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Biomedical subjects

Y Okuyama

Publications and source records attributed to Y Okuyama.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Varicella-zoster virus infection after hematopoietic stem cell transplantation].

Of 264 patients aged 15 years or more who underwent hematopoietic stem cell transplantation between 1989 and September 1998 at the Tokyo Metropolitan Komagome Hospital, 47 were infected by the varicella-zoster virus (VZV). In 2 patients, visceral disease preceded cutaneous dissemination. One of these patients exhibited gastrointestinal symptoms followed by disseminated skin rash 6 days later. In the other patient, epigastralgia developed and was followed by seizures secondary to meningitis; the appearance of a skin rash 5 days after these initial symptoms yielded the diagnosis. Early diagnosis and treatment of VZV infection are important, especially for patients who present with visceral symptoms suspected to be due to VZV.

Acyclovir↗
PubMed2000

[A patient with dysphagia treated successfully and discharged without nutritional support].

One of the main targets of medical care provided in our ward, which specializes in the cooperative practice of hospital- and home-doctors, is to maintain the quality of patients' lives after they are discharged from our hospital through home medical care by home-doctors. Intravenous hyperalimentation and tube-feeding at home are suitable solutions for some patients with dysphagia after cerebral infarction. However, the difficulties faced in their management are the burden on the families, which tends to be an obstacle for at-home-practice. We describe herein a case of severe dysphagia treated successfully through our rehabilitation program and discharged without nutritional supports. An 82-year-old man was admitted to our hospital suffering from pyrexia and dysbasia. The man, who lives with his wife and his son's family, was diagnosed with aspiration pneumonia and multiple cerebral infarctions. The test for swallowing reflex revealed an impaired first phase reflex and intravenous hyperalimentation was performed for his nutritional support. He was still suffering from dysphagia but had the desire to eat orally after his dysbasia and aspiration pneumonia were cured. A rehabilitation program was scheduled with the aims of 1) recovery of ingestion and 2) sufficient expectoration, with an ongoing teaching program for the management of intravenous hyperalimentation. After one month of rehabilitation (ice-massaging, muscle rehabilitation of the tongue and neck and expectoration training in a prone position and after gorging), his ability to swallow was gradually recovered. With the frequent confirmation of absence of aspiration, special forms of diets were served and upgraded from jelly, paste-like-food to soft-cooked steamed rice. The patient is now at home without any nutritional support. Nutritional management without intravenous hyperalimentation or tube-feeding is important or even essential for some families providing home-care for patients. The problem of aging requires us to reduce the burden that families (who may be also getting older) should carry. We try to support patients and families for better home-care through cooperation with society and home-doctors.

Aged↗
PubMed1999

A genetic polymorphism in the promoter region of DRD4 associated with expression and schizophrenia.

The human dopamine D4 receptor gene (DRD4) is an important candidate gene for schizophrenia. We identified a novel -521C>T polymorphism in the 5'-promoter region of DRD4. A transient expression method revealed that the T allele of this polymorphism reduces the transcriptional efficiency by 40% compared with the C allele. This polymorphism is of interest because of reported elevation of D4-like sites and DRD4 mRNA in the postmortem schizophrenic brain. The C allele frequency was significantly higher in 252 Japanese schizophrenics (0.48) than in 269 Japanese controls (0.41) (p = 0. 02) [odds ratio = 1.35 (95% confidence interval 1.05 - 1.72)]. Although the association is weak and should be considered tentative until other studies replicate it, this polymorphism provides a tool with the potential to examine whether DRD4 is related to susceptibility to and neuroleptic response in schizophrenia.

Adult↗
PubMed1999

A patient with rectal cancer associated with ulcerative colitis in whom endoscopic ultrasonography was useful for diagnosis.

Endoscopic ultrasonography (EUS) was helpful for the diagnosis of rectal cancer associated with ulcerative colitis. The patient was a 38-year-old Japanese man with a 19-year history of relapsing-remitting type ulcerative colitis involving the entire colon. Routine colonoscopy revealed multiple polypoid prominences in the upper portion of the rectum. EUS revealed a hypoechoic mass in the submucosa beneath and around the polypoid lesion on the most oral side. Signet ring cells were found in a biopsy specimen from this lesion. Subtotal colectomy was performed. A depressed lesion was observed around the prominence on the most oral side; histologically, this lesion was poorly differentiated mucinous and signet ring cell carcinoma extending into the subserosa. The polypoid lesion on the most anal side was well differentiated adenocarcinoma, which was limited to the mucosa. Our findings suggest that EUS is helpful for detecting invasive cancer associated with ulcerative colitis.

