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Biomedical subjects

H Miyake

Publications and source records attributed to H Miyake.

At least 307 records · Page 17Linked to original sources
PubMed1995

DNA diagnosis of malaria using microtiter plate-hybridization.

We have developed a new diagnostic method "microtiter plate-hybridization" (MPH) for the detection of human malaria parasite in which the target DNA sequence of the 18S ribosomal RNA gene is amplified by polymerase chain reaction and hybridized with the species-specific probes immobilized on a microtiter well. The PCR products bound on a well are visualized by the biotin-streptavidin system and the following chromogenic reaction. This method has allowed us to detect and identify the four species of human malaria parasites. We obtained blood samples by finger puncture from 435 donors in Japan, Solomon Island and Vietnam. The results of our method showed good correlation with the results of Giemsa staining microscopy. Furthermore, we developed a new system for the detection of new human malaria parasites. This system involves an acridine orange (AO) staining microscopic examination and "microtiter plate-hybridization". Using the system, we found a case of new variant of Plasmodium ovale whose PCR-amplified DNA did not hybridize with a probe for typical P. ovale in Vietnam. These results indicate that our new method can serve as a useful tool for the clinical management, epidemiological research of malaria, and investigation of the new type of malaria parasite.

Acridine Orange↗
PubMed1994

Studies on neurokinin antagonists. 4. Synthesis and structure-activity relationships of novel dipeptide substance P antagonists: N2-[(4R)-4-hydroxy-1-[(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl]-N- methyl-N-(phenylmethyl)-3-(2-naphthyl)-L-alaninamide and its related compounds.

As an extension of our studies on discovering a novel substance P (SP) antagonist, we modified the previously reported dipeptide, N2-[N2-(1H-indol-3-ylcarbonyl)-L-lysyl]-N-methyl-N-(phenyl-methyl) -L- phenylalaninamide (2b). The lysine part in 2b was first optimized to a (2S,4R)-hydroxyproline derivative (3h), which is 2-fold more potent than 2b in [3H]SP binding assay using guinea pig lung membranes. Next we modified the 1H-indol-3-ylcarbonyl part in 3h. Introduction of a methyl group at the indole nitrogen enhanced the oral activity, while retaining the binding activity. Finally, we modified the phenylalanine part to culminate in the most potent compound 7k (FK888), which is a potent SP antagonist with NK1 selectivity as well as oral activity.

Animals↗
PubMed1994

Bilateral carotid artery occlusion causes periventricular leukomalacia in neonatal dogs.

At 14 days of age, seven mongrel puppies were anesthetized and bilateral carotid arteries, not only the common but also the external and internal carotid arteries, were ligated with sutures. Seven sham-operated littermates served as controls. They were sacrificed at 3 months of age, and their brains were examined macro- and microscopically. Neuropathological examination revealed dilated posterior communicating and basilar arteries in bilateral carotid artery occlusion (BCAO) animals. Six out of 7 BCAO brains had uni- or multiloculated cysts in the periventricular white matter which were surrounded by a band of GFAP-positive glial cells. Scattered small areas of gliosis were found in all experimental animals. Four BCAO brains also showed ventricular dilatation. Although the cerebral cortex seemed to be intact, the periventricular white matter and the corpus callosum were reduced in width in experimental animals. Myelination in the white matter was significantly reduced in BCAO animals compared with the controls. This study directly demonstrates that cerebral hypoperfusion alone can produce periventricular leukomalacia in neonatal dogs.

Animals↗
PubMed1994

Mechanistic studies of a signaling pathway activated by the organic dimerizer FK1012.

BACKGROUND: The T-cell receptor (TCR) signaling pathway is initiated by regulated association of TCR chains, including the zeta chain. A recently reported method for inducing the dimerization or oligomerization of targeted proteins in cells used the TCR pathway as a test system. In cells transfected with cDNA encoding MZF3E, a chimeric receptor comprising the intracellular domain of the zeta chain and three copies of FK506-binding protein (FKBP), low concentrations of a synthetic dimer of the natural product FK506 (FK1012) activated the expression of reporter genes. We set out to examine the signaling pathway initiated by FK1012. RESULTS: We characterized the effect of FK1012 on MZF3E and a second chimeric receptor, MZF1E, which contains the zeta chain and one copy of FKBP. Only MZF3E gave FK1012-activated signaling, as shown by an increase in the kinase activity associating with MZF3E, and the appearance of specific phosphotyrosine-containing proteins. Signaling required localization of MZF3E to the inner plasma membrane, and activation of gene transcription in response to FK1012 was dependent on the protein phosphatase calcineurin and the transcriptional activator NF-AT. Some signaling events in the pathway had different kinetics when activated by MZF3E instead of the TCR, however. An unexpected requirement for the prolonged activation of calcineurin was observed. CONCLUSIONS: Synthetic dimerizers can be used to gain control over cellular processes that require the association of specific intracellular proteins. The TCR signaling pathway was selected as an initial test system; we show here that one can indeed activate this signaling pathway by inducing the oligomerization of the cytoplasmic tail of the zeta chain with the cell-permeable reagent FK1012.

