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Biomedical subjects

S Kihara

Publications and source records attributed to S Kihara.

At least 109 records · Page 6Linked to original sources

Induced expression and subcellular localization of the Bcl-2 protein in cultured glioma cells.

It has recently been shown that the bcl-2 gene is involved in the growth and development of certain tumors by suppressing apoptosis. To explore the possible involvement of the Bcl-2 protein in gliomas, three human glioma cell lines (T98G, A172, and U251) were examined for the presence of this protein. It could be documented by confocal laser microscopy that the Bcl-2 protein was localized mainly in mitochondria and nuclear membrane of T98G cells. Flow cytometric analysis revealed that 71-87% of the cultured glioma cells expressed the Bcl-2 protein. Treatment of U251 cells with ACNU for 24 h induced increased Bcl-2 protein expression; induction was dose dependent. Exposure of T98G and A172 cells to ACNU did not affect their Bcl-2 protein levels. Southern blot analysis revealed no chromosomal translocation in the cells studied. These findings suggest that Bcl-2 protein overexpression in glioma cells may partly contribute to tumor growth and tolerance to chemotherapeutic agents.

Blotting, Southern↗

Incontinentia pigmenti achromians (hypomelanosis of ITO, MIM 146150): further evidence of localization at Xp11.

We report on a girl with apparent hypomelanosis of Ito (ITO); cytogenetic studies disclosed the karyotype 46,X,t(X;10)(p11;q11)mat. We present further evidence that at least one of the genetic forms of ITO is located at Xp11; reviewing the clinical characteristics of patients with incontinentia pigmenti type 1 (IP1) and ITO with X-autosome translocations, we suggest that IP1 and ITO represent allelic forms or a contiguous gene syndrome. Thus, different genetic alterations in this region (Xp11) give rise to ITO or IP1 or borderline phenotypes. We also suggest that all patients with ITO, due to Xp11 mutation, have functional or genetic mosaicisms.

Abnormalities, Multiple↗

Branch retinal artery occlusion following thyroidectomy for papillary carcinoma of the thyroid: report of a case.

A rare case of branch retinal artery occlusion (BRAO) following a subtotal thyroidectomy for thyroid cancer in a 58-year-old woman is reported herein. Five days after her thyroidectomy, the patient complained of having had a reduction in visual acuity and visual field loss of the superior nasal side in her right eye since the operation. BRAO was diagnosed following the discovery by funduscopy of inferotemporal branch artery occlusion with retinal edema, hemorrhage, and periarterial sheathing in the right eye. Despite immediately puncturing the anterior camera and massaging the eyeball while administering intravenous anticoagulant therapy, the visual field disturbance remained unchanged. The most common causative factor of postoperative sudden BRAO is reported to be emboli. However, in our case, the most likely cause was the stretching and pressure exerted on the carotid artery with consequent atheromatous plaque formation at the time of thyroidectomy.

Carcinoma, Papillary↗

Regulation of hepatic triglyceride lipase by thyroid hormone in HepG2 cells.

Hypothyroidism has been reported to be associated with reduced hepatic triglyceride lipase (HTGL) activity. In order to understand the molecular mechanism by which thyroid hormone regulates HTGL activity, effects of triiodothyronine (T3) on HTGL activity, mRNA level, transcription run-on activity, and protein synthetic rate were studied in HepG2 cells. HepG2 cells treated with 1 nM T3 showed an increase in HTGL activity that was first detected at 24 h; HTGL activity continued to increase at 36 h and stayed at the elevated level at 48 and 60 h. At maximal stimulation (48 h), T3-treated cells had the following HTGL activities: 155% in spontaneously released (SR) and 224% in heparin-releasable (HR) HTGL activities (mean levels compared to control). Stimulation of HTGL activity by T3 was dose-dependent and saturable. There was, however, no change in HTGL mRNA level throughout the course of T3 treatment. The effects of T3 were reduced when transcription was blocked by actinomycin D (mean level compared to actinomycin D treatment in the absence of T3: 109% in SR and 127% in HR activities) or translation was blocked by cycloheximide (127% in SR and 122% in HR activities), but HTGL activities were still significantly higher than control. Nuclear run-on assays indicate that T3 did not change the rate of transcription of the HTGL gene. We further determined the rate of HTGL synthesis by measuring the amount of [35S]methionine incorporated into newly synthesized HTGL immunoprecipitated by a monospecific anti-human HTGL antibody. We found that the T3-stimulated increase in HTGL activity was not accompanied by any change in the rate of HTGL biosynthesis. Our experimental data indicate that the T3 stimulation of HTGL activity in HepG2 cells is mediated at posttranscriptional and posttranslational levels. The partial but significant inhibition of the T3 stimulation of HTGL activity by actinomycin D and cycloheximide suggests that the effects of T3 may be mediated by other cellular processes that are more directly regulated by the hormone. This study represents the initial report on the mechanism of HTGL activation by physiological concentrations of thyroid hormone.

