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Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 271 records · Page 15Linked to original sources

Functional evidence for L-type Ca2+ channels controlling ANG II-induced adrenal catecholamine release in vivo.

The aim of the present study was to investigate the functional involvement of L- and/or N-type Ca2+ channels in adrenal catecholamine secretion in response to exogenous angiotensin II (ANG II) in anesthetized dogs. Plasma catecholamine concentrations in adrenal venous and aortic blood were determined by a high-performance liquid chromatography-electrochemical method. In the first series of experiments, repeated infusions of BAY K 8644 locally into the left adrenal gland at 15-min intervals resulted in significant and reproducible increases in adrenal catecholamine secretion. Nifedipine, similarly administered 5 min before BAY K 8644, diminished BAY K 8644-induced catecholamine secretion in a dose-dependent manner and completely blocked the catecholamine response at the highest dose tested. In the second series of experiments, local infusion of ANG II resulted in a significant increase in adrenal catecholamine secretion. The maximum catecholamine response to ANG II was attenuated by approximately 65% in the presence of nifedipine at the dose that abolished the BAY K 8644-induced catecholamine release. This inhibition by nifedipine remained unchanged in the presence of omega-conotoxin. The present study shows that dihydropyridine-sensitive L-type Ca2+ channels are operative in the adrenal medulla of the dog in vivo. The results indicate that the L-type Ca2+ channels are only partially implicated in the local regulation of ANG II-induced adrenal catecholamine secretion, suggesting the existence of another mechanism. However, omega-conotoxin-sensitive N-type Ca2+ channels are unlikely to be functionally involved in postsynaptic mechanisms mediating adrenal catecholamine secretion in response to exogenous ANG II under in vivo conditions.

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

A case of renovascular hypertension associated with neurofibromatosis.

We report a case of renovascular hypertension associated with neurofibromatosis complicated by moderate proteinuria. A 16-year-old female was admitted to Kensei General Hospital with a complaint of headache and a blood pressure of 230/120 mm Hg. She was referred to us for further evaluation of the hypertension. On examination, cafe-au-lait spots were seen over her extremities and flank, and a bruit was heard in the right upper abdomen. The urinary protein excretion was 2.1 g/day. The plasma renin activity (PRA) and plasma aldosterone concentration were high, but the levels of catecholamines were normal. The renogram was asymmetric and on venous sampling, the PRA in the right renal vein was 58.3 ng/ml/h and that in the left was 22.1 ng/ml/h. CT scan detected an approximately 10-mm mass in the proximal right renal artery. Arteriography disclosed severe stenosis in the right renal artery and the superior mesenteric artery. Therefore, we concluded that her hypertension resulted from stenosis of the right renal artery due to neurofibromatosis. Accordingly, she underwent an operation to reconstruct that artery. After the operation, her blood pressure and PRA normalized without administration of any anti-hypertensive drug and urinary protein disappeared.

Adolescent↗

Proximal ligation of large distal posterior inferior cerebellar artery aneurysm.

A 41-year-old male presented with vertigo, nausea, and vomiting suggesting a space-occupying lesion of the posterior fossa. Computed tomography (CT) and left vertebral angiography revealed a large distal posterior inferior cerebellar artery (PICA) aneurysm. Operation revealed the fusiform aneurysm was partially embedded in the medulla, preventing neck clipping or trapping of the aneurysm. Therefore, proximal ligation of the PICA was performed. The symptoms caused by the mass effect improved, and the aneurysm was not visualized by CT or angiography. Ligation of the PICA proximal to the choroidal point is not necessarily safe. In our case, ligation was distal to the tonsillomedullary segment from which the perforating arteries mainly arose, so the postoperative course was good without new neurological deficits. Proximal ligation is an effective treatment for distal PICA aneurysms manifesting as mass effect if other interventions are not possible.

Adult↗

Traumatic atlanto-occipital dislocation with long-term survival.

A 6-year-old boy presented with traumatic atlanto-occipital dislocation due to a traffic accident. Lateral spinal tomography showed anterior misalignment of the craniocervical junction. Magnetic resonance imaging demonstrated associated cervicomedullary injury. He underwent an occipital-cervical fusion with implantation of a spinal cord electrical stimulation unit. His consciousness level improved, but he remained quadriplegic and dependent on a respirator 2 years after the injury.

Atlanto-Occipital Joint↗

Cancer mortality in Minamata disease patients exposed to methylmercury through fish diet.

