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Biomedical subjects

H Yoshida

Publications and source records attributed to H Yoshida.

At least 1,297 records · Page 72Linked to original sources
PubMed1993

Effects of EXP3174, a non-peptide angiotensin II receptor antagonist, on renal hemodynamics and renal function in dogs.

We examined the effects of intrarenal infusion of EXP3174, a non-peptide angiotensin II receptor antagonist, in order to evaluate the physiological role of endogenous angiotensin II in regulating renal hemodynamics and urine formation and to assess the possibility of a tubular site(s) of action of endogenous angiotensin II in anesthetized dogs. Intrarenal infusion of EXP3174 at 15 micrograms/kg per min caused increases in renal blood flow (RBF), glomerular filtration rate (GFR), urine, flow and urinary electrolyte excretion. The lower dose of EXP3174 (0.5 micrograms/kg per min) did not change mean arterial pressure, RBF and GFR, but did increase urine flow. The fractional excretion of sodium, the fractional proximal excretion of sodium and the fractional distal excretion of sodium increased with lower doses of EXP3174 infusion. EXP3174 did not affect the linear relationship between the free water reabsorption rate and osmolar clearance. These data suggest that endogenous angiotensin II plays a significant role in regulating renal hemodynamics and urine formation and endogenous angiotensin II stimulates sodium reabsorption in the proximal and the distal portions of the tubules, with the exception of the medullary portion of the ascending limb of Henle.

Angiotensin II↗
PubMed1993

Purification and characterization of interferon-gamma-inducing molecule of OK-432, a penicillin-killed streptococcal preparation, by monoclonal antibody neutralizing interferon-gamma-inducing activity of OK-432.

An immunoglobulin M mouse monoclonal antibody (MAb) to streptococcal preparation OK-432, TS-2, was generated. The TS-2 MAb showed positive reaction with butanol extract of OK-432 and fungal, branched (1-->3)-gamma-glucans (lentinan and schizophyllan) as well as lipoteichoic acids. Moreover, the interferon (IFN)-gamma-inducing activity of OK-432 was neutralized by TS-2 MAb. The affinity column of butanol extract of OK-432 on CNBr-activated Sepharose 4B-bound TS-2 antibody was prepared and the fractions containing IFN-gamma-inducing activity were eluted. The polysaccharide sample carrying the IFN-gamma-inducing activity with a molecular weight of 700,000 was destroyed by treatment with acid or sodium metaperiodate, but was stable to treatment with heat, alkali, pronase, or neuraminidase. Survival time of human salivary adenocarcinoma-bearing animals given a combination of the polysaccharide sample purified from butanol extract of OK-432 and TS-2 MAb was significantly shorter compared with that of the tumor-bearing animals given only the purified polysaccharide sample of OK-432. Moreover, a high level of effector cell activity in natural killer (NK) and lymphokine-activated killer (LAK) assays and significant increase of IFN-gamma-positive cells or asialo-GM1-positive cells were detected in the spleen cells from the animals given the polysaccharide sample purified from butanol extract of OK-432. These findings indicate that the polysaccharide sample purified by the affinity chromatography of butanol extract of OK-432 on CNBr-activated Sepharose 4B-bound TS-2 MAb carries the IFN-gamma-inducing activity of OK-432 and marked antitumor activity.

Animals↗
PubMed1993

Crystal structures of ribonuclease F1 of Fusarium moniliforme in its free form and in complex with 2'GMP.

RNase F1, a guanine-specific ribonuclease from Fusarium moniliforme, was crystallized in two different forms, in the absence of an inhibitor and in the presence of 2'GMP. The crystal structure of the RNase F1 free form was solved by the molecular replacement method, using the co-ordinates of the RNase T1 complex with 2'GMP, and was refined to a final R-factor of 18.7%, using the data extended to 1.3 A resolution. For the crystal structure of the RNase F1 complex with 2'GMP, the solution of the molecular replacement method was obtained on the basis of the co-ordinates of the RNase F1 free form, and was refined to a final R-factor of 16.8%, using the data up to 2 A resolution. The two crystal structures of the RNase F1 free form and the complex with 2'GMP are very similar to each other as reflected by a small root-mean-square displacement (r.m.s.d.) value of 0.43 A for all C alpha atoms. The main differences between the two structures are associated with binding of 2'GMP in the substrate recognition site in the loop between Tyr42 and Glu46. A structural comparison between RNase F1 and RNase T1 shows a substantial similarity between all the C alpha atoms, as evidenced by a r.m.s.d. value of 1.4 A. The loop from residues 32 to 38 was strikingly different between these two enzymes, in both its conformation and its hydrogen bonding schemes. The side-chain of a catalytically active residue, His92, is shifted away from the catalytic site in RNase F1 by 1.3 A and 0.85 A with respect to the corresponding positions in the RNase T1 free form and in the RNase T1 complex with 2'GMP, respectively. In the RNase F1 complex, the guanine base of 2'GMP has a syn conformation about the glycosyl bond, and the furanose ring assumes a 3'-exo pucker, which is different from that found in the complex with RNase T1. In the catalytic site of the RNase F1 complex with 2'GMP, one water molecule was observed, which bridges the phosphate oxygen atoms of 2'GMP and the side-chains of the catalytically important residues, His92 and Arg77, through hydrogen bonds. A water molecule occupying the same position was found in the RNase F1 free form. The significance of this water molecule in the hydrolytic reaction is discussed.

