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Biomedical subjects

S Katayama

Publications and source records attributed to S Katayama.

At least 55 records · Page 3Linked to original sources

Induction of apoptosis and necrosis by zinc in human thyroid cancer cell lines.

Zinc at concentrations of 150, microM or higher induced necrosis as well as apoptosis in thyroid cancer cell lines. Necrosis was induced by zinc in a dose-dependent manner, whereas apoptosis did not increase at higher concentrations of zinc. The expression of the antiapoptotic protein phosphorylated Bad was markedly increased, whereas the expression of the proapoptotic proteins Bax and Bad decreased following Zn(2+) exposure. Zn(2+) induced rapid degradation of IkappaB, and an increase in the binding of nuclear transcription factor-kappaB (NF-kappaB). These observations indicate that antiapoptotic pathways were activated in thyroid cancer cells following exposure to Zn(2+). This may be a self-defence mechanism against apoptosis and may underlie the general resistance of thyroid cancer cells to apoptotic stimuli. Zinc may be a potential cytotoxic agent for the treatment of thyroid cancer.

Animals↗

A germline mutation, 1001delC, of the multiple endocrine neoplasia type 1 (MEN 1) gene in a Japanese family.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant inherited disorder characterized by tumors of the enteropancreas, parathyroid and anterior pituitary. The MEN 1 gene was recently cloned, and germline mutations of the gene have been demonstrated in cases of MEN 1. Here, we report a Japanese family with a germline mutation of the MEN 1 gene. The proband (44 y.o., male) had primary hyperparathyroidism (PHP) and pancreatic carcinoid, and his older sister (50 y.o.) had a history of parathyroidectomy for primary hyperparathyroidism at the age of 40. Clinical examination revealed no evidence of PHP or other MEN 1-related tumors in his son. Direct sequencing analysis revealed a heterozygous germline mutation (1001delC) at codon 297 in exon 6 of the MEN 1 gene in the proband and his son. Loss of heterozygosity (LOH) was also found in the resected parathyroid tissue of the proband. The deletion of cytosine 1001 observed in this case induces a frame shift, which causes the appearance of a stop codon (TAG) at codon 367. This mutation appears to be associated with tumors of the endocrine tissues in the cases studied.

Adult↗

Folic acid-responsive neurological diseases in Japan.

Folic acid (folate) levels were measured in the serum of patients with various neurological diseases in Japan. Thirty-six patients showed decreased serum folate levels among 343 consecutive neurological patients (10.5%). Folate administration (15 mg/d) to folate-deficient patients improved neurological symptoms in 24 of 36 cases (67%). Serum folate levels were significantly lower in female than in male folate-deficient patients. Folate-deficient patients showed predominantly axonal neuropathy, which responded to folate supplementation more markedly. Male patients more frequently exhibited neuropathy, especially demyelinating and motor-dominant neuropathy, than females. Anemia was correlated with male sex and low serum folate levels. Male patients were more responsive than females to folate treatment. More male patients had taken excess alcohol or received gastrectomies than females. Neurological symptoms were more frequently improved by folate supplementation in patients with neuropathy than exclusive encephalopathy. Serum folate levels were lower in patients with encephalopathy, especially those with dementia, while folate therapy was more effective in neurological patients without dementia. Dysgeusia and anemia improved in all patients after folate administration. Neurological patients with malabsorption or treated with continuous drip infusion were resistant to folate therapy. Since folate-responsive neuroencepahlopathies are not rare among patients with neurological diseases in Japan, the serum folate level would serve as a valuable indicator for folate supplement therapy.

Anemia↗

[Characterization of a highly proliferative population of adult hepatocytes and its use for tissue engineering].

It is well known among cell biologists that normal hepatocytes of adult mammals are difficult to replicate repeatedly in vitro, irrespective of the fact that these cells can grow well clonally in vivo. We developed a culture medium (HCGM) wherein the normal hepatocytes of adult Fischer rats replicate repeatedly and form clonal colonies. This growth requires the presence of hepatic stellate cells (HSCs). Fractionation and separation of hepatocytes by a combination of centrifugation and cell sorting revealed the presence of a highly proliferative population of hepatocytes in the adult liver, called small-sized hepatocytes (SHs-R3). SHs-R3 showed a 3- to 4-fold higher growth potential than large-sized hepatocytes (SHs-R2) both in vitro and in vivo. The in vivo growth potential was estimated using the retrorsine-dipeptidylpeptidase IV (DPPIV)--rat model in which DPPIV-positive SHs-R3 were transplanted into the liver of retrorsine-treated DPPIV-negative mutant rats which were then subjected to two-thirds partial hepatectomy. The results of our studies suggest a close relationship between SHs-R3 and small hepatocyte-like progenitor cells, as reported by Gordon et al. We showed that the liver of adult humans also contains a highly proliferative population of hepatocytes, which possibly corresponds to SHs-R3. Research is now being undertaken to utilize this population of human hepatocytes to develop an artificial liver.

