Search PubMed⌕ Search

Biomedical subjects

H Nagae

Publications and source records attributed to H Nagae.

At least 55 records · Page 3Linked to original sources

Sn-protoporphyrin plus photoirradiation induces lipid peroxidation in vivo and in vitro in nonjaundiced Gunn rats.

Lipid peroxidation induced by Sn-protoporphyrin (SnPP) plus photoirradiation was investigated in vivo and in vitro using nonjaundiced Gunn rats. Membrane lipids from young adult rat brain were peroxidized by SnPP plus photoirradiation depending on the SnPP concentration and photoirradiance. Similarly, coadministration of SnPP and photoirradiation to suckling rats increased lipid peroxides in the whole blood and was found lethal. The influence of the wavelength distribution of light sources was also examined by using blue-white and green fluorescent lights. The photodynamic effect by green light irradiation whose energy distribution had no overlap with the Soret band of SnPP was about half of that produced by blue-white light with regard to the membrane peroxidation and the lethal effect on neonatal rats. We therefore conclude that the combination of SnPP and photoirradiation is a potentially hazardous treatment of neonatal jaundice.

Animals↗

Maternal and fetal atrial natriuretic peptide levels, maternal plasma renin activity, angiotensin II, prostacyclin and thromboxane A2 levels in normal and preeclamptic pregnancies.

To clarify the possible role of elevated atrial natriuretic peptide (ANP) in the pathophysiology of preeclampsia, we measured ANP, renin activity (PRA), angiotensin II (Ang II), TXB2 (a stable metabolite of TXA2) and 6-keto-PGF1 alpha (a stable end product of PGI2) concentrations in the plasma of 19 normal pregnant women and 35 severe preeclamptic patients at term. Plasma ANP levels in the preeclamptic patients (n = 35, 71.5 +/- 3.8 pg/ml, mean +/- S.E.) and also umbilical plasma ANP (n = 35, 83.0 +/- 4.2 pg/ml) were significantly (p less than 0.01) higher than those of normal pregnant women plasma (n = 19, 58.7 +/- 3.7 pg/ml) and umbilical plasma (n = 19, 47.6 +/- 4.7 pg/ml). There was a significant (p less than 0.01) positive correlation between maternal ANP levels and fetal ANP levels (n = 54, r = 0.44). Plasma PRA and 6-keto-PGF1 alpha levels in preeclampsia were significantly (p less than 0.05) lower than those of normal pregnancy. The ratio of 6-keto-PGF1 alpha/TXB2 in preeclampsia was significantly (p less than 0.01) lower than that of normal pregnancy as we reported previously. There was no significant correlation between plasma ANP level and plasma PRA, Ang II, plasma TXB2 and 6-keto-PGF1 alpha concentrations. Moreover there was no significant correlation between plasma ANP level and the severity of preeclampsia. These data suggest the possibility of a transplacental crossing of ANP secreted by feto-placental unit, which might be, at least in part, responsible for the high ANP levels observed in preeclampsia. The ANP in preeclampsia is not related directly to hypertension, but it may play a substantial role in the regulation or normalization of blood volume and vascular reactivity.

6-Ketoprostaglandin F1 alpha↗

Dangerous effects of tin-protoporphyrin plus photoirradiation on neonatal rats.

In vivo and in vitro effects of porphyrins (tin-protoporphyrin [SnPP], cobalt-mesoporphyrin, haemin and protoporphyrin) on neonatal rats were investigated. Under photoirradiation a high mortality rate was recognized in SnPP injected rats. None died from the application of SnPP without photoirradiation. In photoirradiated rats the median lethal dose (LD50) value of SnPP was calculated to be about 7.4 mumol/kg body weight. Haemolysis and malonaldehyde formation of red blood cells were induced by SnPP together with photoirradiation. SnPP may be useful in reducing bilirubin levels in severely jaundiced infants under non-photoirradiated conditions or dim light, but prophylactic administration of SnPP to the majority of infants is not recommended.

Animals↗

Marked latency change of auditory brainstem response in preterm infants in the early postnatal period.

In order to evaluate the influence of extrauterine life on auditory brainstem response in neonates, we performed serial ABR recordings twice a week in 10 preterm infants. A marked decrease of I-III interpeak latency was observed in 7 infants during the first 2 or 3 weeks after birth. Wave I latency also remarkably reduced during this period in 5. These findings were related not to the conceptional age but to the extrauterine age. In 2 infants III-V interpeak latency increased during the first 1 or 2 weeks after birth, and the rate of latency increase seemed to be inversely proportional to that of decrease of I-III interpeak latency.

