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Biomedical subjects

Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 1,225 records · Page 68Linked to original sources

Effects of antihypertensive drugs on glomerular morphology.

We quantitated the glomerular size and the degree of sclerosis simultaneously in individual glomeruli with the use of three-dimensional histological analysis on serial sections obtained from remnant kidneys with highly heterogeneous glomerular lesions after subtotal nephrectomy (sNPX). Four to six weeks after sNPX (Group I, N = 7), 90% of glomeruli had mild sclerosis (sclerosis index, SI; less than 1.5 on a 0 to 4 scale) with a strong positive correlation between the maximum planar area of glomerulus (PAmax) versus SI. Twelve weeks after sNPX (Group II, N = 6) more than 50% of glomeruli had advanced sclerosis (average SI:1.88), and a significant positive correlation was again found between PAmax and SI in glomeruli with mild to modest sclerosis (SI less than 1.5), whereas these two variables were correlated inversely in glomeruli with advanced sclerosis. Administration of enalapril (50 mg/liter drinking water) or hydralazine (200 mg/liter) + hydrochlorothiazide (50 mg/liter) for 12 weeks (Group III, N = 12) markedly attenuated the sclerosis to comparable degrees (average SI: 0.15 vs. 0.22). The former antihypertensive therapy decreased glomerular capillary hydraulic pressure (PGC) to normal range, whereas the latter triple drug therapy was largely without effect on PGC. Of note, the positive correlation between SI and PAmax remained unaffected by these anti-hypertensive drugs. SI of the glomeruli from both treated groups was expressed as a first-order function of PAmax. The correlation coefficient is identical to that found in non-treated Group II remnant glomeruli, so that the degree of sclerosis is mathematically uniquely correlated with the glomerular size, regardless of drug treatment. Thus, within a given remnant kidney, the magnitude of glomerular hypertrophy has a direct correlation with the degree of sclerosis, while the altered glomerular hemodynamic pattern has little modulatory role in determining the magnitude of this hypertrophy. Enalapril and triple drug therapy, at equi-depressor doses in regard to systemic blood pressure, had identical potency in sparing glomerular structure. The primary determinant for this antisclerotic potency appears to be related to the drugs' potency to inhibit glomerular growth rather than an effect on the abnormal hemodynamics which develop in the glomerulus.

Animals↗

Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis.

In a variety of recent studies in animals with chronic renal diseases, investigators have found a tight correlation between the elevation in glomerular pressures and flows versus glomerular hypertrophy. To investigate a possible causal link between the glomerular hyperfunction and hypertrophy, we studied the functional and morphological sequelae of nephrectomy and those of unilateral ureteral diversion (UD) into the peritoneal cavity (that is, removal of renal clearance function while keeping the kidney tissue in situ). In all nine experimental groups of 54 Munich-Wistar rats, 2/3 of the renal mass was removed from the left kidney by ligation of two or three branches of the left renal artery. In addition, right nephrectomy (NPX) was performed in Groups 1B, 2B and 3B or UD in Groups 1C, 2C and 3C. The right kidney was left untouched in control groups, Groups 1A, 2A and 3A. Micropuncture measurements and histological studies were performed at four days (Groups 1A, 1B and 1C), two weeks (Groups 2A, 2B and 2C) or four weeks (Groups 3A, 3B and 3C). At both four days and two weeks, NPX and UD groups had marked and comparable degrees of glomerular hypertension, hyperperfusion and hyperfiltration compared to the control group in the left kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Surgical margin and recurrence after resection of hepatocellular carcinoma in patients with cirrhosis. Further evaluation of limited hepatic resection.

This report attempts to elucidate the manner in which the surgical margin is linked to a recurrence after curative hepatectomy for hepatocellular carcinoma (HCC) in patients with cirrhosis. Forty patients were divided into two groups: those in whom the margin from the cut surface to HCC in the fresh resected specimen was less than 10 mm wide, and patients in whom the surgical margin was equal to or exceeded 10 mm. These margins were expressed as tumor wedge positive [TW(+)], and tumor wedge negative [TW(-)], respectively. There were 24 and 16 patients in the TW(+) and TW(-) groups, respectively. There was no statistically significant difference in clinicopathologic variables, except for age and values of serum albumin between the two groups. There was a recurrence in ten of 24 patients (42%) of the TW(+) group and in eight of 16 patients (50%) of the TW(-) group. Mean disease-free periods were 21.4 months in the TW(+) group and 23.6 months in TW(-) group. These 40 patients were also divided with regard to the time of recurrence, the early recurrence within 24 months, and the late recurrence after 24 months. There was no statistically significant difference in the rate of recurrence and mean disease-free period between the TW(+) and TW(-) groups in the early and late recurrence groups. In both the TW(+) and TW(-) groups, there were no recurrences in 13 of 16 patients (81.3%) with a tumor less than 4 cm in diameter, yet there were recurrences in seven of eight patients (87.5%) with a tumor exceeding 4 cm in diameter, regardless of the time to recurrence. These results suggest that in patients with a tumor less than 4 cm, the extent of TW is not linked to an early recurrence. However, when the tumor size exceeds 4 cm, 10 mm of TW is inadequate to achieve curability. When a wide resection is not feasible, then adjuvant chemotherapy should be aggressive.

