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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 127 records · Page 7Linked to original sources
PubMed2001

Physiological differences in insulin-like growth factor binding protein-1 (IGFBP-1) phosphorylation in IGFBP-1 transgenic mice.

Insulin-like growth factor binding protein (IGFBP)-1 has been shown to alter cellular responses to insulin-like growth factor 1 (IGF-1). Human IGFBP-1 undergoes serine phosphorylation, and this enhances both its affinity for IGF-1 by six- to eightfold and its capacity to inhibit IGF-1 actions. To investigate the physiological role of IGFBP-1 in vivo, transgenic mice have been generated using either the human IGFBP-1 or rat IGFBP-1 transgene. Both lines of mice expressed high concentrations of IGFBP-1 in serum and tissues; however, human IGFBP-1 transgenic mice did not show glucose intolerance and exhibited no significant intrauterine growth retardation, whereas rat IGFBP-1 transgenic mice showed fasting hyperglycemia and intrauterine growth restriction. The aim of this study was to investigate the physiological differences in the phosphorylation state of human IGFBP-1 and rat IGFBP-1 in these transgenic mice. The phosphorylation status of IGFBP-1 in transgenic mouse serum was analyzed by nondenaturing PAGE. Almost all of the IGFBP-1 in serum from the human IGFBP-1 transgenic mice was present as a nonphosphorylated form. Most of the rat IGFBP-1 in the serum of the mice expressing the rat IGFBP-1 was phosphorylated. Immunoprecipitation showed that mouse hepatoma (Hepa 1-6) cells (exposed to [32P]H3PO4) secrete 32P-labeled IGFBP-1. When the human IGFBP-1 transgene was transfected into Hepa 1-6 cells, all of the IGFBP-1 was secreted in the nonphosphorylated form. However, when the rat IGFBP-1 transgene was transfected into these cells, phosphorylated forms of IGFBP-1 were secreted. To confirm this result, the mouse hepatoma cell protein kinase was partially purified. This kinase activity phosphorylated mouse and rat IGFBP-1 in vitro, but it did not phosphorylate human IGFBP-1. Scatchard analysis showed that the affinity of phosphorylated rat IGFBP-1 for IGF-1 was 3.9-fold higher than that of nonphosphorylated human IGFBP-1. We conclude that the mouse IGFBP-1 kinase activity cannot phosphorylate human IGFBP-1, whereas it can phosphorylate rat IGFBP-1. The phosphorylation state of human IGFBP-1 may account for part of the phenotypic differences noted in the two studies of transgenic mice, and it is an important determinant of the capacity of human IGFBP-1 to inhibit IGF-1 actions in vivo.

Animals↗
PubMed2001

Airborne fiber concentration and size distribution of mineral fibers in area with serpentinite outcrops in Aichi prefecture, Japan.

Airborne fiber concentrations and size distributions of both asbestos and nonasbestos fibers were determined at property boundaries of 4 serpentinite quarries producing crushed stone (quarry property boundary), 10 sites within 10 km of the area with serpentinite outcrops (serpentinite area), and 2 sites in a reference area. The asbestos was identified in 7 rock and 3 soil samples collected in the serpentinite area. The geometric means of airborne concentrations of asbestos and nonasbestos fibers longer than 0.2 microm in length were: 384 and 447 fibers/liter (f/L) in the quarry property boundary (in operation), 12 and 124 f/L in the quarry property boundary (in closed), 5 and 103 fibers/liter in the serpentinite area, and less than 2 and 59 fibers/liter in the reference area, respectively. There was a significant difference in airborne concentrations of both asbestos and nonasbestos fibers among the areas. Ttremolite/actinolite were found with chrysotile in the stones. Airborne concentrations of tremolite/actinolite were higher than those of chrysotile at the quarry property boundary and in the serpentinite area. Tremolite/actinolite were also found in the soils. There was no significant difference among the areas in the arithmetic means of fiber size distribution of both asbestos and nonasbestos fibers.

Air Pollutants↗
PubMed2001

A morphological and immunohistochemical study of the ultimobranchial body in the Japanese lizard and the snake.