Animals↗

[Antihypertensive treatment in diabetics].

Based on many epidemiological studies, hypertensive diabetics have been regarded as high risk for cardiovascular disease. The sixth Joint National Committee guideline (JNC VI) recommended to start hypotensive agents even at high normal blood pressure, i.e. over 130/85 mmHg and lower their blood pressure to less than 130/85 mmHg. If patients are associated with renal dysfunction (proteinuria of more than 1 g/day), the target blood pressure would be less than 125/75 mmHg. These target blood pressures were supported Hypertension Optimal Treatment study and/or UKPDS. ACE inhibitors, Ca-antagonists or alpha-blockers were regarded as one of the first line drugs. Japanese Society of Hypertension has established the guideline for hypertension treatment, in which almost the same recommendation has been made for diabetics except one point, i.e., at high normal blood pressure, lifestyle modification might be the initial treatment followed by hypotensive agents if their blood pressure dose not go down to less than 130/85 mmHg during the next 3-6 months. Based on these guidelines, more vigorous antihypertensive treatment would be recommended in diabetics to reduce micro- and macrovascular disease.

Adrenergic beta-Antagonists↗

[Effect of fluticasone propionate at half dose of beclomethasone dipropionate divided twice daily and once daily in asthmatics inhaling beclomethasone dipropionate 800 micrograms daily or more].

We conducted a 12 weeks' single-arm prospective study comparing beclomethasone dipropionate (BDP), 1/2 doses of fluticasone propionate (FP) twice daily and the same dose of FP once daily in 47 asthmatics who had been inhaling BDP 800 mcg daily or more. Peak expiratory flow (PEF), FEV1, a symptom score and a frequency of beta 2 agonist were all significantly better in FP twice daily phase than BDP phase (329 vs. 306 L/min, 1.87 vs. 1.76 L, 3.6 vs. 6.0/week and 2.7 vs. 4.5 puffs/day, respectively). There was no significant difference in these endpoints between FP twice daily phase and FP once daily phase. FP twice daily produced better plumonary function and symptom relief than the double doses of BDP. Furthermore, FP twice daily could, at least in a short-term basis, safely be changed into the same doses of FP once daily.

Administration, Inhalation↗

[Transthoracic radical esophagectomy after extensive myocardial infarction].

We experienced the perioperative management of a 47 year-old patient for transthoracic esophagectomy after myocardial infarction. He was admitted to our hospital and diagnosed as having advanced esophageal cancer and he developed extensive myocardial infarction on the day of admission. Revascularization with PTCA was not successful, and circulatory support (IABP) was required for 7 days. Complete occlusion of the right coronary artery and extensive akynesis of the right ventricle occurred. Two months later, transthoracic esophagectomy was scheduled. The patient was monitored with pulmonary artery catheter during perioperative period. The postoperative course was uneventful and the patient was discharged 64 th day after the operation.

Catheterization, Swan-Ganz↗

[Multiple spinal arteriovenous fistulas occurring at conus medullaris and dura of the sacral region: a case report].

Multiple arteriovenous fistulas (AVFs) of the spine are rare. The authors reported a case of spinal AVFs occurring at two separate sites including the conus medullaris and the dura of the sacral region. A 31-year-old man had a two-week history of progressive low back pain, mild gait disturbance and dysuria. Examination revealed mild motor weakness of both legs, disturbance of superficial sensibility below the L4 dermatome on both sides and dysuria. Sensory disturbance was most obvious in the perianal region, although deep sensibility was not disturbed. Magnetic resonance images (MRIs) of the spine showed many serpentine flow void signals from the lower thoracic region to the sacral region, and spinal arteriovenous malformations were suspected. Selective spinal angiography revealed two AVFs at the separate sites including intradural perimedullary AVF at the conus medullaris and dural AVF at the sacral region. The dural AVF of the sacral region was fed by the left lateral sacral artery and drained through the dilated coronal venous plexus to Th11 level. Embolization with N-butylcyanoacrylate (NBCA) was performed using an endovascular procedure for both AVFs. Although recanalization of the dural AVF of the sacral region was confirmed by angiography two weeks later, it was treated successfully by the surgical approach.