Aging↗

[Effects of SSM, an extract from human type tubercle bacilli, on syngenic guinea pig tumors].

SSM (specific substance of Maruyama) is used widely in cancer therapy. Rats and mice have generally been used in basic research. In this study the author used guinea pigs because their skin properties are easier to monitor than those of rats and mice. The following experiments were performed on guinea pigs: 1) Potency as sensitizer and elicitor of delayed hypersensitivity. 2) Antitumor effects on methylcholanthrene induced syngenic guinea pig tumors (U-1). Intradermal skin tests with 20 micrograms of SSM per 0.1 ml were done on guinea pigs 4 weeks after sensitization (SSM 1 mg-FIA (Freund's incomplete adjuvant]. SSM induced a delayed skin reactivity and the reaction increased in erythema and in duration after 24 h. In addition, SSM was active in direct inhibition of macrophage migration. The results show that SSM is related to cellular immunity reactions. In this study, antitumor effects of SSM were indicated in that the tumor growth was more greatly suppressed in animals injected intravenously and subcutaneously than in control animals. Histologic study of the tumors showed that collagen fibers enclosed the cancer cells and prevented cancer proliferation.

Animals↗

Pharmacological and biological effects of tin-protoporphyrin on neonatal hyperbilirubinemic Gunn rats.

Our study was undertaken to examine the pharmacological and biological effects of tin-protoporphyrin, a competitive inhibitor of heme oxygenase, on 5- or 6-day-old homozygous (j/j) Gunn rats with hereditary unconjugated hyperbilirubinemia. When j/j neonates were injected subcutaneously with 20 mumol of tin-protoporphyrin/kg of body weight, hepatic heme oxygenase activity decreased to 30% of the initial level 2 h after administration and remained low during the next 46 h. However, the reduction of serum bilirubin was more rapid and transient, reaching the minimum value (40% of the initial level) at 1 h and increasing thereafter at a rate almost comparable to that in nontreated j/j rats. The mortality rate of j/j rats was strikingly reduced by the administration of 1 to 100 mumol of tin-protoporphyrin/kg; the most effective dose was 5 mumol/kg (8% compared with 80% in non-treated j/j rats). However, the protective effect of tin-protoporphyrin on bilirubin cerebellopathy (cerebellar hypoplasia) was less marked than expected. Possible implications of our results are discussed.

Animals↗

[Mesh-graft urethroplasty: a case report].

We used a meshed free-foreskin transplant in a two-stage procedure for reconstruction of the extended stricture of urethra after direct vision urethrotomy. The results were excellent. Mesh-graft urethroplasty is a useful method for patients with extended strictures of the urethra or recurrent strictures after several operations.

Adult↗

Physiological covalent regulation of rat liver branched-chain alpha-ketoacid dehydrogenase.

A radiochemical assay was developed for measuring branched-chain alpha-ketoacid dehydrogenase activity of Triton X-100 extracts of freeze-clamped rat liver. The proportion of active (dephosphorylated) enzyme was determined by measuring enzyme activities before and after activation of the complex with a broad-specificity phosphoprotein phosphatase. Hepatic branched-chain alpha-ketoacid dehydrogenase activity in normal male Wistar rats was 97% active but decreased to 33% active after 2 days on low-protein (8%) diet and to 13% active after 4 days on the same diet. Restricting protein intake of lean and obese female Zucker rats also caused inactivation of hepatic branched-chain alpha-ketoacid dehydrogenase complex. Essentially all of the enzyme was in the active state in rats maintained for 14 days on either 30 or 50% protein diets. This was also the case for rats maintained on a commercial chow diet (minimum 23% protein). However, maintaining rats on 20, 8, and 0% protein diets decreased the percentage of the active form of the enzyme to 58, 10, and 7% of the total, respectively. Fasting of chow-fed rats for 48 h had no effect on the activity state of hepatic branched-chain alpha-ketoacid dehydrogenase, i.e., 93% of the enzyme remained in the active state compared to 97% for chow-fed rats. However, hepatic enzyme of rats maintained on 8% protein diet was 10% active before starvation and 83% active after 2 days of starvation. Thus, dietary protein deficiency results in inactivation of hepatic branched-chain alpha-ketoacid dehydrogenase complex, presumably as a consequence of low hepatic levels of branched-chain alpha-ketoacids, established inhibitors of branched-chain alpha-ketoacid dehydrogenase kinase. With rats fed a low-protein diet and subsequently starved, inhibition of branched-chain alpha-ketoacid dehydrogenase kinase by branched-chain alpha-ketoacids generated as a consequence of endogenous proteolysis most likely promotes the greater branched-chain alpha-ketoacid dehydrogenase activity state.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Polymorphism of dihydrofolate reductase from a methotrexate-resistant subline of L1210 cells.