A morphological and immunohistochemical study of the ultimobranchial body of reptiles Japanese lizard and snake was carried out. The ultimobranchial body of the Japanese lizard was located adjacent to the left arch of the aorta between the trachea and esophagus. It was found as a cluster or group of cells with no capsule. Grimelius' silver impregnation and lead-hematoxylin staining produced positive reactions in some of the clustered cells and follicular cells. The same reaction pattern was observed with anti-calcitonin using the PAP method. The PAP reactions were positive to antiserum against pig calcitonin, but negative to antiserum against synthesized human calcitonin. Furthermore, the PAP reactions were negative to antiserum against tyrosine hydroxylase. The immunofluorescent study of the snake ultimobranchial body revealed that most of the clustered cells and some of the follicular cells were calcitonin-immunoreactive but none was tyrosine hydroxylase-immunoreactive. Certain histological similarities exist between the Japanese lizard ultimobranchial body and snake ultimobranchial body, but the distribution of calcitonin-positive cells were slightly different. In the Japanese lizard, the positive cells were scattered between the foliicles and the number was small. However, most of the cells which formed the cluster in the ultimobranchial body of snake were positive. The findings suggest that the configuration of amino acid in the Japanese lizard calcitonin and snake calcitonin are similar to that of pig calcitonin, and the reptile and the birds is a boundary of the tyrosine hydroxylase existence.

Animals↗
PubMed2001

[Effects of figural complexity and target-distracter similarity on decay rate in short-term visual memory].

We examined the effects of figural complexity and target-distracter similarity on decay rate in short-term visual memory (STVM) for closed contours. The subject's task was to compare two stimuli presented at different points in time. Experiment 1 showed that even a simple pattern with 6 convex parts cannot be handled in STVM for several seconds without loss. Experiments 1 and 2 indicated that decay rate tends to be higher for patterns with higher complexity and for patterns with higher target-distracter similarity regardless of pattern complexity. These results are interpreted that the value of each convex part represented in STVM is an independent Gaussian random variable and that memory noise increases with retention intervals for each convex part separately. Furthermore, they suggest that memory for local features in STVM decays faster. Yet visual rehearsal appears to operate effectively on memorizing even complex patterns. It is concluded that visually presented patterns can be retained in STVM with relatively high fidelity for prolonged periods of time, although some loss of precision occurs inevitably.

Form Perception↗
PubMed2001

[Characteristics of information decay in short-term visual memory and a diffusion model].

The effect of exposure duration of test stimulus on the decay rate in short-term visual memory (STVM) was investigated in a same-different task. In the model, it is assumed that memory noise, the variance of each convex value represented in STVM, increases with time, which causes the decay in STVM. In recognition experiments, the results showed that the decay rate is lower for longer exposure duration regardless of pattern complexity. Furthermore, the decay lasted gradually for 16 s with exposure duration of 1,200 ms, which suggests that prolonged exposure largely acts to reduce the decay rate but does not prevent the decay itself. These experimental data were well predicted by the model, which clearly indicates that memory noise increases as a linear function of retention interval and that the rate of increase of memory noise is inversely proportional to exposure duration. These results are interpreted by an extension of the integration model of Signal Detection Theory: The number of mental scanning, N, monotonically increases with an increase in exposure duration, s, and increase of memory noise is inversely proportional to N, so memory sensitivity d' is predicted to be multiplied by square route of s.

Humans↗
PubMed2001

Immune thrombocytopenia in an elderly patient treated successfully by pulse therapy with cyclophosphamide.

Thrombocytopenia due to immune mechanisms is rare and difficult to manage in elderly patients. We describe a case of an 89-year-old female with severe immune thrombocytopenia (ITP) who rapidly improved by pulse therapy with cyclophosphamide. She was admitted to our hospital because she had arthralgia in both sides of her femoral region since January 1999, aphthous stomatitis and ecchymosis of the leg since April 1999, and bloody phlegm in July 1999. On admission, her peripheral blood count revealed severe thrombocytopenia (0.1 x 10(4)/microl). Her megakaryocyte count from bone marrow was increased to 512/microl without abnormal cells. Systemic lupus erythematosus was suspected because of strong positive protein in the urine in addition to the clinical and hematological findings described above, but she was negative for all the autoantibodies examined. Finally, she was diagnosed as having ITP on the basis of high platelet associated immunoglobulin G in addition to hematological and physical findings and she was treated with prednisolone. It was difficult to maintain her platelet count with only prednisolone, but 600 mg of cyclophosphamide rapidly increased her platelet count in spite of tapering the prednisolone. In September 2000, her platelet count was kept within normal limits by administration of 15 mg/day of prednisolon. It is suggested that immunosuppressive therapy for ITP using high-dose cyclophosphamide is useful in elderly patients as well as in juvenile adult patients.

