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Biomedical subjects

H Noguchi

Publications and source records attributed to H Noguchi.

At least 217 records · Page 12Linked to original sources
PubMed1994

Left ventricular contractile state of early human neonates with patent ductus arteriosus.

Using echocardiographic technique, we studied the left ventricular (LV) contractile state in 32 full-term infants within 24 hr after birth. They were divided into 2 groups based on the timing of the examinations; the group 1 (n = 17), < 3 hr after birth; the group 2 (n = 15), > 3 and < 24 hr after birth, and the additional examinations were performed on day 5. The patency of the ductus arteriosus and its internal diameter were determined by pulsed Doppler and two-dimensional echocardiography. The left atrial to aortic root ratio was obtained from M-mode echocardiography, and the LV contractile state was estimated by the relationship between heart rate-corrected velocity of circumferential fiber shortening (mVcfc) and end-systolic meridional wall stress (ESS). The ductus arteriosus was open in all cases of group 1 and in 83% of the cases of group 2, but the ductal diameter and the left atrial to aortic root ratio significantly decreased in group 2. The relationship between mVcfc and ESS showed no significant differences between 2 groups and the control. Afterload, represented as ESS, was significantly lower in group 1 than the control. We suggest that the low afterload condition helps the adequate LV contraction even under the increased preload through the left-to-right ductus arteriosus shunting after birth.

Blood Flow Velocity↗
PubMed1994

Mechanism of FK506-induced glucose intolerance in rats.

To clarify the mechanism of glucose intolerance induced by FK506, a novel immunosuppressant, 5 or 10 mg/kg/day of FK506 was dosed orally to rats for 2 weeks, and 125I-insulin binding to the erythrocytes, plasma glucose and insulin levels, and pancreatic insulin content were examined. Insulin binding to the erythrocytes of rat dosed with FK506 was similar to that to erythrocytes of the placebo control; Scatchard analysis confirmed that FK506 did not cause damage to the insulin receptor of the erythrocytes. Contrarily, FK506 caused a clear decrease of pancreatic insulin content as well as a slight decrease of plasma insulin level. The results suggest that the glucose intolerance induced by FK506 is associated with a decrease of insulin secretion, but is not associated with impairment of the insulin receptor.

Animals↗
PubMed1994

Tacrolimus (FK506)-induced nephrotoxicity in spontaneous hypertensive rats.

To clarify the profile of the tacrolimus (FK506)-induced nephrotoxicity and its mechanism, 1, 2 and 4 mg/kg/day of tacrolimus was administered intramuscularly (i.m.) to spontaneous hypertensive rats (SHR) for 2 weeks, and biochemical and pathological parameters were studied in the animals. The acute nephrotoxicity of tacrolimus was characterized as increase of blood urea nitrogen (BUN) and plasma creatinine (P-Cr) levels in the groups of 1 mg/kg/day and more, decrease of creatinine clearance (CCr) value in the groups of 2 mg/kg/day and more, and histopathologically luminal narrowing of the arteriole adjacent the glomerulus in the groups of 1 mg/kg/day and more. These changes were associated with an increase of plasma renin activity (PRA) and urinary thromboxane B2 content and decrease of 6-keto-prostagrandinF1 alpha (6-keto-PGF1 alpha) content. Nilvadipine, which is one of the Ca2+ antagonist and is known to have renal vasodilating activity, prevented both biochemical and histopathological changes due to tacrolimus. The results indicated that the acute nephrotoxicity of tacrolimus was derived from impairment of glomerular function associated with the constriction of the renal arteriole brought about by the drug. All of these renal disorders induced by tacrolimus recovered completely or partially when the drug was withdrawn for 2 or 4 weeks. Consequently, the acute nephrotoxicity of tacrolimus in SHR was considered to be reversible.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Toxicokinetics of zenarestat, an aldose reductase inhibitor in animals and man.

1. The relationship between dose and plasma concentrations is important in extrapolating toxicity between species. Therefore, we determined this relationship for zenarestat in animals and man. 2. The biopharmaceutics of zenarestat was assessed prior to toxicity testing. The bioavailability of zenarestat in rat administered zenarestat in 0.5% (w/v) methyl cellulose suspension and aqueous solution was similar. Bioavailability in dog administered zenarestat treated with excipients and in aqueous solution was similar. 3. Cmax increases dose-relatedly both in animals and man. AUC increased almost in proportion to the dose in mouse, rat and man, but increased to a greater extent at the highest dose in dog. Cmax, AUC and C24h were not significantly different during/after multiple dosing. 4. After 13 and 53 weeks of toxicity testing, plasma concentrations were not significantly different between the days and sexes except at 560 mg/kg in the female rat and at 56 mg/kg in the female dog in 13 week toxicity tests. 5. The exposure of zenarestat in man, administered 300 mg b.i.d., seemed to be no more than that in animals at non-toxic doses.