Amino Acid Sequence↗
PubMed1993

Effects of a novel thyrotropin-releasing hormone analogue, JTP-2942, on extracellular acetylcholine and choline levels in the rat frontal cortex and hippocampus.

The effects of a novel thyrotropin-releasing hormone (TRH) analogue, N alpha-[(1S,2R)-2-methyl-4-oxocyclopentanecarbonyl]-L-histidyl-L-pr olinamide (JTP-2942) on acetylcholine (ACh) release and on the extracellular choline level were investigated in rat frontal cortex and hippocampus by microdialysis, and were compared with effects of TRH. JTP-2942 (0.3 mg/kg i.p.) produced a marked (> 300%) and persistent increase of ACh release in both the frontal cortex and hippocampus, while TRH (3 mg/kg i.p.) caused a significant but transient increase of ACh to about 200% in the frontal cortex. Both drugs significantly decreased the choline levels in both brain regions. Investigation of the effects of JTP-2942 (0.001-1 mM) and TRH (1 and 10 mM) on ACh release and choline levels when perfused through the dialysis probe revealed that JTP-2942 had a greater effect than TRH in both the frontal cortex and the hippocampus. The action of JTP-2942 was about 1000-fold more potent than that of TRH in both brain regions. Oral administration of JTP-2942 at a dose of 10 mg/kg markedly and persistently increased the release of ACh and at doses of 1-10 mg/kg decreased the extracellular choline level in the frontal cortex and hippocampus. These results also suggest that JTP-2942 has some selectivity for the hippocampus compared to the frontal cortex after both systemic administration and local injection. The increase of ACh release caused by JTP-2942 was completely antagonized by perfusion with tetrodotoxin (TTX, 1 microM), suggesting that the action of JTP-2942 on cholinergic neurons was mediated via neuronal activity.

Acetylcholine↗
PubMed1993

Molecular cloning and expression of the mouse 105-kDa gelatinase cDNA.

We have detected a potent gelatinolytic activity in the culture supernatant of a metastatic tumor line, SN-H, derived from a murine squamous cell carcinoma. The relative molecular weight of the gelatinase was estimated as 105-kDa by gelatin zymography. We have cloned the cDNA of this gelatinase and the 3160-bp sequence has been determined. From the translated amino acid sequence, the positions of the cysteine residues and the functional domain structure are highly homologous to the human 92-kDa gelatinase. The nucleotide and amino acid sequence homology between these two cDNAs are 75% and 72%, respectively. Transfection of the cDNA in an expression vector resulted in production of the 105-kDa gelatinase, thus confirming that this cDNA is functional.

Amino Acid Sequence↗
PubMed1993

Evaluation of bone marrow metastasis of neuroblastoma and changes after chemotherapy by MRI.

To evaluate the usefulness of MRI for diagnosing bone marrow metastasis of neuroblastoma, we compared MRI findings with histological findings. MRI was performed 26 times in 20 patients with neuroblastoma to detect metastasis to the bone marrow of the femur and tibia. Abnormal areas observed by MRI were histologically examined. The lesion visualized by MRI as a low-intensity area on T1-weighted images and as a high-intensity area on T2-weighted images was histologically confirmed to be neuroblastoma in 81% (17/21). The percentage varied according to the treatment state: 89% (8/9) by MRI imaging performed before the initiation of chemotherapy, 67% (6/9) within 3 weeks after cessation of chemotherapy (during chemotherapy), and 100% (3/3) in recurrent cases 1 year or more after chemotherapy. During the follow-up period after chemotherapy, tissue with signal intensities similar to that of bone marrow was observed in a speckled pattern in the intramedullary space on T1- and T2-weighted images. This tissue was histologically demonstrated to be normal bone marrow and was considered to be bone marrow remaining after chemotherapy. In this small series, histological findings supported the results of MRI, confirming the usefulness of MRI for diagnosing bone marrow metastasis of neuroblastoma. However, bone marrow metastasis after chemotherapy was difficult to evaluate by comparing signal intensities alone.

