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Biomedical subjects

A Osawa

Publications and source records attributed to A Osawa.

At least 19 recordsLinked to original sources

Diffusion-weighted MRI of subdural and epidural empyemas.

We reviewed diffusion-weighted images (DWI) from eight patients with subdural and four with epidural empyemas to assess the possibility of differentiating between these lesions by DWI. The signal intensities of the empyemas on DWI, and maps of the apparent diffusion coefficient (ADC) were analysed in seven patients. In seven of the eight patients with subdural empyema, the lesions appeared as areas of high signal. The ADC maps confirmed that these areas were the result of restricted diffusion. (In the remaining patient, the lesion showed a mixture of high and low signal.) The epidural empyemas contained areas of low signal in all four patients; part of the empyema was isointense or gave high signal in two. DWI may be an adjunct to conventional sequences for differentiating between subdural and epidural empyemas.

Adult↗

Chromophobe renal cell carcinoma with sarcomatoid change. A case report.

Chromophobe renal cell carcinoma (RCC) is a newly established entity of renal neoplasm with histological and molecular biological features different from those of common RCCs. Chromophobe RCC shows characteristically cloudy and reticular cytoplasm and cellular features resembling distal nephron. Its prognosis has been reported to be more favorable than that of common RCCs. Recently, however, several cases have been reported which showed sarcomatoid change to present poor prognosis. Here we present a case of chromophobe RCC with sarcomatoid change which was once resected surgically. The surgically resected tumor was histologically composed of chromophobe epithelial cell sheets and sarcomatoid elements. The former showed positivity for colloid iron staining, and was immunohistochemically positive for E-cadherin and epithelial membrane antigen (EMA), whereas the latter was positive for vimentin instead of colloid iron and E-cadherin. EMA was focally positive in the sarcomatoid element. The patient died with systemic metastases 14 months after the operation. Histologically, the metastatic tumors were composed only of sarcomatoid element lacking epithelial element. Based on these findings and previous reports, this case supports the existence of a tumor progression pathway from chromophobe to sarcomatoid RCC. It is necessary to perform careful postoperative investigation of chromophobe RCC due to its possible histological progression to the sarcomatoid subtype.

Adenocarcinoma↗

Catalytic asymmetric syntheses and biological activities of singly dehydroxylated 19-nor-1alpha,25-dihydroxyvitamin D(3) A-ring analogs in cancer cell differentiation and apoptosis.

BACKGROUND: 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) has been shown to modulate not only proliferation and differentiation, but also apoptosis in malignant cells, indicating that it could be useful for treating cancer. Little information is available concerning the structural motifs of the 1alpha, 25(OH)(2)D(3) molecule responsible for modulation of differentiation and apoptosis, however. We set out to synthesize singly dehydroxylated A-ring analogs of 19-nor-1alpha,25(OH)(2)D(3) in a catalytic asymmetric fashion, and to investigate their biological activities in leukemia HL-60 cells. RESULTS: A series of singly dehydroxylated 19-nor-1alpha,25-dihydroxyvitamin D(3) A-ring analogs were synthesized using a combinatiorial sequence of regioselective propiolate-ene reaction and catalytic asymmetric carbonyl-ene cyclization. Surprisingly, the analogs could be clearly divided into two categories; one group, bearing 1alpha-hydroxy or 3beta-hydroxy groups in the A-ring, were potent differentiators and the second group, bearing 1beta-hydroxy or 3alpha-hydroxy groups, were potent stimulators of apoptosis. CONCLUSIONS: We have clearly identified the structural motifs of 19-nor-1alpha,25(OH)(2)D(3) analogs responsible for differentiation and apoptosis in HL-60 cells. These findings will provide useful information not only for development of therapeutic agents for treatment of leukemia and other cancers, but also for structure-function studies of 1alpha,25(OH)(2)D(3).

Antineoplastic Agents↗

Above- and belowground biomass and primary productivity of a Larix gmelinii stand near Tura, central Siberia.

