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Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 505 records · Page 28Linked to original sources
PubMed2000

Study on eight patients with malignant tumors after renal transplantation.

The high incidence of cancer after renal transplantation is now a critical concern since the graft survival rate has been improved extensively. We experienced 9 malignancies in 8 patients out of 168 recipients up to December 31, 1999 in our hospital, consisting of a case of gastric plasmacytoma and cases of cancer in the liver (2), thyroid (2), prostate (1), breast (1), sigmoid colon (1) and gall-bladder (1). Two patients were diagnosed as having tumors within 3 months after transplantation, suggesting post-transplant acceleration of growth of the latent tumors. The other patients were diagnosed at an average of 128 months, ranging from 84 to 263 months after transplant. Two patients died of gastro-intestinal bleeding and acute heart failure. Four patients died directly of progressive neoplasm within 3 months after diagnosis. These results suggest that the course of malignancies developing in post-transplant recipients is more aggressive than that expected in non-transplant patients, and it is very important to intensively follow long-term surviving cases to detect the malignant tumors as early as possible.

Adolescent↗
PubMed2000

Rapid detection of M1S1 mutations by the protein truncation test.

PURPOSE: To determine a method of rapid detection of M1S1 gene mutations in patients with gelatinous droplike corneal dystrophy. METHODS: Forty-one patients from 35 families with gelatinous drop-like corneal dystrophy were studied. The entire coding region of the M1S1 gene was screened using the protein truncation test (PYT), with a polymerase chain reaction fragment amplified from genomic DNA serving as a template of in vitro translation. RESULTS: Homozygous or compound heterozygous mutations were detected in all patients by a single reaction of the PTT. This result matched those obtained using the polymerase chain reaction-restriction fragment length polymorphism and direct sequence analyses. The Q118X mutation was present in 63 of the 70 alleles, accounting for 90% of the disease-associated chromosomes in Japanese patients. CONCLUSIONS: The PTT is useful for detecting mutations in the M1S1 gene. This technique showed that the Q118X mutation is a founder mutation in Japanese patients with gelatinous droplike corneal dystrophy, and it reflects the linkage disequilibrium reported previously.

Antigens, Neoplasm↗
PubMed2000

Grafting of stomach tissue into the duodenum in F344 rats results in chimeric crypts and tumor development.

Gastric tissue was transplanted from the fundic and pyloric mucosa of 8-week old female F344 rats into the duodenum of males. Autopsy, 12 months after the operation, revealed grafts associated with persistent stones in the duodenum and/or calcification in the tissue. Pepsinogen positive chimeric glands with goblet cells also appeared in the grafts which gave rise to tumors in 18 out of 45 animals (40%). In conclusion, stomach grafts re-differentiate into intestine with goblet cells in the duodenum and this process predisposes to tumor development.

Animals↗
PubMed2000

[Prevalence of problem drinkers among dental students].

In 1997 and 1998 we statistically studied fourth-year dental students for their drinking and smoking habits. The subjects numbered 103 (65 males, 38 females) in 1997 and 127 (79 males, 48 females) in 1998, totaling 230. The questionnaire included the Kurihama Alcoholism Screening Test (KAST), the Adolescent Alcohol Involvement Scale (AAIS), and the Fagerström Tolerance Questionnaire (FTQ). Problem drinkers as defined by KAST, scoring at least 2 points, represented 12.6% of the total in 1997 and 13.4% in 1998, exceeding 10% in both years. Alcoholic misusers, with at least 42 point on the AAIS, stood at 19.4% in 1997 and 17.3% in 1998. The incidence of students assessed as having 6 points on the Quantity-Frequency Scale (QF Scale) stood at 18.4% in 1997 and 10.2% in 1998. Compared between two sexes, KAST detected no significant difference between the two groups: 13.9% for males and 11.6% for females. Alcoholic abusers on the AAIS, however, were estimated at 22.9% in males and 9.3% in females, the ratio for males being more than twice as high as that for females. It was also found that 47.9% of the male students and 33.7% of their female counterparts drank every weekend and that 31.3% of the males and 5.8% of the females kept drinking until they were drunk. Female students thus appeared to drink more frequently, though they consumed smaller amounts of alcohol at a time. The smoking rate was lower than the average in the Japanese for both groups; nicotine dependence was also lower in dental students. It was demonstrated that dental students drink more alcohol more frequently, with a higher incidence of problem drinkers.

