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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 775 records · Page 43Linked to original sources

The effect of serum Ca2+ compensation on the efficacy of chlorpropamide in alloxan-diabetic rabbits.

A decrease in serum Ca2+ concentration was observed in alloxan-diabetic rabbits, with recovery of serum Ca2+ levels achieved following insulin therapy. This suggested that the diabetic condition directly relates to the decrease in serum Ca2+ levels. The efficacy of chlorpropamide in alloxan-diabetic rabbits after intravenous injection (150 mumol kg-1) was less than that in normal rabbits as measured by the serum insulin levels, and the efficacy did not change when the dose was increased. However, compensation of serum Ca2+ levels in alloxan-diabetic rabbits caused an increase in the efficacy of chlorpropamide observed as an increase in serum insulin and a decrease in serum glucose levels.

Animals↗

Regulated expression of human immunodeficiency virus type 1 in human glial cells: induction of dormant virus.

Human neural cells are susceptible to infection with human immunodeficiency virus type 1 (HIV-1) in vitro; however, virus replication in these cells is strongly restricted. To understand the mechanism of this restriction, we examined the regulation of HIV-1 expression in glial cell cultures expressing high levels of HIV-1 after transfection of infectious viral DNA and selection. In all cases, high HIV-1 expression declined to low basal levels within 4-8 weeks of cultivation. The decrease in HIV-1 protein production wa paralleled by the decline in the relative levels of the 9.2-, 4.3- and 1.8-kilobase HIV-1 transcripts, but not by significant loss of HIV-1 DNA. Analysis of one long-term cell culture revealed 5 full-length unrearranged HIV-1 DNA copies per cell, but no viral transcripts on Northern blots, and minimal production of infectious virus. HIV-1 replication in these cells was markedly augmented by treatment with sodium butyrate (Na But) and to a lesser extent by 5-azacytidine, dibutyryl AMP and human herpes virus type 6. The virus induced by Na But was infectious. Transient expression assays revealed that Na But was more effective than phorbol myristate acetate in increasing the HIV-1 promoter activity in glial cells. Thus, one phase where glial cells can limit HIV infection is the expression of viral RNA from stable HIV provirus. However, such provirus remains responsive to inductive signals and may be activated to produce infectious HIV.

Cells, Cultured↗

Glomerular deposition of alpha 2-macroglobulin in a child with steroid refractory nephrotic syndrome.

A four-year-old male with steroid refractory nephrotic syndrome was found to have diffuse deposition of alpha 2-macroglobulin (alpha 2M) in the glomeruli which showed diffuse mesangial proliferation and partial hyalinization by light microscopy. Camostat mesylate, a commercially available synthetic proteinase inhibitor, led to biochemical and clinical improvement. Twenty-two patients with 7 biopsy-proven renal diseases did not have any deposition of alpha 2M in their kidney tissue. Though the pathogenetic mechanism is unknown, this is probably the first report of the deposition of alpha 2M in renal tissue.

Child, Preschool↗

Surface-modulated skin layers of thermal responsive hydrogels as on-off switches: II. Drug permeation.

'On-off' regulation of drug permeation through membranes in response to external temperature change has already been achieved using thermosensitive copolymers of N-isopropyl acrylamide (IPAAm) with butyl methacrylate (BMA). Increasing temperature induced formation of a dehydrated polymeric surface skin layer that stopped drug permeation. In this study, to control 'on-off' permeability of a drug, the polymer surface shrinking process was regulated by changing the length of alkyl side chain of the copolymer methacrylate component. Permeation experiments with indomethacin were performed in response to stepwise temperature changes between 20 and 30 degrees C with copolymers of IPAAm with BMA, hexyl methacrylate (HMA), and lauryl methacrylate (LMA). Burst permeation was found at the initial stage of the second 'on' period for both poly(IPAAm-co-HMA) and poly(IPAAm-co-LMA). These results suggest that drug diffuses during 'off' periods to change the concentration profile in the polymer gel. Polymer surface skin formation maintains a localized high water content inside the polymer gel even if drug permeation stops. The length of the alkyl side chain is an important parameter to control 'on-off' permeability of drug.

Acrylic Resins↗

The expression of a cerebellar degeneration-associated neural antigen in human tumor line cells.

We examined the expression of the paraneoplastic cerebellar degeneration-associated autoantigen (PCD-AA) protein in human tumor lines of different origins by using an immunoaffinity-purified antibody from a patient with paraneoplastic cerebellar degeneration (PCD) and uterine adenocarcinoma. Immunocytochemical studies revealed that this antigen is expressed in the cytoplasm of two different uterine carcinoma lines and the tumor lines of neural origin as well as in the cytoplasm of a normal skin fibroblast line. By immunoblot analysis, we detected a 52-kd antigen identical to the PCD-AA protein in all the cell lines studied, including a colon adenocarcinoma line, a small-cell lung carcinoma line, and a squamous cell lung carcinoma line. These results indicate that the PCD-AA protein is expressed in a wide range of tumor cells. In this respect, this antigen is distinguishable from the cerebellar degeneration-related--34 antigen, of which expression is confined to tumor lines of neuroectodermal origin and not detected in colon, breast, or ovarian carcinoma lines derived from patients without PCD. These findings suggest the variability of the immune response to antigens in PCD.

