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M Hirota

Publications and source records attributed to M Hirota.

At least 199 records · Page 11Linked to original sources

Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter.

Okadaic acid is a polyether compound of a C38 fatty acid, isolated from a black sponge, Halichondria okadai. Previous studies showed that okadaic acid is a skin irritant and induces ornithine decarboxylase (OrnDCase; 3-hydroxyl-L-glutamate 1-carboxy-lyase, EC 4.1.1.17) in mouse skin 4 hr after its application to the skin. This induction was strongly inhibited by pretreatment of the skin with 13-cis-retinoic acid. A two-stage carcinogenesis experiment in mouse skin initiated by a single application of 100 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) and followed by application of 10 micrograms of okadaic acid twice a week revealed that okadaic acid is a potent additional tumor promoter: tumors developed in 93% of the mice treated with DMBA and okadaic acid by week 16. In contrast, tumors were found in only one mouse each in the groups treated with DMBA alone or okadaic acid alone. An average of 2.6 tumors per mouse was found in week 30 in the group treated with DMBA and okadaic acid. Unlike phorbol 12-tetradecanoate 13-acetate (TPA), teleocidin, and aplysiatoxin, okadaic acid did not inhibit the specific binding of [3H]TPA to a mouse skin particulate fraction when added up to 100 microM or activate calcium-activated, phospholipid-dependent protein kinase (protein kinase C) in vitro when added up to 1.2 microM. Therefore, the actions of okadaic acid and phorbol ester may be mediated in different ways. These results show that okadaic acid is a non-TPA-type tumor promoter in mouse skin carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Developmental changes of C-series polysialogangliosides in chick brains revealed by mouse monoclonal antibodies M6704 and M7103 with different epitope specificities.

We have established many mouse monoclonal antibodies detecting developmentally regulated antigens in chicken embryonic neural tissues of the otic vesicles and neural tube by immunizing mice with the membrane fraction of the neural tube and somite prepared from 3-d chick embryos. Among them, three monoclonal antibodies (MAbs) M6703, M6704, and M7103 were shown to react with the gangliosides isolated from chicken embryonic brains. The precise specificity of the antibodies was determined mainly by enzyme-immunostaining on thin layer plates. MAbs M6703 and M6704 bound to C-series polysialogangliosides including GT3, GT2, GT1c, GQ1c, and GP1c isolated from cod fish brains, but never to A-series, B-series, or X-series gangliosides. On the other hand, MAb M7103 antibody has a rather narrow specificity, reacting with GT1c, GQ1c, and GP1c, but not with ganglioside GT3. This indicates that the epitopes defined by these two MAbs are not with ganglioside GT3. This indicates that the epitopes defined by these two MAbs are different from each other. MAbs M6703 and M6704 recognize a trisialosyl residue, NeuAc alpha 2-8NeuAc alpha 2-8NeuAc alpha 2-3, while M7103 requires both a trisialosyl residue and the gangliotetraosy backbone structure for binding. As compared to similar MAbs which have been reported in the literature. M6703 and M6704 are unique in that they react equally with all of the C-series gangliosides and belong to the IgG3 subclass.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Efficacy of NY-198 against experimental Legionnaires disease.

The in vitro and in vivo effects of NY-198 against Legionella pneumophila were compared with those of ciprofloxacin. The MIC of NY-198 against 15 standard reference strains of Legionella of various species, between 0.03 and 0.125 micrograms/ml, was the same as that of ciprofloxacin. The peak concentration of NY-198 in the lungs and sera of guinea pigs with experimentally induced Legionella pneumonia was higher than that of ciprofloxacin after oral administration. The overall survival rate was higher in animals treated with NY-198 than in those treated with ciprofloxacin. Thus, NY-198 appears valuable in the treatment of Legionnaires disease.

Animals↗

Asymptomatic hyperbromidaemia detected as pseudohyperchloridaemia measured with an ion selective electrode meter.

Six patients were found to have increased serum chloride concentrations when these concentrations were determined with an ion-selective electrode, but not when determined by continuous flow mercuric thiocyanate colorimetry or amperometric-coulometric titration. Their serum bromide levels of 1.8-8.0 mmol/l were much higher than those of 0.07-0.13 mmol/l in normal controls. The urinary bromide excretion, measured in two of these patients, was higher than that in normal subjects. No common symptoms or abnormalities in laboratory findings except hyperbromidaemia were found in these patients, who claimed not to have taken any drugs containing bromide. For determination of the incidence of subclinical hyperbromidaemia, the serum bromide concentrations were measured in sera of 1,323 outpatients sent to Tokushima University Hospital for routine measurements of blood chemistry over a one-month period. Five samples showed abnormally high bromide levels. It is concluded that subclinical hyperbromidaemia is not as rare as generally thought, though the aetiology of this state is unknown. Chloride determination with an ion-selective electrode can be used to screen for hyperbromidaemia, since increased levels of bromide ion result in apparently high chloride values.