We assessed above- and belowground biomass and net primary production (NPP) of a mature Larix gmelinii (Rupr.) Rupr. forest (240-280 years old) established on permafrost soils in central Siberia. Specifically, we investigated annual carbon budgets in roots in relation to root system development and availability of soil resources. Total stand biomass estimated by allometry was about 39 Mg per ha. Root biomass (17 Mg per ha) comprised about 43% of total biomass. Coarse root (>/= 5 mm in diameter) biomass was about twice that of fine roots (< 5 mm). The aboveground biomass/root biomass ratio (T/R) of the larch stand was about unity, which is much less than that of other boreal and subalpine conifer forests. The proportion of fine roots in total root biomass (35%) was relatively high compared with other cold-climate evergreen conifer forests. Total NPP, defined as the sum of annual biomass increment of woody parts and needle biomass, was estimated to be 1.8 Mg per ha per year. Allocation of total NPP to needle production was 56%. The proportion of total NPP in belowground production (27%) was less than for evergreen taiga forests. However, belowground NPP was probably under-estimated because root mortality was excluded. We conclude that L. gmelinii trees invested annual carbon gains largely into needle production or roots, or both, at the expense of growth of aboveground woody parts. This carbon allocation pattern, which resulted in the construction of exploitative root networks, appeared to be a positive growth response to the nutrient-poor permafrost soil of central Siberia.

Journal Article↗

Singly dehydroxylated A-ring analogues of 19-nor-1alpha,25-dihydroxyvitamin D3 and 19-nor-22-oxa-1alpha,25-dihydroxyvitamin D3: novel vitamin D3 analogues with potent transcriptional activity but extremely low affinity for vitamin D receptor.

1Alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] mediates its biological activities through specific binding to the nuclear vitamin D receptor (VDR). The VDR, bound to 1alpha,25(OH)2D3, forms a heterodimer with a nuclear accessory factor, retinoid X receptor (RXR), and the complex subsequently binds to specific nucleotide sequences or a vitamin D-responsive element (VDRE) to induce gene transcriptions. Thus, an ideal analogue of 1alpha,25(OH)2D3 for therapeutic applications has been considered to be one which has a high binding affinity for VDR, thus forming a stable VDR/RXR complex, and binding strongly to VDRE. By contrast, we report here evidence contrary to this hypothesis. Several singly dehydroxylated A-ring analogues of 19-nor-1alpha,25-dihydroxyvitamin D3 and 19-nor-22-oxa-1alpha,25-dihydroxyvitamin D3, all of which have an extremely low binding affinity for VDR, and some of which lack the 1alpha-hydroxyl group that is considered to be essential for VDR-mediated gene expression, have greater or equivalent potencies to 1alpha,25(OH)2D3 for inhibiting the proliferation and inducing the differentiation of HL-60 cells, as well as inducing the transactivation of a luciferase reporter gene combining a rat 25-hydroxyvitamin D3 24-hydroxylase gene promoter containing two VDREs. The present findings open interesting possibilities as to the role of the VDR in the genomic action of 1alpha,25(OH)2D3 and the development of new 19-nor-analogues of 1alpha,25(OH)2D3.

Animals↗

[Prognosis of renal cell carcinoma coexisting with renal cystic diseases--results of nation-wide survey in Japan].

OBJECTIVE: To study the outcome of the patients with renal cell carcinoma (RCC) coexisting with renal cystic disease. SUBJECTS AND METHODS: The nation-wide survey conducted in 1989 enrolled 223 patients with RCC coexisting with renal cystic disease. Of those 223, we could follow up 216 patients in the second survey in 1994. RESULTS: Renal cystic diseases coexisting with RCC included simple renal cysts in 69 cases, acquired cystic disease of the kidney (ACDK) in 61, cystic RCC in 54, multilocular renal cysts in 19, polycystic kidney in 3, miscellaneous cysts in 9, and unspecified cyst in 1. The overall 5-year survival was 84%. The mean survival of the patients without any symptoms was significantly higher than that of those with symptoms. The survival of those with ACDK was lowest, and that will cystic RCC was highest. The survival was significantly different between the two groups, however the disease specific survival excluding the effect of dialysis was not significantly different between the two groups. Regarding TNM category, those with pT1 or pT2, comprising 87% of the subjects, carried a prognosis more favorable than those with pT3 or pT4. Among those undergoing cyst puncture (47 patients), positive cytology resulted in poorer prognosis. However, there was no such difference in the prognosis between punctured group and non-punctured group. CONCLUSION: Those with RCC coexisting with renal cystic disease carried a favorable prognosis. Cyst puncture were not concluded to exert an unfavorable effect on the prognosis at least in this study.

