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Biomedical subjects

D Watanabe

Publications and source records attributed to D Watanabe.

At least 73 records · Page 4Linked to original sources
PubMed1992

Loss of sperm in juvenile spermatogonial depletion (jsd) mutant mice is ascribed to a defect of intratubular environment to support germ cell differentiation.

C57BL/6(B6)-jsd/jsd mice are sterile due to the defective spermatogenesis in the testes. To know the cause of the deficient spermatogenesis in B6-jsd/jsd mice, we examined whether the problem is within or outside the seminiferous tubules by transplanting tubules from cryptorchid testes of B6- +/+ mice into B6-jsd/jsd testes or tubules from B6-jsd/jsd mice into testes of (WB x C57BL/6)F1-W/Wv (hereafter, WBB6F1-W/Wv) mice. Type A spermatogonia differentiated into spermatids in seminiferous tubules from cryptorchid testes transplanted into B6-jsd/jsd testes. In contrast, in B6-jsd/jsd tubules transplanted into WBB6F1-W/Wv testes, type A spermatogonia were stimulated to mitotic proliferation, but didn't proceed to any differentiated germ cells. The present results suggest that the cause of the deficient spermatogenesis in B6-jsd/jsd mice is a defect of intratubular environment to support germ cell differentiation.

Animals↗
PubMed1992

A trial of adjuvant chemoimmunotherapy with mitomycin C and OK-432 for stage III gastric carcinoma.

We previously found that the ability to generate cytotoxic cells induced by in vitro activation of peripheral blood mononuclear cells (PBM) with OK-432, a bacterial immunopotentiator, was markedly increased following intravenous administration of a single dose of mitomycin C (MMC) in cancer patients. On the basis of this clinical finding, we designed a treatment regimen that consisted of MMC 12 mg/m2 intravenously on day 1 and OK-432 5 Klinische Einheit (KE) intradermally on days 6, 8, and 11, when the generation of OK-432 activated killer cells had been shown to be significantly augmented. Then, it was followed by long-term tegafur. Fifteen patients with stage III gastric carcinoma who had undergone curative resection were treated with the above regimen. The survival of these patients was significantly better than that of 26 comparable stage III patients concurrently treated with MMC 12 mg/m2 alone, followed by long-term tegafur (P less than 0.01). The results indicate that OK-432 combined with MMC may be effective against stage III gastric carcinoma, when these agents are used probably in an appropriate combination.

Carcinoma↗
PubMed1992

Characterization of male meiotic germ cell-specific antigen (Meg 1) by monoclonal antibody TRA 369 in mice.

We have identified a male meiotic germ cell-specific antigen (Meg 1) with monoclonal antibody (mAb) TRA 369 in mice. The Meg 1 antigen was strongly expressed in specific steps of meiotic germ cells from pachytene spermatocyte to early spermatid, and not in other germ cells or somatic cells. Immunohistochemical examination revealed that the antigen was localized to the cytoplasm and was not distributed in the nucleus or on the cell surface. This antigen was demonstrated to have a molecular weight of 93 kDa and an isoelectric point of 5.2 by Western blotting. This molecule was first detected in the testis of 13-day-old mouse when pachytene spermatocytes first appeared. Thus this is a differentiation-specific antigen in male meiotic germ cells, and mAb TRA 369 is a useful tool to study the regulation of germ cell differentiation and to define germ cell development in a molecular level.

Animals↗
PubMed1992

Correlation of eosinophilia with clinical response in patients with advanced carcinoma treated with low-dose recombinant interleukin-2 and mitomycin C.