Adult↗

[Surgical treatment and problem of massive small intestinal resection in children--assessment of background diseases and actual management].

From 1971 to 1986, massive small intestinal resection was done in twenty-five cases; intestinal atresia 12, intestinal volvulus 9, necrotizing enterocolitis 2, intussusception 1 and gastroschisis 1. Thirteen cases (52%) of them have survived. Of 12 cases with intestinal atresia undergoing small intestinal resection, 7 cases had atresias of multiple type, on the other hand, in intestinal volvulus, 4 of 9 cases without malrotation have had massive small intestinal resection, compared with 5 of 30 cases with malrotation. Many clinical problems have occurred after massive small intestinal resection, especially in cases with short bowel syndrome (shorter than 30 cm in length), but home parenteral nutrition has become one of the key treatments for cases with short bowel syndrome.

Child↗

[Analbuminemia].

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Animals↗

Radioimmunoassay of glycosylated albumin with monoclonal antibody to glucitol-lysine.

An immunoassay specific for glycosylated albumin was developed by the use of beads coated with antibody to human serum albumin (beads) and 125I-labelled monoclonal antibody to reduced bovine glucosylated low density lipoprotein. One bead was capable of binding 100 ng of serum albumin which had been treated with sodium borohydride (NaBH4) to reduce the Schiff base in the protein. The monoclonal antibody reaction with glucitol-lysine epitopes on the reduced glucosylated proteins and amino acids studied, including human serum albumin (HSA), bovine serum albumin and hippuryl-L-lysine. The detection limit of this assay was 100 pmol/mg HSA, which was sensitive enough for clinical use. The mean serum reduced glycosylated albumin concentration measured by this new method was significantly higher in diabetic patients (2.63 +/- 0.35 nmol/mg HSA, n = 32) than in healthy subjects (0.53 +/- 0.05 nmol/mg HSA, n = 38). The serum reduced glycosylated albumin concentration correlated with both hemoglobin A1c (r = 0.69, p less than 0.005) and the fasting blood glucose level (r = 0.51, p less than 0.005) in diabetic patients.

Aged↗

A large molecular form of glucagon-like peptide-1 (GLP-1) immunoreactivity is co-released with glucagon from pancreas by arginine in normal subjects.

Plasma immunoreactivities of glucagon-like peptide-1 (GLP-1IR) in normal subjects were measured with a specific radioimmunoassay during the arginine tolerance test. Plasma GLP-1IR after arginine infusion showed a 3-fold increase in parallel to plasma glucagon immunoreactivity and plasma glucagon-like immunoreactivity, measured with a glucagon C-terminal specific antiserum (OAL 123) and an N-terminal and/or central region specific glucagon antiserum (OAL 196), respectively. This finding suggested that the increased immunoreactivities of GLP-1 as well as that of glucagon were of pancreatic origin. Upon gel chromatography, plasma at the basal state showed three GLP-1 immunoreactive peaks, eluted in the position of void volume, synthetic GLP-1(72-108), and a smaller molecular fraction. Gel chromatography of plasma after an arginine load showed an additional peak (Mr 13,000-15,000) with little change in other GLP-1 immunoreactive peaks. This large molecular form of GLP-1IR was also shown to exist in the human pancreatic extract. Moreover, the free GLP-1 concentrations in plasma before and after an arginine load were shown to be about equal by reverse phase HPLC. These data suggested that in normal subjects arginine stimulation co-releases GLP-1IR, predominantly large molecular form, with glucogen from the pancreas.

Adult↗

Detection of gangliotriaose-series glycosphingolipids in serum of cord blood and patients with neuroblastoma by a sensitive TLC/enzyme-immunostaining method.

Concentration of gangliotriaose-series glycosphingolipids, including GA2, GM2, GD2 and GT2, was measured in human sera by a thin-layer chromatography/enzyme-immunostaining method. By this method, as little as 5-10 ng/ml of these glycolipids in serum could be determined simultaneously. Although GD2 ganglioside could be consistently detected in normal cord blood (1-2 ng/ml of serum), the ganglioside was never detected in normal adult serum. However, the same ganglioside was found to be present in large quantity in preoperative sera of 6/9 patients with neuroblastomas (25-658 ng/ml of serum). In addition to GD2, gangliosides GM2 and GA2 increased concomitantly than usual. It is concluded that this highly sensitive quantification of the tumor-associated glycolipids circulating in serum of neuroblastoma patients could be useful in their diagnosis.

Adult↗

A newly developed immunoliposome--an egg phosphatidylcholine liposome coated with pullulan bearing both a cholesterol moiety and an IgMs fragment.

