Biomedical subjects
Publications and source records attributed to K Koike.
Immunocytochemical double-staining analysis revealed that in the rat anterior pituitary 86% of cells containing the beta II-subspecies of protein kinase C also contained follicle stimulating hormone (FSH), and that 22% of these FSH cells expressed the beta II-subspecies. These findings suggest a close relationship between the beta II-subspecies of protein kinase C and FSH regulation.
It is generally accepted that the agonists, full agonist and partial agonist, interact with the same receptors according to the classical receptor mechanisms. We tried to modify the drug receptor mechanisms in muscarinic cholinoceptors, alpha 1-adrenoceptors and beta-adrenoceptors. In the muscarinic cholinoceptor, there are two subtypes of M3-cholinoceptors, propylbenzilylcholine mustard (PrBCM)-sensitive receptors and PrBCM-resistant ones. The full agonists contract the longitudinal muscle through the interaction of two cholinoceptors, PrBCM-sensitive and-resistant ones, while the partial agonists produce the contraction through only the activation of PrBCM-sensitive ones. Upon activation PrBCM-sensitive receptors may use cytosolic Ca2+ more effectively than PrBCM-resistant receptors. In the alpha 1-adrenoceptor, the full agonist induces contraction through both alpha 1A and alpha 1B subtypes and the partial agonist through only alpha 1A subtype. The adrenoceptors activated by full agonist may be partly different from that by partial agonist in the arteries. In both the common iliac artery and thoracic aorta treated with the irreversible antagonist, phenoxybenzamine the slopes of schild plots of the results obtained from an antagonism between full agonist (phenylephrine) and alpha 1A-selective competitive antagonist (WB4101) equal to 1, suggesting that phenoxybenzamine preferably interacts with alpha 1B subtype. In the beta-adrenoceptor, the pD2-values of the partial agonists obtained from the concentration-response curves are significantly different from their pA2-values against full agonist (isoprenaline). The Scatchard plot of the specific [3H]befunolol (the partial agonist) binding showed two affinity sites of the receptors in the absence of Gpp(NH)p but the low affinity site was reduced while the high affinity site was not affected in the presence of Gpp(NH) p. The beta-adrenergic partial agonists are able to discriminate these two different binding sites of the beta-adrenoceptors. Our results suggest that the receptors activated by full agonists are partly different from those by partial agonists in muscarinic cholinoceptors, alpha 1- and beta-adrenoceptors, and that the irreversible antagonist can discriminate between the sites interact with full agonists and those with partial agonists in muscarinic cholinoceptors and alpha 1-adrenoceptors.
Effect of aging on alpha 1A-adrenoceptor mechanisms in rabbit bronchial preparations was studied. The potency (pD2 value) of norepinephrine increased with age from 5 to 13 weeks and thereafter did not alter with age from 13 to 180 weeks. The affinity of norepinephrine (pKA value) and of a selective alpha 1A-adrenoceptor blocker, 5-methylurapidil (pA2 value) did not alter with age. Efficacy of norepinephrine was proportional to receptor reserve (pD2-pKA). These results suggest that age-related changes in alpha 1A-adrenoceptor mechanisms are due to changes in receptor reserve or total concentration of receptors, but not to changes in affinity of drugs to alpha 1A-adrenoceptors and in contraction mechanisms.