Aged↗
PubMed2001

[Development of new hydrophilic catheter kit for self-catheterization: study in pediatric cases].

PURPOSE: To increase the management of self-catheterization in children of school age, a catheter kit consisting of hydrophilic catheter and a packet containing sterilized water was developed. We evaluated the lubricating characteristic and clinical efficacy of this new catheter kit. MATERIALS AND METHODS: The catheter kit used in the study was a pocket-size plastic container in which a polyurethane catheter coated with hydrophilic polymer and a packet containing sterilized water were packed in combination. The lubricating characteristic of catheter was assessed by the measurement of friction value. For clinical assessment, male children aged over 6 years old who were doing self-catheterization at 17 medical institutions nationwide were selected as the subjects. The 32 children who had given informed consent (mean age: 11.6 years old) were asked to use the catheter kit continuously for 1 week. The results were investigated by a questionnaire survey in which the assessment before and after the use was expressed in scores. At the same time, urinalysis and urine culture were examined. RESULTS: The friction value of hydrophilic catheter was equivalent to or less than that observed by applying a lubricant to the conventional catheter. The comparison of conventional catheter with the kit indicated significantly higher scores (assessment in 5 grades expressed in scores) for the portability and operability of the kit. Though there was no significant difference in the ease of insertion between the two catheters, there were several comments that the kit got stuck in the urethra when it was withdrawn. The global assessment gave a significantly higher score to the kit and 30 (94%) of the 32 children wanted to use the kit continuously. No increase in hematuria which caused a clinical problem or no new apparent urinary tract infection occurred after the use of the kit. CONCLUSIONS: Compared with the conventional catheter, the hydrophilic catheter kit highly satisfied a large number of children at the time of self-catheterization. Depending on the condition of children, the kit is considered useful for continued self-catheterization for a long term.

Child↗
PubMed2001

Role of dorsal raphe neurons in paradoxical sleep generation in the cat: no evidence for a serotonergic mechanism.

Using in vivo microdialysis either alone or in combination with extracellular unit recordings, we have examined the effect of serotonergic and nonserotonergic drugs applied to the dorsal raphe nucleus (DRN) on behavioural states in the cat. We found that 8-hydroxy-2-(n-dipropylamino)tetralin hydrobromide (8-OH-DPAT), a selective 5-HT1A receptor agonist, induced a dose-dependent increase in wakefulness (W) and decrease in deep slow-wave sleep (SWS), but had no significant effect on the generation of paradoxical sleep (PS) at concentrations of 5-500 microM. At the highest concentration tested, however, PS occurred directly after W, as in narcolepsy. N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohex anecarboxamide maleate (WAY-100635), a selective 5-HT1A receptor antagonist, had no effect on overall behavioural states at concentrations of 50 or 500 microM. Muscimol, a potent GABAA receptor agonist, had little or no effect at concentrations of 10, 50 or 100 microM, but concentrations of 500 or 1000 microM caused a pronounced increase in W and decrease in SWS without inducing any changes in the amount of PS, although PS episodes occurred as in narcolepsy. Bicuculline, a GABAA receptor antagonist, or kainate, an excitatory amino acid agonist, produced a dose-dependent increase in W and decrease in deep SWS and PS. Extracellular unit recordings combined with microdialysis infusion into the DRN demonstrated that only high concentrations of 8-OH-DPAT or muscimol significantly affect a large population of DRN neurons. Taken together, these findings indicate that DRN serotonergic activity does not play any crucial role in PS generation, but is involved in the regulation of W and SWS as well as in narcolepsy.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

[Three-dimensional reconstructions with volume-rendering method of the arytenoid and cricoid cartilages by means of multidetector row CT].

We created volume-rendering (VR) three-dimensional (3-D) images of the larynx using a multidetector row CT. The study included 17 examinations of 15 patients. After obtaining volume data of the larynx, VR 3-D images of airways and arytenoid and cricoid cartilages were reconstructed. The threshold of airways and calcification were set as -1025/-625 HU and 80/1560 HU, respectively. The base of the vocal processes of arytenoid cartilages and cricoarytenoid joints were demonstrated at rates of 70.6% and 53.4%, respectively. VR 3-D laryngeal images were more useful in assessing anatomy than the surface-rendering images previously reported.