Adult↗

Increased risk of cardiovascular disease with erythropoietin in chronic dialysis patients.

Recombinant human erythropoietin is widely used in chronic dialysis patients. However, the long-term effect, especially on the incidence of cardiovascular disease, has not been critically evaluated. We observed the annual incidence of stroke and acute myocardial infarction from April 1988 through March 1993 in Okinawa, Japan. Until April 1990, erythropoietin was not generally used. Therefore, we have two periods: pre-erythropoietin, April 1988 through March 1990, and post-erythropoietin, April 1990 through March 1993. Two thousand one hundred and sixteen patients (1,219 males and 897 females) were on chronic dialysis during the study period by March 31, 1993. Every case of stroke and acute myocardial infarction during the study period was registered. The odds ratio was calculated using the data of the general population in each sex and age class obtained in the same area. A total of 86 cases of stroke and 15 cases of acute myocardial infarction were registered during the study period. The annual incidence, per 1,000 patient-years, of stroke was 12.5 (1988), 10.5 (1989), 12.7 (1990), 14.0 (1991), and 17.5 (1992). The incidence of stroke was increased in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.22 and 95% confidence interval (95% CI 1.06-1.41, p < 0.01). The annual incidence of acute myocardial infarction was 1.0 (1988), 1.8 (1989), 0.8 (1990), 2.9 (1991) and 4.7 (1992). The incidence of acute myocardial infarction was increased significantly in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.87 (95% CI 1.66-2.10, p < 0.01). The odds ratio of stroke to the general population was 4.25 (95% CI 3.10-5.82) in the pre-erythropoietin and 4.58 (95% CI 2.14-9.80) in the post-erythropoietin period. In acute myocardial infarction, it was 2.98 (95% CI 2.84-3.12) and 3.81 (95% CI 3.18-4.56). The odds ratio of acute myocardial infarction was significantly increased (p < 0.01). The introduction of erythropoietin was associated with an increased risk of cardiovascular disease, especially acute myocardial infarction. Erythropoietin may unmask the sclerotic lesion in chronic dialysis patients.

Cardiovascular Diseases↗

[Evidence for association between renal cell carcinomas and renal cystic diseases: nationwide survey in Japan].

OBJECTIVE: A scanty evidence previously reported regarding renal cell carcinomas occurring in association with renal cystic diseases prompted us to conduct a nationwide survey in July 1991. METHODS: A total of 507 hospitals responded to the questionnaire inquiring the clinical and pathological characteristics of renal cell carcinoma associated with renal cystic diseases over the previous 2 years. RESULTS: Renal cystic diseases were identified in 223 (3.9%) of 5,721 patients with renal cell carcinoma. The patients consisted of 181 men and 42 women who had a mean age of 55.2 +/- 12.5 years (SD). The renal cystic diseases comprised simple renal cysts in 72 patients (32%), acquired cystic diseases of the kidney (ACDK) in 62 (28%), cystic renal cell carcinoma in 56 (25%), multilocular renal cysts in 20 (9%), polycystic kidney in 3 (1.3%), miscellaneous cysts in 9 (4.0%), and unspecified cysts in 1 (0.4%). Simple renal cysts were more common in older patients, while ACDK and multilocular cysts were more predominant in younger patients. They included 71 dialysis patients (32%), of whom 62 (87%) had ACDK. Renal cell carcinoma occurred bilaterally in 12 patients (17%) on dialysis. Young male patients over a longer dialysis period were more susceptible to renal cell carcinoma. Low stage tumor, papillary type and granular cell subtype were more common in those on dialysis than in those without dialysis. In consideration of the Japanese general and dialysis population, we confirmed that dialysis patients with ACDK are more susceptible to renal cell carcinoma and those with polycystic kidney are less so. CONCLUSION: Renal cystic diseases may be associated with about 4% of renal carcinoma. Young male patients over a longer dialysis period who are diagnosed to have renal cysts should be regularly and closely followed by imaging study.

