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Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 1,027 records · Page 57Linked to original sources

Ovulation defect and its restoration by bone marrow transplantation in osteopetrotic mutant mice of Mitf(mi)/Mitf(mi) genotype.

Mutation within the Mitf gene causes, in microphthalmic Mitf(mi)/Mitf(mi) (mi/mi) mice, multiple defects, including white coat color and functional defects in macrophages and osteoclasts. Our previous mating experiments have demonstrated that the mi mutation reduces the numbers of newborns and induces uterine inversion at delivery. The present study was designed to determine the causes of these pregnancy defects. The histology and number of F4/80-positive macrophages were not different between the ovaries of 23-day-old mi/mi and +/+ mice given eCG 48 h earlier. When ovulation was induced in these mice by hCG, the number of ovulated ova was significantly smaller in mi/mi mice than in wild-type (+/+) mice (p < 0.05). When bone marrow cells from +/+ mice were transplanted i.p. into 42 mi/mi female newborns, successful transplantation was observed in 16 of them at 20 days after birth. In one of these, the upper incisors had erupted. The mean number of tubal ova in mi/mi mice significantly increased after transplantation (p < 0.05) and was almost equal to that of +/+ mice. No uterine inversion occurred at 6 deliveries in 5 mi/mi females after bone marrow transplantation, while it occurred at 4 of 5 deliveries in mi/mi females during the same observation period (p < 0.05). These results indicate that bone marrow-derived cells, defective in mi/mi mice, are necessary for normal ovulation and delivery; the findings are consistent with the notion that macrophages play major roles in ovulation.

Animals↗

Epidermization in the esophageal mucosa: unusual epithelial changes clearly detected by Lugol's staining.

A 58-year-old Japanese man with superficial esophageal cancer accompanied by unusual epithelial changes, including esophageal mucosal epidermization, is reported. Staining with Lugol's iodine clearly showed irregular unstained lesions, which could not be seen clearly macroscopically, in the resected specimen. Histologic examination of the irregular unstained areas showed definite granular and horny layers regarded as epidermization, acanthosis with slight nuclear enlargement, and epithelial atrophy. The immunohistochemical staining patterns of keratins in the epidermized and atrophic lesions were similar to those in the epidermis, and the keratin staining patterns of the acanthotic lesion were similar to those of the oral epithelium.

Coloring Agents↗

Reversible change of bladder hypertrophy due to benign prostatic hyperplasia after surgical relief of obstruction.

PURPOSE: Ultrasound estimated bladder weight was compared before and after surgery for benign prostatic hyperplasia (BPH) to reveal a possible reversible change in bladder hypertrophy. MATERIALS AND METHODS: Ultrasound estimated bladder weight was measured before and after subcapsular (17) or transurethral (16) prostatectomy in 33 male patients with BPH. Sequential changes in the American Urological Association symptom score and urinary flow rate were also examined. RESULTS: Along with a significant improvement in the American Urological Association symptom scores and maximum flow rate, ultrasound estimated bladder weight decreased from 52.9 +/- 22.6 to 31.6 +/- 15.8 gm. in 12 weeks after treatment. In all but 4 patients (29 of 33, or 87.9%) ultrasound estimated bladder weight decreased to less than 35.0 gm. in 12 weeks after treatment. Interestingly, in all patients with an initial ultrasound estimated bladder weight of greater than 80 gm. the bladder weight still remained at an abnormally high level 12 weeks after treatment. CONCLUSIONS: Bladder hypertrophy was completely reversible after the surgical treatment of the obstruction in the majority of patients with BPH. The measurement of ultrasound estimated bladder weight was of value in monitoring therapeutic effects in BPH patients. An extraordinarily high ultrasound estimated bladder weight of 80 gm. or more might suggest degenerative and irreversible pathological changes in the bladder detrusor.

Aged↗

Recurrent brief depression in Prader-Willi syndrome: a case report.

Prader-Willi syndrome is caused by a deletion of 15q11-13 or maternal disomy of chromosome 15. A female patient with Prader-Willi syndrome, who was 19 years of age at the first onset of her recurrent brief episodes, is described. The episodes showed a near-monthly rhythm and were followed by a spontaneous remission in 7-18 days. The symptoms during the episodes were anorexia, insomnia, guilt feelings, ideas of being doomed, ostracized and persecuted, and stupor alternating with agitation.

Adult↗

Efficient protein production using a Bombyx mori nuclear polyhedrosis virus lacking the cysteine proteinase gene.