Base Sequence↗

A missense mutation (Trp86----Arg) in exon 3 of the lipoprotein lipase gene: a cause of familial chylomicronemia.

We have investigated a patient of English ancestry with familial chylomicronemia caused by lipoprotein lipase (LPL) deficiency. DNA sequence analysis of all exons and intron-exon boundaries of the LPL gene identified two single-base mutations, a T----C transition for codon 86 (TGG) at nucleotide 511, resulting in a Trp86----Arg substitution, and a C----T transition at nucleotide 571, involving the codon CAG encoding Gln106 and producing Gln106----Stop, a mutation described by Emi et al. The functional significance of the two mutations was confirmed by in vitro expression and enzyme activity assays of the mutant LPL. Linkage analysis established that the patient is a compound heterozygote for the two mutations. The Trp86----Arg mutation in exon 3 is the first natural mutation identified outside exons 4-6, which encompass the catalytic triad residues.

Amino Acid Sequence↗

[Traumatic sinus pericranii. Case report].

The patient was involved in a traffic accident at the age of 1 and the left parieto-occipital scalp was contused without skull fracture. At the age of 5, an extracranial scalp mass was first noticed just beneath the multiple scalp scars. Angiography through the mass revealed that the extracranial mass cavity was connected to the superior sagittal sinus through the emissary veins. The mass located in the subgaleal, epiperiosteal space was totally resected and the connection with the intracranial sinus was closed with bone wax. Histologically, there were many capillaries and some large blood cavities with only one layered endothelium and connective tissue. Therefore, the mass was diagnosed as sinus pericranii and considered to be secondary to previous head trauma because: 1) The patient had a history of head trauma with considerably severe scalp injuries. 2) The extracranial blood sinus was located exactly beneath the traumatic scar. 3) There was no neoplastic tissue histologically. 4) No scalp mass was noticed before the traffic accident. 5) There was an elapsed time between the trauma and the growth of the mass. 6) No scalp nevus such as port-wine stain existed.

Child↗

Epstein-Barr virus and other herpesvirus infections in Kawasaki syndrome.

Epstein-Barr virus (EBV), a possible cause of Kawasaki syndrome (KS), is not pathenogenically associated with KS in Hawaii. The prevalence of EBV capsid antibody in KS patients was found not to differ significantly from that in controls, and the antibody response in those infected with EBV was the same as that in other children similarly infected. No EBV was isolated from acute-phase patients. All patients with capsid antibody at the onset of KS also had Epstein-Barr nuclear antigen antibody: 36 patients developed antibody within 3 months after onset of KS; in 10, EBV infection could have been coincidental with the disease. Cytomegalovirus (CMV) was isolated from 9 patients with KS and 10 controls. A similar number of controls and patients had antibody to human herpesvirus 6 (HHV6); one patient seroconverted. None of the herpes viruses (EBV, CMV, HHV6, varicella-zoster virus, or herpes simplex virus) plays a unique or dominant role in the etiology or pathogenesis of KS in Hawaii.

Age Factors↗

Inhibition of purified human postheparin lipoprotein lipase by beta-adrenergic blockers in vitro.

We examined the effects of five beta-adrenergic blockers on the hydrolysis of phosphatidylcholine-stabilized triolein particles by purified human postheparin lipoprotein lipase (PHLpL) in order to evaluate the possible role of direct inhibition as a mechanism of drug-induced hypertriglyceridemia. The relative inhibitory potencies were observed in the following order: propranolol much greater than pindolol greater than metoprolol greater than atenolol greater than nadolol. There was a positive correlation between the octanol/water partition coefficients of these agents and their inhibition of lipoprotein lipase, suggesting that hydrophobicity may be one of the major determinants for PHLpL inhibition. The amount of the beta-adrenergic blockers required to produce 50% inhibition of human PHLpL was much greater than that required to inhibit purified bovine lipoprotein lipase.

Adrenergic beta-Antagonists↗

Absence of significant RNA-dependent DNA polymerase activity in lymphocytes from patients with Kawasaki syndrome.

Kawasaki syndrome, an acute febrile multisystem illness of young children, is a panvasculitis with prominent rheumatic features. Arthritis and pancarditis are frequent during the acute stage; coronary artery aneurysms occur in 20% of cases and the disease is now the leading cause of acquired heart disease in childhood. A microbial aetiology is suggested by the acute febrile self-limited character of the disease, the regular occurrence of epidemic outbreaks at intervals of 2-3 years, and the virtual restriction to young children, consistent with the early acquisition of immunity. Reports of elevated DNA polymerase activity (assumed to be RNA-dependent reverse transcriptase) in cultured lymphocytes from patients with acute Kawasaki syndrome suggest that a retrovirus might be the causative agent. We have measured supernatant DNA polymerase activity in lymphocyte cultures from 49 Hawaiian patients in acute and convalescent stages of Kawasaki syndrome and have been unable to demonstrate significant reverse transcriptase activity or other evidence of involvement of a retrovirus in the aetiology of the disease.