Adult↗

[Study on clinical courses of 7 patients undergone resection of adjacent organs in the treatment of locally extensive renal cell carcinoma].

Significance of surgical extirpation of a massive tumor involving adjacent viscera is still controversial, because this sort of extensive resection is unusual and its results are poor in terms of a short survival time. Here, we summarize the clinical courses of 7 patients who had been diagnosed as invasive renal cell carcinoma (RCC) and undergone extensive resection of the bowel and/or other adjacent visceras. In addition, a percentage of patients who had direct invasion and/or metastasis to adjacent viscera in routine autopsies was looked up in the Annual Report of the Pathological Autopsy Cases in Japan. Pathological diagnosis indicated that direct invasion was confirmed in 4 out of 7 patients. One patient was relieved from septic shock due to pelvicocolic fistula caused by a direct invasion of RCC. New metastases developed in all patients after the radical operation (2 - 30 mos), and 3 of them further underwent resection of the metastastic lesion(s). Although 5 patients ultimately died of cancer or its related diseases (mean survival time: 14.2 +/- 10.7 mos), other 2 (pT4 and pT3) who underwent resection of lung metastasis have survived for 19 and 72 months. Either an early occurrence of metastasis after local resection or a tumor predominantly composing of spindle cells might indicate a poor prognosis. Surgical extirpation should not be precluded when the patient is having severe symptoms related to extensive involvement of the adjacent visceras. We believe that it is appropriate to individualize in case of choosing patients for such extended radical surgery.

Aged↗

Cytokine production and cytotoxicity of lymphocytes in patients on maintenance short- or long-term haemodialysis.

The lymphocyte-mediated cytotoxicity and cytokine production of patients under maintenance haemodialysis were studied. The patients were subdivided into two groups; 27 patients receiving haemodialysis treatment for up to 3 years (group 1) and 27 patients for longer than 10 years (group 2). Twenty-six healthy volunteers (group 3) were used as controls. The immunological parameters assayed were NK cell and lymphokine-activated killer (LAK) cell activities, and production of both interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha by either peripheral blood mononuclear cells (PBMC) cultured with IL-2 or LAK cells. In group 1 both NK- and LAK-cell-mediated cytotoxicities were significantly suppressed as compared to those in group 3. The titre of IFN produced by LAK cells was also less than that in group 3. On the contrary there were no significant differences in cytokine production by PBMC in all three groups. Percentage of the cases with suppressed cytokine production seemed higher in group 1 than group 3. In addition there was a close correlation between the value of IFN-gamma and of TNF-alpha produced by PBMC in the patients on haemodialysis. Both the type of dialysis membranes used and the primary diseases did not significantly influence the results in group 1 and group 2. From these results it could be speculated that there are more patients with impaired immune function in group 1 than in group 3. In contrast there was no significant difference in the immune function tested between group 2 and group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of renal diseases and comorbid conditions on survival in chronic dialysis patients.

International and geographical differences in the survival rates of chronic dialysis patients can be explained by differences in primary renal disease, in the acceptance rate of elderly patients, and in predialysis comorbid conditions. Several studies have shown the effects of these factors on survival. However, in most studies, a large number of patients may leave for renal transplantation or transfer to other centers, so that precise analysis becomes impossible. Although the number of patients in our registry is not so large (n = 1,982), we have few such problems and were able to examine the effects of the above-mentioned factors on patient survival using the Cox proportional hazard model. Hazard ratios (HR) and 95% confidence intervals were 0.739 and 0.366-1.491 in patients with polycystic kidney disease (n = 38), 2.669 and 1.513-4.708 in patients with systemic lupus erythematosus (n = 39), 1.245 and 0.935-1.660 in patients with nephrosclerosis (n = 122), 1.815 and 1.447-2.229 in patients with diabetes mellitus (n = 374), and 1.595 and 1.201-2.117, respectively, in patients with other renal diseases (n = 146) when the HR in patients with chronic glomerulonephritis (n = 1,263) was taken as 1.00. HR and 95% confidence intervals were 1.222 and 1.016-1.470 in patients with one comorbid condition (n = 217) and 1.494 and 1.033-2.160, respectively, in patients with two comorbid conditions (n = 24) when the HR of patients with no predialysis comorbid conditions (n = 1,741) was taken as 1.00. Our data demonstrate the effects of renal diseases and number of predialysis comorbid conditions on the survival in chronic dialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Treatment of advanced renal cell carcinoma using regional arterial administration of lymphokine-activated killer cells in combination with low doses of rIL-2.