Adult↗

[Perioperative management for radical esophagectomy in a patient with polycythemia vera].

We experienced perioperative management of a 75 year-old patient with polycythemia vera (PV) who underwent transthoracic esophagectomy. After treatment for 14 days of ranimustine and hydroxycarbamid, the preoperative hemoglobin, hematocrit values and platelet count were 17.9 g.dl-1, 58% and 54 x 10(4).mm-3 respectively. During the perioperative period, phlebotomy, elastic stockings, intermittent pneumatic compression, infusion of nafamostat, and early extubation (the day of operation) were performed to prevent deep venous thrombosis. The postoperative course was uneventful and the patient was discharged 34 days after the operation.

Aged↗

Influence of antigenic forms and adjuvants on protection against a lethal infection of Aujeszky's disease virus.

The influence of antigenic forms and adjuvant types on protection against a lethal infection of Aujeszky's disease virus (ADV) in mice was investigated. Antiviral IgG2a antibody response against particulate (inactivated ADV) and soluble antigen (ADV solubilized with deoxychorate-Na) in approximate order of extent was ISA70>QS-21>positively charged liposome>negatively charged liposome>weak negatively charged liposome>ISA25>lablabside F saponin>aluminum phosphate gel>non adjuvant. Particulate antigen induced higher IgG2a antibody production than soluble antigen. Particulate antigen combined with ISA70, ISA25 or positively charged liposome gave 100, 50 and 40% protection to mice, respectively. In contrast, soluble antigen plus ISA70 conferred 30% protection on mice. Immunogens using the other adjuvants gave </=20% protection to mice. These results indicate that a combination of particulate antigen and an appropriate adjuvant effectively induces the production of antiviral IgG2a antibody and provides protection against a lethal ADV infection in mice.

Adjuvants, Immunologic↗

Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells.

We examined the effects of four 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (pravastatin, simvastatin, fluvastatin, and cerivastatin) on the production and expression of inflammatory cytokines and on enzyme expression involving prostaglandin and superoxide production in cultured human umbilical vein endothelial cells (HUVEC). All HMG-CoA reductase inhibitors significantly reduced interleukin-1beta and -6 mRNA expression and their protein levels in the culture medium, and also inhibited cyclooxygenase-2 mRNA expression and their protein levels. And these drugs induced peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma mRNA expression and their protein levels in HUVEC and hepatocyte. Moreover, the mRNA levels of p22phox, a 22-kD subunit and the protein levels of p47phox, a 47-kD subunit of nicotine adenine dinucleotide phosphate (NADPH) oxidase, was decreased by treatment with either simvastatin, fluvastatin or cerivastatin, and this effect was reversed by mevalonate, geranylgeraniol, farnesol, and cholesterol. The changes induced by HMG-CoA reductase inhibitors might be due to regulation of cellular cholesterol content level, cellular cholesterol metabolic pathway, and cellular PPARalpha activity, which was related with inflammation. This unique anti-inflammatory effect in addition to its hypolipidemic action, may be beneficial in preventing the vascular complications that are induced by hyperlipidemia.

Anti-Inflammatory Agents↗

Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast.

A ubiquitin-like modifier, NEDD8, is covalently attached to cullin-family proteins, but its physiological role is poorly understood. Here we report that the NEDD8-modifying pathway is essential for cell viability and function of Pcu1 (cullin-1 orthologue) in fission yeast. Pcu1 assembled on SCF ubiquitin-ligase was completely modified by NEDD8. Pcu1(K713R) defective for NEDD8 conjugation lost the ability to complement lethality due to pcu1 deletion. Forced expression of Pcu1(K713R) or depletion of NEDD8 in cells resulted in impaired cell proliferation and marked stabilization of the cyclin-dependent kinase inhibitor Rum1, which is a substrate of the SCF complex. Based on these findings, we propose that covalent modification of cullin-1 by the NEDD8 system plays an essential role in the function of SCF in fission yeast.

Amino Acid Sequence↗

Destabilization of tumor necrosis factor-alpha mRNA by 5-alpha dihydrotestosterone in Jurkat cells.