Infection by a baculovirus (Bombyx mori nuclear polyhedrosis virus, BmNPV) in silkworm (Bombyx mori) larvae is highly efficient as an expression system for the production of useful proteins. However, the amount of the protein of interest expressed tends to decrease in the later stages of infection presumably due, in part, to a proteinase produced in the larval haemolymph. The N-terminal amino acid sequence of a proteinase purified from the haemolymph of BmNPV-infected larvae was identical to the internal amino acid sequence of the viral cysteine proteinase gene of BmNPV, suggesting that the cysteine proteinase in the haemolymph originated from the BmNPV gene. We constructed a mutant virus (CPd) which had a deletion in the cysteine proteinase gene. No proteinase activity corresponding to this proteinase was detected in the haemolymph of silkworm larvae infected with CPd. The firefly luciferase and the human growth hormone genes were separately introduced into CPd under control of the polyhedrin promoter. These constructs produced these proteins very efficiently, because of a greatly reduced degree of degradation of these proteins. A BmNPV vector system using CPd enhances the stability of foreign expressed proteins, especially for those that are cysteine proteinase-sensitive.

Animals↗

The role of glucuronidation in 7-ethyl-10-hydroxycamptothecin resistance in vitro.

Although glucuronidation catalyzed by uridine 5'-diphosphoglucuronosyltransferase (UGT) is a major pathway of drug inactivation in humans, glucuronidation in malignant cells has received little attention as a cause of anti-cancer drug resistance. In this study, we tried to elucidate the role of SN-38 glucuronidation in the CPT-11-resistant human lung cancer cell line PC-7/CPT. PC-7/CPT cells possessed an increased activity to glucuronidate SN-38 compared to the parent cells, PC-7. Furthermore, sensitivity of PC-7/CPT cells to SN-38 was improved by inhibiting UGT activity. Western and northern blot analyses demonstrated that this increased activity was due to increased levels of UGT protein and mRNA. These results not only imply that upregulation of UGT activity in PC-7/CPT cells may contribute in part to SN-38 resistance, but also illustrate the important of drug metabolism within malignant cells themselves, as a cause of drug resistance.

Antineoplastic Agents, Phytogenic↗

Morphogenesis and development of superficial spreading tumor of the colon and rectum.

The aim of this study was to clarify the morphogenesis and mechanism of a wide intramucosal extension of a superficial spreading (epithelial) tumor (SST; defined as an epithelial tumor with wide intramucosal spreading involving a diameter of 30 mm or more) in the colon and rectum. For this purpose favorable sites, histological components, and histological growth patterns were compared between 95 cases of SST (16 adenomas and 79 carcinomas) and 2356 non-SST cases, which served as controls. The frequency of SST was significantly higher in the cecum and rectum, and lower in the sigmoid colon when compared to the locations of the control. Among the SST cases, 82.3% of superficial spreading carcinoma (SSC) had an adenomatous component and 96.2% had a cytologically low-grade carcinoma (CAL). In intramucosal SSC, the adenomatous and/or CAL component was predominant, and the proportion of high-grade carcinoma (CAH) was significantly smaller in intramucosal SSC in comparison with the control group. In the mucosal spreading area of SST, 78.9% were tubulovillous in histological type and 86.3% showed a replacing growth pattern. These results indicate that an SST initially develops as an adenoma in at least 85.3% of cases and CAL in 14.7% cases at most; spreads superficially in the mucosa by a replacing growth mechanism that forms a tubulovillous and villous structure; and is affected by intestinal peristalsis less than non-SST.

Adenoma↗

Correlation of p53 protein expression with gene mutation in gall-bladder carcinomas.

The correlation of p53 protein expression and p53 mutation of 33 gall-bladder carcinomas was studied according to the depth of invasion and grade of cytological atypia. Overexpression of p53 protein was detected by immunostaining in seven (70.0%) of 10 intramucosal and in 16 (69.6%) of 23 invasive carcinomas. p53 mutation was detected in five (71.4%) of the seven intramucosal carcinomas with overexpression and in eight (50.0%) of the 16 invasive cancers with overexpression and in one (10%) of the 10 non-overexpressing carcinomas at exons 5-8 by nested polymerase chain reaction-single-strand conformation polymorphism. The overexpression of p53 protein was present in nine (56.3%) of 16 low-grade carcinomas and in 14 (82.3%) of 17 high-grade carcinomas. In cases of overexpression, p53 mutation was detectable in four (44.4%) of nine low-grade and in nine (64.3%) of 14 high-grade carcinomas. In total, p53 mutation was verified in 56.5% (13/23) of cases involving protein overexpression and in 10% (1/10) of cases of non-overexpression. The sensitivity of p53 mutation was 56.5% (13/23), the specificity was 90.0% (9/10) and the validity was 1.47. In conclusion, our study indicates that p53 protein overexpression correlates well with gene mutation and that p53 alteration may be related to increasing grade of cytologic atypia of carcinomas.