Adolescent↗
PubMed1993

The quality of mass screening for breast cancer by physical examination.

Mass screening for breast cancer using physical examination alone has been carried out since 1983 in Zentsuji, Kagawa Prefecture, Japan. Over a 7-year period, breast cancer was detected in 11 of a total 8,271 examinees, the detection rate being high at 0.13%. The detected cases included a few early-staged breast cancers, suggesting that mass screenings are of slight efficacy. Seven cases of interval cancer were found by breast self-examination after the mass screenings, supporting the value of breast self-examination. A relatively large number of interval breast cancers was detected in 1985 and 1986, when the rates of required further examination remained under 1%. The sensitivity and specificity of this screening were 61.1% and 94.5%, respectively, indicating a low sensitivity. These results suggest that the qualitative diagnoses made from the first screening by physical examination alone were often revealed to be false negatives. Therefore, the existing diagnosis should be employed in the first screenings. It is recommended that mammography be introduced to detect breast tumors which are nonpalpable or undetectable by physical examination alone.

Adult↗
PubMed1993

Pulmonary oxygen transfer deficits of diabetic origin in patients undergoing coronary artery bypass grafting.

The objective of this study was to determine the effects of a diabetic disposition on pulmonary gas exchange by examining 72 patients who underwent coronary artery bypass grafting (CABG), using the arterial/alveolar oxygen tension ratio [(a/A)PO2] as a criterion. Patients were divided into a diabetic (DM) group and a nondiabetic (non-DM) group. The postoperative blood gases and hemodynamic data measured when the blood glucose level was at a maximum on the day of CABG were used as the postoperative pulmonary gas exchange indices, and the physicians who managed these patients were unaware of this study. The preoperative (a/A)PO2 ratio was 0.66 +/- 0.03 (SE) in the DM group and 0.78 +/- 0.02 in the non-DM group (P < 0.01), while the postoperative ratios were 0.42 +/- 0.03 and 0.52 +/- 0.03, respectively (P = 0.01). The correlation coefficient (r) for regression analysis of the relation between the postoperative PaO2/FIO2 ratio and the postoperative (a/A)PO2 ratio was 0.99 in the DM group (P < 0.01) and 0.88 in the non-DM group (P < 0.01). The r values of the relation between (a/A)PO2 and (A-a)PO2 were -0.68 (P < 0.00) and -0.84 (P < 0.01), while those for the respiratory index were -0.87 (P < 0.01), and -0.93 (P < 0.01), respectively. Thus, pulmonary oxygen transfer was compromised before and after CABG in the DM group compared to the non-DM group. Moreover, the PaO2/FIO2, being the simplest pulmonary gas exchange index to calculate, was a reliable substitute for the (a/A)PO2 ratio during the early postoperative management of CABG patients.

Coronary Artery Bypass↗
PubMed1993

Cutaneous signs (Raynaud's phenomenon, sclerodactylia, and edema of the hands) and hand-arm vibration exposure.

Dermatological tests and examinations of the hand(s) were carried out in vibration-exposed and unexposed males. The subjects were 179 chain-saw workers in private forestry companies and 205 local inhabitants who had never used vibrating tools. The prevalences of Raynaud's phenomenon (RP), sclerodactylia, and edema of the hands were estimated in both groups, and associations between these cutaneous signs and vibration exposure were evaluated. The prevalences of RP and edema in the exposed group were 9.5% and 1.7%, respectively, and in the unexposed group, 2.9% and 1.5%, respectively. Sclerodactylia was seen in 31.8% of the chain-saw workers but in only 6.4% of the unexposed individuals. In statistical analyses based on unconditional logistic regression models with adjustment for age, RP was associated with long-term (> or = 20 years) vibration exposure [odds ratio (OR) = 7.06; 95% confidence interval (CI) = 2.51-19.87]. Sclerodactylia was associated with both short- and long-term vibration exposure (OR = 6.54, CI = 3.30-13.36; OR = 7.05; CI = 3.41-14.60, respectively). There were significant dose-response relationships between RP and duration of exposure and between sclerodactylia and duration of exposure. Results of function tests indicated a longer recovery time and a higher vibration threshold for the workers with RP. The presence of sclerodactylia, however, did not have any significant influence on function test results. It is possible to conclude that not only RP but also sclerodactylia could be induced by vibration exposure. However, most cases of sclerodactylia were not so serious as to involve disturbances of peripheral circulatory and nerve function.