Administration, Oral↗
PubMed1994

[Antibacterial activities of a carbapenem antibiotic, biapenem (L-627), against penicillin-resistant Streptococcus pneumoniae].

Antibiotic susceptibilities were evaluated for 48 strains of Streptococcus pneumoniae collected in 1992-1993 at Ichihara City of Chiba Prefecture. Twenty two (46%) of the 48 strains were benzylpenicillin (PCG) insensitive or resistant (PRSP) judged from the MICs of PCG to higher than 0.1 microgram/ml. MICs of piperacillin and cefotaxime increased as the MICs of PCG increased. However, elevations of MICs of imipenem and biapenem (L-627) were small in spite of the increases of MICs of PCG. L-627 was effective in a case of purulent meningitis due to PC-insensitive S. pneumoniae. Thus, L-627 is a candidate to be used in treatment of PRSP infections including purulent meningitis.

Humans↗
PubMed1994

[A study of the drug distribution on intra-hepatic arterial infusion chemotherapy; how much difference between continuous infusion and rapid infusion?].

The subjects were 41 cases with implantable reservoir systems for unresectable hepatic tumors. We evaluated the difference in drug distribution between intra-hepatic arterial continuous infusion and rapid infusion using hepatic perfusion scintigraphy by 99mTc-macroaggregated albumin via reservoirs. The 41 cases were divided into 2 groups (A and B) according to the imaging of the perfusion scintigraphy. There were 17 cases in group A with equal distribution and 24 cases in group B with a different distribution between the continuous infusion and the rapid infusion. The 24 cases in group B were subdivided into groups according to the distribution of 99mTc-MAA in and around liver. In some cases the distribution pattern after rapid infusion improved more than with continuous infusion. These results suggested that the infusion method must be selected for every case.

Antineoplastic Agents↗
PubMed1994

Evidence against a significant implication of carbonic anhydrase inhibitory activity of zonisamide in its anticonvulsive effects.

To clarify whether the inhibitory effect of zonisamide (Excegran, CAS 68291-97-4) on carbonic anhydrase contributes to its anticonvulsant activity, the anticonvulsant activity of 7-methylated zonisamide, a zonisamide analogue which has the same potency of activity as zonisamide in inhibiting carbonic anhydrase in vitro, has been examined. The study using mice did not reveal 7-methylated zonisamide to have any anticonvulsant activity even though its brain concentration level was more than two times the minimal effective concentration of zonisamide. These findings indicate that the anticonvulsant effect of zonisamide is derived from a mechanism(s) other than inhibition of carbonic anhydrase.

Animals↗
PubMed1993

Alpha 1-adrenoceptor subtype involved in the positive inotropic response to phenylephrine in rat atria.

Phenylephrine produced positive inotropic responses in isolated rat right and left atria. The responses were competitively inhibited by alpha 1-adrenoceptor antagonists (prazosin, WB4101 and HV723) with relatively low affinities (pA2 values close to 8.0). Chloroethylclonidine had no significant effect on the responses to phenylephrine. These results suggest that the positive inotropic response to phenylephrine in rat atria is mediated through alpha 1-adrenoceptors which cannot be defined by the alpha 1A, alpha 1B subclassification.

Acetonitriles↗
PubMed1993

Ano-urethral fistula, a special type of anomaly: report of two cases.

Two cases of an ano-urethral fistula, being a low malformation, are reported herein. Both patients underwent a colostomy under the diagnosis of a recto-urethral fistula during the neonatal period. As a urethro-rectogram later revealed the fistula to be located between the anus and anterior urethra, revision of the urethral fistula and an anoplasty were performed through the perineal approach. It is very difficult to establish a correct diagnosis of an ano-urethral fistula at the initial stage of treatment, but we found the urethro-rectogram invaluable in this regard. This type of malformation can be treated through the perineal approach, while the additional anterior perineal incision is very helpful for revising the urethral fistula.

Anal Canal↗
PubMed1993

PGE2 protects isolated cells against injury through multiple mechanisms.

In order to clarify how PGE2 regulates gastric mucosal integrity, we examined the effects of PGE2 on ethanol-caused injury of isolated gastric chief cells, cultured gastric mucous cells from guinea pigs and Balb/c 3T3 fibroblasts. Pretreatment of these cells with PGE2 reduced ethanol-caused injury of the cells. Furthermore, pretreatment of gastric mucous cells with indomethacin enhanced ethanol-caused injury, suggesting that endogenous PGE2 may be involved in the cell protection. PGE2 stimulated an increase in diacylglycerol (DG) accumulation in chief cells and treatment of chief cells with synthetic DG reduced the injury of the cells. However, DG accumulation was not observed in gastric mucous cells treated with PGE2. Therefore PGE2 may protect the cells from injury through a variety of mechanisms. In addition, PGE2 enhanced the survival of the quiescent fibroblasts cultured in the absence of serum, while PGE2 had no survival enhancing effect on gastric mucous cells. These results suggest that the mechanism by which PGE2 preserves the cell viability may depend on not only cell types used but also how the cells are injured.