Adenocarcinoma↗
PubMed1999

Antibody response to OspC-I synthetic peptide derived from outer surface protein C of Borrelia burgdorferi in sera from Japanese forestry workers.

The prevalence of antibodies against Lyme disease spirochaetes in serum samples from 80 forestry workers at high occupational risk of Lyme disease was surveyed by enzyme-linked immunosorbent assay (ELISA) with the OspC-I synthetic peptide. The peptide is part of the outer surface protein C (OspC) amino acid sequence located in the region conserved among Borrelia burgdorferi sensu stricto or sensu lato. Positivity for antibodies against OspC-I was observed in 25 (313%) of the forestry workers. Of these positive cases, 12 (15.0%) and 19 (23.8%) were positive for immunoglobulin M (IgM) and IgG antibody, respectively. Among 62 workers who were negative for IgG antibody against B. garinii or B. japonica in our previous study, 9 (14.5%) and 4 (6.5%) were positive for IgM and IgG antibody, respectively, in OspC-I ELISA. These results demonstrate for the first time that Lyme disease in forestry workers can be revealed using OspC-I ELISA. We conclude that forestry workers who show positive results for antibodies against OspC-I have very likely been exposed to Lyme disease spirochaetes, and that those who show positivity for IgM antibody against OspC-I may be in the early stage of Lyme disease.

Adolescent↗
PubMed1999

Molecular remission in adult T cell leukemia after autologous CD34+ peripheral blood stem cell transplantation.

This report describes a patient with acute-type adult T cell leukemia/lymphoma (ATLL) successfully treated by autologous CD34+ peripheral blood stem cell transplantation after fractionated total body irradiation and high-dose cytarabine and cyclophosphamide. A newly established inverse polymerase chain reaction method was used to demonstrate the disappearance of ATLL clonal cells. The patient achieved a sustained molecular remission after transplantation, but died from opportunistic infection 4 months after transplantation. Thus, autologous CD34+ peripheral blood stem cell transplantation is promising for this type of malignancy. However, a prudent clinical attitude toward immunological fragility after transplantation is needed for better outcome.

Antigens, CD34↗
PubMed1998

The effects of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K+ channel expressed in a mammalian cell line, HEK293T cells.

The effects of potassium channel opening drugs and intracellular nucleotides on the ATP-sensitive K+ (KATP) channel composed of SUR2A and Kir6.2 in HEK293T cells were examined using the patch-clamp technique. The SUR2A/Kir6.2 channel was activated effectively by pinacidil, marginally by nicorandil but not by diazoxide. The pinacidil-activated channel currents were inhibited by glibenclamide with a Ki value of 160 nM. Upon formation of inside-out (I-O) patches, spontaneous openings of the channels appeared, which were inhibited by intracellular ATP (ATPi) equipotently in the presence and in the absence of intracellular Mg2+ (Mg2+i). The channel activity ran-down gradually in I-O patches. The run-down channels could be reactivated by ATPi only in the presence of Mg2+i. Uridine 5'-diphosphate (UDP) antagonized the ATPi-mediated inhibition of the channel activity before run-down. After run-down, UDP activated the channel without antagonizing ATPi-mediated channel inhibition. Thus, the SUR2A/Kir6.2 reproduced the major properties of the native cardiac KATP channel well in terms of nucleotide regulation and pharmacology, and therefore can be a useful tool with which to elucidate the molecular mechanisms characterizing the KATP channel.

ATP-Binding Cassette Transporters↗
PubMed1998

A comparative study of a new, fully automated procedure and the standard mononuclear cell program using the Cobe Spectra for peripheral blood stem cell collection.

