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Biomedical subjects

H Shibuya

Publications and source records attributed to H Shibuya.

At least 19 recordsLinked to original sources

Functioning ovarian carcinoids induce severe constipation.

Five patients with ovarian carcinoid who had severe constipation for a long period preoperatively showed marked reduction of this symptom postoperatively. Because this phenomenon was believed to be caused by some biologically active substance rather than a mechanical effect of the tumor, reactivity to 17 amine and peptide hormones was studied immunohistochemically in these patients. Numerous peptide YY (PYY)-positive cells were detected, with PYY-positive cells representing more than 50% of all carcinoid tumor cells in each patient. PYY, which has a pharmacologic inhibitory action on intestinal motility, was presumably the cause of the constipation in these patients.

Adult

IL-2 and EGF receptors stimulate the hematopoietic cell cycle via different signaling pathways: demonstration of a novel role for c-myc.

Stimulation via cytokine receptors such as IL-2 and IL-3 receptors, but not by the EGF receptor (EGFR), induces cells of the BAF-B03 hematopoietic cell line to transit the cell cycle. We demonstrate that the IL-2 receptor beta chain (IL-2R beta) is linked to at least two intracellular signaling pathways. One pathway may involve a protein tyrosine kinase of the src family, which leads to the induction of the c-jun and c-fos genes, among others. A second pathway, involving an as yet unknown mechanism, leads to c-myc gene induction. Stimulation of the EGFR, expressed following transfection of an appropriate recombinant construct, can activate the former, but not the latter, pathway in this cell line and cause the cells to enter S phase but not progress further. This deficiency can be rescued by ectopic expression of the c-myc gene, indicating a novel role for this proto-oncogene in the S to G2/M transition of the cell cycle.

Animals

New human gene encoding a positive modulator of HIV Tat-mediated transactivation.

The human immunodeficiency virus-1 (HIV-1) protein Tat is a potent activator of virus gene expression. Tat functions through a sequence known as TAR, located immediately downstream of the transcription start site in the long terminal repeat. Several observations suggest that cellular factors cooperate with Tat in the overall transactivating process. We have isolated a human complementary DNA from the new gene MSS1, which may encode such a cellular factor, by transcomplementation of a yeast sgv1- mutant. The MSS1 protein shares 42% sequence identity with the human TBP-1 protein, which binds Tat in vitro and suppresses Tat-mediated transactivation in vivo (ref. 6). We report here that the levels of HIV activation by Tat correlate with endogenous levels of MSS1 messenger RNA. Furthermore, we provide evidence that expression of MSS1 enhances the Tat-mediated transactivation. Our results suggest that MSS1 has a key role in activation of HIV genes regulated by Tat.

ATPases Associated with Diverse Cellular Activitie

Familial cataracts and concurrent ocular anomalies in chow chows.

A closely inbred line of Chow Chows affected with congenital cataracts was studied. Sixteen dogs were examined including 1 adult male, 2 adult females, and 13 pups. Twelve of the pups were from 6 different litters, out of 6 different bitches, all sired by 1 adult male. The exact relationship of the thirteenth pup was undetermined. Clinical evaluation included slit-lamp biomicroscopy, biomicroscopic photography, and indirect ophthalmoscopy. Clinical appearance of the cataracts was variable, ranging from incipient nuclear or capsular lesions to advanced cortical opacity. The lens nucleus was most consistently affected, with variable involvement of the lens cortex. Concurrent ocular anomalies of some eyes included wandering nystagmus, entropion, microphthalmia, persistent pupillary membrane remnants, and multifocal retinal folds. A correlation was not apparent between the character or severity of the cataracts and the finding of the other anomalies. Histologic examination of 12 lenses revealed posterior displacement of the lens nucleus, retained lens epithelial cell nuclei in the nuclear and cortical lens, anterior capsular irregularity and duplication, anterior lens epithelial duplication, and posterior subcapsular migration of epithelium. The high incidence of cataract in this family of Chow Chows suggested an inherited defect, although the inheritance pattern was undetermined.