Dihydrofolate reductase, purified to homogeneity (as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis), from a subline of L1210 murine leukemia cells resistant to 10(-6) M methotrexate, was resolved into two principal forms (1 and 2) by polyacrylamide gel electrophoresis at pH 8.3 or isoelectric focusing. In the latter procedure, these forms had pI values of 7.4 and 8.2, respectively; both stained for protein and catalytic activity. Form 1 appears to be a single component, comprising ca. 10% of the total protein and at least 20% of the total catalytic activity. It is also more sensitive to inhibition by MTX, more heat-stable, and less susceptible to activation than form 2. Multiple components of 2 were observed by narrowing the pH range in isoelectric focusing, and further resolution was achieved by urea denaturation. Substrate and inhibitor complexes of 1 and 2, differentiated by polyacrylamide gel electrophoresis or isoelectric focusing, provided information about the ability of the enzyme to undergo conformational changes. Interconversion of 1 with one of the components of 2 may also involve conformational isomerism. These conclusions are consistent with the well-known ability of eukaryotic dihydrofolate reductases to exhibit increased catalytic activity (attributed to transformations to more open conformations) when treated with salts, chaotropes, or cysteine-modifying agents. Treatment of the L1210/R6 enzyme preparation with one of these activating agents, 5,5'-dithiobis(2-nitrobenzoic acid), derivatized both 1 and 2 (changing their pI values to 7.3 and 6.9, respectively) and altered the enzyme such that stoichiometric inhibition for MTX was observed.

Animals↗

Structure of pestalotan, a highly branched (1----3)-beta-D-glucan elaborated by Pestalotia sp. 815, and the enhancement of its antitumor activity by polyol modification of the side chains.

Pestalotia sp. 815, a newly isolated fungus, produces extracellularly a highly (1----6)-branched (1----3)-beta-D-glucan in high yield when grown in a D-glucose-containing medium. This extracellular glucan, designated "Pestalotan", has [alpha]25D-0.1 degree (c 0.5, M NaOH) and a molecular weight greater than 2 X 10(6). Chemical and enzymic studies indicated that pestalotan has a very highly branched structure containing a back-bone chain of beta-D-(1----3)-linked D-glucosyl residues, and three out of five D-glucosyl residues are substituted at O-6, mostly with single D-glucosyl groups, and a very few with short beta-(1----6)-linked oligosaccharide units. This D-glucan becomes water-insoluble after isolation from the culture filtrate followed by dehydration, and shows moderate growth-inhibitory activities against mouse-implanted tumors. However, when the D-glucosyl groups of the side chains were modified by periodate oxidation and borohydride reduction, the resulting, still water-insoluble, D-glucan polyol exhibited potent antitumor activities, confirming that the attachment of many polyhydroxy groups to the beta-D-(1----3)-linked D-glucan back-bone gives a remarkable enhancement effect on the antitumor activity of the branched D-glucan. Prolonged treatment of the D-glucan polyol by ultrasonic irradiation afforded a low-molecular-weight D-glucan polyol (SD-pestalotan polyol), without alteration of its chemical structure. The water-soluble, SD-pestalotan polyol, having a molecular weight of 4.7 X 10(5), exhibited remarkable antitumor activities against both allogeneic and syngeneic, mouse-implanted tumors, at small dosages (1-5 mg/kg for 10 days) by intraperitoneal administration. A comparison of values of the molecular weight of SD-pestalotan polyol, estimated by 3-MPa l.c. for the aqueous solution and the dimethyl sulfoxide solution, strongly suggested that the D-glucan polyol must form a triple-chain conformation in aqueous solution.

Animals↗

Acycloguanosine therapy of the localized form of herpes simplex virus infection in a low-birth-weight infant.

It is known that the localized form of herpes simplex virus (HSV) infection does not always show a good prognosis. A preterm infant who evidenced skin and tongue lesions, caused by HSV type 1, was treated by acycloguanosine. The result was satisfactory without any complications. Therefore, a localized form of HSV infection of the newborn infant, even though the patient has a low-birth-weight, should be treated by the drug immediately after the observation of the positive HSV culture.

Acyclovir↗