We report here a historical cohort study on cancer mortality among Minamata disease (MD) patients (n = 1,351) in Kagoshima and Kumamoto Prefectures of Japan. Taking into account their living area, sex, age and fish eating habits, the residents (n = 5,667; 40 years of age or over at 1966) living in coastal areas of Kagoshima, who consumed fish daily, were selected as a reference group from the six-prefecture cohort study conducted by Hirayama et al. The observation periods of the MD patients and of the reference group were from 1973 to 1984 and from 1970 to 1981, respectively. Survival analysis using the Poisson regression model was applied for comparison of mortality between the MD patients and the reference group. No excess of relative risk (RR) adjusted for attained age, sex and follow-up period was observed for mortality from all causes, all cancers, and non-cancers combined. Analysis of site-specific cancers showed a statistically significant decrease in mortality from stomach cancer among MD patients (RR, 0.49; 95% confidence interval, 0.26-0.94). In addition, a statistically significant eight-fold excess risk, based on 5 observed deaths, was noted for mortality from leukemia (RR, 8.35; 95 % confidence interval 1.61-43.3). It is, however, unlikely for these observed risks to be derived from methylmercury exposure only. Further studies are needed to understand the mechanisms involved in the observed risks among MD patients.

Adult↗

[A research on the importance of the clinical certificate to the medical practitioners outside the field of psychiatry. Committee on graduate education sub-committee on Feasibility of Implementing Specialty Board Certification in the Japanese Society of Psychiatry and Neurology].

OBJECTIVES AND METHODS: The main objectives of the research was to identify the merits and demerits of the specialty board certification system, that had been implemented in the other medical societies than the society of psychiatry in Japan. As a measure of the research, we conducted a survey by distributing questionnaires to medical institutions. The subjects of this survey included medical practitioners, other than the psychiatrists, who belong to general hospital, university hospital and the Japan Medical Association. FINDINGS: We received 228 responses out of the subjects. The findings were that 86% of the subjects have acquired the specialty board certificate, and that half of them have more than two kinds of qualifications on the average. Thus, the report suggests that the specialty board certification system have been long pervaded throughout the medical fields outside psychiatry. In addition, the subjects pointed out as the merits of the specialty board certification system that it helps to achieve the higher level of technique, and to organize and sophisticate as well as widen the knowledge of their specialty. They also reported that it contributes to instigate the life-long education and to earn identification and recognition of their specialty from other fields of medicine than their own. Fifty-three percent of the subjects acknowledged the necessity of the specialty board certification system while 13% regarded it unnecessary. This result proves that, despite higher percentage of the doctors with qualifications, the system itself is not approved of with full acknowledgement in the medical world. This rather negative attitudes toward the system is originated in the fact that acquiring and maintaining the certificate, i.e., renewal fees, are considerably high. In fact, as many as 62% of the subjects felt these points as disadvantages of the system. The medical practitioners outside the fields of psychiatry did not show any particular concern about the lack of the specialty board certification system in our field that is distinct as a field of medicine. Only 18% of the subjects expressed that urgent actualization of the system is desirable in our fields. In addition, securing the cites required for learning the technique and giving the exam to the applicants is the most important matter to be concerned. On the contrary, in other fields of medicine, the matter does not need to be discussed. Therefore, this is a problem unique to the fields of psychiatry. CONCLUSION: Although there are disadvantage of the specialty board certification system pointed out as shown above, we believe that it is necessary to introduce the system in the field of psychiatry. These disadvantage are mainly the matter of individual income. We need to consider the introduction of the system from the perspective of sophisticating the quality of psychiatry as a field of medicine in our country. We, the Subcommittee on feasibility of implementing specialty board certification in the Japanese Society of Psychiatry and Neurology have been contemplating over the system up to this moment. The progress has been made to the point of presenting, Discussion of the Specialty Board Certification System in Psychiatry, Yamauchi, May, 1994.

Certification↗

Recurrence of hepatocellular carcinoma after surgery.

A total of 386 patients who underwent complete resection of hepatocellular carcinoma over an 8-year period were assessed retrospectively for tumour recurrence. Some 219 (56.7 per cent) of the patients developed recurrence. Patients with a greater degree of cirrhosis showed a longer interval to recurrence; the median (range) interval until recurrence was 7.9 (1.8-84.2) months in patients with a normal liver, 13.4 (2.0-79.5) months in those with chronic hepatitis and 16.7 (1.5-73.1) months in those with cirrhosis. Intrahepatic recurrence was observed more frequently in either the same (26.4 per cent) or the adjacent (24.8 per cent) Healey segment than in the lobe contralateral to the primary tumour (17.8 per cent). The presence of portal venous invasion and/or intrahepatic metastasis, underlying liver cirrhosis and perioperative blood transfusion were determined to be independent predictors of recurrence by multivariate analysis. Because intrahepatic spread of hepatocellular carcinoma occurs in a segment-by-segment manner, surgeons should use an anatomically wide resection within the hepatic functional reserve.