Adult↗
PubMed1993

Inhibition of herpes simplex virus replication by genistein, an inhibitor of protein-tyrosine kinase.

Genistein, an inhibitor of protein-tyrosine kinase, inhibited the replication of herpes simplex virus type 1 (HSV-1) at genistein concentrations of more than 25 microM, whereas the related compounds, which do not inhibit protein-tyrosine kinases, did not affect the replication of HSV-1. In the presence of genistein, the phosphorylation of tyrosine residues in specific viral polypeptides was markedly reduced. These results indicate that the phosphorylation of tyrosine residues in viral polypeptides may be essential for the replication of HSV-1.

Animals↗
PubMed1993

Antitumor effects of a novel monoclonal antibody with high binding affinity to ganglioside GD3.

Ganglioside GD3, which is one of the major gangliosides expressed on the cell surface human tumors of neuroectodermal origin, has been studied as a target molecule for passive immunotherapy. We established ten kinds of anti-GD3 monoclonal antibodies (mAb) of the mouse IgG3 subclass by immunization with purified GD3 and melanoma cells. One of the established mAb, KM641, showed major reactivity with GD3 and minor reactivity with GQ1b out of 11 common gangliosides in an enzyme-linked immunosorbent assay. Immunostaining of gangliosides, separated on thin-layer chromatography plates, using KM641 revealed that most of the melanoma cell lines contained immunoreactive GD3 and GD3-lactone at a high level, but only the adrenal gland and the urinary bladder out of 21 human normal tissues had immunoreactive GD3. In immunofluorescence, KM641 bound to a variety of living tumor cell lines especially melanoma cells, including some cell lines to which another anti-GD3 mAb R24, established previously, failed to bind. High-affinity binding of KM641 to a tumor cell line was quantified by Scatchard analysis (Kd = 1.9 x 10(-8) M). KM641 exerted tumor-killing activity in the presence of effector cells or complement against melanoma cells expressing GD3 at a high level. Not only natural killer cells but also polymorphonuclear cells were effective as the effector cells in antibody-dependent cellular cytotoxicity. Intravenous injection of KM641 markedly suppressed the tumor growth of a slightly positive cell line, C24.22 (7.2 x 10(5) binding sites/cell), as well as a very GD3-positive cell line, G361 (1.9 x 10(7) binding sites/cell), inoculated intradermally in nude mice. KM641, characterized by a high binding affinity for GD3, has the potential to be a useful agent for passive immunotherapy of human cancer.

Animals↗
PubMed1993

Relationship between biliary excretion of bilirubin and glutathione disulfide.

The effects of two glutathione-oxidizing agents, t-butyl hydroperoxide and diamide, on biliary excretion of bilirubin and glutathione disulfide were investigated in anesthetized male Sprague-Dawley rats. Bilirubin (unconjugated) was infused at a constant rate of 100 nmol/kg/min through the jugular vein. When biliary excretion of bilirubin was stabilized, either of the glutathione-oxidizing agents was administered via the mesenteric vein. Biliary excretion of glutathione disulfide increased temporarily after the administration and returned to its basal levels within 20 min. The biliary excretion of bilirubin decreased during the same period and returned to the former levels thereafter. Changes in bile flow rates remained within 20% of the basal levels. A linear correlation was found between the increments in the bile concentration of glutathione disulfide and the decrements in that of bilirubin. Furthermore, separate experiments revealed that reduction of hepatocellular glutathione per se had little effect on biliary excretion of bilirubin. The results thus indicate that the reduction of biliary excretion of bilirubin by glutathione-oxidizing agents was due to the increase in biliary excretion of glutathione disulfide, and suggest that a common biliary excretory mechanism is shared, at least partially, by bilirubin and glutathione disulfide in Sprague-Dawley rats.

Animals↗
PubMed1993

Paratesticular neuroblastoma with N-myc activation.