Adolescent↗
PubMed2001

Immunochemical detection of a lipofuscin-like fluorophore derived from malondialdehyde and lysine.

The accumulation of fluorescent age pigment or lipofuscin is a frequently observed age-associated cellular alteration in a variety of postmitotic cells of many species. These pigments are observed within granules composed, in part, of damaged protein and lipid. Modification of various biomolecules by aldehyde products of lipid peroxidation is believed to contribute to lipofuscin and ceroid formation. In the present study, we raised a monoclonal antibody (MAb 1F83) directed to the malondialdehyde-modified protein and identified a lipofuscin-like dihydropyridine fluorophore as the major epitope. This antibody was used to conclusively demonstrate that the fluorophore forms on oxidatively modified low density lipoproteins. In addition, we demonstrated that the materials immunoreactive to MAb 1F83 indeed constituted the atherosclerotic lesions, in which intense positivity was associated primarily with macrophage-derived foam cells. The results of this study suggest that the reaction between the lipid peroxidation-derived aldehyde and primary amino groups of protein might represent a process common to the formation of the lipofuscin-like fluorophore during aging and its related diseases.

Animals↗
PubMed2001

[The changes of the methods of the right ventricle outflow tract reconstruction].

There are many situation that we need to do some procedure for the right ventricle outflow tract reconstruction (RVOTR) among the congenital heart diseases. The procedures have changed during past decade. Also the changes have shown about the materials for outflow patches. We reviewed the changes through our experience. There were seventy-six cases or RVOTR from August, 1988 to December, 2000. Most of them were tetralogy of Fallot. Fifteen cases were done the Rastelli procedure. There were some other congenital heart diseases. The materials were mainly artificial in the period before 1995. Then it has been changed mainly to the autologous pericardium in the period after 1996. The sizes of the tract were made to match the standard of Rowlatt. We found some re-stenosis and late mortality because of the pulmonary valve regurgitation. We are trying to reduce such complications.

Adolescent↗
PubMed2001

Renin containing cells are present predominantly in scarred areas but not in dysplastic regions in multicystic dysplastic kidney.

PURPOSE: Hypertension is an important complication of multicystic dysplastic kidney and it has been suggested that it is induced by renin. Little information is available on renin production in this disease. To assess renin production we examined the distribution of renin containing cells in multicystic dysplastic kidneys using immunohistochemical methods. MATERIALS AND METHODS: Immunohistochemical examination of renin was performed in 29 multicystic dysplastic kidneys from 14 boys and 15 girls 1 month to 10 years old using rabbit anti-human renin antibodies. In all cases normal renal function was confirmed by the serum creatinine level and no proteinuria on urinalysis. Two patients had the complication of hypertension before removal of the multicystic dysplastic kidney but plasma renin activity was normal. RESULTS: Immunostaining of renin was observed in 26 of 29 multicystic dysplastic kidneys (90%). Histologically multicystic dysplastic kidney involved scarred and dysplastic areas. Renin positive cells were observed predominantly in the scarred areas, mainly in the juxtaglomerular apparatus of mature glomeruli, interlobular arteries and some mature tubules. Immunopositive renin was sparsely noted in the juxtaglomerular apparatus or Bowman's capsules of occasional immature glomeruli in dysplastic areas. CONCLUSIONS: Our observations suggest that multicystic dysplastic kidney may have the ability to produce renin. Renin producing cells in the juxtaglomerular apparatus of mature glomeruli and interlobular arteries in the scarred areas may be the predominant source of renin production in this organ.

Female↗
PubMed2001

Overexpression of eNOS in the RVLM causes hypotension and bradycardia via GABA release.