Alcohol Drinking↗
PubMed2000

State dependent response of the locus caeruleus neurons to bladder distention.

PURPOSE: The precise mechanism by which normal persons wake upon urinary sensation is unclear. The locus caeruleus in the pons is suggested to be involved in the activating systems for arousal. We evaluated the effects of bladder distention on the neural activity in the l. caeruleus under different states of anesthesia. MATERIALS AND METHODS: Experiments were performed on 20 male Sprague-Dawley rats. The spontaneous discharge rate of single neurons in and around the l. caeruleus was recorded with the rat under urethane anesthesia administered intraperitoneally, while the electroencephalogram was monitored simultaneously. The changes of the discharge rate of the neurons were observed during saline infusion into the bladder or during tail pinch stimulation. After recording the location of the neurons was confirmed histologically. RESULTS: Of 42 l. coeruleus neurons whose response was examined during deep anesthesia 31 showed an excitatory response to bladder distention, followed by a change in electroencephalogram pattern to a faster and smaller rate, while the remaining 11 showed no response. Of 28 l. coeruleus neurons examined during light anesthesia only 1 neuron was excited and the remaining 27 showed no response. Virtually all of the l. coeruleus neurons unresponsive to bladder distention were responsive to tail pinch stimulation. Of the nonnoradrenergic neurons ventromedial to the l. coeruleus 4 of 7 during deep anesthesia and 5 of 8 during light anesthesia showed an excitatory response to distention. CONCLUSIONS: The excitatory response of the l. coeruleus neurons to bladder distention was strongly affected by the state of anesthesia. The response was observed only during deep anesthesia and was accompanied by lightening of the anesthesia. L. coeruleus may be involved in arousal which is mediated by bladder distention.

Anesthesia↗
PubMed2000

Clustering on the forward surfaces of migrating neutrophils of a novel GPI-anchored protein that may regulate neutrophil adherence and migration.

We previously reported a novel glycosylphosphatidylinositol (GPI)-anchored glycoprotein (tentatively designated GPI-80) on human leukocytes that may be involved in the regulation of neutrophil adherence and migration. In this study, we examined by immuno- and scanning electron microscopy, the distribution of GPI-80 on neutrophil surfaces. GPI-80 was diffusely distributed on the surface of resting neutrophils and on the peripheral areas of adherent cells after stimulation with N-formyl-methionyl-leucyl-phenylalanine. After longer stimulation (60 min), GPI-80 decreased in number and was again diffusely distributed on the surfaces of round neutrophils. Few GPI-80 were detected on the ventral surfaces of adherent neutrophils. Clusters of GPI-80 were detected on the forward surfaces of neutrophils transmigrating through pores of nitrocellulose membranes. These results may give a morphological background of possible role of GPI-80 for neutrophil extravasation.

Amidohydrolases↗
PubMed2000

[Evaluation of hepatic resection following hepatic arterial infusion chemotherapy for colorectal liver metastases].

We evaluated the significance of hepatectomy following hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. The prognosis of 4 cases with initially resectable tumors was discouraging, indicating no benefit of preoperative HAI for resectable tumors. The 2- and 3-year survival of patients who underwent hepatectomy after downstaging by HAI of originally unresectable metastases were 100% and 67%, respectively, suggesting that hepatectomy combined with HAI is a promising modality for those patients. However, it seems that the control of extrahepatic disease and decision making for the timing for surgical therapy are issues requiring improvement.