The authors describe a case of disseminated neuroblastoma discovered as a paratesticular tumor in a 7-month-old boy. The ectopic adrenal tissues adjacent to the paratesticular tumor and multiple lesions in the adrenal gland and skin suggested the possibility of multifocal primary tumors. Although infantile neuroblastoma diagnosed at less than 1 year of age generally responds well to treatment irrespective of distant metastases, metastases developed, and the boy died of disease within 7 months. All multiple lesions had amplification and overexpression of the N-myc protooncogene, which might explain the aggressive phenotype of this rare case.

Blotting, Northern↗
PubMed1993

Imaging of neuroblastoma in patients identified by mass screening using urinary catecholamine metabolites.

Between April 1983 and August 1991, mass screening in Chiba Prefecture found 25 infants to be positive for neuroblastoma based on elevated urinary levels of catecholamine metabolites. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy (BS), and 67Ga scintigraphy (GS) detected neuroblastomas in 12 of the 25 infants. The primary site of tumor was the mediastinum in 1 patient, the adrenal gland in 7, retroperitoneum in 3, and pelvis in 1. To determine the accuracy of each imaging technique, the percent sensitivity (SE), percent specificity (SP), and percent accuracy (AC) were determined for each technique from surgical findings and a follow-up study. MRI showed the highest diagnostic accuracy (100% for SE, SP, and AC), followed by CT (100%, 92%, 96%), US (82%, 92%, 88%), BS (58%, 100%, 80%), and GS (42%, 85%, 64%) in that order. MRI is most suitable for the imaging of individuals judged to be positive in the mass screening for neuroblastoma because of the advantages of visualization of the spread of tumor and the relationship of tumor to the great blood vessels, important determinants of resectability and therapy.

Adrenal Gland Neoplasms↗
PubMed1993

Effect of 17 beta-estradiol on secretion of platelet-activating factor acetylhydrolase by HepG2 cells.

Estrogen has been shown to decrease plasma platelet-activating factor (PAF) acetylhydrolase activity, but the precise mechanisms are not known. We examined the effect of estradiol on the secretion of PAF acetylhydrolase by HepG2 cells. In our previous study, we demonstrated the production of this enzyme by HepG2 cells, which we used as an experimental model of normal hepatocytes. 17 beta-Estradiol mildly but consistently inhibited the secretion of PAF acetylhydrolase by HepG2 cells in a concentration-dependent manner. Under basal conditions, HepG2 cells secreted 42.3 pmol/mg cell protein/min PAF acetylhydrolase in 24 hours (mean of 8 dishes), and the presence of 10(-7) mol/L 17 beta-estradiol decreased the secretion to 77% +/- 10.3% of control values (mean +/- SD, n = 8, P < .02). 17 beta-Estradiol treatment affected neither the secretion of apolipoprotein (apo) A-I nor cell-associated PAF acetylhydrolase activity. Electrophoretic separation of [35S]methionine-labeled PAF acetylhydrolase revealed a single band whose molecular weight was approximately 43,000 d. We conclude that estrogen decreases the secretion of PAF acetylhydrolase by the liver, and it may explain, at least in part, the effect of estrogen on plasma PAF acetylhydrolase.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1993

Effects of sialoadenectomy and epidermal growth factor administration on 9,10-dimethyl-1,2-benzanthracene-induced tumor formation in hamster cheek pouch.

The effects of removal of the submandibular gland (sialoadenectomy) and administration of human urinary epidermal growth factor on the 9,10-dimethyl-1,2-benzanthracene-induced tumor formation were investigated with the use of a hamster cheek pouch model. Syrian hamsters were treated with 0.5% 9,10-dimethyl-1,2-benzanthracene for 6 weeks. Thereafter hamsters in group 1 underwent a sham operation and those in groups 2 and 3 underwent a sialoadenectomy. Subsequently, hamsters in groups 1 and 2 were given 0.9% sodium chloride and group 3 received the human urinary epidermal growth factor at a dose of 0.25 mg/kg body weight subcutaneously three times a week for 8 weeks. Sixteen weeks after the start of the experiment, the mean number of tumors that were less than 3-mm in diameter in groups 1 and 3 was significantly greater than that in group 2 (p < 0.05). The overall incidence and mean number of all carcinomas irrespective of size showed no differences among the experimental groups. These results indicate that epidermal growth factor synthesized in the submandibular gland may enhance the induction of cheek pouch tumor.

9,10-Dimethyl-1,2-benzanthracene↗