Adenocarcinoma↗

p53 protein overexpression and K-ras codon 12 mutation in pancreatic ductal carcinoma: correlation with histologic factors.

The correlation of p53 protein overexpression and the K-ras codon 12 mutation with histologic type, grade of cytologic atypia, depth of invasion and other histologic prognostic factors was studied in paraffin sections from 43 ductectatic- and 70 solid-type pancreatic ductal carcinomas. Overexpression of p53 was found in 23.3% (10/43) of ductectatic carcinomas (17.2% of intraductal and 35.7% of invasive carcinomas) and in 61.4% (43/70) of solid carcinomas. In ductectatic cancers, p53 overexpression was detected in 14.8% (4/27) of carcinomas with low-grade atypia (CAL), 50.0% (5/10) of carcinomas with high-grade atypia (CAH) and in 16.7% (1/6) of mixed low- and high-grade cancers. In the last group, expression was restricted to an area of CAH. In solid cancers, p53 overexpression did not differ by histologic type or grade. Overexpression of p53 and K-ras mutations did not correlate with histologic prognostic factors (lymphatic, venous and perineural invasion, and lymph node metastasis) in ductectatic and solid cancers or depth of invasion of solid carcinomas. Our data suggest that p53 alteration occurs at an early intraductal stage of solid carcinoma, irrespective of cellular atypia, but is low in ductectatic CAL and becomes higher in ductectatic CAH. K-ras mutation, present in a high percentage of tumors of all groups and not correlating with the factors above, showed no changes in frequency with tumor progression.

Carcinoma↗

Solitary esophageal metastasis of breast cancer with 15 years' latency: a case report and review of the literature.

A 68-year-old woman with a history of breast and colon cancer at the ages of 48 and 65 years, respectively, who presented with dysphagia is described. An upper gastrointestinal series and endoscopic examination revealed a circumferential stricture without ulceration in the middle-third area of the esophagus. Computed tomography demonstrated a submucosal tumor in the esophageal wall. A biopsy specimen obtained from the mucosa overlying the tumor revealed poorly differentiated adenocarcinoma, suggesting metastasis from the previous breast cancer. Subtotal esophagectomy with reconstruction was performed. Macroscopically, a submucosal tumor measuring 2.0 x 1.7 cm was observed in the resected esophagus. Microscopic examination revealed poorly differentiated adenocarcinoma, which was quite similar histologically to the breast cancer resected 15 years previously. Enzyme immunoassay and immunohistochemical analyses of the resected tumor revealed positivity for both estrogen and progesterone receptor, confirming the diagnosis of a metastatic cancer from the previous breast tumor.

Adenocarcinoma↗

[Isolation of enterohemorrhagic Escherichia coli (O157:H7) by an immunomagnetic separation method].

Three sporadic cases of enterohemorrhagic Escherichia coli (EHEC) O157 infection which occurred in Kanagawa in 1996 were investigated. In an attempt to determine sources of the infection, a novel method of immunomagnetic separation (IMS) was employed to isolate the bacterium from feces, foods, and other associated items. In the first case, strains of EHEC O157:H7 producing Vero toxin (VT) 2 were isolated from both feces of the patient and suspected food (cattle liver) kept at a restaurant, and the strains were found to be genotypically identical through an analysis of pulsed-field gel electrophoresis (PFGE). Subsequent investigation in the meat processing store, from which the above cattle liver had been retailed to the restaurants revealed that the store was contaminated with EHEC O157:H7 producing both VT1 and VT2. In the second case, a strain isolated from the patient was EHEC O157:H7 producing both VT1 and VT2 while strains isolated from the patient's family (without apparent symptom) and the suspected facility were O137:NM producing VT2. PFGE analysis indicated that the latter two strains were genotypically identical, suggesting that the facility thus contaminated with EHEC O157 caused the infection in question. In the third case, EHEC O157:NM producing VT2 was isolated from 4 out of 7 family members including the patient, and these strains were found to be genotypically identical by subsequent PFGE analysis. Source of the infection was, however, not determined due to lack of suspected food items. In this context, four slaughterhouses in Kanagawa Prefecture were investigated for presence of EHEC O157. As a result, strains of EHEC O157:H7 producing VT1 and VT2 were isolated from the contents of cattle's distal colon and surface of the skinned carcasses. Additional attempt was also made to determine a possibility of river water being contaminated with EHEC O157. The bacterium was, however, not isolated from water samples collected from 4 major rivers in the prefecture (at 10 collecting sites). Experiments were undertaken in order to evaluate the use of IMS in isolation of EHEC O157 from food items, with different pre-enrichment media and conditions. The results indicated that pre-enrichment by trypticase soy broth at 36 degrees C for 6 h followed by inoculating onto sorbitol MacConkey agar plate containing cefixime and tellurite was most appropriate to isolate EHEC O157 strains.