Aged↗
PubMed2000

Three elderly patients with lower esophageal cancer successfully treated by transhiatal esophagectomy assisted by mediastinoscopy.

Mediastinoscopy-assisted transhiatal esophagectomy recently has been applied in patients with intrathoracic esophageal cancer. Elderly patients with esophageal cancer experience several types of complications and often cannot undergo standard transthoracic esophagectomy. In this study, three elderly patients with preoperative complications underwent mediastinoscopy-assisted transhiatal esophagectomy for esophageal cancer located in the lower part of the esophagus. Patient 1 was an 80-year-old man with alcoholic liver cirrhosis. Patient 2 was a 78-year-old man with bronchial asthma. Patient 3 was an 81-year-old-man with diabetes mellitus and an atherosclerotic obstruction of the lower extremities. In these patients, mediastinoscopy-assisted transhiatal esophagectomy concomitant with reconstruction by means of a gastric tube was performed. Lymph node dissections of the middle and lower mediastinum and of the abdomen, including the regions surrounding the left gastric and celiac arteries, were performed. Postoperative complications developed only in patient 1; minor leakage of the esophagogastrostomy and high bilirubinemia were observed. Metastasis was detected in the lymph nodes surrounding the celiac artery in patient 1 and surrounding the left gastric artery in patients 2 and 3. Patient 2 died of pneumonia 18 months later, but the other patients have been well, without recurrence of the cancer after surgery. In conclusion, mediastinoscopy-assisted transhiatal esophagectomy has some benefits for elderly esophageal cancer patients who experience preoperative complications.

Adenocarcinoma↗
PubMed2000

[Effects of endocrine disruptors on ecology--reports from the Gordon Reserch Conference of Environmental Endrocrine Disruptors].

This article described impression and overview of the topics presented at the Gordon Research Conference of Environmental Endocrine Disruptors held at Plymouth State College from June 18-23, 2000. More investigations using invertebrate species are needed in order to elucidate effects of hormonally active agents on wildlife populations. Molecular biological research is also important to understand molecular mechanism of hormonally active agents on animals including humans.

Animals↗
PubMed2000

[Effects of tandospirone citrate on frozen gait in patients with early stage of progressive supranuclear palsy, investigated by walk-induced activation single photon emission computed tomography method].

We reported a 64-year-old woman in the early stage of progressive supranuclear palsy presenting as pure akinesia syndrome who showed marked improvement with tandospirone citrate. She revealed bradykinesia, severe frozen gait and disturbance of postural reflex without rigidity or tremor. Treatment with L-dopa and L-threo DOPS was not effective, but tandospirone citrate at a daily dosage of 30 mg significantly lessened the severity of frozen gait. Activation single photon emission computed tomography study with 99mTc-ethyl cysteinate dimer during gait revealed a significant increase in brain activity in the right cingulate cortex after tandospirone citrate treatment. The effect lasted ten months until neck rigidity and ventricular supranuclear palsy were evident.

Brain↗
PubMed2000

In vivo imaging of increased oxidative stress in the liver by electron spin resonance-computed tomography.

The aim of this study was to investigate whether increased hepatic oxidative stress could be visualised in living animals before the onset of obvious liver injury. Acute hepatic injury was induced in mice by priming with heat-killed Corynebacterium parvum followed by injection of a low dose of lipopolysaccharide (LPS). Low frequency band electron spin resonance-computed tomography (ESR-CT) with 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) was used to visualize hepatic oxidative stress. Biochemical and histological investigations performed 3 h after injection of LPS revealed no obvious injury to the liver. Conversely, significant hepatic oxidative stress could be detected at this time. Nitroxides such as carbamoyl-PROXYL are rapidly reduced to the corresponding hydroxylamine in vivo. resulting in the disappearance of their ESR signals. The kinetic clearance of carbamoyl-PROXYL after intravenous administration was delayed significantly in mice that had received LPS, due to impairment of the reduction system by hepatic oxidative stress. ESR-CT of the murine abdomen revealed a high intensity area of carbamoyl-PROXYL which consisted mainly of the liver and enlarged spleen. Time-course observations with ESR-CT using carbamoyl-PROXYL showed that the high intensity area in the liver disappeared rapidly due to reduction of carbamoyl-PROXYL. Three hours after LPS injection into the same mouse, ESR-CT images were obtained again by intravenous injection of carbamoyl-PROXYL. The ESR-CT images of the mouse with hepatic oxidative stress clearly showed that the high intensity area of carbamoyl-PROXYL in the liver persisted for a long period of time. This study is the first report to describe the use of in vivo ESR-CT for visualizing the state of increased oxidative stress in the liver before the onset of obvious hepatic injury.