Animals

c-fos gene induction by interleukin 2: identification of the critical cytoplasmic regions within the interleukin 2 receptor beta chain.

Interleukin 2 (IL-2) plays a critical role in the growth and differentiation of lymphoid cells. The IL-2 signal is delivered intracellularly by the IL-2 receptor beta chain (IL-2R beta); however, the mechanism by which the signal reaches the nucleus remains unclear. In this study, we demonstrate the rapid activation of c-fos protooncogene transcription by IL-2 and provide evidence that the serum-responsive element (SRE) within the c-fos promoter is responsible for the activation in a murine pro-B-cell line, BAF-B03, expressing the human IL-2R beta cDNA. Interestingly, the same SRE is also responsible for c-fos gene activation by interleukin 3 or erythropoietin. Further, we show that the activation of c-fos by IL-2 requires defined cytoplasmic regions of IL-2R beta--i.e., the "serine-rich" region, which is known to be essential for growth-signal transduction in BAF-B03 cells, and the "acidic region," which is located more distal to the cell membrane. These results indicate the functional importance of the two distinct regions within the IL-2R beta cytoplasmic domain in IL-2-induced c-fos gene activation and point to a potential role of the acidic region in IL-2 signal transduction that could not be adequately assessed in a previous study.

Animals

Causes of oral tongue cancer treatment failures. Analysis of autopsy cases.

Eighty-three autopsy cases of squamous cell carcinoma of the oral tongue were reviewed to identify retrospectively the causes of treatment failure. The cure rate for the primary cancers at autopsy was 48.2% (40 of 83). Regional lymph node metastases were found in 71.1% (59 of 83). Regional metastases and/or juxtaprimary recurrence frequently spread continuously and diffusely, forming bulky neck tumors in 38.6% (32 of 83). The incidence of distant lymph node metastasis (below the clavicle) and hematogenous metastasis was 35.4% (29 of 82) and 58.5% (48 of 82), respectively. The lung was the most common site of hematogenous metastases (52.4%, 43 of 82). Hematogenous metastasis occurred more frequently in the younger age group (less than 40 years of age; P = 0.03). Distant lymph node metastases were identified in the lung hilar, bifurcation, and paratracheal nodes in 89.7% (26 of 29) and had a statistically significant association with lung hematogenous metastasis. Univariate analysis revealed that gross appearance, tumor stage, clinical stage, presence of cervical lymph node metastasis, and interval from N0 to NX were significant predictors of survival time (duration from initial treatment to death). Rupture of the neck vessels was fatal in eight patients (9.6%), and hypercalcemia was seen in six (7.2%). Pulmonary infection was the direct cause of death in 33.7% of patients (28 of 83). Secondary malignant lesions occurred in 22.9% (19 of 83).

Adult

Sigma receptors in schizophrenic cerebral cortices.

Antipsychotics represent high affinity for sigma receptors and sigma-like drugs often have the psychotomimetic properties. Besides, the receptors are unevenly distributed in human brain. These findings suggest that sigma receptors might be involved in the pathophysiology of schizophrenia. Sigma receptors in rat and human brain were measured with [3H]-1, 3, di-o-tolylguanidine (DTG) and non-specific binding of [3H]DTG was determined in the presence of 10(-5)M haloperidol. Monovalent and divalent cations strongly inhibited [3H]DTG binding. Glutamate, aspartate and glycine also decreased the binding to human cerebral membranes. With post-mortem brain samples from 12 schizophrenics and 10 controls, sigma receptors were measured in 17 areas of cerebral cortex. Sigma receptors binding showed the regional differences in the cortex, but no significant differences between schizophrenics and controls were observed except the superior parietal cortex where the binding significantly increased in the schizophrenic group. These results suggest that sigma receptors in cerebral cortices might not be directly concerned with the pathophysiological role in schizophrenia.

Adult

Gastrointestinal endoscopy in Henoch-Schönlein purpura.

