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Biomedical subjects

T Negishi

Publications and source records attributed to T Negishi.

At least 19 recordsLinked to original sources

Suppression of genotoxicity of carcinogens by (-)-epigallocatechin gallate.

Epidemiological evidence shows that green tea may be a factor in lowering cancer risk. We have investigated the possibility that (-)-epigallocatechin gallate (EGCG), a major polyphenol in green tea, might be an antimutagenic substance. In the Ames Salmonella test, EGCG suppressed the direct-acting mutagenicity of 3-hydroxyamino-1-methyl-5H-pyrido-[4,3-b]indole (Trp-P-2(NHOH)) and 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1(NHOH)), the activated forms of food-derived carcinogens 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole. EGCG was also effective in reducing the mutagenicity of Trp-P-2(NHOH) in mouse FM3A cells in culture. Furthermore, EGCG demonstrated a suppressive effect in the in vivo Drosophila mutation assays, i.e., the wing spot test, and the DNA repair test, on several carcinogens. EGCG was also effective in inhibiting DNA single-strand breaks in vitro caused by Glu-P-1(NHOH). We conclude that the mechanism of inhibition may not have resulted from direct interaction between EGCG and the mutagens, but rather from indirect interception of mutagen action by EGCG.

Animals

The genotoxicity of UVA irradiation in Drosophila melanogaster and the synergistic action of 8-methoxypsoralen and UVA.

To study the genotoxicity of near-ultraviolet light (UVA) on a whole body, Drosophila melanogaster larvae were irradiated with UVA and the emerging flies were examined for the mutant wing spot formation. The genotoxicity of UVA was also assayed with the in vivo DNA-repair test using males with repair-deficiency at the mei-9 and mei-41 locus and the matching repair-proficient females. Third-instar larvae were placed in a plastic Petri dish, which was covered with soft glass, and irradiated with black light at 4-5 W/m2. This irradiation resulted in an increase in mutant wing-hair spots. After a 15 h irradiation (approximately 240 kJ/m2), the mutant clone frequencies found in the adult flies (spots/wing) were: 1.68 for the small single spots, 0.38 for the large single spots and 0.11 for the twin spots, while at zero time they were 0.68, 0.06 and 0.02 respectively. On the other hand, the UVA irradiation was negative in the in vivo DNA-repair test, indicating that the UVA-induced DNA lesion may not be subject to repair by the mei-9 and mei-41 functions. The presence of 8-methoxypsoralen (8-MOP) during the irradiation remarkably enhanced somatic mutations, and showed a strong DNA-damaging effect in the repair test. For example, a 15 h UVA irradiation with 26.7 microM 8-MOP resulted in a 14-fold increase in the number of twin spots per wing as compared with the frequency obtained on treatment with UVA alone. Treatment of the larvae with 8-MOP alone gave no mutant clones or DNA damage. A high frequency in twin spot formation was also observed in this UVA + 8-MOP treatment, indicating that extensive chromosomal recombinations took place in the somatic cells.

Animals

[Clinical pathology of hypopharyngeal cancer--comparison between TN and pTN].

Seventy patients with the hypopharyngeal cancer who underwent pharyngolaryngoesophagectomy with bilateral neck dissection between 1978 and 1990 were examined retrospectively to compare TN and pTN in these patients and clarify the clinical pathology of the hypopharyngeal cancer. Among the 70 cases of hypopharyngeal cancer, there were 46 cases of piriformis sinus cancer (PSC) and 24 cases of postcricoid cancer (PCC). The pathological diagnosis of all these cases was squamous cell carcinoma (SCC). The following results were obtained: 1. Invasion of the thyroid gland was seen in 8 cases of PCC (33.3%) and 6 cases of PSC (13.0%). The thyroid gland can be preserved in PSC, whereas its removal is indicated in PCC. 2. Twenty-nine cases of N0 necks proved to be pN0-2b in 27 cases (93.1%) which may be controlled by homolateral neck dissection, and pN2c in 2 cases (6.9%), which requires bilateral neck dissection. On the other hand, 29 cases of N1-2b necks which represent one-sided neck metastasis were pN0-2b in 15 cases (51.7%) and pN2c in 14 cases (48.3%). These results demonstrate that N0 necks can, in the majority of cases, be controlled by homolateral neck dissection alone but that N1-2b necks require bilateral neck dissection. 3. Occult neck metastases were observed in PCC more often than in PSC, because paratracheal metastases of PCC were difficult to expose before surgery. 4. Pathological neck metastases of both PSC and PCC were most commonly situated in the superior and middle internal jugular nodes. Paratracheal metastases of PCC was found pathologically in 10 cases (41.7%). Paratracheal nodes must be dissected meticulously during the resection of PCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Adjuvant chemotherapy for invasive bladder cancer. Multicenter study].