Acute Disease↗

Lymphoepithelial cystic lesion related to adenocarcinoma in the mediastinum.

The authors report here a case of lymphoepithelial cystic lesion (LECL) of unknown origin in the mediastinum, which is closely related to a signet-ring cell adenocarcinoma. A 73-year-old man presented with a mass as revealed on a chest x-ray. During surgical operation, a solid, well-circumscribed and encapsulated 9 X 9 X 8 cm tumor was isolated from the right anterior mediastinum. This tumor had neither undergone metastasis nor invaded into the surrounding tissue and lymph nodes. Light microscopy revealed the tumor to be a signet-ring cell adenocarcinoma. Clinically, the neoplasm was coupled with an elevation in serum CEA level, which promptly returned to normal values following surgical removal. Immunohistochemistry pointed out that the majority of neoplastic cells stained positive for CEA. In addition, LECL of unknown origin was distinguished at the periphery of the tumor. LECL was characterized by microcysts which were lined by columnar epithelial and surrounded by lymphoid tissue with germinal centers. Transition between the neoplastic cells and benign epithelial cells of LECL was evident, showing that the previously mentioned mediastinal adenocarcinoma may be derived from the epithelial elements of LECL. This paper discusses the histogenesis of LECL.

Adenocarcinoma, Mucinous↗

Cholesterol-lowering effect of N-(alpha-methylbenzyl)linoleamide (melinamide) in cholesterol-fed diabetic rats.

Cholesterol loading of diabetic rats is known to induce marked hyperlipoproteinaemia, and we have reported that enhancement of the activity of intestinal acyl-CoA:cholesterol acyltransferase (ACAT), one of the key enzymes involved in cholesterol absorption, might play an important role in the development of hypercholesterolaemia in these animals. In the present study, we have shown that treatment with N-(alpha-methylbenzyl)linoleamide (melinamide), a new hypocholesterolaemic drug, caused a substantial decrease of the enhanced intestinal ACAT activity in diabetic rats, but did not affect intestinal cholesterol esterase activity. Furthermore, marked improvement of hypercholesterolaemia in cholesterol-fed diabetic rats occurred concomitantly with the drug treatment. These results suggest that intestinal ACAT activity is closely related to the serum cholesterol level in diabetic rats, and show that melinamide lowers intestinal ACAT activity.

Animals↗

Increased activity of intestinal acyl-CoA: cholesterol acyltransferase in rats with streptozocin-induced diabetes and restoration by insulin supplementation.

We examined the activities of intestinal acyl-CoA:cholesterol acyltransferase (ACAT) and cholesterol esterase, enzymes regulating cholesterol absorption, in rats with streptozocin-induced diabetes (STZ-D) to clarify the effect of diabetes on cholesterol absorption. Three weeks after the induction of diabetes, plasma cholesterol levels were slightly but significantly increased in diabetic rats compared with control animals, whereas a far more remarkable increase in plasma cholesterol was observed in diabetic rats when fed an atherogenic diet containing 1% cholesterol, 0.5% cholic acid, and 5% lard. Microsomal ACAT activity in intestinal mucosa was three times higher in diabetic than in control rats. However, no significant difference in the enzyme activity could be detected between diabetic animals fed control chow and those fed the atherogenic diet. Furthermore, insulin supplementation given to diabetic rats caused a reduction of enzyme activity to the levels found in control animals. In contrast, cholesterol esterase activity in rat intestinal mucosa was unaffected by either the induction of diabetes or the atherogenic diet feeding. In conclusion, we disclosed that apparent ACAT activity in intestinal mucosa is elevated in STZ-D rats. Therefore, we postulate that enhancement of CoA-dependent cholesterol esterification in the intestine might be one of the major factors responsible for hypercholesterolemia in diabetes.

Animals↗

Nasal allergen sensitivity and mucosal IgE antibodies.

Skin tests, nasal provocation tests, nasal smear tests, and serum-radioallergosorbent tests were performed on 17 patients with perennial allergic rhinitis, who had suffered nasal congestion without receiving any antiallergic treatment. After the above tests, tissue-radioallergosorbent tests (t-RAST) were conducted to determine IgE antibody levels in inferior turbinate mucosal samples taken peroperatively. The results obtained in this study suggest that the allergen sensitivity of the nasal mucosa correlates to some extent with the mucosal IgE antibody level, and that the t-RAST can provide us with objective data about nasal allergen sensitivity.

Humans↗