Recently, a completely automated procedure, the AutoPBSC program for the COBE Spectra cell separator, has been developed for peripheral blood stem cell harvest (PBSCH). We compared the performance of the AutoPBSC program with the standard mononuclear cell (MNC) program in the same patients and in a donor. Peripheral blood stem cells (PBSC) were collected from 3 patients or a donor alternately using the MNC program and the AutoPBSC program in a course of PBSC mobilization. Equal blood volume was processed from each patient (200 ml/kg) and a donor (150 ml/kg). We used a harvest volume of 3 ml and a chase volume of 7 ml in all AutoPBSC procedures. The procedure duration was almost equivalent for both programs. The volume of products was significantly lower in the AutoPBSC program (71 +/- 13 ml) than in the MNC program (183 +/- 30 ml). MNC yields were fewer, and total nucleated cell (TNC) and MNC collection efficiency was less for the AutoPBSC program compared to the MNC program. The CD34+ cell collection efficiency was less for the AutoPBSC program (26.5 +/- 13.7%, compared with 77.7 +/- 60.6%; p > 0.05). The contamination of platelets and red cells was significantly less in the AutoPBSC program than in the MNC program. In conclusion, we consider that the collection efficiency in the new program should be improved by modification of parameters because there exist great advantages to automated procedures.

Adult↗
PubMed1998

Paraoxonase has a major role in the hydrolysis of prulifloxacin (NM441), a prodrug of a new antibacterial agent.

NM441 is a prodrug of the new quinolone carboxylic acid antibacterial agent NM394. A rat serum enzyme (NM441-hydrolase) that catalyzes the hydrolysis of NM441 to NM394 was purified by ultracentrifugation, heparin-Sepharose column chromatography, and HPLC with a Mono Q anion exchange column. The enzyme showed a single protein band after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its molecular mass was estimated as 46 kDa. The amino-terminal sequence and two internal amino acid sequences of the NM441-hydrolase resemble those of mouse, rabbit, and human serum paraoxonases. Moreover, its enzymatic characteristics (optimum pH, calcium requirement, and molecular mass) were similar to those of the paraoxonases. These findings identify the NM441-hydrolase as rat serum paraoxonase. To determine whether the paraoxonase catalyzes the hydrolysis of NM441 to NM394 in human serum, we investigated whether the paraoxonase and NM441-hydrolase activities were correlated. There was a positive correlation (r = 0.653, p < 0.005) found in the sera of 67 healthy volunteers, indicating that paraoxonase is responsible for the conversion of NM441 to NM394 in humans. Human paraoxonase shows polymorphism. There was a 9-fold variation in paraoxonase activity but only a 2-fold variation in NM441-hydrolase activity. These findings show that paraoxonase polymorphism does not cause marked interindividual variation in NM441-hydrolase activity and is substrate dependent.

Amino Acid Sequence↗
PubMed1997

Role of protein kinase C-alpha in activation of ecto-5'-nucleotidase in the preconditioned canine myocardium.

We have reported that activation of protein kinase C (PKC) increases ecto-5'-nucleotidase activity, which may contribute to the infarct size-limiting effect of ischemic preconditioning. Since we have reported that Ca(2+)- and phospholipid-sensitive PKC is activated due to ischemic preconditioning, we further tested 1) whether PKC-alpha or -beta is translocated to the cellular membrane of the preconditioned canine myocardium, and 2) whether activation of PKC contributes to the increase in ecto-5'-nucleotidase activity via phosphorylation-dependent mechanisms. Four times of 5 minutes coronary occlusion separated by 5 minutes of reperfusion (ischemic preconditioning) translocated PKC-alpha to the cellular membrane in the canine hearts, although PKC-beta, -delta, -epsilon, and -zeta were not translocated. The activity of Ca(2+)- and phospholipid-sensitive PKC increased, which was attenuated by the removal of either Ca2+ or phosphatidylserine. Ecto-5'-nucleotidase was also activated in the preconditioned myocardium compared with control. Inhibition of PKC due to GF109203X blunted the activation of myocardial ecto-5'-nucleotidase. Okadaic acid (an inhibitor of phosphatase) enhanced the increases in ecto-5'-nucleotidase activity due to preconditioning, and this enhancement was blunted by GF109203X. We conclude that ischemic preconditioning activates PKC-alpha, and thus ecto-5'-nucleotidase.

Adenosine Triphosphatases↗
PubMed1997

Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line.