Gastrointestinal (GI) endoscopy was performed in seven patients with Henoch-Schönlein purpura (HSP). In two patients there were no cutaneous lesions at the time of endoscopy, but inflammation of the duodenum, especially of the second part, led to suspicion of the disease. Upper GI endoscopy showed abnormalities in six of seven cases, and sigmoidoscopy in one of four cases. The changes were more marked in the second part of the duodenum rather than in the bulb or the stomach. The endoscopic findings included redness, swelling, petechiae or haemorrhage, erosions and ulceration of the mucosa. Histology of the mucosal biopsy specimens revealed non-specific inflammation with positive staining for IgA in the capillaries, but failed to show vasculitis. Upper GI endoscopy, including study of IgA, can be useful in the diagnosis of HSP. Colonoscopy is less helpful, especially if limited to the sigmoid colon.

Adolescent

Pre-synaptic dopaminergic control mechanisms for CCK-8 like immunoreactivity in the rat medial frontal cortex.

In order to study the control mechanism of cholecystokinin (CCK) contents of the rat brain mediated by pre-synaptic receptors in dopamine (DA) neurons, R(+) and S(-) compounds of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP), which are selective pre-synaptic dopaminergic agents, were administered in rats at low and high doses. CCK-8-like immunoreactivity (CCK-8 LI) was measured in the medial frontal cortex. In another experiment, a neurotoxin, N-methyl-D-aspartic acid (NMDA) was used to degenerate efferent CCK neurons and CCK interneurons of the medial frontal cortex, followed by an intraperitoneal administration of apomorphine hydrochloride (APO) to study the effect on CCK-8 LI via the pre-synaptic DA receptor. According to the results of these experiments, CCK-8 LI was increased in the medial frontal cortex in response to the stimulation of pre-synaptic DA receptor, suggesting a control of CCK-8 release, at least in part, by the pre-synaptic DA receptor.

Animals

Computed tomography and ultrasonography in submandibular tumours.

The value of computed tomography (CT) and ultrasound (US) for assessing submandibular tumours has been assessed. Thirty-five patients with 23 benign submandibular gland tumours and 12 malignant tumours have been investigated. In 33/35 patients, 18 plain CT (PCT), 19 CT sialography (CTS), and eight intravenous contrast-enhanced CT (CECT) procedures were performed. PCT did not allow clear delineation of 78% of the lesions, due to the similar density of the tumour and normal submandibular gland parenchyma. The tumours were easily recognized as low-echogenic or low-density masses by US, CTS and CECT. Benign lesions were usually sharply demarcated and had smooth borders on US, CTS and CECT. In addition, lobulation was often recognized in pleomorphic adenomas. Malignant tumours were poorly defined with irregular borders in 11/12 cases on US, CTS and CECT. CECT was superior to PCT and CTS in providing images of the tumour and its involvement of adjacent structures. It was concluded that US is the most useful primary examination method for submandibular tumours, while CECT provides the best evaluation of extension to the surrounding structures and/or adjacent lymph nodes. CTS seems to be unnecessary, if a submandibular tumour can be visualized by US and CECT.

Adenoma, Pleomorphic

Acute transverse myelitis in a 15-month-old girl: report of a case with MRI findings.

A 15-month-old girl demonstrated progressive weakness in all limbs. Magnetic resonance imaging (MRI) on admission revealed (1) diffuse and symmetric cervical cord swelling, (2) diffuse decrease and increase in signal intensity within the affected cord on T1- and T2-weighted images, respectively, (3) preserved anatomic structure of gray and white matter of the cord, and (4) lack of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancing effect. She showed rapid clinical improvement in response to steroid therapy, and repeat MRI showed marked reduction in the degree of cord swelling and abnormal signal intensity. Based on the above clinical and MRI findings, the diagnosis of acute transverse myelitis was made. Although various pathologic conditions also could produce similar cord swelling and abnormal signal intensity on MRI, the third and fourth findings mentioned above suggested that the lesion was inflammatory rather than neoplastic. Our case indicates that MRI may be informative in differentiating acute transverse myelitis from other intramedullary disorders.

Acute Disease

Syntheses of a glycerophospholipid, C16-platelet activating factor and a palmitoyl analogue of M-5, an anti-inflammatory glyceroglycolipid.