Antigens, Neoplasm↗

Lipid lowering effects of high linoleate and high alpha-linolenate diets in rats and mice. Consequence of long-term feedings.

Diets high in linoleate (safflower oil) or high in alpha-linolenate (perilla oil) were fed to rats for 11 months, and the effects of the diets on plasma and tissue lipids were compared. The plasma levels of total cholesterol (Cho), phospholipids (PL) and triacylglycerol (TG) were significantly lower in the high alpha-linolenate group than in the high linoleate group, the differences being more than 30% in the levels of total Cho and TG. The diets had differential effects on the lipid contents of major tissues: the TG level in muscle was higher but both the TG level in depot fat and the PL level in muscle were lower in the high alpha-linolenate group than in the high linoleate group. In order to clarify whether or not the hypolipidemic effect of the high alpha-linolenate diet was due to changes in the distribution of lipids among tissues, whole body lipids were estimated in mice fed these diets for 5 months. The whole body Cho content was significantly lower, by 28%, in the high alpha-linolenate group compared with the high linoleate group, but the total lipid content, PL and neutral lipids were similar between the groups. Our results indicate that the high alpha-linolenate diet has a more potent cholesterol lowering effect in plasma and body tissue than the high linoleate diet; interestingly, whole body TG levels are similar but tissue distributions of TG are different between the two dietary groups.

Animals↗

Recent advances in assisted circulation using centrifugal pump in surgical and non-surgical patients with acute heart failure or related conditions.

During the last 3 years, left or bi-ventricular support using a centrifugal pump as a ventricular assistance device was performed in 10 patients after open heart surgery. The basic lesions were coronary heart disease in 8 and valvular disease in 2 patients. Bypass support ranged in time from 33 to 240 h (average 114 h), and 3 patients received biventricular support. Six patients have survived in this group. Other supportive methods, in the form of emergency or elective use of portable cardiopulmonary bypass support, were used in 8 patients; 4 with cardiogenic shock and 4 for supported percutaneous coronary angioplasty. These assisted circulations appear to be useful and promising in the management of the critical cardiac patient.

Adolescent↗

High prevalence of coronary artery spasm in survivors of cardiac arrest with no apparent heart disease.

The pathogenesis of cardiac arrest in the absence of any apparent heart disease remains unclear. Based on the hypothesis that coronary spasm may be a cause of cardiac arrest in the absence of apparent heart disease, ergonovine testing and/or electrophysiologic studies (EPS) were performed to evaluate the cause of cardiac arrest. Fourteen patients resuscitated from cardiac arrest had no apparent heart disease. A spontaneous episode of angina with ST-segment elevation occurred in 4 patients while under observation. Ergonovine testing was performed in 9 patients, and coronary spasm was induced in 5. EPS were performed in 8 patients, including 3 patients with coronary spasm. No electrophysiologic abnormalities were found in the 3 patients with coronary spasm. Ventricular fibrillation was induced by programmed ventricular stimulation in 2 patients with documented ventricular fibrillation at the time of resuscitation. All but one of the patients with coronary spasm had chest pain preceding cardiac arrest or at least a history of chest pain at rest, while 4 of 5 patients without coronary spasm had no prodromal symptoms. Patients with coronary spasm had a good prognosis when treated with a Ca-antagonist and/or long-acting nitrate. In conclusion, coronary spasm is the most frequent cause of cardiac arrest in cardiac arrest survivors with no apparent heart disease. Ergonovine testing should be performed to evaluate the cause of cardiac arrest when patients have no apparent heart disease.

Cardiac Pacing, Artificial↗

Recurrent hemoptysis due to aortobronchopulmonary fistula of false aortic aneurysm associated with repair of rupture of the sinus of Valsalva.

A 54-year-old man presented with recurrent hemoptysis of one year duration. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a saccular aneurysm of the ascending aorta. The aneurysm was intraoperatively found to have formed on the superior surface of the site of aortotomy suture placed during previous repair of rupture of the sinus of Valsalva and to have a fistulous communication to the lung. CT and MRI were very useful in the diagnosis of the aneurysm as the cause of hemoptysis.

Aortic Aneurysm↗

Paraneoplastic cerebellar degeneration: successful early detection and treatment of cancer through characterization of the anti-Purkinje cell antibody.