Animals↗
PubMed1999

Chimeric virus-like particle formation of adeno-associated virus.

Adeno-associated virus (AAV) capsids are composed of three proteins, VP1, VP2, and VP3. These capsid proteins have a common amino acid sequence, being expressed from different initiation codons on the same open reading frame. Although VP1 is necessary for viral infection, it is not essential for capsid formation. The other capsid proteins, VP2 and VP3, are sufficient for capsid formation, but their functions are poorly understood. To investigate the role(s) of the capsid proteins in capsid formation, we used a baculovirus protein expression system to produce virus-like particles (VLPs). We found that varying the ratios of VP2 and VP3 did not affect VLP formation. Further, their physical properties were equivalent to those of empty wild-type particles. The function of VP3 was studied further by fusing a peptide tag, FLAG, to its N-terminus. This chimeric viral protein, in combination with VP2, could assemble into VLPs, indicating that the chimerism of VP3 did not affect VLP formation. Although the monomeric native form of the FLAG-VP3 chimera could react with anti-FLAG antibody, VLP containing the chimeric VP3 could not, suggesting that the N-terminal region of VP3 is located inside the VLP. These observations indicate that it may be possible to utilize AAV VLP as vectors of a broad range of drugs since fusion of the VP3 N-terminus with defined molecules could impose distinct physical properties onto the internal environment of the VLP.

Animals↗
PubMed1999

Synergistic transcriptional activation by hGABP and select members of the activation transcription factor/cAMP response element-binding protein family.

The Ets-related DNA-binding protein human GA-binding protein (hGABP) alpha interacts with the four ankyrin-type repeats of hGABPbeta to form an hGABP tetrameric complex that stimulates transcription through the adenovirus early 4 (E4) promoter. Using co-transfection assays, this study demonstrated that the hGABP complex mediated efficient activation of transcription from E4 promoter synergistically with activating transcription factor (ATF) 1 or cAMP response element-binding protein (CREB), but not ATF2/CRE-BP1. This synergy also partially occurred when hGABPalpha was used alone in place of the combination of hGABPalpha and hGABPbeta. hGABP activated an artificial promoter containing only ATF/CREB-binding sites under coexistence of ATF1 or CREB. Consistent with these results, physical interactions of hGABPalpha with ATF1 or CREB were observed in vitro. Functional domain analyses of the physical interactions revealed that the amino-terminal region of hGABPalpha bound to the DNA-binding domain of ATF1, which resulted in the formation of ternary complexes composed of ATF1, hGABPalpha, and hGABPbeta. In contrast to hGABPalpha, hGABPbeta did not significantly interact with ATF1 and CREB. Taken together, these results indicate that hGABP functionally interacts with selective members of the ATF/CREB family, and also suggest that synergy results from multiple interactions which mediate stabilization of large complexes within the regulatory elements of the promoter region, including DNA-binding and non-DNA-binding factors.

Activating Transcription Factor 1↗
PubMed1999

Molecular analysis of the Deinococcus radiodurans recA locus and identification of a mutation site in a DNA repair-deficient mutant, rec30.