Adult↗

Brief repetitive ischemia: effect on norepinephrine release, arrhythmias, and functional recovery in isolated perfused rat heart.

The objective of the present study was to determine norepinephrine release, functional recovery, and incidence of arrhythmias following multiple episodes of brief (5 min) ischemia and to compare these variables with those obtained after continuous ischemia (30 min) in isolated rat hearts perfused with modified Krebs-Henseleit solution. Left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and cardiac rhythm were continuously recorded. The amount of norepinephrine in perfusate was measured by high-performance liquid chromatography. The data showed no increases in LVEDP during the six successive 5-min periods of ischemia interrupted by 5-min reperfusion. The six repetitive periods of reperfusion after repetitive 5-min periods of ischemia were associated with a restoration of left ventricular diastolic function and preservation of reactive hyperemia (23.3 +/- 1.5 mL/min vs. baseline 16.5 +/- 1.3 mL/min; p < 0.05). The incidences of ventricular fibrillation (VF) (10/10) and ventricular tachycardia (VT) (10/10) upon reperfusion in the continuous ischemia group were higher than those in the repetitive ischemia group (VF, 2/10; VT, 3/10; p < 0.05). Norepinephrine washout upon reperfusion after 30-min continuous ischemia was 58.2 +/- 17.4 ng/g of heart, but no increase in norepinephrine washout was observed after brief repetitive ischemic episodes (11.2 +/- 2.4 ng/g of heart) (p < 0.05). Our results show a substantial release of norepinephrine only after 30 min of continuous ischemia, in the isolated rat heart.

Animals↗

Maternal allergen stimulation suppressed respiratory allergy in offspring: with special reference to allergy related cells in the tonsil.

Pregnant mice and Hartley guinea pigs were immunized with T dependent antigen, heterologous erythrocyte and ovalbumin (OVA), and the active immune responsiveness as well as the allergic symptoms of the offspring were investigated. Guinea pigs were also sensitized to OVA intraperitoneally and subcutaneously with a 100 mg/ml solution of saline containing 5 mg of AI(OH)(3) as an adjuvant. Six weeks after the initial allergen stimulation, systemic and local anaphylaxis as elicited by 1-min aerosol administration of a nebulizer and monitored by macroscopic vision accompanied by a time trial for respiratory and cardiac arrest. Serum antibody levels were tested by passive hemagglutination as well as passive cutaneous anaphylaxis especially for the estimation of IgE levels. Nasal, tonsillar and bronchial tissues were also prepared and fixed, followed by hematoxylin and eosin staining for histological observation. In the offspring of mothers who had been stimulated with optimal amounts of the allergen and had fully developed specific antibodies against the allergen, there was a clear-cut suppression in the development of a specific respiratory allergy over a significant period after delivery. The effect was confirmed by systemic and local anaphylaxis, eosinophil infiltration, ciliary deformation in nasal mucosae and the tonsillar site in the complex interaction of various cell types and mediators eliciting the clinical respiratory symptoms, in particular nasal hypersensitivity. In a different experimental model, the mouse model, these biological findings were not regulated by maternal transferable antibody or antigen fragments from the mother. The induction of suppressor T cell (CD(4+)) in offspring depends on the recognition of the antigens presented in association with the same MHC haplotype as that utilized in the maternal T cell response during pregnancy. These results suggest the presence of suppression mechanisms in the offspring of mothers stimulated during pregnancy. From these results, we discuss the mechanisms for suppression and protective efficacy for respiratory allergy as well as possible side effects in the young of mothers stimulated during pregnancy.

Allergens↗

Immunohistochemical detection of K-sam protein in stomach cancer.

