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Biomedical subjects

H Miyake

Publications and source records attributed to H Miyake.

At least 19 recordsLinked to original sources
PubMed1992

[The effectiveness of radiotherapy for Merkel cell carcinoma].

Merkel cell carcinoma is a high-grade malignant tumor of the skin that tends to extend locally and metastasize to regional lymph nodes. Surgical resection is the treatment of choice, and the effectiveness of radiotherapy for this disease has not yet been established. We report two cases of biopsy-proven Merkel cell carcinoma effectively treated with radiotherapy. Histopathological examination of the resected specimens after radiotherapy of 50 Gy and 38 Gy, respectively, using 6 approximately 15 MeV electrons showed no malignant cells in either case. No evidence of recurrence or metastasis has been noted in 11 to 21 months after radiotherapy. To our knowledge, no case of Merkel cell carcinoma in which complete cure was obtained by radiotherapy alone has been reported previously. It is considered that preoperative radiotherapy would contribute to the management of this locally invasive but radiosensitive tumor.

Aged↗
PubMed1992

Effects of FR 113680 and FK 224, novel tachykinin receptor antagonists, on cigarette smoke-induced rat tracheal plasma extravasation.

We examined the effects of novel tachykinin antagonists, FR 113680 (N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-phenylmethyl-L-phenylalaninamide) and FK 224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N[3-(2-phenthylpheny l) - propionyl]-L-threonyl]-tyrosyl]-L-leucynyl]-D-phenylalanyl]-L-allo - threonyl]-L-asparaginyl]-L-serine nu-lactone) on rat tracheal plasma extravasation induced by cigarette smoke. Intravenous injection of FK 224 (0.032-3.2 mg kg-1) inhibited rat tracheal plasma extravasation induced by cigarette smoke and capsaicin. FR 113680 (32 mg kg-1 i.v.) also significantly inhibited cigarette smoke-induced plasma extravasation, whereas D-chlorpheniramine maleate, FPL 55712, atropine sulfate and indomethacin had no effect. Tracheal plasma extravasation induced by substance P (SP) and neurokinin A (NKA), but not histamine, was also reduced by intravenous administration of FR 113680 and FK 224. These findings suggest that cigarette smoke stimulates primary afferent sensory nerves, releases tachykinins and evokes plasma extravasation in rat trachea.

Amino Acid Sequence↗
PubMed1992

Studies on neurokinin antagonists. 2. Design and structure-activity relationships of novel tripeptide substance P antagonists, N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-(phenylmethyl)-L-phenylalaninamide and its related compounds.

Continuing studies on the chemical modification of the previously reported novel tripeptide SP antagonist, N alpha-[N alpha-[N alpha- (tert-butyloxycarbonyl)glutaminyl]-N1-formyl-D-tryptophyl]phenylalanine benzyl ester [Boc-Gln-D-Trp-(CHO)-Phe-OBzl (1)], are described herein. We initially investigated the stability of 1 in guinea pig plasma and liver homogenate to elucidate the most labile part in the structure. It was consequently revealed that the benzyl ester part was easily hydrolyzed to produce the inactive acid analog. Thus we searched for a benzyl ester surrogate that would be more resistant to hydrolytic enzymes. This approach found an isosteric amide structure, N-methyl-N-(phenylmethyl)amide, suitable in terms of potency and stability. Subsequent modification of the amino terminal into N alpha-acetyl-L-threonine led to the most potent compound, N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-(phenylmethyl)-L-phenylalaninamide [Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (5a, FR113680)]. This compound 5a potently blocked 3H-SP binding to guinea pig lung membranes with IC50 of (5.8 +/- 0.78) x 10(-9) M. In vitro, 5a inhibited SP-induced contraction of isolated guinea pig trachea strips with IC50 of 2.3 x 10(-6) M and caused no contraction when used alone in this preparation up to 3.2 x 10(-5) M. In addition 5a exhibited no effect on the contraction induced by histamine or acetylcholine. Intriguingly, it was demonstrated in vivo that 5a suppressed the SP-induced bronchoconstriction and airway edema in guinea pigs with ED50 of 0.42 mg/kg and 0.66 mg/kg, respectively, when administered intravenously.