On the basis of our clinical findings that the ability of cancer patients to generate lymphokine-activated killer cells became markedly augmented after mitomycin C administration, we designed a treatment regimen comprising mitomycin C 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 700 U/m2 (8000 IU/kg), i.v. every 12 h from day 4 through day 8. The treatment course was repeated at almost 7-day intervals. Altogether 33 patients with advanced carcinoma, including mainly gastrointestinal carcinoma, were treated with this regimen. Of these, 10 had a partial response (PR) and 4 had a minor response (MR). Since eosinophil counts peaked 1 day after either the first or second course of the therapy, the posttreatment values were compared to each pretreatment level, with regard to the clinical antitumor response to this treatment. When patients who showed PR were defined as responders, absolute eosinophil counts and the percentage of eosinophils in responders after both the first and second courses of the therapy were significantly greater than each pretreatment value or the posttreatment level in nonresponders. Further, these findings were almost identical, when both PR and MR were considered to be a true remission and therefore patients who exhibited PR or MR were defined as responders, although the difference between posttreatment levels of eosinophils in responders and nonresponders was not significant at the second course. These results indicate that eosinophilia induced by this treatment correlates with the clinical response to this therapy.

Aged↗
PubMed1992

A useful cholesterol solvent for medical dissolution of gallstones.

Dissolution of cholesterol gallstones by direct instillation of an agent into the biliary tract has been considered an alternate to surgical procedures. We developed an excellent direct solubilizer by combining d-limonene and medium-chain monoglyceride. This mixture enhances the advantages of each individual solvent and minimizes the disadvantages. In vitro experiments were done to determine the viscosities and the cholesterol dissolving rates of various combinations, and in vivo experiments were conducted to study their irritation effects on tissues. The optimal combination was a 3:2 mixture of d-limonene and medium-chain monoglyceride. It could quickly dissolve cholesterol gallstones with minimal or no observable side effect.

Animals↗
PubMed1992

Effects of W (c-kit) gene mutation on gametogenesis in male mice: agametic tubular segments in Wf/Wf testes.

Mutations of the W (c-kit) gene, which encodes a transmembrane tyrosine kinase receptor, affect the development and differentiation of many types of stem cell. Most homozygous W mutant mice are sterile, due to a lack of germ cells arising during embryonic development, but one of the notable exceptions is Wf/Wf mice, which are fully fertile in both sexes. In order to elucidate the effects of the Wf mutation on spermatogenesis, postnatal spermatogenesis in Wf/Wf mice was histologically examined. The number of gonocytes at birth was significantly reduced and small portions of agametic seminiferous tubule segments were observed in mutant mice. It is suggested that this is due to a deficiency of primordial germ cells (PGC). Other than the agametic tubules, there was no evidence of reduced spermatogenesis after birth. These results indicate that the function of the W (c-kit) gene is more necessary for the development of PGC than for postnatal germ cells.

Animals↗
PubMed1991

White-spotting mutations affect the regenerative differentiation of testicular germ cells: demonstration by experimental cryptorchidism and its surgical reversal.

The effect of white-spotting (W) mutations on differentiation of testicular germ cells was investigated by using experimental cryptorchidism and its surgical reversal. All mutant mice used in this study (Wv/+, Wsh/+, Wf/+ and Wf/Wf) showed normal fertility and well-ordered spermatogenesis, as in congenic +/+ mice. In the cryptorchid testis, which contains only type A spermatogonia as germ cells, the number and the proliferative activity of type A spermatogonia in mutant mice were comparable to +/+ mice. On the other hand, surgical reversal of the cryptorchid testis in mutants resulted in impaired regenerative differentiation of germ cells. Although complete recovery of spermatogenesis was observed in +/+ mice, testicular weight in Wsh/+, Wf/+ and Wf/Wf mice recovered to approximately 60-70% of intact levels, and some portions of seminiferous epithelium showed incomplete spermatogenesis. In Wv/+ mice, however, ability to recover the weight was completely lost, and only type A spermatogonia existed as germ cells in seminiferous tubules 3 mo after surgical reversal. These results suggest that W mutation affects the differentiation through type A spermatogonia to type B spermatogonia, indicating the functional significance of W (c-kit) in early spermatogenesis.

Animals↗
PubMed1991

Steel-Dickie (Sld) mutation affects both maintenance and differentiation of testicular germ cells in mice.