The effect of a male steroid hormone, 5DHT, on the expression of TNF-alpha was examined using a human leukemia T cell line, Jurkat. Cells were treated with 5DHT in the presence or absence of PHA, and RNA was isolated followed by a reverse transcriptase - mediated PCR (RT-PCR) to measure the steady state levels of TNF-alpha mRNA. The treatment of cells with 5DHT resulted in a 50% of decrease in the level of TNF-alpha mRNA compared to that in untreated conditions (basal level). A similar level of reduction of the message by 5DHT was also observed in PHA-stimulated cells. The reduction of the steady state levels of TNF-alpha mRNA in Jurkat cells was a result of destabilization of the gene as demonstrated by actinomycin D treatment; a half-life of TNF-alpha message in 5DHT treated cells and non-treated cells was 1 hr and 2.5 hr, respectively, whereas that in 5DHT/PHA and PHA-treated cells was 3hr and 6hr, respectively.

DNA Primers↗

Missense variations of the gene responsible for Wolfram syndrome (WFS1/wolframin) in Japanese: possible contribution of the Arg456His mutation to type 1 diabetes as a nonautoimmune genetic basis.

Recently, a novel gene for a putative transmembrane protein (WFS1/wolframin) was found to be mutated in patients with Wolfram syndrome or DI-DM-OA-D (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) syndrome. It is suggested that the WFS1 protein is important in the survival of islet beta-cells. We studied the WFS1 gene in a Japanese population to assess its possible role in common type 1 diabetes. Mutation screening revealed four missense mutations; R456H, G576S, H611R, and I720V. By genetic association studies of 185 type 1 diabetes patients and 380 control subjects, we found that R456H was significantly increased in the type 1 diabetes group compared to the control group (P = 0.0005); H611R and I720V were also significantly increased with weaker significance. Furthermore, in patients with the R456H mutation, type 1 diabetes-resistant HLA-DRB1 alleles (DRB1*0406, 1501, and 1502) were significantly increased compared to mutation-negative patients while susceptible DRB1*0901 was significantly decreased. Frequencies of autoimmunity characteristics (ICA or GAD-Ab positiveness and combination of autoimmune thyroid disease) were decreased in the R456H-positive patients compared to the R456H-negative patients. These data suggest that the WFS1 gene may have a role in the development of common type 1 diabetes as a nonautoimmune genetic basis.

Adult↗

Age-specific effects of noradrenergic alpha-2 agonist clonidine on the development of amygdaloid kindling in developing rats.

The effects of clonidine on the development of amygdaloid kindling were studied in rats of various ages (14, 21, 28 and 70 postnatal days). Administration of clonidine (0.2, 0.5 mg/kg i.p.) caused a significant retardation of kindling development in the 28-day-old rats as well as in the adult rats, whereas, in the 14-day-old rats, the development of kindling was significantly facilitated by clonidine. No significant effect of clonidine was observed in the 21-day-old rats. These results indicate that in rats the effects of clonidine on the development of amygdaloid kindling vary during development.

Adrenergic alpha-Agonists↗

Serial diffusion-weighted imaging in MELAS.

Clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) resemble those of cerebral infarcts, but the pathogenesis of infarct-like lesions is not fully understood. To characterise these infarct-like lesions, we studied two patients with MELAS using diffusion-weighted (DWI) MRI before and after stroke-like episodes and measured the apparent diffusion coefficient (ADC) in the new infarct-like lesions. These gave high signal on DWI and had much higher ADC than normal-appearing regions. The ADC remained high even 30 days after a stroke-like episode then decreased in lesions, with or without abnormality as shown by conventional MRI. We speculate that early elevation of ADC in the acute or subacute phase reflects vasogenic rather than cytotoxic edema. The ADC of the lesions, which disappeared almost completely with clinical improvement, returned to normal levels, which may reflect tissue recovery without severe damage. To our knowledge, this is the first study of DWI in MELAS.

Adult↗

Antibacterial carbohydrate monoesters suppressing cell growth of Streptococcus mutans in the presence of sucrose.

The growth-inhibitory effect of 23 carbohydrate monoesters synthesized by lipases and proteases were assayed to obtain antibacterial agents that suppress the cell growth of Streptococcus mutans. Among the carbohydrate esters synthesized, galactose and fructose laurates showed the highest growth-inhibitory effect, while the other analogs of hexose laurates showed no antibacterial activity, indicating that configuration of the hydroxyl group in carbohydrate moiety markedly affects the antibacterial activity. The cell growth of S. mutans was suppressed by fructose laurates even in the presence of sucrose. Thus, enzymatic synthesis of carbohydrate esters with different core structures has great potential for developing antibacterial agents applicable to food additives.

Alcaligenes↗