Paraneoplastic cerebellar degeneration (PCD) is thought to be caused by an autoantibody against both tumor and neuronal tissue. Such autoantibodies are most frequently detected in patients with gynecological or breast cancer, and are designated as anti-Yo. We report here a patient with PCD whose underlying cancer could not be detected despite extensive tumor survey. IgG in her serum and cerebrospinal fluid reacted with the cytoplasm of cerebellar Purkinje cells immunohistochemically. On immunoelectron microscopy, the endoplasmic reticulum and Golgi complex were stained. Her IgG bound to the 58 kD band on immunoblots of cerebellar proteins. A reaction was also observed with the recombinant proteins deduced from the complementary DNA clone encoding a neuronal cell antigen reported by Sakai et al (Ann Neurol 28: 692, 1990). Based on these results, successful early resection of fallopian tube adenocarcinoma was performed. It is crucially important to characterize these PCD related autoantibodies for the early treatment of underlying malignant tumors.

Adenocarcinoma↗

Ruptured aneurysm arising from the anomalous anterior cerebral artery--case report.

A 64-year-old male presenting with subarachnoid hemorrhage had a saccular aneurysm arising from the anomalous anterior cerebral artery. The aneurysm was located on the curved mid-portion of the anomalous artery and extended underneath the right optic nerve. The aneurysm was clipped without unroofing the right optic canal. Postoperatively, he suffered from temporary mild deterioration of the right visual acuity. Hemodynamic stress may be important in the development of such aneurysms.

Aneurysm, Ruptured↗

Morphological study of parafollicular cells and the parathyroid gland in the house shrew (Suncus murinus).

A morphological study of parafollicular cells in the thyroid gland and parathyroid gland of the house shrew (Suncus murinus) was made. The results indicated that (1) there were two pairs of parathyroid glands which were located in the upper part of the house shrew thyroid gland, (2) the volumes of the house shrew parathyroid glands ranged from 0.014 to 0.079 mm3, (3) the number of parafollicular cells along the follicles was largest in the upper part of the thyroid lobe, while no parafollicular cells were present in the isthmus, and (4) there were about 20 parafollicular cells per 100 follicular cells and 1.519 parafollicular cells per follicle. The number of parafollicular cells per 100 follicular cells was thus about 5 times larger than that in rats and the number of parafollicular cells per follicle about 2.5 times larger than that in rats.

Animals↗

The formation of metabolites of mephentermine by microsomal and cytosolic preparations of male Wistar rat livers.

1. Metabolites of mephentermine (MP), phentermine (Ph), p-hydroxy-MP, p-hydroxy-Ph, N-hydroxy-MP and N-hydroxy-Ph on incubation with rat liver microsomal and cytosolic preparations were identified by g.l.c. and g.l.c.-mass spectrometry. 2. Identification of the metabolites indicated the following new metabolic routes of MP: NADPH-dependent microsomal formation of p-hydroxy-MP from MP, of p-hydroxy-Ph from p-hydroxy-MP, and the NADH-dependent microsomal formation of Ph from N-hydroxy-Ph.

Animals↗

Effects of 2-mercaptopropionylglycine on the development of X-ray-induced cataract in rats.

The effect of 2-mercaptopropionylglycine on the development of cataract induced by a single dose of X-ray (10 Gy) was investigated in rats. Intraperitoneal injection of 20 mg/kg, three times weekly starting 1 day after irradiation delayed the development of X-ray-induced cataracts significantly. The amounts of non-protein SH groups, malondialdehyde and the Na+/K+ ratio, in the lenses of rats post-treated with the drug were significantly maintained at normal levels even at 27 weeks after irradiation. On the other hand, a single administration of 250 mg/kg of the compound, 30 min prior to irradiation had no effect on cataract progression induced by X-ray.

Animals↗

[Adjuvant chemotherapy for invasive bladder cancer. Multicenter study].

During 2 years and 10 months from November 1985 to September 1988, 50 patients with invasive bladder cancer (pT2-4, pN0-2, M0) were treated with total cystectomy followed by adjuvant combination chemotherapy including cis-platinum. In addition, so-called immunopotentiator (OK-432) and Kanpo (Juzentaihoto: TJ-48) were given to the patients in a random fashion to evaluate whether or not these agents had any significant effect on patients' prognosis. The 3- and 5-year survival rates for 48 evaluable patients were 71% and 67%, respectively. Histologic grade of primary tumors and number of cycles of adjuvant chemotherapy administered had a significant correlation to patients' survival: patients with grade 2 anaplasia had a better 3- and 5-year survival rates than those with grade 3 anaplasia, and patients receiving 3 or more cycles of chemotherapy had a better 3-year survival rate than those with 2 or less cycles. pT and pN categories also affected patients' survival, though not statistically significant. Administration of OK-432 or TJ-48 and pre-operative treatment such as irradiation and intra-arterial chemotherapy had no favourable effects on the survival. Side effects of the adjuvant chemotherapy were minimal to moderate and more than 70% of the patients tolerated at least 3 cycles of chemotherapy. It is likely that adjuvant chemotherapy, when given in a post-operative setting, should be repeated at least 3 cycles or more.

Adult↗