Acetylcholine↗
PubMed1992

Studies on neurokinin antagonists. 1. The design of novel tripeptides possessing the glutaminyl-D-tryptophylphenylalanine sequence as substance P antagonists.

To discover a novel and low molecular weight substance P (SP) antagonist we postulated that the essential binding domain of peptide ligands was only a small portion in the whole structure. On the basis of this assumption, we selected the known octapeptide SP antagonist D-Pro-Gln-Gln-D-Trp-Phe-D-Trp-D-Trp-Phe-NH2 (1) as a lead and synthesized its fragment tripeptides which were evaluated for their activity to block 3H-SP binding on guinea pig lung membranes. The protected tripeptide N alpha-[N alpha-[N alpha-(tert-butyloxycarbonyl)-L-glutaminyl]-N1-formyl-D-tryptophyl]- L-phenylalanine benzyl ester [Boc-Gln-D-Trp(CHO)-Phe-OBzl (4a)], corresponding to the Gln-D-Trp-Phe part of 1, exhibited 7-fold potent inhibitory activity in comparison with 1. Studies on structure-activity relationships revealed that the D-tryptophan, L-phenylalanine, and benzyl ester were quite important to maintain the high binding affinity. It was also indicated that 4a antagonized the SP-induced contraction of isolated guinea pig trachea strips (IC50 = 4.7 x 10(-6) M).

Amino Acid Sequence↗
PubMed1992

Catecholamine alterations in experimental hydrocephalus.

Experimental hydrocephalus was induced in rats by intracisternal injection of kaolin suspension. The amounts of norepinephrine and dopamine were determined in the whole brain and specific brain regions at 1 week (acute phase) and 4 weeks (chronic phase). The turnover of catecholamine, an index of the activity of catecholamine-containing neurons, was determined by measuring the decrease in catecholamine contents 2 h after intraperitoneal injection of alpha-methyl-p-tyrosine (250 mg/kg), an inhibitor of tyrosine hydroxylase. We observed that the catecholamine contents in kaolin-induced hydrocephalus were not significantly different from control values. Following injection of alpha-methyl-p-tyrosine, there was decrease in levels of catecholamines in both control and hydrocephalic rats. This decrease was, however, significantly less in induced hydrocephalus than in control animals. This result suggested that in hydrocephalus, the activities of norepinephrinergic and dopaminergic neurons are reduced.

Animals↗
PubMed1992

Adenomyomatosis of the gallbladder with subserosal fatty proliferation: CT findings in two cases.

Adenomyomatosis of the gallbladder is frequently seen in ordinary operative specimens. Subserosal fat may proliferate in the presence of adenomyomatosis, but the amount of subserosal fat may be quite variable. Typical and atypical computed tomographic (CT) findings in two cases of adenomyomatosis with subserosal fatty proliferation of the gallbladder are presented. The thick fatty layer surrounding the thickened gallbladder wall with intramural diverticula and stones, typical of CT findings, was seen in one case, and fat interspersed in the periphery of the thickened gallbladder wall without intramural stones, atypical of CT findings, was seen in a second case.

Adipose Tissue↗
PubMed1992

Neurochemical effects in rats following gestational exposure to styrene.