Adult↗

Detection of granulocyte colony-stimulating factor produced by a newly established human hepatoma cell line using a simple bioassay system.

A colony-stimulating factor(CSF)-producing tumor cell line (KX-87) was established from a patient with hepatocellular carcinoma and marked granulocytosis. This cell line formed tumors on nude mice in high frequency and the mice revealed marked granulocytosis. In clonogenic assays of human bone marrow cells, KX-87 conditioned medium (CM) supported the formation of colonies mainly consisting of neutrophilic granulocytes but had no burst-promoting activity. The molecular weight of the colony-stimulating activity (CSA) in KX-87CM was estimated about 25,000 daltons by gel filtration and a new bioassay system. In principle, a subline of murine hemopoietic cell line NFS-60 was cloned which was dependent on KX-87CM. Then the growth of this subline was examined by a rapid and sensitive colorimetric tetrazolium assay. From these results, it was concluded that the CSA which KX-87 cell line produced was G-CSF.

Animals↗

Inotropic and chronotropic effects of N6-substituted derivatives of cyclic AMP as assessed in guinea-pig isolated right atria and papillary muscle.

1. The inotropic and chronotropic actions of N6-substituted adenosine 3':5'-cyclic monophosphate (cyclic AMP) derivatives (N6-R cyclic AMPs) were studied in guinea-pig isolated right atrial preparations and in the papillary muscle preparations from guinea-pig right ventricle. 2. All the N6-R cyclic AMPs except N6-C14H29 produced positive inotropic effects in papillary muscle. The C5H11, C6H13, C7H15, C8H17 and C9H19 compounds were the most potent as inotropic agents, the potency being lower with compounds having longer or shorter N6-side chains than these. 3. In right atria N6-C2H5-C7H15 cyclic AMPs produced negative chronotropic effects. However, after treatment of the preparations with 8-phenyltheophylline the negative chronotropic effects were either much attenuated or abolished, indicating the involvement of adenosine receptors. 4. All the N6-R cyclic AMPs except N6-C14H29 were more potent activators of bovine myocardial protein kinase than cyclic AMP. The partition coefficients between octanol and an aqueous phase of N6-R cyclic AMPs became greater as the numbers of carbon atoms increased, and there appeared to be a relationship between partition coefficient and inotropic potency. It was concluded that membrane penetrativeness rather than potency as activators of protein kinase determined the potencies of N6-R cyclic AMPs as positive inotropic agents. 5. Derivatives such as N6-C7H15 cyclic AMP, which have positive inotropic activity without any marked negative chronotropic effect, may be useful as cardiotonic agents in heart failure.

Animals↗

Determination of urine thiocyanate in patients with amyotrophic lateral sclerosis.

It has been reported that amyotrophic lateral sclerosis-Parkinsonism-dementia in Guam might be related to the eating of Cycas seeds, which contain cyanide. Based on this assumption, we determined the urinary thiocyanate excretion level in patients with ALS and compared this with that of other neurological diseases. The assay method was designed to use column chromatography with Amberlite IRA 402. The thiocyanate level was determined using pyridine-barbiturate method. The 24-h thiocyanate level was higher in the ALS patients of the middle stages than in the normal control group (Wilcoxon's test, P less than 0.02). There were no significant differences between the ALS patient groups of the early and terminal stages, Kugelberg-Welander disease group, Duchenne type muscular dystrophy group and control group. From these results, we concluded that ALS patients were contaminated with cyanide or thiocyanate and that, along with rapid muscular atrophy, the thiocyanate excretion levels were high.

Adult↗

Effects of recombinant G-CSF and GM-CSF on in vitro differentiation of the blast cells of RAEB and RAEB-T.

To evaluate the effects of recombinant G-CSF and GM-CSF on RAEB and RAEB-T cells, blast cells from 6 patients were incubated in liquid culture systems with these CSFs for 7 days, and their numerical, morphological and functional changes were assessed. Both CSFs stimulated cell growth, but decreased the proportion of blast cells in 5 of the 6 cases. Karyotypic abnormalities persisted during cultivation in some cases. The CSFs also stimulated the expression of part of the esterase activities, and a positive interaction of both CSFs was seen in part. Although CSFs had no significant effects on the ability of cells to reduce NBT or to phagocytize latex particles, the results indicated that they induce partial differentiation of blast cells. It appears that such pathological cells still retain the capacity to respond to growth factors.