In this study, we examine the role of NO located in the rostral ventrolateral medulla (RVLM) in the control of blood pressure and the activity of the sympathetic nervous system. To determine the effect of an increase in NO production in the RVLM on blood pressure in conscious rats, adenovirus vectors encoding either endothelial NO synthase (AdeNOS) or beta-galactosidase (Adbetagal) were transfected into the bilateral RVLM. The local expression of endothelial NO synthase (eNOS) protein in the RVLM was confirmed by immunohistochemical staining for the eNOS protein and by Western blot analysis. Mean arterial blood pressure (MAP) and heart rate, which were monitored using a radio-telemetry system, were significantly decreased in the AdeNOS-treated group from day 5 to day 10 after the gene transfer. Urinary norepinephrine excretion was decreased on day 7 after the gene transfer in the AdeNOS-treated group. Microinjection of either N(G)-monomethyl-L-arginine (L-NMMA) or bicuculine, a gamma-amino butyric acid (GABA) receptor antagonist, into the RVLM at day 7 after the gene transfer increased MAP to significantly greater levels in the AdeNOS-treated group. However, microinjection of kynurenic acid into the RVLM on day 7 after the gene transfer did not alter MAP levels in either group. GABA and glutamate levels in the RVLM, when measured by in vivo microdialysis, were significantly increased in the AdeNOS-treated group. These results suggest that the increase in NO production caused by the overexpression of eNOS in the bilateral RVLM decreases blood pressure, heart rate, and sympathetic nerve activity in conscious rats. Furthermore, these responses may be mediated by an increased release of GABA in the RVLM.

Adenoviridae↗
PubMed2001

[Brain metastases from esophageal cancers: clinical features and treatment results].

Metastatic brain tumors from esophageal cancer are relatively rare. We analyzed the clinical features and results of treatment in 14 cases of brain metastases from esophageal carcinoma. The average time to diagnosis of brain metastases in the 11 patients with metachronous lesions was 13 months. The average age of patients at the diagnosis of brain metastasis was 65 years. Most patients had T4 or N1 disease at the time of diagnosis of esophageal cancer. Performance status of grade 3 was most frequent at the time of diagnosis of brain metastasis. Treatment for brain metastases was surgery followed by radiation in five cases, radiotherapy alone in seven cases, and conservative treatment in two cases. The median survival time of all patients from the treatment of brain metastases was 2 months, with only one patient alive after more than one year. Improvement in neurological symptoms was demonstrated in 42% of cases. These extremely poor treatment results reflect the fact that most patients at the time of diagnosis of brain metastasis had poor performance status and the presence of extracerebral metastases. Therefore, a short-course, high-dose-per-fraction treatment for brain metastases from esophageal cancer should be selected from the viewpoint of quality of life.

Adult↗
PubMed2000

Tissue transglutaminase facilitates the polymerization of insulin-like growth factor-binding protein-1 (IGFBP-1) and leads to loss of IGFBP-1's ability to inhibit insulin-like growth factor-I-stimulated protein synthesis.

Insulin-like growth factor-binding protein-1 (IGFBP-1) binds to insulin-like growth factors (IGFs) and has been shown to inhibit or stimulate cellular responses to IGF-I in vitro. This capacity of IGFBP-1 to inhibit or stimulate IGF-I actions correlates with its ability to form stable high molecular weight multimers. Since the ability of some proteins to polymerize is dependent upon transglutamination, we determined if tissue transglutaminase could catalyze this reaction and the effect of polymerization of IGFBP-1 upon IGF-I action. Following incubation with pure tissue transglutaminase (Tg), IGFBP-1 formed covalently linked multimers that were stable during SDS-polyacrylamide gel electrophoresis using reducing conditions. Dephosphorylated IGFBP-1 polymerized more rapidly and to a greater extent compared with native (phosphorylated) IGFBP-1. Exposure to IGF-I stimulated transglutamination of IGFBP-1 in vitro. An IGFBP-1 mutant in which Gln(66)-Gln(67) had been altered to Ala(66)-Ala(67) (Q66A/Q67A) was relatively resistant to polymerization by Tg compared with native IGFBP-1. Tg localized in fibroblast membranes was also shown to catalyze the formation of native IGFBP-1 multimers, however, Q66A/Q67A IGFBP-1 failed to polymerize. Although the mutant IGFBP-1 potently inhibited IGF-I stimulated protein synthesis in pSMC cultures, the same concentration of native IGFBP-1 had no inhibitory effect. The addition of higher concentrations of native IGFBP-1 did inhibit the protein synthesis response, and this degree of inhibition correlated with the amount of monomeric IGFBP-1 that was present. In conclusion, IGFBP-1 is a substrate for tissue transglutaminase and Tg leads to the formation of high molecular weight covalently linked multimers. Polymerization is an important post-translational modification of IGFBP-1 that regulates cellular responses to IGF-I.

Amino Acid Sequence↗