During 2 years and 10 months from November 1985 to September 1988, 50 patients with invasive bladder cancer (pT2-4, pN0-2, M0) were treated with total cystectomy followed by adjuvant combination chemotherapy including cis-platinum. In addition, so-called immunopotentiator (OK-432) and Kanpo (Juzentaihoto: TJ-48) were given to the patients in a random fashion to evaluate whether or not these agents had any significant effect on patients' prognosis. The 3- and 5-year survival rates for 48 evaluable patients were 71% and 67%, respectively. Histologic grade of primary tumors and number of cycles of adjuvant chemotherapy administered had a significant correlation to patients' survival: patients with grade 2 anaplasia had a better 3- and 5-year survival rates than those with grade 3 anaplasia, and patients receiving 3 or more cycles of chemotherapy had a better 3-year survival rate than those with 2 or less cycles. pT and pN categories also affected patients' survival, though not statistically significant. Administration of OK-432 or TJ-48 and pre-operative treatment such as irradiation and intra-arterial chemotherapy had no favourable effects on the survival. Side effects of the adjuvant chemotherapy were minimal to moderate and more than 70% of the patients tolerated at least 3 cycles of chemotherapy. It is likely that adjuvant chemotherapy, when given in a post-operative setting, should be repeated at least 3 cycles or more.

Adult

Matlystatins, new inhibitors of typeIV collagenases from Actinomadura atramentaria. I. Taxonomy, fermentation, isolation, and physico-chemical properties of matlystatin-group compounds.

During the course of a screening for inhibitors of typeIV collagenases, new metabolites, designated matlystatins, have been isolated from an actinomycete strain, which was identified as a strain of Actinomadura atramentaria. Matlystatins were composed of five congeners, which were separated and purified by n-butanol extraction and chromatography.

Acetylcysteine

[A case of staphylococcal enterocolitis caused by methicillin resistant Staphylococcus aureus].

Recently, the frequency of methicillin resistant Staphylococcus aureus (MRSA) infection has been increasing. We experienced a case of postoperative enterocolitis due to MRSA. The patient was an 81-year-old male with benign prostatic hypertrophy. Urine leakage from the penrose drain tube appeared 1 day after suprapubic prostatectomy. We had used intravenous infusion of antibiotic agents including cefodizine (CDZM), imipenem (IPM/CS) and cefmetazol (CMZ). He developed severe diarrhea, high fever, oliguria, leg edema and ascites 24 days after the operation. MRSA was detected from his feces. Toxic shock syndrome toxin-I (TSST-I) was produced by this bacteria the coagulase type of which was type II. The patient was treated with oral vancomycin (1 g/day), to which this bacteria showed sensitivity and the patient showed, improvement, including symptoms, leucocytosis and serum CRP level 12 days after administration of vancomycin.

Administration, Oral

[Primary carcinoma in situ of the ureter: a case report].

A 47-year-old man presented with gross hematuria and left lower abdominal dull pain of 6-weeks duration. Cystoscopic examination revealed bloody efflux from the left ureteral orifice but no tumor in the bladder. Retrograde pyelogram showed irregular stricture of middle portion of the left ureter. Cytologic studies of the voided urine and left ureteral urine were positive for cancer, and nephro-ureterectomy with excision of a bladder cuff was carried out. The surgical specimen showed no intraluminal mass but histologically, transitional cell carcinoma in situ with G3 anaplasia and squamous metaplasia was found in the narrowed portion of the ureter. Followup examinations, including exfoliative urinary cytology, cystoscopy and IVP revealed no abnormalities until intravesical recurrence was confirmed 34 months later. Transurethral resection of bladder tumor was performed and superficial papillary transitional cell carcinoma with G2 anaplasia was found in the trigone of the bladder. Followup examinations for the last one year have revealed no abnormalities.

Carcinoma in Situ

[Primary sclerosing lipogranuloma of the male genitalia: report of three cases].

Recently, genital sclerosing lipogranuloma having no history of trauma and foreign body infusion are more common in Japan. We report three cases recently encountered in which tumors were diagnosed as sclerosing lipogranuloma on histological examination. In case 1, lipid analyses of the tissues by infrared absorption spectrometry proved that it was endogenous in origin.

Aged

[Two cases of thyroid metastases from renal cell carcinoma].

The identification and diagnosis of thyroid metastases from renal cell carcinoma are rare in living patients in spite of more frequent incidence during autopsy. We reported two cases of thyroid metastases from renal cell carcinoma. In both cases, histological examination revealed metastasis from renal cell carcinoma and negative immunohistological stain for thyroglobulin ruled out primary thyroid carcinoma.

