +/- 7.8 mmHg to 10.5 +/- 4.2 mmHg (p < 0.001). MVR group: There was one hospital death, and the other 4 patients were discharged with satisfactory results. It is concluded that although PTMC has been routinely performed for mild cases, this method is also very helpful in treating patients having various complications which impede open heart surgery.

Adult↗

[Interstitial hyperthermia (MINERVE) for perineal local recurrence of rectal cancer].

Interstitial hyperthermia (MINERVE) was performed for 2 patients with perineal local recurrence of rectal cancer. The MINERVE was a 20 W generator of 550-610 kHz with 4 pairs of probes creating an electromagnetic field (Odam Co., France). The basic regimen was five irradiation treatments of 2 Gy per week, with two hyperthermia treatments (for 60 minutes at more than 43.5 degrees C) a week, 500 mg of 5-FU or 25 mg of CDDP per hyperthermia treatment, and 3 g/day of PSK. The radiation therapy was performed prior to hyperthermia, the chemotherapy at the same time. Perineal tumors and symptoms disappeared completely in 1 patient and were reduced in 1 patient. This treatment is expected to be clinically as a part of multidisciplinary treatment for superficial malignant tumors.

Adult↗

[A case of aortoduodenal fistula following radiotherapy of retroperitoneal metastatic disease].

A new case of aortoduodenal fistula was added to the five cases previously reported in the literature, in which malignancy and/or its treatments could be implicated. This 67 year-old woman, six years previously had been placed on a therapy including irradiation on the pelvis for cancer of uterine cervix. For this time she underwent a radiotherapy completed in a total dose of 55.6 Gy combined with hyperthermia and chemotherapy for retroperitoneal metastatic disease with excellent response. Three months later she had hematemesis followed by melena and deteriorated to hemorrhagic shock. Emergent aortography detected contrast extravasation from the aorta with subsequent opacification of the duodenum, and immediate intraaortic balloon occlusion was done, but she died soon thereafter. Postmortem examination revealed the fistula from the aorta just above the bifurcation to a 2 by 1.5 cm. area of the posterior wall of the third portion of the duodenum. Accentuated arteriosclerosis in locally irradiated portion of the aorta, obstruction of small arteries from organized thrombus and hyaline necrosis in the wall of the fistulous tract were defined without evidence of tumor invasion. Based upon the findings of the patient reported herein, radiation might be another possible etiologic factor in aortoduodenal fistula, as well as tumor invasion per se.

Aged↗

[Carcinoma of the gastric remnant fed by the accessory left gastric artery--a case report].

A 65-year-old female, who had undergone partial gastrectomy with Billroth II reconstruction for duodenal ulcer 22 years ago, visited our hospital with a complaint of anorexia. Roentgenogram and endoscopic examination revealed a protruding lesion on the posterior wall of the gastric remnant. An endoscopic biopsy specimen was histologically regarded as carcinoma. Proper hepatic arteriography revealed an accessory left gastric artery arising from the left hepatic artery, which was a main feeder to the tumor. Total gastrectomy with lymph node dissection and splenectomy were performed. Histology of the tumor was poorly differentiated adenocarcinoma located in the submucosal layer. To our knowledge, there is no report about the carcinoma of the gastric remnant fed by the accessory left gastric artery.

Adenocarcinoma↗

Genetic changes and histopathological types in colorectal tumors from patients with familial adenomatous polyposis.

Loss of heterozygosity (LOH) and K-ras mutation were analyzed in 111 colorectal polyps and 26 invasive carcinomas from 40 patients with familial adenomatous polyposis of distinct histopathological types. LOH, being less than 2% in moderate adenomas, was detected on chromosome 5q (20%) in severe adenomas, on 5q (26%) and 17p (38%) in intramucosal carcinomas, and on 5q (52%), 17p (56%), 18 (46%), and 22q (33%) in invasive carcinomas. LOH on chromosome 5q occurred most frequently in the region close to the APC gene both in adenomas and carcinomas, and a loss of the normal allele of the APC gene was demonstrated in 3 cases. K-ras mutation markedly increased in the step of development from moderate (11%) to severe (36%) adenomas. These results suggest the following mechanisms for the development of colon tumors in patients with familial adenomatous polyposis: (a) the heterozygous mutant/wild-type condition at the APC gene causes formation of mild or moderate adenoma; (b) the loss of the normal allele in the APC gene leads to a change from moderate to severe adenoma; (c) LOH on chromosome 17p contributes to the conversion of adenoma to intramucosal carcinoma; (d) LOH on other chromosomes, such as 18 and 22q, are involved in the progression of intramucosal carcinoma to invasive carcinoma; and (e) K-ras mutation may also affect the development of moderate to severe adenoma.

Adenomatous Polyposis Coli↗

Epidermal growth factor stimulated phosphorylation of a 120-kilodalton endogenous substrate protein in rat hepatocytes.

Endogenous substrates of the EGF receptor have been described in transformed cells; however, little is known about substrates in normal tissue. To characterize epidermal growth factor (EGF) receptor phosphorylation and search for endogenous substrates in normal rat hepatocytes, cells were labeled with [32P]orthophosphate, and phosphotyrosine-containing proteins were sought by using a high-affinity, specific anti-phosphotyrosine antibody. Exposure of 32P-labeled freshly isolated hepatocytes to 1 microgram/mL EGF caused phosphorylation of several proteins of Mr 185K, 160K, and 120K. The 185- and 160-kDa proteins (pp185 and pp160) were identified as the intact and proteolyzed forms of the EGF receptor by virtue of their immunoprecipitation with anti-EGF receptor antibody. This antibody failed to recognize the 120-kDa phosphoprotein (pp120). The phosphopeptide map derived from pp120 was by trypsinization and HPLC separation different from that of pp185, further indicating that pp120 is distinct from the EGF receptor. This pp120 was also immunologically distinct from the pp120 substrate of the insulin receptor kinase and from ATP-citrate lyase. Phosphoamino acid analysis revealed pp120 to be phosphorylated on both tyrosine and serine residues. Autophosphorylation of EGF receptor and phosphorylation of pp120 were almost maximal within 1 min of EGF stimulation. The dose-response curves for phosphorylation of the EGF receptor and pp120 were identical (ED50 = 30 ng/mL) and were superimposable with the fractional occupancy of the EGF receptor. In A431 cells, a transformed cell line whose growth is inhibited by EGF, EGF produced a decrease in pp120 phosphorylation. These data suggest that pp120 is an endogenous substrate for the EGF receptor in hepatocytes whose phosphorylation may be closely related to EGF stimulation of cell growth.

Animals↗

Preparation and evaluation of octadecyl-treated porous glasses. Application to the determination of methotrexate in serum.

The retention and selectivity of methotrexate (MTX) in serum were studied by high-performance liquid chromatography on octadecyl-treated porous glasses and silicas. From elemental analysis data for carbon, the maximum number of bonded octadecyl surface groups per gram (mean pore diameter 153 A, specific surface area 193 m2/g, pore volume 0.83 ml/g) in octadecyl-treated glass was calculated to be 0.131 x 10(21). MTX in human serum could be separated on both glasses and silicas with methanol-acetate buffer mixtures as eluents.

Chromatography, High Pressure Liquid↗