Styrene was evaluated for the reproductive effects of pregnant rats and the neurochemical effects in the offspring of rats exposed during gestation. Pregnant Wistar rats were exposed to 0, 50, or 300 ppm styrene for 6 h/day during days 7 to 21 of gestation. No significant differences in the number of offspring delivered were observed between the exposed and control groups. Body weights at 1 day of age of the offspring whose mothers were exposed to styrene were significantly lower than those of the control group. Although, there were neither statistically significant differences of protein contents nor brain weights among styrene-exposed and their control offsprings of rats, analyses of neurotransmitter studies showed dose-dependent decreases of neuroamines, especially 5-HT (serotonin) and its metabolite 5HIAA (5-hydroxyindoleacetic acid) in the newborn offspring of styrene-exposed rats. The results suggest that gestational exposure to styrene at these concentrations does not produce apparent reproductive toxicity but affects the body weight of pups and causes lowering of the neurotransmitter levels in the brain.

Administration, Inhalation↗
PubMed1992

Central cholinergic action produces antagonism to ketamine anesthesia.

Ketamine sometimes produces posthypnotic emergency reactions, such as prolonged hallucination or delirium. In a previous paper, we showed that physostigmine, an anticholinesterase agent, counteracts the manifestation of effects of ketamine at some doses. In the present study, we investigated the mechanism of the antagonistic effect of physostigmine on ketamine anesthesia. At first, rats were given ketamine 75 mg/kg. Immediately after the loss of righting reflex, the four groups of rats were given one of the three central cholinergic agents, physostigmine 0.1 mg/kg, oxotremorine 0.05 mg/kg, 4-aminopyridine 3 mg/kg, or saline as the control. The sleeping times were 10.7 +/- 1.0, 12.3 +/- 0.9, 11.4 +/- 1.3 and 21.2 +/- 0.7 min, respectively. The three cholinergic agents antagonized ketamine anesthesia. In the other groups of rats, the central anticholinergic agent, l-hyoscyamine, 0.5 mg/kg, was given subcutaneously for premedication before the above-mentioned procedure. The sleeping times were 16.3 +/- 1.2 min in the physostigmine group, 18.7 +/- 1.0 min in the oxotremorine group and 18.6 +/- 0.8 min in the 4-aminopyridine group. The sleeping time was significantly longer in the premedicated group than in the non-premedicated group, in the case of the three central cholinergic agents. The sleeping time in the saline group, 20.0 +/- 0.4 min, was not significantly different from that of the control in the non-premedicated case. It is, therefore, considered that the central cholinergic action produces antagonism to ketamine anesthesia.

4-Aminopyridine↗
PubMed1992

FR 113680: a novel tripeptide substance P antagonist with NK1 receptor selectivity.

1. We have discovered a novel tripeptide substance P (SP) antagonist, FR 113680 [N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N'-formyl-D- tryptophyl]-N-methyl-N-phenylmethyl-L-phenylalaninamide]. In binding experiments, FR 113680 inhibited [3H]-SP binding to guinea-pig lung membranes (NK1) in a competitive manner but had not effect on [3H]-SP binding to rat cerebral cortical membranes (NK1), [3H]-neurokinin A ([3H]-NKA) binding to rat duodenum smooth muscle membranes (NK2) and [3H]-eledoisin (Ele) binding to rat cerebral cortical membranes (NK3). 2. In bioassay experiments, FR 113680 dose-dependently inhibited SP-induced guinea-pig ileum contraction (NK1), but did not inhibit either NKA-induced rat vas deferens contraction (NK2) or neurokinin B (NKB)-induced contraction of rat portal vein (NK3). According to Schild plot analysis, the inhibitory effect of FR 113680 on SP-induced guinea-pig ileum contraction is competitive and the pA2 value is 7.53. 3. The inactivity of FR 113680 on NK1 receptors in rat compared to guinea-pig may represent species-specific forms of the NK1 receptor. 4. These findings suggest that FR 113680 interacts selectively with the NK1 neurokinin receptor.

Animals↗
PubMed1992

Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888.