Animals↗
PubMed1994

Expression of tumor-associated glycoantigen, sialyl Lewis(a), in human head and neck squamous cell carcinoma and its application to tumor immunotherapy.

The glycoantigen sialyl Lewis(a) (sLe(a)) is widely expressed on a variety of gastrointestinal tumor cells. Here, we immunohistochemically demonstrated the expression of sLe(a) antigen in 54% (7 out of 13) of human head and neck squamous cell carcinoma (H-NSCC) samples. Frequent expression of sLe(a antigen was also demonstrated on a variety of H-NSCC cell lines using flow cytometry. Both CD4+ and CD8+ T cells, which were activated with immobilized OKT3 monoclonal antibody plus interleukin-2, showed augmented cytotoxicity against sLe(a)-positive H-NSCC, including autologous tumor cells, on targeting with anti-CD3 x anti-sLe(a) bispecific antibody, suggesting that sLe(a) antigen is a good target molecule for bispecific antibody-dependent adoptive tumor immunotherapy of human head and neck cancer.

Adult↗
PubMed1994

Familial congenital hypopituitarism with central diabetes insipidus.

Congenital hypopituitarism (CH) presenting with central diabetes insipidus is typically associated with midline facial deformities or ophthalmological abnormalities. We present three brothers with CH and central diabetes insipidus not associated with any of these predisposing conditions. All three subjects presented with clinical features typical for CH (neonatal hypoglycemia, short stature, protruding forehead, and microgenitalia). All had hypoplastic genitalia indicating in utero gonadotropin deficiency, and all had complete GH deficiency. One represented low levels of thyroid hormones and TSH, indicating central hypothyroidism. Water deprivation examination in two of the brothers demonstrated complete arginine vasopressin deficiency in one and partial deficiency in the other. Magnetic resonance imaging indicated absence of the pituitary stalk, severe hypoplastic anterior pituitary in all three brothers, and absence of any posterior pituitary gland in two of the three. The other sibling had an ectopic posterior pituitary. This first report of familial CH with central diabetes insipidus may represent a previously unknown midline anomaly and provide new insights into the genetic control of pituitary and hypothalamic development.

Antibodies↗
PubMed1994

[Multiple cavernous angiomas accompanied with a convexity meningioma: a case report].

We reported a rare case of multiple cavernous angioma accompanied with a convexity meningioma. A 41-year-old female developed generalized convulsion on October 8, 1985. Plain computed tomography (CT) scan revealed a round heterogeneous density mass in the right parietotemporal region, which was homogeneously enhanced. Angiography demonstrated a tumor stain fed by the right angular artery and the posterior branch of the right middle meningeal artery. Total removal of the tumor was performed. Since histological examination disclosed meningothelial cells, whorl formation, polymorphism and necrotic tissue, she received radiation therapy (total 50Gy) under the diagnosis of anaplastic meningioma. On November 10, 1988, she suddenly developed headache, nausea, motor weakness and homonymous hemianopia on the left side. CT scan revealed intracerebral hemorrhage (ICH) near the region where the meningioma used to be. Magnetic resonance image (MRI) demonstrated a high intensity mass at T1-weighted image and mixed intensity mass at T2-weighted image. Furthermore, there were multiple low intensity spotty lesions at the cerebral and cerebellar hemisphere in T1 and T2-weighted image. A few parts of these lesions showed central high intensity cores and perifocal low intensity areas, which were called ring formations or reticulated cores with black rims. The multiple lesions could not be detected by CT scan. ICH was evacuated. Histological examination revealed no specific pathology except necrotic tissue around the hematoma wall. Diagnosis of radiation necrosis was made. On October 25, 1992 she suddenly complained of left hemihypesthesia. CT scan demonstrated two high density spotty areas at the left caudate head and right thalamus. MRI showed these two lesions as reticulated cores with black rims.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A trial to discriminate spontaneous regression from non-regression cases during mass screening for neuroblastoma.