Carcinoma, Renal Cell

[Efficacy of sodium imipenem/cilastatin on patients of complicated urinary tract infections--following the failure of prior antimicrobial agents].

Clinical efficacy of sodium imipenem/cilastatin was studied on 45 patients with complicated urinary tract infections, on whom prior antimicrobial agents were ineffective. A 0.5g dose of IPM/CS was administered by drop infusion twice a day for 5 days. The clinical efficacy was evaluated according to the criteria of the Japanese UTI committee. Of a total of 65 strains, 29 strains of gram positive bacteria and 36 strains of gram negative bacteria, were detected as causative microbials. Bacteriologically, 23 strains of gram positive bacteria (79%) and 34 strains of gram negative bacteria (94%) were eradicated following the treatment. S. aureus, E. faecalis and Flavobacterium sp. were less sensitive to IPM/CS. Overall clinical effectiveness rate of IPM/CS in the present study was 87%. Adverse drug side effects were observed in six patients, namely they were eruption, headache and slight elevation of serum transaminase. These findings suggest that IPM/CS is an effective agent for the treatment of complicated UTI even when the prior medicine was ineffective.

Adolescent

[Clinical efficacy of tosufloxacin on the patients with urinary tract infections].

We evaluated a newly developed quinolone agent, tosurofloxacin (TFLX), for its safety and clinical efficacy on patients with urinary tract infections (UTI). Among 138 cases satisfying the UTI criteria, 75 cases were acute simple UTI and 63 cases were chronic complicated UTI. In principle, a daily dose of 450 mg of TFLX was administered for 3 days and for 5 days for acute simple UTI and for chronic complicated UTI, respectively. Clinical efficacy of TFLX in these cases was evaluated according to the criteria of Japanese UTI committee. Bacteriologically, all 80 strains isolated from acute simple UTI were eradicated following TFLX administration. However, 2 gram positive strains and 1 gram negative strain, appeared following the treatment. In cases of chronic complicated UTI, 29 out of 32 gram positive strains and 29 out of 44 gram negative strains were eradicated. Among the isolated strains, P. aeruginosa and S. marcescens persisted, which suggests that they were less sensitive to TFLX. Overall clinical effectiveness rate of TFLX on acute simple UTI was 100%, while that on chronic complicated UTI was 73%. Adverse drug side effects were minimum, stomach discomfort and constipation was observed in one case each. These findings indicate that TFLX is a useful agent for the treatment of both simple and complicated UTI.

4-Quinolones

[Enterovesical fistula complicating Crohn's disease: report of two cases].

Two female patients with enterovesical fistula complicating Crohn's disease are presented. Case 1: A 40-year-old woman having a 10-year history of diarrhea presented with vesical irritability of a three months duration. Administration of antibiotics did not relieve her of the symptoms and then pneumaturia appeared. Cystoscopic examination revealed fistulous opening. Barium enema study depicted rectovesical fistula. After partial cystectomy and temporary colostomy, ileocecal lesion was shown by contrast study and resection of ileocecal segment was performed seven months later. Case 2: A 33-year-old woman presented with vesical irritability of 7 years duration and pneumaturia and fecaluria of 4 years duration. Cystoscopic examination revealed localized bullous edema but no apparent fistula. Cystography, as well as contrast studies demonstrated ileo-vesical, ileo-ascending colonic and ileo-sigmoidal fistulas. One-stage resection of diseased intestine and partial cystectomy were performed. In both cases, pathological diagnoses of Crohn's disease was made, and postoperative course was uneventful for over 10 months. Thirty eight cases of enterovesical fistula complicating Crohn's disease are reviewed.

Adult

[Adrenal pseudocyst: a case report].

A 23-year-old man presented with high fever and left abdominal pain. Ultrasonography, CT scan and angiography visualized a left adrenal cyst. Cyst fluid obtained preoperatively by percutaneous needle puncture under ultrasonographic guidance was purulent, and had a higher level of aldosterone, and lower level of amylase than the plasma. These findings suggested that this cyst originated from the adrenal gland. Histopathological examination of the surgically removed specimen confirmed the adrenal pseudocyst.

Adrenal Gland Diseases

The genotoxicities of N-nitrosamines in Drosophila melanogaster in vivo: the correlation of mutagenicity in the wing spot test with the DNA damages detected by the DNA-repair test.