Adolescent↗

[A case of pseudomembranous enterocolitis which diagnosis was delayed in the outpatient clinic].

A 71-year-old male visited our hospital because of diarrhea. At first we suspected infectious colitis and levofloxacin (300 mg/day) was administered for four days. But the diarrhea continued, so performed a barium enema after about 3 weeks from onset. Round polyposis from the rectum to the sigmoid colon were found. Colonoscopy was suggested to the patient, but was rejected. However diarrhea continued and fever appeared. Ceftriaxone (1 g/day) and sparfloxacin (200 mg/day) were administered, but the symptoms increased. He was admitted about 6 weeks from onset, and the colonoscopy showed multiple round yellow-white pseudomembranes. Pseudomembranous enterocolitis diagnosed because Clostridium difficile and its toxin were positive in the feces. After oral administration of vancomycin (1.5 g/day) was started, the symptoms alleviated rapidly and disappearance of pseudomembrane was confirmed by colonoscopy.

Aged↗

Nephrotoxicity of vancomycin and drug interaction study with cilastatin in rabbits.

The nephrotoxic effects of vancomycin hydrochloride (VCM) and the potential drug-drug interaction with cilastatin sodium (CS) were examined in rabbits. The aim of the study was to measure the possible dose-related suppressive effects or elimination by cilastatin of the adverse reactions generated by vancomycin in the kidneys of rabbits. To clarify the interactions of these two drugs, we examined the nephrotoxicity and pharmacokinetics of VCM in the rabbit when administered alone and when coadministered with CS. VCM administered alone (300 mg/kg of body weight as an intravenous bolus; n = 5) caused typical symptoms of nephrotoxicity, such as increases in serum creatinine and blood urea nitrogen (BUN) levels, as well as morphological changes in the kidneys. A lack of such signs of nephrotoxicity was observed in the groups administered VCM plus CS (i.e., CS at 150 mg/kg plus VCM at 300 mg/kg or CS at 300 mg/kg plus VCM at 300 mg/kg, intravenous bolus; n = 5/group). At a reduced combination ratio of VCM plus CS (4:1 ratio, VCM at 300 mg/kg plus CS at 75 mg/kg, intravenous bolus; n = 5) some symptoms of nephrotoxicity induced by VCM were present, but the degree of this effect was much reduced and was significantly different from preadministration values by only modest increases of the BUN and N-acetyl-beta-D-glucosaminidase levels (P < 0.05). Overall clearance of VCM was accelerated by coadministration of CS and was found to be dose dependent upon CS. No changes in renal function values from the preadministration values were observed for animals receiving CS alone (300 mg/kg, intravenous bolus; n = 3). These results suggest that CS has the ability to reduce or eliminate in a dose-dependent manner the nephrotoxic effects caused by VCM administration in rabbits.

Animals↗

Molecular typing of enterohemorrhagic Escherichia coli O157:H7 isolates in Japan by using pulsed-field gel electrophoresis.

Pulsed-field gel electrophoresis (PFGE) was applied for molecular typing of 825 enterohemorrhagic Escherichia coli (EHEC) O157:H7 isolates, most of which were from 19 outbreaks and 608 sporadic cases in Japan, mainly in May to August 1996. By PFGE, the EHEC O157:H7 isolates were classified into six types (type I to V and ND [nondescript]) and UT untypeable isolates. Fifty isolates from seven outbreaks in May to June and 60 isolates from patients with sporadic cases of infection showed almost identical PFGE patterns which differed in only 1 of 22 DNA fragments. They were classified into type I. Ninety-nine isolates from 10 other outbreaks and 156 isolates from patients in the Kinki area with sporadic cases of infection obtained in the early summer of 1996 showed identical PFGE patterns, suggesting that they were derived from one huge outbreak. They were classified into type II. Type IV EHEC isolates, which had only the stx2 gene, caused another outbreak in a primary school in June. EHEC isolates of two other types, types III and V, were not related to the outbreak but were isolated in several parts of Japan. ND EHEC isolates included a variety of patterns which could not be classified into either of the types mentioned above. Twenty-five isolates could not be analyzed due to degradation of their genomic DNAs and were represented as UT. These results indicate that EHEC O157:H7 strains with various PFGE types have already spread to Japan and caused the multiple outbreaks and sporadic infections in Japan in the summer of 1996.

Bacterial Typing Techniques↗