Animals↗
PubMed1993

A case of fatal infectious mononucleosis presenting with fulminant hepatic failure associated with an extensive CD8-positive lymphocyte infiltration in the liver.

We describe a fatal case of infectious mononucleosis presenting with fulminant hepatic failure associated with extensive CD8-positive lymphocyte infiltration and diffuse karyorrhexis in the liver. Immunohistochemical analysis of mononuclear cells showed that Leu-2a (CD8)-positive lymphocytes were heavily distributed in the portal areas and the sinusoidal spaces, but Leu-3a (CD4)-, Leu-14 (CD22)-, or My 4 (CD14)-positive cells were undetectable in sections of the liver. Southern blot hybridization studies disclosed the presence of Epstein-Barr virus DNA fragments in the liver tissue. The unusual pathologic and immunologic responses observed in this case could not simply be explained by severe Epstein-Barr virus infection. Some superimposed factors should be considered.

CD8 Antigens↗
PubMed1993

Effects of flunarizine and diltiazem on physical dependence on barbital in rats.

The effects of flunarizine and diltiazem both on development of physical dependence on barbital and on barbital withdrawal signs in rats were examined using the drug-admixed food (DAF) method. Rats were chronically treated with barbital or barbital in combination with flunarizine (fixed at 1.5 mg/g of food) or diltiazem (fixed at 0.75 mg/g of food)-admixed food on the schedule of gradually increasing doses of barbital. Motor incoordination during the treatment was potentiated by coadministration of flunarizine, but not by coadministration of diltiazem. After the termination of drug treatment, the body weight loss and withdrawal scores were significantly suppressed in the group coadministered flunarizine, but not in that coadministered diltiazem. There were no significant differences in plasma barbital levels after the withdrawal between groups. In the substitution test, flunarizine (20 and 40 mg/kg, IP) significantly suppressed the body weight loss and withdrawal scores after the withdrawal, but diltiazem (20 mg/kg, IP) did not. These results indicated that flunarizine suppressed both the development of physical dependence on barbital and barbital withdrawal signs, mainly according to the suppression of convulsions, but not diltiazem, which is known to poorly penetrate into the brain. Therefore, the present findings suggest that central calcium channels may be involved in both the development of physical dependence on barbital and the appearance of barbital withdrawal signs.

Animals↗
PubMed1993

Regulation of nerve growth factor secretion in L-M cells by catechol derivatives.

We investigated the mechanism responsible for the stimulation of nerve growth factor (NGF) secretion by catechol derivatives in L-M cells, using L-threo-3,4-dihydroxyphenylserine (L-DOPS). Treatment of the cells with L-DOPS increased the NGF content in the L-M cell medium by approximately 3-fold. This stimulatory effect was not blocked by a decarboxylase inhibitor, or by alpha- or beta-adrenergic blockers. Intracellular cAMP levels were not changed by exposure to L-DOPS. The antioxidants, ascorbic acid and sodium pyrosulfite, completely prevented the stimulatory effect of L-DOPS, and radical scavengers (superoxide dismutase plus catalase) caused a significant partial inhibition of the response to L-DOPS. Quinone derivatives (adrenochrome, 4-n-propyl-1,2-benzoquinone), which are the oxidative products of the catechol derivatives, increased the NGF content in the medium, and their potency was greater than that of the catechol derivatives themselves. These findings suggest that L-DOPS and other catechol derivatives might be oxidized in the medium to form quinone derivatives, and that it is these which predominantly express a stimulatory effect on NGF secretion by a novel cAMP-independent mechanism in L-M cells.

Animals↗
PubMed1993

Protective activity of anti-exotoxin A monoclonal antibody against mice infected with toxin-producing Pseudomonas aeruginosa.

The neutralizing and protective effect of murine monoclonal antibody (MAb) 3C7 (IgG1) against Pseudomonas aeruginosa exotoxin A was examined in an experimental mouse model of infection with exotoxin A-producing strains. Treatment with MAb 3C7 blocked the reduction of functional elongation factor 2 (EF-2) in the liver of mice but could not clear the bacteria. Administration of gentamicin caused bacteria to be cleared but did not block reduction of hepatic EF-2 level. Treatment with either MAb 3C7 or gentamicin individually did not prolong time to death; however, the combined therapy with both MAb 3C7 and gentamicin cleared bacteria and blocked the reduction of hepatic EF-2 level, resulting in a significant increase in the survival rate of mice. These results suggest that anti-exotoxin A MAbs show effectiveness against pseudomonal infection caused by exotoxin A-producing strains.