The genotoxicities of a series of N-nitrosamines were assayed in the wing spot test and a new short-term test of Drosophila melanogaster. In the spot test, larval flies trans-heterozygous for the somatic cell markers mwh and flr3 were fed the test reagents and the wing hairs in adults were inspected for clones expressing the phenotypes of the markers. In the other test, larval stock consisting of meiotic recombination-deficient (Rec-) double mutant mei-9a and mei-41D5 males and repair-proficient Rec+ females were grown on feed containing the reagents and the DNA damages were detected with the preferential killing of the Rec- larvae as an endpoint. The carcinogenic nitrosamines tested, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-butylamine (NDBA), N-nitrosomorpholine (NMOR), N-nitro-sopiperidine (NPIP) and N-nitrosopyrrolidine (NPYR), all showed clearly positive activities in both tests. The activities in the wing spot test were ranked in a sequence of NDMA much greater than NMOR greater than NPIP greater than NDEA greater than NPYR greater than NDBA. A similar ranking was obtained in the repair assay. The genotoxicity of N-nitrosodiphenylamine (NDPhA), carcinogenicity studies of which are inconclusive, was marginal in the spot test. The non-carcinogenic N-nitrosoproline (NPRO) and the non-mutagenic N-nitrosothioproline (NTPRO) were negative in the spot test. NDPhA and NPRO were negative in the repair test as well. The DNA-repair test is thus a convenient technique for estimating the mutagenicity of compounds because of its simplicity compared with the wing spot test. These Drosophila tests may be useful in predicting carcinogenic potentials of compounds.

Animals

Activated T lymphocyte subsets in experimental allergic neuritis.

Changes in activated T cell subsets in peripheral blood were examined during the course of experimental allergic neuritis (EAN), using two-color immunofluorescence flow cytometry. Both CD4+ and CD8+ activated T cells decreased transiently before the onset of clinical signs, and increased just around the time of onset of the disease. In contrast, during the recovery phase, the numbers of CD4+ activated T cells returned to the normal range, whereas CD8+ activated T cells continued to increase. These findings imply that activation of CD4+ helper/inducer cells contributes mainly to the evolution of EAN, and that of CD8+ suppressor cells are necessary for recovery.

Animals

Application of transrectal ultrasonography in modified Stamey procedure for stress urinary incontinence.

From June 1989 to August 1990, 21 women with genuine stress urinary incontinence were treated with the Gittes procedure combined with transrectal ultrasonography. The urethrovesical junction was well pinpointed on an ultrasonographic image. The strength of suspension providing the optimal posterior urethrovesical angle was changed by each patient. Posterior urethrovesical angles averaged 89.3 +/- 9.5 degrees at operation and 93.6 +/- 9.5 degrees (mean +/- standard deviation) on a postoperative lateral cystourethrogram with the patient straining while in the standing position. An indwelling urethral catheter was removed on postoperative day 1. None of the patients had residual urine of more than 50 ml. by 4 days postoperatively. Furthermore, the average maximum urinary flow rates significantly increased from 21.0 +/- 7.1 ml. per second preoperatively to 26.1 +/- 9.8 ml. per second postoperatively (p less than 0.01). Therefore, application of ultrasonography during bladder neck suspension is simple and reliable for determination of the optimal suspension as well as identification of the suspension site.

Adult

[Simultaneous bilateral neck dissections].

From April 1985 to December 1989, 65 patients with advanced head and neck squamous cell carcinoma, underwent simultaneous bilateral neck dissection (SBND) at Saitama Cancer Center. Three and five year survival percentages were 53 and 42%, respectively. In patients without histologic involvement of cervical nodes, five year survival rate was 83%, whereas in those with nodal involvement five year survival fell to 32% (p less than 0.005). The conclusion were the following: (1) Of 38 patients diagnosed to have lymph node involvements on one side of neck before operation, 8 patients (22%) were found to have bilateral lymph node metastasis in clinicopathological study. Of 13 patients having no clinical lymph node metastasis on both sides of neck, 7 patients (54%) were found to have unilateral lymph node metastasis. Of 16 patients diagnosed to have bilateral lymph nodes involvement, 10 patients were found to have bilateral neck metastasis and 2 had unilateral neck metastasis. (2) Of 35 cases of hypopharyngeal canners, 19 cases had clinically positive lymph nodes on one side of neck. Of these 19 cases, 5 cases (26%) had histologically positive nodes on the opposite side. 14 (40%) of 35 cases had metastasis on the opposite side. In conclusion, SBND is a proper treatment for metastatic cervical cancer from a primary lesion of the head and neck, especially in hypopharyngeal cancers, because the rate of recurrence seems to be related more to the difficulty in controlling lymph node metastasis than to the failure in treatment of the primary cancer.

Aged