From a chiral C4-epoxide (-)-3, which is one of the synthons in our synthetic strategy for complex lipids, a glycerophospholipid C16-platelet activating factor (C16-PAF, 1) and a palmitoyl analogue (2) of an anti-inflammatory glyceroglycolipid M-5, which was previously isolated from the Okinawan marine sponge Phyllospongia foliascens, have been synthesized.

Anti-Inflammatory Agents, Non-Steroidal

Indonesian medicinal plants. I. Chemical structures of calotroposides A and B, two new oxypregnane-oligoglycosides from the root of Calotropis gigantea (Asclepiadaceae).

Two new oxypregnane-oligoglycosides named calotroposides A (1) and B (2) have been isolated from the root of Calotropis gigantea (Asclepiadaceae), an Indonesian medicinal plant, and their chemical structures have been elucidated by chemical and spectroscopic methods as 12-O-benzoyllineolon 3-O-beta-D-cymaropyranosyl(1----4)-beta-D-oleandropyranosyl( 1----4)- beta-D-oleandropyranosyl(1----4)-beta-D-cymaropyranosyl(1--- -4)-beta-D- cymaropyranoside and 12-O-benzoyldeacetylmetaplexigenin 3-O-beta-D-cymaropyranosyl(1---4)-beta-D-oleandropyranosyl(- ---4)- beta-D-oleandropyranosyl(1----4)-beta-D-cymaropyranosyl(1--- -4)- beta-D-cymaropyranoside, respectively.

Parasympathomimetics

Indonesian medicinal plants. II. Chemical structures of Pongapinones A and B, two new phenylpropanoids from the bark of Pongamia pinnata (Papilionaceae).

Two new phenylpropanoids named pongapinone A (1) and pongapinone B (2) were isolated from the bark of Pongamia pinnata (Papilionaceae), an Indonesian medicinal plant, and their chemical structures have been elucidated on the basis of their physicochemical properties. Pongapinone A (1) was found to inhibit interleukin-1 production.

Chromones

Indonesia medicinal plants. III. On the constituents of the bark of Fagara rhetza (Rutaceae). (1): Alkaloids, phenylpropanoids, and acid amide.

Two new phenylpropanoids, named O-geranylsinapyl alcohol (1) and O-geranylconiferyl alcohol (2), and a new acid amide, named hazeleamide (3), were isolated from the bark of Fagara rhetza (Rutaceae), an Indonesian medicinal plant from Flores Island, Indonesia. The chemical structures of 1, 2, and 3 have been elucidated on the basis of their chemical and physicochemical properties. Among the three new compounds, hazeleamide (3) was found to show a pungent taste and to exert a moderate antimalarial activity in an in vitro test system.

Alkaloids

Pulmonary artery disease in Takayasu's arteritis: angiographic findings.

One hundred sixteen arteriographic examinations in 98 patients with Takayasu's arteritis were studied retrospectively to evaluate the extent of aortic and pulmonary disease. Stenosis was the most frequent finding in the aorta and its branches, but occlusion, dilatation, and aneurysms were also seen. Adventitial vascular structures, consistent with dilated vasa vasorum, were observed in five patients (5%) and systemic artery-pulmonary artery communication was seen in six (6%). Twenty-one (70%) of 30 patients who had pulmonary arteriography were shown to have pulmonary artery involvement. Upper lobe pulmonary arterial branches showed abnormalities most frequently; segmental branches, followed by subsegmental branches, were most often involved. The frequency of abnormal findings on pulmonary arteriograms correlated with the number of involved brachiocephalic vessels. Stenotic lesions in the aorta and its branches progressed in five (45%) of 11 patients, and those in the pulmonary artery progressed in one (33%) of three cases. Takayasu's arteritis characteristically involves the systemic and pulmonary arteries, and the extent of arteritis in the major branches of the aortic arch appears to correlate with pulmonary arterial involvement. Both thoracic and abdominal aortographic studies and pulmonary arteriography are necessary to properly diagnose the extent of the disease, and angiography should be repeated for appropriate patient follow-up.

Adolescent