The effects of Steel-Dickie (Sld) mutations on testicular germ cell differentiation were investigated using experimental cryptorchidism and its surgical reversal in mutant, C57BL/6-Sld/+ and wild-type C57BL/6- +/+ mice. In Sld/+ cryptorchid testes the maintenance of undifferentiated type-A spermatogonia was impaired and their numbers decreased. In contrast, the proliferative activity of type-A spermatogonia in the cryptorchid testis of mutant mice appeared normal as judged by their progression through the cell cycle. Surgical reversal of cryptorchidism resulted in regenerative differentiation of mature germ cells in +/+ testes. However, the regenerative differentiation of type-A spermatogonia which remained in Sld/+ cryptorchid testes was strongly impaired, particularly at two steps of cellular differentiation, from type-A spermatogonia to intermediate or type-B spermatogonia and at meiotic division. Furthermore, in mutant mice, no significant recovery of testicular weight was observed after surgical reversal compared with +/+ mice.

Animals↗
PubMed1991

Extraskeletal osteosarcoma in the axilla associated with breast carcinoma.

A case of extraskeletal osteosarcoma arising in the axilla in a 77-year-old woman is described. Because of its association with an ipsilateral breast carcinoma, the axillary mass was at first assumed to be a lymph node with metastatic breast carcinoma. The occurrence of extraskeletal osteosarcoma in the axillary is rare and association with breast carcinoma has never, to our knowledge, been described.

Aged↗
PubMed1990

The effect of recombinant interleukin 2 in combination with mitomycin C on advanced cancer.

We recently discovered that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C (MMC) administration. Based on our clinical findings, we designed a treatment regimen comprised of MMC 12 mg/m2 given intravenously on day 1 and recombinant interleukin 2 (rIL 2) 700 U/m2 given intravenously every 12 hr from day 4 through day 8, when the generation of LAK cells had been shown to be markedly increased. Ten patients with various advanced carcinomas for which standard therapy had failed or no standard therapy was available, were treated with this regimen. Of these ten, three had a partial response and three others had a minor response. Fevers were common and anemia occurred in four patients, but nevertheless, severe toxicity was not encountered. These results indicated that rIL 2 in combination with MMC might be effective against advanced carcinoma without causing severe toxicity when these drugs are used in an appropriate combination.

Aged↗
PubMed1988

Flaws in mortality data. The hazards of ignoring comorbid disease.

Recent public releases of hospital mortality data have sparked debate over methods to identify poor-quality care. We examined variations among hospitals in patient characteristics known independently to affect the risk of adverse outcomes and focused on patient comorbidity, defined as the state of health at admission apart from the primary diagnosis. Data from a study of 2935 incident cancer patients treated in seven Southern California hospitals revealed substantial variations among hospitals in age, cancer stage, and the burden of comorbid conditions. In the highest-ranked hospital, 17.9% of patients had high levels of comorbidity, compared with 9.3% in the lowest-ranked hospital. The three hospitals with the highest comorbidity were also identified as high-mortality outliers in a recent California report on hospital mortality rates. We conclude that comorbidity must be considered in any hospital quality assessment method based on patient outcome. If it is not considered, variations in referral and admission patterns may be misinterpreted as differences in hospital quality.

Age Factors↗
PubMed1983

Liquid crystal formation in ursodeoxycholate-rich human gallbladder bile.

We studied liquid crystal formation in bile samples obtained from the patients with radiolucent gallstones who had been administered either ursodeoxycholic acid (UDCA) at a dose of 600 mg/day or chenodeoxycholic acid (CDCA) at 400 mg/day for one week preoperatively. The UDCA/total bile acids ratio was found to range from 50 to 60% and the CDCA/total bile acids ratio ranged from 70 to 80%. Cholesterol molar percent was 5 in UDCA-rich bile and 6 in CDCA-rich bile. Phospholipid molar percentage was about the same in both groups. Liquid crystal formation was confirmed only in the UDCA-rich bile samples but not in the CDCA-rich bile samples. This result suggests that cholesterol in the UDCA-rich bile samples is not solubilized by the bile salt and phospholipid mixed micelles but also consumed to form liquid crystals.

Bile↗