Adult↗

[Serovars, antimicrobial resistance and conjugative R plasmids of Salmonella isolated from human during the period of 1966-1986 in Tokyo. Research Group for Infectious Enteric Diseases].

We examined 4,739 isolates of Salmonella isolated from patients with gastroenteritis during the period of 1966-1986 in Tokyo for the incidences of serovars, antibiotic resistance and conjugative R plasmids. The period of study was divided into three: 1966-73 (early period), 1974-79 (middle period), and 1980-86 (late period). The predominant serovars were S. typhimurium (34.3%), Infantis (5.6%), Panama (4.9%) in the middle period, S. typhimurium (31.7%), Paratyphi B (9.4%), Litchfield (7.3%) in the late period. These results were consistent with serovars of isolates from healthy citizens. The frequency of resistant isolates was as high as 86.9% in the early period, mostly streptomycin (SM)- and tetracycline (TC)-resistant isolates, but decreased significantly in the middle and the late periods, to 53.3 and 39.4%, respectively. The percentages of ampicillin (ABPC)-, chloramphenicol (CP)-, and kanamycin (KM)-resistant isolates increased in the late period. Strains carrying conjugative R plasmids were isolated as frequently as 57.8% of the total isolates in 1973, but as less frequently as 6.7% in 1981 indicating that the rate was roughly proportional to the incidence of the drug resistant isolates. The rate, however, increased gradually after 1981. The predominant resistance pattern of the R plasmids was TC-resistance in the early period, gradually changed into multiple and finally to AP-, CP-, KM-, SM-, TC- and sulfonamides-resistance in the late period.

Conjugation, Genetic↗

Restoration of ATP contents in the transplanted liver closely relates to graft viability in dogs.

Searching for a marker of graft viability, adenosine triphosphate (ATP) content in the graft tissue was measured sequentially during orthotopic liver transplantation (OLT) in 24 adult mongrel dogs. According to the survival period, 12 recipients were divided into two groups: group I - early-death group (n = 6), death within 3 days after OLT and group II - survival group (n = 6), survived more than 7 days after OLT (average 12 days). Serum biochemical findings showed no differences between the two groups except that the prothrombin time on the first postoperative day in group I was significantly longer (p less than 0.05). The ATP content ratio (% of initial value) was significantly higher in group II, compared to that of group I (p less than 0.05), 94 versus 53% at 10 min after perfusion, 31 versus 17% at just before recirculation, respectively. The ATP content ratio recovered significantly to more than 80% at 10 min after recirculation in group II but only to less than 50% in group I. These results suggest that restoration of ATP content in the liver after graft recirculation reflects the viability of the graft and can serve as an appropriate prognostic marker in cases of OLT.

Adenosine Triphosphate↗

Expression and function of protein kinase C isozymes.

Three protein kinase C (PKC) isozymes, type I, II, and III, have been identified as the major Ca2+/phospholipid-stimulated protein kinases in the various animal tissues. Based on the immunochemical analysis it was demonstrated that PKC I was encoded by gamma cDNA, PKC II by the alternatively spliced beta I and beta II cDNAs, and PKC III by alpha cDNA. The expression of these enzymes appears to be tissue-specific and developmentally regulated. The central nervous system expresses high level of all three isozymes and the peripheral tissues mainly PKC II and III. During brain development, the expression of PKC I appears to follow the progress of synaptogenesis, whereas PKC II and III increase progressively from fetus up to 2-3 weeks of age. The level of PKC I in adult brain is highest in the cerebellum, hippocampus, amygdala, and cerebral cortex especially in those cortical regions being important for visual information processing and storage. The role of PKC II and III in cellular regulation was investigated by treatment of rat basophilic leukemia cells with the phorbol ester, phorbol 12-myristate 13-acetate. This phorbol ester caused a faster degradation of PKC II than III, indicating a differential down-regulation of these two enzymes by this compound. The results presented in this study support the contention that each species of PKC has a distinct function in the regulation of a variety of cellular processes.

Animals↗

Role of right ventricular asynergy and tricuspid regurgitation in hemodynamic alterations during acute inferior myocardial infarction.

To elucidate the role of right ventricular asynergy and tricuspid regurgitation (TR) in hemodynamic alterations occurring during right ventricular infarction, left and right ventriculography with pressure measurements were performed in 22 patients with acute inferior myocardial infarction. Twelve patients with a proximal right coronary artery (RCA) occlusion (Group I) had elevated right atrial pressure (16 +/- 4 vs 8 +/- 5 mmHg, p less than 0.01), low cardiac output (2.5 +/- 0.7 vs 3.5 +/- 0.6 l/min/m2, p less than 0.05) and a greater degree of TR, compared with 10 patients with a distal RCA occlusion (Group II). Inferoposterior wall asynergy of the right and left ventricles was similar in Groups I and II. In Group I, there was an additional asynergy of the anterolateral free wall of the right ventricle. Cardiac output in those patients was not related to the left ventricular ejection fraction (EF) but to the right ventricular EF. A greater degree of TR was found in association with a lower right ventricular EF. The decrease in cardiac output was closely related to the extent of TR. These results indicate that right ventricular asynergy and TR due to proximal RCA occlusion may play important roles as causes of hemodynamic alterations seen during the acute phase of inferior myocardial infarction.