Butyrate is a well known colonic luminal short chain fatty acid, which arrests cell growth and induces differentiation in various cell types. We examined the effect of butyrate on the expression of WAF1/Cip1, a potent inhibitor of cyclin-dependent kinases, and its relation to growth arrest in a p53-mutated human colon cancer cell line WiDr. Five millimolar butyrate completely inhibited the growth of WiDr and caused G1-phase arrest. WAF1/Cip1 mRNA was rapidly induced within 3 h by treatment with 5.0 mM butyrate, and drastic WAF1/Cip1 protein induction was detected. Using several mutant WAF1/Cip1 promoter fragments, we found that the butyrate-responsive elements are two Sp1 sites at -82 and -69 relative to the transcription start site. We also found that a TATA element at -46 and two overlapping consensus Sp1 sites at -60 and -55 are essential for the basal promoter activity of WAF1/Cip1. These findings suggest that butyrate arrests the growth of WiDr by activating the WAF1/Cip1 promoter through specific Sp1 sites in a p53-independent fashion.

Base Sequence↗
PubMed1997

Retinoblastoma binding factor 1 site in the core promoter region of the human RB gene is activated by hGABP/E4TF1.

We previously reported two oncogenic point mutations present in the RB (retinoblastoma) gene promoter region, found at consensus Sp1 and ATF sites, respectively, and in two separate hereditary RB families. However, Sp1 protein was shown not to bind to the Sp1 site; this indicated that the Sp1 consensus site mutation was blocking the action of an alternative transcription factor, which we called RBF-1 (retinoblastoma binding factor 1). Subsequent purification of RBF-1 revealed it to be hGABP/E4TF1, a transactivator from the adenovirus early-region 4 promoter. In this study, we directly examined the effects of hGABP/E4TF1 on transactivation of the RB gene promoter through the RBF-1 site. As expected, hGABP/E4TF1 enhanced the core RB promoter activity, whereas it did not stimulate a mutant RBF-1 site. We therefore conclude that the most essential transcription factor in the human RB gene is likely to be hGABP/E4TF1.

Animals↗
PubMed1997

Vesnarinone inhibits adenosine uptake in endothelial cells, smooth muscle cells and myocytes, and mediates cytoprotection.

Vesnarinone is a novel synthetic inotropic agent. Recently, it has been reported that vesnarinone inhibits adenosine uptake in the B-lymphocytoid cell line. Since extracellular adenosine is cardioprotective, we examined whether vesnarinone inhibits adenosine uptake in cells constituting the cardiovascular system. 1 microCi of -3H-adenosine was added to cells of the myocyte cell line (C2C12), human coronary smooth muscle cell line (HCASMC), human and bovine coronary endothelial cell lines (HCAEC and BCAEC), bovine arterial endothelial cell line (BAEC), and human umbilical venous endothelial cell line (HUVEC). After 10 s-5 min, cells were separated from free [3H]adenosine, and the radioactivity was measured. When 0.1-100 microM of vesnarinone was added to each cell line, the uptake of adenosine was inhibited dose-dependently {% inhibition of -3H-adenosine uptake at 10 and 30 microM of vesnarinone: 14 and 33% (C2C12), 47 and 72% (HCASMC), 37 and 58% (HCAEC), 42 and 68% (BCAEC), 19 and 68% (BAEC), 29 and 59% (HUVEC)}. The cellular viability of HCAEC exposed to 60 min of hypoxia and 60 min of reoxygenation increased from 34+/-5 to 67+/-6% (Trypan blue exclusion test) and 23+/-5 to 78+/-6% (LDH release), which was completely blunted by 8-sulfophenyltheophylline, an adenosine receptor antagonist, and was partially blunted by alpha,beta-methyleneadenosine 5'-diphosphate, an inhibitor of ecto-5'-nucleotidase. We also found that vesnarinone is cytoprotective against hypoxia and reoxygenation in C2C12 and HCASMC. We conclude that vesnarinone inhibits the uptake of adenosine in cardiovascular cells, which contributes to cytoprotection.

Adenosine↗
PubMed1997

Amyotrophic lateral sclerosis with anti-acetylcholine receptor antibody.

We report a case of amyotrophic lateral sclerosis (ALS) with anti-acetylcholine receptor (AChR) antibody in a 73-year-old female patient. She showed the typical course of ALS. She had no clinical findings of myasthenia gravis and had never undergone neurotoxin therapy using snake venom. Anti-AChR antibody was positive with a titer of 0.50 nmol/l on admission. We traced the titers during the progression of ALS; the titer was positive when muscle weakness worsened, and it became negative when the general condition became stable. We suppose that the occurrence of anti-AChR antibody may be partially relevant with abnormalities at the neuromuscular junction during the progression of ALS.