The administration of thyrotrophin-releasing hormone (TRH) causes a variety of dopamine-related biological events. To understand the specific role of TRH on rat hypothalamic dopamine neurones, we examined the in-vivo effects of intraventricular (i.c.v.) infusion of TRH on the release and synthesis of prolactin in the rat pituitary gland and on the changes in binding of [3H]MeTRH and dopamine turnover rates in rat hypothalamus. We have also examined the in-vitro effects of TRH on the release of [3H]dopamine from dispersed tuberoinfundibular dopamine neurones. Female rats were treated with i.c.v. infusions of 1 mumol TRH/1 daily for 1, 3 and 7 days using Alzet osmotic pumps. Following 7 days of treatment the serum prolactin concentrations were significantly decreased. A reduction in hypothalamic TRH-binding sites (Bmax) was also apparent but the dissociation constant (Kd) was unaffected. Northern blot analysis of total RNA isolated from the pituitary glands of control animals using 32P-labelled prolactin cDNA as a probe indicated the presence of three species of prolactin gene transcripts of approximately 3.7, 2.0 and 1.0 kb in size, and these were decreased by TRH treatment. We examined the turnover rate of dopamine in the rat hypothalamus when TRH was administered i.c.v. for 7 days. There was a significant increase in 3,4-dihydroxyphenylacetic acid/dopamine ratio with TRH treatment. Moreover, exposure to TRH stimulated [3H]dopamine release from rat tuberoinfundibular neurones in a time- and dose-dependent manner. Dopamine receptor antagonists such as SCH23390 and (-)sulpiride, and other neuropeptides such as vasoactive intestinal peptide and oxytocin did not affect TRH-stimulated [3H]dopamine release.(ABSTRACT TRUNCATED AT 250 WORDS)
Genomic clones encompassing the entire genes for the human pyruvate dehydrogenase alpha and beta subunits (PDH alpha or beta) have been isolated by screening the leukocyte genomic libraries with a nick-translated human foreskin fibroblast PDH alpha or beta cDNA probe. These genomic clones were characterized by restriction enzyme analysis. extensive DNA sequencing and primer extension analysis. The PDH alpha gene spans 17.08 kilobases and is composed of 11 exons and 10 introns within its coding region. The 18-kilobase clone of PDH beta gene is composed of 10 exons and 9 introns. All intron-exon splice junctions of two genes follow the GT/AG rule. A total of seven Alu repeats in the PDH alpha gene were found in five introns and two Alu family in the PDH beta gene were found in intron 2 and 8. The 5'-flanking region of the PDH alpha gene contains typical CCAAT and TATA-like consensus promoter sequence and two Sp1 binding sequences. That of the PDH beta gene contains a TCAAT sequence but no TATA sequence. Primer extension analyses indicated that the PDH alpha and beta genes transcription start sites are thymine and adenine residues located 124 and 132 bases upstream from initiation codon in exon 1, respectively. Genomic DNA of patient, died 93 hours after birth with acidemia and defect of PDH activity, was isolated and all of the exons of PDH alpha and beta genes were amplified by PCR.(ABSTRACT TRUNCATED AT 250 WORDS)
Based on the pathophysiology of Bell's palsy that edema as well as ischemia lead to both compression and hypoxia, Stennert employed high doses of cortisone and dextran and reported a high recovery rate. In the past 5 years, we have been treating patients with Bell's palsy and Hunt syndrome with a high dose of steroids or low-molecular dextran (SD therapy). SD therapy was administrated in 71 cases of Hunt syndrome, and the results were compared with those of a group of 36 patients who had been treated with orally administrated low-dose steroids. All patients with incomplete palsies recovered completely, regardless of the mode of treatment. In cases of complete palsy, 62% of patients recovered completely when treated with SD therapy. In contrast, 29% of the patients treated with orally administrated steroids recovered completely. These results indicate that for patients with complete palsy SD therapy is more effective than oral steroid therapy, while patients with incomplete palsy recover completely with oral steroids. On the basis of this study, oral steroids are best used in cases of incomplete palsy unless complete palsy develops. In these latter cases, we now believe that SD therapy should be started immediately.
We evaluated the clinical significance of two novel assays for the detection of crosslinked fibrin degradation products (XDP) in whole blood using the agglutination of the red blood cells (SimpliRED D dimer and SimpliRED D dimer-500, AGEN, Australia). XDP made serially by plasmin in vitro, were detected by the SimpliRED D dimer assay, but fibrinogen degradation products showed weak reactivity. Ten of the fifty four clinical samples collected with EDTA-2K, changed to positive on these assays after overnight incubation at 4 degrees C. Anemia and hemolytic samples had no effect on the assay results. The results obtained by the SimpliRED D dimer were negative for the normal subjects (n = 50) without exception. In our study, 81% and 95% of the patients, who showed abnormal levels of XDP in plasma and E fragments in serum respectively, were positive on the SimpliRED D dimer assay. The assay was as sensitive as the Rapidia-D dimer assay. In conclusion, the SimpliRED D dimer assay was clinically useful as a screening assay for the diagnosis of hypercoagulable and fibrinolytic states, since it could be performed simply and quickly.
The cause of aplastic anemia associated with hepatitis (AAH) is as yet still unknown. There is a supposed relation to the immune mechanisms, however few reports have shown the effects of monocytes on the pathogenesis in the patients with AAH. We have reported a case of a 12-year-old boy with AAH related to cytomegaloviruses, and studied the hemopoietic progenitors. He showed pancytopenia and hypoplasia of the bone marrow on admission to our hospital. The culture studies showed that mononuclear cells (MNC) of the bone marrow produced few hemopoietic colonies in all cell lineages. However, the depletion of adherent cells from the MNC increased numbers of erythroid, neutrophil-macrophage and megakaryocyte colonies. Furthermore, the addition of adherent cells of the peripheral blood suppressed the colony formation in the aforementioned cell lineages by marrow MNC from which adherent cells, phagocytic cells and T-cells were abrogated. The results way suggest that monocytes play some soles in the pathogenesis of aplasia through inhibitor of hemopoiesis.