ADP Ribose Transferases↗
PubMed1993

Human cervical epidermal carcinoma-associated intracellular localization of glycosphingolipid with blood group A type 3 chain.

A monoclonal antibody, MRG-1, was produced by immunizing a mouse with a human ovarian mucinous cyst adenocarcinoma-derived cell line, RMUG-L. By immunohistochemical staining, the antigen was found to be exclusively localized in the intracellular structures of the cells used as the antigen and of the epithelial cells in normal human cervical glands. However, although the antigen was predominantly detected in the plasma membrane and the intercellular structure of the middle layer of normal human cervical squamous epithelium (92%), it was also contained in the intracellular structure of cervical epidermal carcinoma at a high frequency (80%). The striking difference in the distribution of the MRG-1 antigen between normal and cancerous tissues was found to be a cervical carcinoma-associated phenomenon and a useful tumor marker for immunohistochemical examination. Since the antigen was found to be of a blood group A-related nature by immunohistochemical staining of the tissues and to be a glycosphingolipid, it was purified from human erythrocytes of blood group A, and the structure was concluded to be GalNAc alpha 1-3Gal(2-1 alpha Fuc)beta 1-3GalNAc alpha 1-3Gal(2-1 alpha Fuc)-beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1' Cer, blood group A type 3 chain-containing glycosphingolipid, by NMR, negative ion FABMS and permethylation analysis. In the subcellular localization analysis of the antigen, type 3-A glycosphingolipid antigen was detected in the Golgi body and the microsomes of RMUG-L cells, and the distribution coincided with the finding by immunohistochemical staining. In addition, in cervical epidermal carcinoma, although the blood group A, mainly type 2-A chain, was localized in the plasma membrane and the intercellular structure, the blood group A type 3 chain was selectively found in the perinuclear structure. Also, the blood group A type 3 chain in cervical dysplasia as well as that in normal cervix was predominant in the plasma membrane. Thus, the selective intracellular localization of blood group A type 3 chain was a phenomenon characteristic of cervical epidermal carcinoma and the carcinoma in situ.

Animals↗
PubMed1993

The high incidence of atrial thrombosis in mice given doxorubicin.

Doxorubicin (DX)-treated mice represent an animal model for studying new drugs for heart disease. Coincidentally, in the collection of damaged myocardial tissue, thrombosis was detected in the atrium. The incidence reached 75% in mice given 4 mg/kg DX iv 10 times. They were white thrombi consisting of the fibrin, platelets, and neutrophils. Cardiac muscle damage was more prominent in the atria than in the ventricles. Light microscopically, vacuolization and degeneration of atrial myocytes and interstitial inflammatory cell infiltration were observed. Electron microscopy revealed dilatation of the sarcoplasmic reticulum and an increase in number of normal and/or degenerate mitochondria. Inflammation extended from the cardiac muscle to the endocardium. The cause of atrial thrombosis in DX-treated mice is unknown but may relate to endocardial damage and changes of blood flow in the atrium secondary to cardiac muscle damage. DX-treated mice could serve as an experimental animal model for the evaluation of efficacy and toxicity of antithrombotic or antiplatelet drugs.

Animals↗
PubMed1993

Toxicity of polyoxyethylene hydrogenated castor oil 60 (HCO-60) in experimental animals.

HCO-60, a polyoxyethylene castor oil derivative, is used as a solubilizer in the injectable formulations of lipophilic agents. This study was performed to examine the toxicity of HCO-60 in various experimental animals including dogs, monkeys, rabbits, guinea pigs and rats. With 1.25 or 2.5 mg/kg of HCO-60 injected i.v. to dogs, blood pressure decreased, flush, swelling and itching appeared after injection, and with 10 mg/kg of HCO-60 there was additionally a decrease of spontaneous motility. In the two higher dose groups, these symptoms paralleled an increase of histamine levels. Since degranulation was observed after injection in the mast cells of the skin, but not in the liver of dogs, the histamine in the plasma was considered to be released from the mast cells of the skin. Pretreatment with diphenhydramine, a H1-receptor antagonist, suppressed the decrease of blood pressure induced by HCO-60. These findings show that the toxicity of HCO-60 is associated with histamine release from the mast cells. No symptoms occurred in monkeys, rabbits, guinea pigs or rats with 50 or 100 mg/kg of i.v. of HCO-60, and there was no change in plasma histamine levels. This study demonstrated that the toxicity of HCO-60 is species specific to dogs among the animals tested.

Animals↗