The K-sam gene, originally isolated as an amplified gene from the stomach cancer cell line KATO-III, is characterized by its preferential amplification in the undifferentiated type (diffuse type) of stomach cancer and encodes one of the receptors for heparin-binding growth factors or fibroblast growth factors. The K-sam gene has been isolated by different methods and has been designated BEK, TK14, and Cek2. The receptor for keratinocyte growth factor was also found to be encoded by the same gene. To examine the expression of the K-sam protein in stomach cancer, polyclonal antibody pK1-2 was raised against the extracellular domain of the gene product. This antibody detected K-sam proteins by Western blot and flow cytometry analyses in stomach cancer cell lines KATO-III and HSC39, in which the K-sam gene is amplified and overexpressed. By immunohistochemical analysis, 20 of 38 cases of the undifferentiated type of advanced stomach cancer were K-sam positive, whereas none of 11 cases of the differentiated or intestinal type revealed K-sam staining. The K-sam product was observed predominantly in diffusely infiltrative lesions. In one autopsy case, the K-sam protein was detected only focally in the primary tumor, whereas markedly increased staining for the K-sam product was detected diffusely in the metastasized tumor in the lymph node and liver. These results suggest that K-sam overexpression is associated with the malignant phenotype of the undifferentiated type of stomach cancer, such as infiltrative growth and metastasis.

Amino Acid Sequence↗

Species differences in the concentration of acetylcholine, a neurotransmitter, in whole blood and plasma.

Various concentrations of acetylcholine (ACh) were detected in samples of bovine, goat, horse, porcine, rat and sheep blood and plasma using a specific, sensitive radioimmunoassay. The ACh levels in whole blood in bovine and horse samples were about 40- and ten-fold higher, respectively, than in humans, but levels comparable to those in humans were measured in porcine samples. Goat, rat and sheep samples had lower whole blood ACh concentrations than those of humans. When plasma samples were assayed, the ACh contents of bovine and porcine plasma were found to be about two- to five-fold those of human. On the other hand, levels in horse, goat, rat and sheep samples were much lower than in humans. The ratio of the ACh contents of plasma to whole blood was high in porcine and rat samples, indicating that porcine and rat blood ACh is distributed mostly in the plasma, while in the other species tested most of the ACh is present in the blood cells. These results demonstrate that variable levels of ACh are present in the blood of different species, and that the distribution of ACh in the blood constituents varies according to species.

Acetylcholine↗

Allelotype of neuroblastoma.

Although relatively high incidence of loss of heterozygosity (LOH) on chromosomes 1p, 11q, and 14q have been reported in neuroblastoma, it is still unclear whether or not LOH occurs specifically on these chromosome arms in neuroblastoma since only a few chromosomal arms have been examined for LOH in previous studies. Therefore, we screened 81 cases of tumors for LOH on all 22 autosomes and chromosome X using 35 restriction fragment length polymorphism markers and eight microsatellite markers. High incidence of LOH (> 20%) was observed on six chromosome arms; 1p (26%), 2q (30%), 9p (36%), 11q (24%), 14q (22%), and 18q (31%). Frequencies of LOH on other chromosome arms were less than 13%. Patients with 9p LOH in the tumors showed statistically significant association with advanced stage of the disease and poor prognosis (P = 0.037 and P = 0.003, respectively) independently from N-myc amplification, while LOH on other chromosomes did not show association with stage, prognosis, and N-myc amplification. Thus, besides LOH on chromosomes 1p, 11q, and 14q, LOH on chromosomes 2q, 9p, and 18q also occurs relatively frequently in neuroblastoma, indicating the involvement of multiple tumor suppressor genes in the development of neuroblastoma. It is possible that there is a novel tumor suppressor gene on chromosome 9p which is involved in the progression of neuroblastoma.

Alleles↗

Terminal differentiation of murine resident peritoneal macrophages is characterized by expression of the STK protein tyrosine kinase, a receptor for macrophage-stimulating protein.

STK, a new member of the hepatocyte growth factor receptor family, is the receptor for macrophage-stimulating protein (MSP), which acts on murine resident peritoneal macrophages. We established polyclonal and monoclonal antibodies against STK and characterized the structure of STK protein and STK expression on cells of the mononuclear phagocyte system. Western blotting showed that the STK transcript is translated into a single-chain precursor and then cleaved into a 165-kD disulfide-linked heterodimer composed of a 35-kD alpha-chain and a 144-kD beta-chain. Western blotting detected STK protein on resident peritoneal macrophages, a target of MSP, and showed that it was autophosphorylated in cells stimulated by MSP. By flow cytometric analysis using a monoclonal anti-STK antibody, we showed that STK protein is expressed on restricted macrophage populations such as resident peritoneal macrophages, but not on exudate peritoneal macrophages or mononuclear phagocytes of the bone marrow, peripheral blood, spleen, or alveoli. Resident peritoneal macrophages were classified into two fractions according to their reactivity with an anti-STK antibody and a marker antibody for macrophages: STKhigh-F4/80high cells and STKnegative-F4/80low cells. Acute exudative macrophages were all STKnegative-F4/80low, but they gradually became predominantly STKhigh-F4/80high several days after entrance into the peritoneal cavity. These results showed that after monocytes migrate into the peritoneal cavity, they undergo terminal differentiation in the peritoneal microenvironment. This is the first evidence of tissue-specific terminal differentiation of peritoneal macrophages, and this terminal differentiation can be characterized by the expression of STK receptor tyrosine kinase.