We tried to discriminate between cases of spontaneous regression and non-regression during mass screening for neuroblastoma, taking advantage of differences in respect to the urinary homoranillic acid/vanillyl mandelic acid (HVA/VMA) ratio and the original tumor site among true positive, false negative and natural occurrence cases. After classifying them into a total of six groups depending on the two factors, ratio: < 1, 1-2 or > or = 2 and tumor site: adrenal or extra-adrenal in origin, we calculated the mathematical probability of a given true positive case being one of spontaneous regression. A tumor of extra-adrenal origin was likely to regress spontaneously, especially one with an HVA/VMA ratio < 1 or > or = 2 (82.2-100%). A tumor of adrenal origin with an HVA/VMA ratio < 1 seemed unlikely to regress spontaneously (0-4%). The present method, employing simple preoperative information, would be useful in future for the selection of true positive cases which should be observed without treatment.

Adrenal Gland Neoplasms↗
PubMed1994

Role of hepatic copper-metallothionein on liver function of Long-Evans cinnamon rats with a new mutation causing hereditary hepatitis.

Liver slices from Wistar and Long-Evans Cinnamon (LEC) rats were incubated while open to the atmosphere to assess the liver function in LEC rats. Leakages of glutamic-oxaloacetic transaminase (GOT) and lactic dehydrogenase (LDH) into the medium were significantly lower in the LEC rat than in the Wistar rat. Furthermore, no pronounced enhancement of the concentration of thiobarbituric acid-reactive substances (TBARS) was found in the LEC rat. Hepatic Cu and Cu-metallothionein (Cu-MT) concentrations were 355.0 +/- 18.7 micrograms/g liver and 2559 +/- 181 micrograms/g protein in the LEC rats, whereas Wistar rats showed 4.1 +/- 0.1 Cu microgram/g liver accompanied by 16 +/- 4 micrograms/g protein of MT. The decrease of intrahepatic Cu-MT in LEC rats was stimulated by incubation with Fenitrilotriacetate (Fe-NTA). There was a direct correlation between the enhancement of TBARS and disappearance of Cu-MT. Our results suggest that hepatic Cu-MT in LEC rats protects against liver injury stimulated by oxidative stress.

Animals↗
PubMed1994

[Imaging and clinical significance of hepatic portal venous gas seen in adult patients].

In 10 adult patients with hepatic portal venous gas (HPVG), the clinical significance of HPVG and the efficacy of X-ray computed tomography (CT) were evaluated. HPVG was associated with ischemic bowel disease (n = 3), trauma (n = 4), liver abscess (n = 1), sepsis (n = 1), and unknown etiology (n = 1). The diagnostic ability of CT for the detection of HPVG was far superior to that of plain abdominal radiograph. Of 9 patients who underwent CT, HPVG located in the left hepatic lobe in all patients, and also in right hepatic lobe in 7 patients. Gas could be recognized in the left lobe and the anterior segment of the right lobe more clearly than in the posterior segment of the right lobe because of its larger amount of intravenous collection. The mortality rate of our cases was 100%. Gas was demonstrated simultaneously in the portal vein radicles and hepatic veins on CT in 4 patients with no clinical evidence of sepsis, which suggested the possibility of intraparenchymal shift of gas from the portal vein into the hepatic vein. In a single case with sepsis, gas was noted in various vessels, including arteries, in addition to the portal venous system. The authors conclude that HPVG is still a grave sign in Japan and prompt appropriate treatment is required. CT may be of great value in the early detection of HPVG and may indicate its etiology.

Abdominal Injuries↗
PubMed1994

[Role of neoadjuvant chemotherapy for management of resectable head and neck cancer].

This review covers the clinical significance of neoadjuvant chemotherapy as initial treatment for squamous cell carcinoma of the head and neck, especially focusing on advanced but resectable disease. The rates of complete response (CR) after chemotherapy depended on the regimens and varied from 15% to 35%. Combined use with DDP/5-FU was considered as a most effective regimen. In addition of leucovorin to DDP/5-FU regimen, CR rate increased more than 50%. A randomized clinical trial has not shown any advantage for survival in advanced head and neck cancer. Recent reports have shown that distant metastases diminished in patients treated with neoadjuvant chemotherapy. When primary lesions disappeared completely after neoadjuvant chemotherapy, sequential use of radiotherapy can make the long term relapse-free in those lesions. This effort may lead to a modality of cancer treatment without surgery, so organ preservation will be possible.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Rounded atelectasis with emphasis on its wide spectrum].