An improved methodology for providing a more stable and targetable drug carrier has been developed. This method involves the synthesis of a newly designed immunoliposome by coating the outermost surface of large oligolamellar vesicles of egg phosphatidylcholine with the polysaccharide pullulan, modified to carry both cholesterol, as the hydrophobic anchor, and the monoclonal antibody fragment (anti-sialosyl Lewis X, IgMs) as the sensory device. Compared with the binding of pullulan-coated liposomes, that of this immunoliposome to specific cells in vitro was significantly increased by factors of 447 to PC-9 and 295 to KATO-III, but only by a factor of 148 to the less specific cell, 3LL. This strong and specific binding of the immunoliposome to the cell surface of PC-9 was also confirmed by a fluorescence-microscopic investigation using the immunoliposome, which bore the hydrophobic fluorescent probe, terbium trisacetylacetonate, in the liposomal membrane.

Antibodies, Monoclonal↗

Effect of the enteroinsular axis on both the A- and B-cell response to arginine after oral glucose in man.

Studies were made on the effect of the enteroinsular axis on amino acid-induced insulin and glucagon secretion during hyperglycaemia in man. The responses of plasma immunoreactive insulin, C-peptide, and immunoreactive glucagon to arginine infusion were investigated in nine healthy subjects after induction of hyperglycaemia by an oral glucose load and by intravenous glucose infusion to produce similar glucose concentrations in the arterialised blood. The plasma immunoreactive insulin and C-peptide levels increased to higher levels after an oral glucose load than after an intravenous infusion of glucose. The incremental areas under the immunoreactive insulin and C-peptide curves during arginine infusion were significantly greater (p less than 0.01) after oral than after intravenous glucose administration. The plasma immunoreactive glucagon level was suppressed equally after oral and intravenous glucose loads. However, during subsequent arginine infusion, the plasma immunoreactive glucagon level rose more in the presence of hyperglycaemia induced by oral than intravenous glucose. The incremental area under the plasma immunoreactive glucagon curve during arginine infusion was 1.6-fold greater after glucose ingestion than after intravenous glucose infusion. These results suggest that the enteroinsular axis has a stimulatory effect on the responses of pancreatic A and B cells to arginine after oral glucose administration.

Administration, Oral↗

Effects of gut hormones on bile acid uptake and release in cultured rat hepatocytes.

In cultured rat hepatocytes, the effects of gut hormones on bile acid uptake and release were studied. It was found that cultured hepatocytes continued to secrete bile acids into the culture medium and incorporated them effectively as a function of incubation time. Gut hormones such as secretin, glucagon, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), gastric inhibitory polypeptide (GIP), tetragastrin, cholecystokinin-octapeptide (CCK-8), pancreatic polypeptide (PP), neurotensin substance P, beta-endorphin (beta-End), methionine-enkephalin (Met-enk), motilin, bombesin and somatostatin (SS) had no effect on bile acid uptake by cultured hepatocytes. In bile acid release studies, only secretin caused a dose-dependent stimulation of bile acid release, while other gut hormones had no effect on bile acid release into medium. These results indicate that secretin acts directly on cultured rat hepatocytes and/or bile canaliculi, besides its effect on the bile duct, and influences bile acid metabolism.

Animals↗

Failure of human insulin to influence endogenous basal insulin secretion in mild diabetics.

In evaluating the possibility of self-regulation of insulin secretion in man, human insulin may be more appropriate as an inhibitor to be considered than insulins from other species because the differences in the structure of the hormones might play some part in this conflicting proposal. The present study was carried out to examine whether human insulin per se can exert a feedback effect on the insulin secretion of B-cell in mild diabetics under physiologic condition. Fifteen mild diabetics were given a two-hour infusion of human insulin at a constant rate of 40 mU/m/min after a priming dose of 160 mU/m/min for the first two minutes. The plasma glucose in nine of these patients were maintained at their basal level of 92.8 +/- 3.7 mg/dL (Group A) with a glucose clamp technique (the coefficient of variation = 5.0 +/- 0.8% during the clamp), while that in the remaining six patients were intentionally altered, within physiologic range, from 114.5 +/- 8.4 mg/dL to 83.8 +/- 4.9 mg/dL (Group B). During insulin infusion the plasma immunoreactive insulin (IRI) level were well-maintained at about 50 microU/mL level in both groups, whereas the C-peptide reactivity (CPR) in group B decreased from 1.28 +/- 0.15 ng/mL to 0.59 +/- 0.14 ng/mL in parallel to the change of plasma glucose, in contrast to the relatively stable CPR level of 0.92 +/- 0.08 ng/mL in group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A case of congenital colonic atresia associated with atresia ani.

The association of atresia ani with congenital colonic atresia is extremely rare, with only one such case having been reported up to date. We have recently treated a female infant with atresia ani (covered anus complete) accompanied by atresia of the sigmoid colon, who was managed by three stage surgery.

Anal Canal↗