Animals↗

Molecular cloning and expression of megakaryocyte potentiating factor cDNA.

The human megakaryocyte potentiating factor (hMPF) has been previously purified from a culture supernatant of human pancreatic cancer cells HPC-Y5 (Yamaguchi, N., Hattori, K., Oh-eda, M., Kojima, T., Imai, N., and Ochi, N. (1994) J. Biol. Chem. 269, 805-808). We have now isolated hMPF cDNA from a HPC-Y5 cDNA library using polymerase chain reaction and plaque hybridization methods. The hMPF cDNA encodes a polypeptide consisting of 622 amino acids, including a signal peptide of 33 amino acids, and with a deduced molecular mass of 68 kDa, although HPC-Y5 cells secrete a 33-kDa form of hMPF. Human MPF does not show any significant homology with other previously described sequences. The cDNA was expressed in COS-7 and Chinese hamster ovary (CHO) cells, and megakaryocyte potentiating activity was detected in their culture supernatant. The COS-7 cells secreted only a 33-kDa recombinant hMPF, whereas an additional 30-kDa form was detected in the culture medium of CHO cells. The 33-kDa rhMPF purified from CHO cells showed megakaryocyte potentiating activity, but not the purified 30-kDa rhMPF. The difference in structure and activity between the 33- and 30-kDa forms of hMPF was ascribed to the existence in the 33-kDa form of the C-terminal 25 amino acid residues.

Amino Acid Sequence↗

Microsatellite instability in primary and metastatic colorectal cancers.

Microsatellite instability characterizes a sub-set of sporadic colorectal cancers (CRCs) as well as CRCs from patients with hereditary non-polyposis colorectal cancer (HNPCC). In order to clarify when the cells acquire a replication-error phenotype (RER) during colorectal-tumor progression, we examined the incidence of RER in 80 primary tumors and 36 liver metastases at 8 microsatellite loci; 1 mono-, 5 di-, 1 tetra- and 1 pentanucleotide. RER were detected in 20.1% (17/80) of primary tumors, including 5 tumors showing RER at 2 or more loci (RER2), while the incidence of RER in liver metastases (22.2%, 8/36) was almost the same as that in primary tumors, and there was only one RER2 case in metastases. There were 3 cases in which both primary tumors and liver metastases had the same type of RER at the same locus, and there were 2 cases that showed RER in primary tumors but not in liver metastases. In contrast, there was no case in which RER was detected in a metastasis but not in the corresponding primary tumor. The RER phenotype did not show correlation with any clinicopathological parameters of cancer-cell aggressiveness, such as clinical staging, histological grade and survival. These results indicate that a sub-set of CRCs acquire the RER phenotype in the relatively early stages of colorectal carcinogenesis, and that the RER phenotype is not associated with aggressiveness of CRCs.

Adult↗

DIDS binding 30-kDa protein regulates the calcium release channel in the sarcoplasmic reticulum.

The gating properties of the Ca2+ release channel in the heavy fraction of the sarcoplasmic reticulum (HSR) was monitored by measuring the choline permeation through the channel using a light scattering method. The choline permeation was increased by the treatment of the HSR vesicles with 4,4'-diisothiocyano-stilbene-2,2'-disulfonic acid (DIDS), and this effect was only observed at low extravesicular Ca2+ concentrations. This result indicates that DIDS locked the Ca2+ channel at the open state. An SDS-PAGE of the junctional face membrane (JFM) that was treated with 3H2-DIDS showed that 3H2-DIDS binding protein is not the Ca2+ release channel but the 30 kDa protein. Furthermore, it was found that this 30 kDa protein is also one of the calsequestrin interacting proteins. These results suggest that this 30 kDa protein regulates the Ca2+ release channel.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