Deinococcus radiodurans strain rec30, which is a DNA damage repair-deficient mutant, has been estimated to be defective in the deinococcal recA gene. To identify the mutation site of strain rec30 and obtain information about the region flanking the gene, a 4.4-kb fragment carrying the wild-type recA gene was sequenced. It was revealed that the recA locus forms a polycistronic operon with the preceding cistrons (orf105a and orf105b). Predicted amino acid sequences of orf105a and orf105b showed substantial similarity to the competence-damage inducible protein (cinA gene product) from Streptococcus pneumoniae and the 2'-5' RNA ligase from Escherichia coli, respectively. By analyzing polymerase chain reaction (PCR) fragments derived from the genomic DNA of strain rec30, the mutation site in the strain was identified as a single G:C to A:T transition which causes an amino acid substitution at position 224 (Gly to Ser) of the deinococcal RecA protein. Furthermore, we succeeded in expressing both the wild-type and mutant recA genes of D. radiodurans in E. coli without any obvious toxicity or death. The gamma-ray resistance of an E. coli recA1 strain was fully restored by the expression of the wild-type recA gene of D. radiodurans that was cloned in an E. coli vector plasmid. This result is consistent with evidence that RecA proteins from many bacterial species can functionally complement E. coli recA mutants. In contrast with the wild-type gene, the mutant recA gene derived from strain rec30 did not complement E. coli recA1, suggesting that the mutant RecA protein lacks functional activity for recombinational repair.

Amino Acid Sequence↗
PubMed1999

Increased cytosolic Ca(2+) concentration in endothelial cells by calmodulin antagonists.

Many functions of endothelial cells are Ca(2+)/calmodulin dependent, whereas the role of calmodulin in the regulation of cytosolic Ca(2+) ([Ca(2+)](i)) remains largely unexplained. In the present study, effects of various calmodulin antagonists on [Ca(2+)](i) were investigated in cultured aortic endothelial cells loaded with the Ca(2+)-sensitive dye fura-2/AM, and were compared with those of calmodulin-dependent protein kinase II (CaM kinase II) inhibitors. The calmodulin antagonists W-7, calmidazolium and fendiline provoked dose-dependent increases in [Ca(2+)](i). However, the CaM kinase II inhibitors KN-93 and lavendustin C had no effect on [Ca(2+)](i). In the absence of extracellular Ca(2+), pretreatment of cells with bradykinin (BK) and thapsigargin completely prevented W-7-stimulated increase in [Ca(2+)](i). Alternatively, pretreatment with W-7 also completely blocked BK- and thapsigargin-stimulated increases in [Ca(2+)](i). The time course of the Ca(2+)-response in W-7 treated cells was identical to that in thapsigargin-treated cells, but not that in BK-stimulated cells, suggesting that calmodulin antagonists could share a common signaling pathway with thapsigargin to increase [Ca(2+)](i) in endothelial cells. These findings indicate that calmodulin is involved in the regulation of [Ca(2+)](i), and may play an important role in the uptake of Ca(2+) to intracellular stores.

Animals↗
PubMed1999

Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation.

Synthesis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4-phosphate 5-kinase [PI(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPgammaS-dependent activator of PI(4)P5Kalpha is the small G protein ADP-ribosylation factor (ARF) and that the activation strictly requires phosphatidic acid, the product of phospholipase D (PLD). In vivo, ARF6, but not ARF1 or ARF5, spatially coincides with PI(4)P5Kalpha. This colocalization occurs in ruffling membranes formed upon AIF4 and EGF stimulation and is blocked by dominant-negative ARF6. PLD2 similarly translocates to the ruffles, as does the PH domain of phospholipase Cdelta1, indicating locally elevated PI(4,5)P2. Thus, PI(4)P5Kalpha is a downstream effector of ARF6 and when ARF6 is activated by agonist stimulation, it triggers recruitment of a diverse but interactive set of signaling molecules into sites of active cytoskeletal and membrane rearrangement.

ADP-Ribosylation Factor 1↗