1. In our search for compounds that inhibit the binding of [3H]-substance P (SP) to guinea-pig lung membranes, the dipeptide SP antagonist, FK888, was developed by chemical modification of the parent compound, (D-Pro4, D-Trp7,9,10, Phe11)SP4-11. 2. In a [3H]-SP binding assay using guinea-pig lung membranes and rat brain cortical synaptic membranes, FK888 displaced [3H]-SP binding with a Ki value of 0.69 +/- 0.13 nM and 0.45 +/- 0.17 microM, respectively, in a competitive manner. 3. FK888 inhibited the contraction of guinea-pig isolated ileum induced by SP in the presence of atropine and indomethacin (a NK1 receptor bioassay) with a pA2 value of 9.29 (8.60-9.98). 4. FK888 inhibited contractions of rat vas deferens by NKA (a NK2 receptor bioassay) and of rat portal vein by NKB (a NK3 receptor bioassay) at concentrations at least 10,000 times greater than that required to inhibit contractions of guinea-pig ileum. 5. FK888 also inhibited SP-induced airway oedema in guinea-pig after both intravenous and oral administration. 6. These data demonstrate that FK888 is a potent and selective NK1 antagonist which is active both in vitro and in vivo.

Administration, Oral↗
PubMed1992

Time course of intraventricular pressure change in a canine model of hydrocephalus: its relationship to sagittal sinus elastance.

Hydrocephalus was induced in adult greyhounds by intracisternal kaolin. Intraventricular pressure (IVP) was monitored in the conscious animal for 2 weeks using a small implantable sensor, and the time-course of IVP change was characterized. Intraventricular pressure increased significantly within 36 h of kaolin infusion and gradually subsided to normal values within 1 week. Enlargement of the lateral ventricles was not observed during the early phase of intracranial hypertension (less than 2 days). Evolving hydrocephalus and intracranial hypertension increased the elasticity (dP/dV) of the sagittal sinus. This effect was statistically significant (p < 0.05) and is possibly reversible in the acute stage. Normotensive hydrocephalus (1 and 2 weeks after kaolin) was associated with an irreversible increase in resistance to outflow (i.e., increased sagittal sinus elasticity). Sagittal sinus venography of animals with obvious ventricular enlargement (at least 1 week after kaolin) showed development of venous collaterals and atypical outflow pathways.

Animals↗
PubMed1992

Giant air cell of the petrous apex: a possible cause of facial hypalgesia.

A giant air cell of the left petrous apex was found in a 23-year-old man with ipsilateral facial hypalgesia. The size of the giant air cell depicted on computed tomography was 1.5 x 2.0 x 2.0 cm. A coronal T1-weighted magnetic resonance image showed that the trigeminal nerve was compressed superomedially by a large signal void area that was probably a result of excessive pneumatization of the petrous apex. It is suggested that the facial hypalgesia was caused by the compression by the giant air cell of the petrous apex on the trigeminal nerve.

Adult↗
PubMed1992

An index for proportion of head size to body mass during infancy.

The index "head circumference (cm)3/body weight (g)" gave an almost constant average (about 10) and standard deviation (about 1) in more than 2000 children at birth and at 4, 10, and 18 months. Application of this index to the data previously published confirms that the average is almost constant throughout the period from birth to 18 months, irrespective of sex or race. Head circumference cubed and body weight correlate significantly. This index seems to be useful to assess the proportion of head size to body mass during infancy, and to contribute to early diagnosis of diseases such as hydrocephalus or microcephaly.

Body Mass Index↗
PubMed1992

Effects of nitric oxide synthase inhibitors on gastric alkaline secretion in rats.

The effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on gastric HCO3- secretion were examined in anesthetized rats. Intravenous administration of L-NAME (1, 2.5, 5 mg/kg) increased HCO3- secretion in a dose-related manner. This effect of L-NAME was mimicked by NG-mono-methyl-L-arginine (50 mg/kg, i.v.) and was antagonized significantly by concurrent administration of L-arginine but not D-arginine (200 mg/kg, i.v.). These results indicate that gastric HCO3- secretion is stimulated by inhibition of NO biosynthesis.