Aged↗
PubMed1997

Pharmacokinetics of prulifloxacin. 1st communication: absorption, distribution and excretion in rats, dogs and monkeys after a single administration.

The pharmacokinetics of prulifloxacin ((+/-)-6-fluoro-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-car boxylic acid. CAS 123447-62-1, NM441), a quinolone antibacterial prodrug, was investigated after i.v. (14C-NM394, CAS 112984-60-8) or oral (14C-NM441) administration to rats, dogs and monkeys. 1. 14C-NM441 was absorbed mainly from the upper small intestine and then metabolized to NM394 partly in the intestinal membrane but mainly in the portal blood and liver. Thus NM441 was not detected in the systemic circulation. 2. After i.v. administration of 14C-NM394 (5 mg/kg), the plasma concentration of radioactivity decreased biexponentially, and the elimination half-life in rats, dogs and monkeys was 4.2, 5.8 and 7.0 h, respectively. After oral administration of 14C-NM441 (20 mg/kg), the plasma concentration of radioactivity reached a maximum at 0.7-3.3 h, and thereafter decreased as observed after i.v. administration of 14C-NM394. An effect of food on the absorption of NM441 was found. No clear sex-related differences were observed in the plasma concentration profiles of rats. 3. The concentration of radioactivity in most tissues of rats reached a maximum within 1 h after oral administration of 14C-NM441 and thereafter decreased along with the plasma concentration. At 0.5 h, the radioactivity concentrations were highest in the liver and kidney, moderately high in the spleen, pancreas, lung and mandibular gland and extremely low in the cerebrum and cerebellum. 4. The radioactivity in the excreta collected over a 96-h period was 96-98% of the oral dose (urine, 22-32%; feces, 64-75%) in rats, dogs and monkeys, 35% of the radioactivity administered was excreted in the bile of rats during a 48-h period after oral administration, and only a small portion of the biliary radioactivity was reabsorbed. 5. The proportion of 14C-NM394 that bound to serum proteins in vitro in rats, dogs, monkeys and humans was 41-59% in a concentration range of 0.1-10 micrograms/ml.

Administration, Oral↗
PubMed1997

Pharmacokinetics of prulifloxacin. 2nd communication: pharmacokinetics and effect on hepatic drug-metabolizing enzyme activities after repeated administration and transfer into fetus and milk after a single administration in rats.

Prulifloxacin ((+/-)-6-fluoro-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-car boxylic acid, CAS 123447-62-1, NM441) is a prodrug of a new quinolone carboxylic acid antibacterial agent, NM394 (CAS 112984-60-8). The pharmacokinetics of radioactivity after repeated oral administration of 14C-NM441, the effects of NM441 on hepatic drug-metabolizing enzyme activities after repeated oral administration of NM441, and the transfer of radioactivity into the fetus and milk after a single oral administration of 14C-NM441 were investigated in rats. 1. The plasma concentration of radioactivity 6 h after each oral dose of 14C-NM441 (20 mg/kg) to male rats once a day for 21 days was almost constant. There was no marked difference in the plasma concentration-time curves for radioactivity after the single, 7th, 14th or 21st administration. The averaged cumulative urinary and fecal excretion of radioactivity during repeated administration did not differ from the corresponding values after a single administration. The concentration of radioactivity 8 h after each dose had reached a plateau in most tissues by the 14th administration. After the 21st dose, the radioactivity concentration in most tissues decreased along with the plasma concentration, whereas a slower elimination was observed in the skin and bone. 2. Repeated oral administration of 20 or 200 mg/kg of NM441 to male rats did not affect hepatic drug-metabolizing enzyme activities. 3. In pregnant rats, the maximum concentration of radioactivity in the fetus was lower than that in the maternal plasma. Furthermore, the total amount of radioactivity in the fetus was only 0.01% of the dose at 0.5 h. 4. In lactating rats, the concentration of radioactivity in the milk was substantially higher than in the plasma. 5. In conclusion, repeated administration of NM441 did not alter its pharmacokinetics, and no evidence was found that it accumulated in the body. Furthermore, there was little placental transfer. These characteristics add to the suitability of NM441 as an effective prodrug of NM394.

Animals↗