BACKGROUND: Phospholipase A2 (PLA2) has recently been implicated as a key enzyme of local inflammation after gut ischemia-reperfusion (I/R). The hypothesis of this study is that PLA2 inhibition decouples remote organ injury from gut I/R. METHODS: Sprague-Dawley rats were pretreated with a PLA2 inhibitor, quinacrine (10 mg/kg, intravenously), before the induction of gut ischemia (45 minutes of superior mesenteric artery occlusion) followed by 6 hours of reperfusion. 125I-labeled albumin leak was employed as a marker of pulmonary endothelial permeability and myeloperoxidase as a monitor of neutrophil (PMN) traffic in the gut and lung. To further characterize the impact of PLA2 inhibition, PMNs were harvested at 6 hours of reperfusion and superoxide production was measured in the presence or absence of an activating stimulus, N-formyl-methionyl-leucyl-phenylalanine. RESULTS: Gut I/R increased gut PLA2 activity, elicited gut PMN influx, and produced lung leak; these events were prevented by PLA2 blockade. Gut I/R also markedly enhanced PMN superoxide production with N-formyl-methionyl-leucyl-phenylalanine, and this priming was ablated by PLA2 inhibition. CONCLUSION: These data suggest that PLA2 activation is a proximal step in the pathogenesis of distant organ injury after splanchnic hypoperfusion, a process that appears to involve PMN priming in the gut bed.
We analyzed platelet-associated antigens from a hemophilia B patient with human immunodeficiency virus type 1 (HIV-1)-related thrombocytopenia. Two bands appeared at 31,000 and 37,000 daltons in the platelet lysate after reaction with autologous serum in SDS-PAGE and Western blots. The band at 37,000 daltons was obtained using anti-herpes simplex type 1 (HSV-1) rabbit antiserum. Doublet bands at 36,000 and 37,000 daltons also appeared after reaction with HSV-1 seropositive human serum. The band at 31,000 daltons appeared after reaction with anti-HIV-1 rabbit serum. These results suggest that the platelet-associated antigens in this patient are components of both HSV-1 and HIV-1 antigens. In addition, acyclovir decreased his PAIgG level and increased his platelet count, and zidovudine increased his platelet count. Thus, we concluded that each of the platelet-associated antigens is partially responsible for the thrombocytopenia by causing deposition of immune complexes in this patient.
Human hepatitis B virus (HBV) carriers run an increased risk of hepatocellular carcinoma (HCC), where the expression of HBV genes play the most important role in the initial stage of hepatocarcinogenesis. As the integration of HBV DNA into the cellular DNA of HCC as well as chronic hepatitis was demonstrated very frequently, the virus-cell fusion gene was considered to be most essential for hepatocarcinogenesis. Among the virus-cell fusion genes, the X gene is known to function as a transactivator for viral and cellular genes at the time of chronic infection. One mechanism for hepatocarcinogenesis that appears particularly reasonable is transactivation of cellular oncogenes by the X-cell fusion protein. In 1990, we found a part of the amino acid sequences in the X protein to be highly homologous to functionally essential sequences in the Kunitz domain, characteristic of Kunitz-type serine protease inhibitors. It has been recently demonstrated that X protein expressed in E. coli or from the in vitro translation system binds to a specific serine protease from the liver cells. These results indicate that transactivation function of X protein may be exerted by acting as a protease inhibitor analogue to control the proteolytic pathway of cellular transcription factor(s). On the other hand, viral hepatitis resulting from viruses other than hepatitis A virus and HBV has been referred to as non-A, non-B hepatitis. In 1989, the viral genome was molecularly cloned as a positive-strand RNA having about 10 kb in size and named as hepatitis C virus (HCV). Details of genetic structure and mechanism of expression are currently under investigation at molecular level.
To determine the indication for surgery from the point of pulmonary function, we have performed the unilateral pulmonary artery occlusion test in lung cancer patients. In these patients, we gave a surgery in 13 cases whose total pulmonary vascular resistance were over 700 dyne.sec.cm-5/M2 per body surface area. The pulmonary hemodynamics before and during pulmonary artery occlusion were 549 +/- 82 and 798 +/- 78 dyne.sec.cm-5/M2 in total vascular resistance, 18.7 +/- 3.8 and 27.2 +/- 4.3 cmHg in mean pulmonary arterial pressure and 2.69 +/- 0.36 and 2.73 +/- 4.3 L/min/M2 in cardiac index respectively. In 7 cases out of 13, we performed selective pulmonary artery occlusion test. In pulmonary function test, 10 cases had a chronic obstructive diseases, 2 cases had a disturbance of diffusion and one case has a contractive disease. We gave a lobectomy in 12 cases and completion pneumonectomy in one case. Two of lobectomy cases died in the early phase: 42 and 72 days after surgery due to pulmonary complications. One of these cases needed an additional completion pneumonectomy because of bronchial fistel. Surgical complications were seen in 12 cases. These 13 cases used to be recognized that they have no indication of surgery because of low pulmonary function, however it revealed that we can give a lobectomy through a high intensive care after surgery.