Aged↗

An eight year experience with gradually longer interval postremission therapy for adults with acute leukemia.

Between January 1980 and March 1983, a study was conducted into the effects of postremission therapy on 20 patients with acute leukemia who had achieved complete remission through induction therapy. Postremission therapy consisted of cyclic administration of six combination therapies given at gradually longer intervals. Postremission therapy used DCMP (D, daunorubicin; C, cytosine arabinoside; M, 6-mercaptopurine; P, prednisolone), DCyMP (Cy, cyclocytidine), DCVP (V, vincristine), BHAC-DMP (BHAC, behenoyl-ara-c), BHAC-AMP (A, aclarubicin) and ACM-MP (ACM, aclacinomycin). Six combinations were given sequentially starting at one month interval, and then at 2, 3, 4, 5 and eventually 6 month intervals until 5 year survival was reached. The median remission duration was 38 months for acute myelogenous leukemia (AML), and 17 months for acute lymphoblastic leukemia (ALL). The median survival was 66 months for AML, and 33 months for ALL. The survival rate at 5 years was 60% for AML., 40% for ALL, and 50% in all 20 patients. Methotrexate and prednisolone were administered intrathecally for prophylaxis of CNS leukemia on Day 4 of each stage of postremission therapy. There was no CNS leukemia. This postremission therapy was shown to be effective in improving the prognosis of adults with acute leukemia.

Acute Disease↗

Factor XIII is not involved in human platelet-collagen interaction.

A role of factor XIII (FXIII) on the interaction of human platelets with collagen was investigated using either formaldehyde fixed-washed platelets (FWP) or nonfixed platelets. The adhesion of FWP to bovine type I collagen was measured by using either an aggregometer or a collagen immobilized glass beads column. The interaction of non-fixed human platelets with collagen was measured with in vitro bleeding time (Thrombostat-4,000), which was performed by passing citrated whole blood through the filter covered with rat type I collagen under the constant shear stress. FWP adhesion to the collagen immobilized column (1,300 micrograms collagen) was not changed by the addition of commercial FXIII preparation (Fibrogammin); the adhesion was 42.7% in the presence of 1% human serum albumin, 42-43% in the presence of 1-2 U/ml of FXIII. The addition of rabbit antibody to FXIII to normal FWP did not change the degree of adhesion; 42.3% (1:100 anti-FXIII) and 46.1% (normal rabbit serum). Furthermore, platelets from the patient with congenital FXIII deficiency normally aggregated by bovine collagen and the adhesion of the patient FWP to the collagen was similar to that of normal FWP. Prolongation of partial thromboplastin time and the changes of thromboelastograph of normal plasma were observed after mixing with the collagen, and factor VIII, FXIII and von Willebrand factor were adsorbed by the collagen. The amount of FXIII in normal human plasma bound to collagen was 17, 23 and 54% at the concentration of the collagen 250, 500 and 1,000 micrograms/ml, respectively. The binding of plasma ristocetin cofactor was not different between normal control and the patient with FXIII deficiency. These data suggest that FXIII is not involved in human platelet interaction with the type I collagen, while FXIII in normal human plasma binds to the collagen.

Bleeding Time↗

Permeability increase in rat submandibular gland by glandular substance P.

When the chorda tympani was stimulated at 20 Hz, infused horseradish peroxidase (HRP) entered the saliva through the tight junctions in the rat submandibular gland. This response was not inhibited by atropine but was reduced by a substance P(SP)-antagonist. The increase in junctional permeability for HRP never occurred in the gland that was stimulated at 5 Hz or in the SP-depleted gland. Our data suggest that the effect of parasympathetic stimulation on the increase in junctional permeability for macromolecules was due to the release of SP in the gland.

Animals↗

Current aspects of trace element research in environmental health.

The field of research on trace element and its relationship to human health and disease is one of the most rapidly advancing fields among the health sciences. The methods of measuring elements in the body can be classified into two categories: i.e., destructive and non-destructive method. The latter analysis includes X-ray fluorescence (XRF) analysis, by which the authors determine fluorine (F) and elements in hair specimens among patients with chronic diseases and workers exposed to polluted elements. Some advantages offered by this method are a lack of necessity for the preliminary treatment of specimens and relative ease of operation. In this paper, the authors review the current aspect of trace element researches in the environmental health field, especially those in our laboratory.

Environmental Health↗