While rounded atelectasis (RA) is considered to be rather common in the United States and Europe, the total number of RA cases reported from Japan still remains approximately 30. We have long been aware that there are many variations in the radiographic appearance of so-called RA and that RA has never been clearly defined. We retrospectively reviewed 22 cases collected as RA and its variants from several institutions. We defined RA as "peripheral atelectasis mimicking tumor secondary to shrinkage or bending of the pleura of various degrees, and accompanied by lung distortion." The diagnostic criteria of typical RA include (1) peripheral tumoral shadow in contact with pleural effusion or thickened pleura, (2) acute angle between the pleura and the shadow, (3) convergence of the pulmonary vessels and bronchi and (4) volume loss of the affected lobe. However, there are cases which lack some of these criteria but are considered to be included in the broad category of RA. We propose that RA should be considered to be an entity having a wide spectrum. Typical lesions showing "cranial tilting" of Hanke are on one side of the spectrum and small linear or strand shadows extending from the thickened pleura are on the other.

Adult↗
PubMed1993

Studies on neurokinin antagonists. 3. Design and structure-activity relationships of new branched tripeptides N alpha-(substituted L-aspartyl, L-ornithyl, or L-lysyl)-N-methyl-N-(phenylmethyl)-L-phenylalaninamides as substance P antagonists.

As an extension of our study on discovering a novel substance P (SP) antagonist, we designed new branched tripeptides containing L-aspartic acid (2 and 5), L-ornithine (3 and 6), and L-lysine (4 and 7) by reconstructing the structure of the previously reported tripeptide SP antagonist [Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (1), FR113680]. The strategy for this design was based on the postulate that the dipeptide half D-Trp(CHO)-Phe-NMeBzl in 1 is essential for receptor recognition. Molecular modeling studies implied that these newly designed tripeptides could mimic the spatial orientations of the essential dipeptide structure. As expected, all of these compounds potently inhibited 3H-SP (1 nM) binding to guinea pig lung membranes in the 10(-8) M range. The 1H-indol-3-ylcarbonyl derivatives (5-7) were slightly more potent than the corresponding 1H-indol-2-ylcarbonyl derivatives (2-4), as predicted by the molecular modeling studies. The structure-activity relationships studies on the selected 1H-indol-3-ylcarbonyl derivatives indicated that the threonine moiety at the side chain can be modified into a variety of structures without any significant loss of the activity. Furthermore in the L-lysine series, even dipeptide compounds having nothing or a simple acyl group at the epsilon-amino group, such as N alpha-[N alpha-(1H-indol-3-ylcarbonyl)-L-lysyl]-N-methyl-N-(phenylmethyl)- L-phenylalaninamide (18b), exhibited potent activity. These dipeptides belong to a new structural class of SP antagonist.

Animals↗
PubMed1993

MPC-1304, another type of dihydropyridine, possessing highly potent vasodilating action.

We investigated the vasodilating action of MPC-1304, one of the most potent dihydropyridines causing hypotension, in anesthetized dogs and compared this with its binding properties. After intraarterial injection, MPC-1304 was 3 times less potent than other dihydropyridines (nitrendipine, nifedipine, nicardipine and nisoldipine) in increasing femoral blood flow. After infusion of these drugs, however, MPC-1304 was the most potent in increasing femoral blood flow. The onset and recovery of the effect of MPC-1304 on femoral blood flow were slower than for nifedipine. Higher doses of Bay K 8644 were needed to antagonize the stimulating activity of MPC-1304 than for nifedipine. In a competition assay of [3H]nitrendipine binding, MPC-1304 and its metabolites bound to the dihydropyridine receptor with lower affinity than the other dihydropyridines. The binding affinity of [3H]MPC-1304 was lower than that of [3H]nitrendipine, consistent with the potency of this drug to increase femoral blood flow by bolus injection. The association and dissociation of [3H]MPC-1304 was slower than those of [3H]nitrendipine, which is consistent with the slow onset and long-lasting vasodilating effects of MPC-1304 on femoral blood flow. Moreover, diltiazem reduced a part of [3H]MPC-1304 binding in a competitive manner. In ex vivo binding assays with serum and aorta obtained after oral administration of the drug in spontaneously hypertensive rats, MPC-1304 inhibited [3H]nitrendipine binding to membrane preparations less potently than nifedipine. From these results, we conclude that MPC-1304 is a different type of dihydropyridine possessing the most potent vasodilating action of the representative dihydropyridines tested. Its activity cannot be explained solely by a slow interaction with voltage-dependent Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