Amino Acid Oxidoreductases↗
PubMed1992

Localized fat collection adjacent to the intrahepatic portion of the inferior vena cava: a normal variant on CT.

We describe a normal focal collection of fat that has the appearance of a mass on CT scans. The fat is adjacent to the intrahepatic portion of the inferior vena cava and is contiguous to the fat around the subdiaphragmatic portion of the esophagus. This finding occurred in 11 (0.5%) of 2227 patients who had CT scans at our institution. The fat collections did not change in size or shape on follow-up CT scans obtained 2 to 29 months later (mean, 14 months). The localized fat collections were at the level of or above the confluence of the hepatic veins and the inferior vena cava, and were medial to the inferior vena cava. They were less than 22 mm in length, oval, and had attenuation values ranging from -113 H to -23 H on unenhanced CT scans. The collections enhanced slightly on scans obtained after contrast administration. T1-weighted (600/15) MR images obtained in three cases showed a high-intensity mass that was contiguous to high-intensity fat around the esophagus, medial to the intrahepatic portion of the inferior vena cava. Our experience suggests that a masslike fat collection adjacent to the intrahepatic portion of the inferior vena cava is a normal variant on CT scans and should not be mistaken for an abnormality.

Adipose Tissue↗
PubMed1992

Antihypertensive effects of MPC-1304, a novel calcium antagonist, in experimental hypertensive rats and dogs.

Antihypertensive effects of a novel calcium antagonist, MPC-1304, (+-)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5- pyridine-dicarboxylate and its active metabolites were investigated in experimental hypertensive rats and dogs and compared with those of other dihydropyridine derivatives (nifedipine, nisoldipine, nicardipine, and nitrendipine). MPC-1304 had a dose-related antihypertensive effect with a slight increase in heart rate (HR) in rats. The antihypertensive effects of MPC-1304 were more potent than those of other dihydropyridines, and its active metabolites had antihypertensive effects comparable to those of other dihydropyridines. The hypotensive effects of MPC-1304 were stronger in hypertensive rats than in normotensive rats. During repeated oral administration of MPC-1304 to spontaneously hypertensive rats (SHR, once daily for 4 weeks, 0.3-3 mg/kg), dose-response curves of the antihypertensive effect did not change and body weight gain was equal to that of the vehicle-treated group. When given orally to conscious renal hypertensive dogs, MPC-1304 0.1-0.3 mg/kg had a potency and duration of antihypertensive action comparable to that of nitrendipine (1-3 mg/kg). MPC-1304 increased coronary blood flow (CBF) and aortic blood flow (ABF) in conscious normotensive dogs. In conclusion, MPC-1304 and its active metabolites have potent antihypertensive effects and cause slight tachycardia, and they may be useful in treating hypertension.

Administration, Oral↗
PubMed1992

Mass screening of neuroblastoma in Sapporo City, Japan.

In Sapporo City a mass screening program for neuroblastoma aiming at 6-month-old infants has been performed since April 1981. By March 1990, 136,001 infants were screened; 26 true-positive cases of neuroblastoma and six false-negative cases were detected. The sensitivity of the mass screening method was about 80% throughout the 9 years. During the 9-year period, a total of nine children with neuroblastoma who were not screened were also identified. Clinical stage, age at diagnosis, and survival rate for the 32 patients who were screened (26 true positives and six false negatives) were much more favorable than those for the nine patients who were not screened. A remarkable decrease in the incidence of cases of neuroblastoma with advanced clinical stages over 1 year of age, especially among children 1-4 years of age, was noted after the start of the mass screening. The mortality from this tumor in children up to 4 years of age significantly decreased after the start of the urinary screening program. Rescreening at 14 months of age was begun in April, 1991 in Sapporo City. Performing two screening examinations decreases the probability of overlooking a patient. Thus, it is expected that tumors missed on the first screening would be detected by the second screening.

Biomarkers, Tumor↗