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A case of diffuse large cell lymphoma of B-cell type with unusual azurophilic granules is reported. Lymphoma occurred primary in the upper anterior mediastinum and was suggested to be of thymic origin. Histologically, lymphoma cells showed diffuse proliferation and were large in size, frequently with multilobulated nuclei. In imprint preparations stained by May-Giemsa, most lymphoma cells had basophilic cytoplasm with azurophilic granules. Cytochemical studies showed the granules to be negative for PAS, peroxidase, acid phosphatase, and beta-glucuronidase. Electron-dense granules and electron-lucent granules were found on ultrastructural analysis. The cells were characterized as B-cell type by immunophenotypes of L26+, CD20+, CD21-, CD22+, and PCA1+, the possession of surface monotypic IgA kappa immunoglobulin, and a genotype of immunoglobulin heavy and kappa light chain gene rearrangements.
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Our recent experiences of the autogenous pericardial patch augmentation of Blalock-Taussig anastomotic orifice are reported. In Case 1, the direct suture between the left subclavian artery and the left pulmonary artery was difficult on the anterior wall because of the shortness of the left subclavian artery. Therefore, a piece of the patient's own pericardium was excised and sutured anteriorly between the two vessels by interrupted 7-0 polypropylene sutures. A 19 months postoperative angiogram showed so-called parrot-beaking of the subclavian artery probably due to tension, but there was no distortion or stenosis of the pulmonary artery. In Case 2, the right subclavian artery distal to the bifurcation of the vertebral artery was longitudinally split measuring approximately 2.5 cm in length, and widened by a piece of the autogenous pericardium in a wedge shape. Then, it was anastomosed to the right pulmonary artery without undue tension. Seven months postoperatively the patient died from severe AV valve regurgitation. The autopsy showed widely patent anastomosis and good healing as well as slight expansion of the pericardial patch but without aneurysm formation. In Case 3, the same operation as in Case 2 was performed. A 6 months postoperative angiogram showed no stenosis or distortion of either the subclavian or the pulmonary artery. Although it is premature to draw any conclusion, the use of the autogenous pericardium may be indicated to widen the anastomotic orifice of Blalock-Taussig shunt without sacrificing the length of the subclavian artery even in small infants or neonates.
We experienced an operation of a 16-year-old female of mediastinal vagal neurinoma. Abnormal shadow was pointed out on chest X-ray at physical examination of high school. Right thoracotomy was performed under the diagnosis of mediastinal tumor. There was a walnut sized mass on the right vagal nerve at just peripheral side of the recurrent nerve branch. The vagal nerve was cut at both sides of the mass not to injure the recurrent nerve. The tumor was removed en block. Two little finger sized masses were recognized in serratus anterior muscle and 5 th. intercostal nerve. These removed masses were diagnosed as neurinoma pathologically. While the mother of this case had been admitted on another hospital because of multiple neurinomatosis with bilateral acoustic neurinoma. Thus this case is of familial neurinomatosis, suggesting it's heredity like as neurofibromatosis (von Recklinghausen's disease).
The X protein of hepatitis B virus (HBV) consists of 154 amino acids and trans-activates various cellular and viral promoters and enhancers. To investigate the essential amino acid sequences of X protein for trans-activation function, various mutations were introduced into the X open reading frame and analysed for trans-activation activity by chloramphenicol acetyltransferase assay. The amino acid sequences 46-52 (especially Pro-46, His-49 and His-52), 61-69 (especially Cys-61, Gly-67 to Pro-68 and Cys-69) and 132-139 (especially Phe-132, Cys-137 and His-139) of HBV X protein were found to be essential for the trans-activation function. These three sequences are included in the conserved amino acid sequences among hepadna virus X proteins. The first one could form a domain-like structure characteristic of histidine/aspartic acid requirement. The second and the third are homologous to the Kunitz domain of Kunitz-type serine protease inhibitors. The amino acids 5-27 region was found to make no positive contribution to the trans-activation function like the last 12 amino acids in the carboxy-terminal region [Takada, S. & Koike, K. (1990). Proc. Natl. Acad. Sci. USA, 87, 5628-5632]. From these findings, the trans-activation function of X protein appears to be dependent on at least two types of domain-like structures.