We investigated the usefullness and problems of arterial administration of lymphokine activated killer (LAK) cells in combination with systemic IL-2 in the treatment of metastatic renal cell carcinoma (RCC). Ten nephrectomized patients with extrapulmonary and/or nonresectable metastases were treated with arterial infusions of LAK cells and systemic rIL-2 (5 x 10(5) IU twice a day) for 1-12 weeks. Leukapheresis was carried out once or twice a week, and two LAK cell populations generated from two gravity subtypes of peripheral blood lymphocytes were administered separately. Five of 15 metastases treated showed appreciable regression of metastatic sites including bone, muscle and lymph nodes. Two of 15 showed a minor response. Local pain due to metastasis was relieved or disappeared in 6 patients. There was no correlation between the response of the patients and the number of LAK cells used. The 24- and 56-month survival rate was 50 and 25%, respectively. No serious side effects were experienced during treatment. We conclude that regional arterial administration of LAK cells in combination with a low dose of IL-2 is worthwhile as an alternative treatment modality to conventional therapy for a selected group of patients with advanced RCC.

Adult↗

[Clinical experience with modified Studer's bladder substitute].

We modified Studer's bladder substitute technique and constructed continent urinary reservoir for 7 patients with bladder tumors after transprostatic cystoprostatectomy. Studer's bladder substitute technique is characterized by both a tubular isoperistatic proximal limb of 20 cm of the ileum in continuity with the pouch constructed using the detubularized ileum and the ureters reimplanted into the proximal part of the limb using a simple lateral anastomosis of the ureters to the end of the limb. Our modifications, transprostatic resection, was that distal one third or fourth of the prostate was left after cystoprostatectomy followed by either enucleation of the whole residual prostatic tissue including the urethra (type II) or sharp resection of the tissue leaving the urethra (type III). A small hole in the lowest part of the pouch was anastomosed either to the residual prostatic capsule (type II) or to the residual prostatic urethra (type III). Our modified Studer's technique was simple, easy to perform, and had low risk of massive bleeding especially from the central vein overlying the appex of the prostate. Clinical results were as follows; 1) all patients were satisfied with the passing of their urine per urethra without any cutaneous stoma, 2) no patients had clinical signs of pyelonephritis after discharge, 3) urine was not infected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Evidence for increased cancer deaths in chronic dialysis patients.

We analyzed longitudinal data on the cancer mortality rate in chronic dialysis patients and in the general population in Okinawa, Japan. In the general population from 1980 to 1990, the mortality rate has been stable at approximately 1.300 males and 0.897 females per thousand persons year, the male to female ratio being 1.45. In the period from 1971 to 1990, we found 91 (4.6%) patients with cancer in a group of 1,982 (824 females and 1,158 males) chronic dialysis patients; forty-nine of the 91 patient (53.8%) died by April 1, 1991. Using the standard mortality rate in the general population, which was obtained for each sex and age class (0 to 34 years, 35 to 44 years, 45 to 54 years, 55 to 64 years, and > or = 65 years), we calculated the relative risk of death from cancer in dialysis patients. The risk ratio in dialysis patients was significantly increased, being 2.48 (P < 0.05) for males and 3.99 (P < 0.05) for females. The mean (+/- SEM) age at the time of death from cancer in the dialysis group was 60.1 +/- 2.0 years in the males and 60.1 +/- 2.1 years in the females; the males were 6.3 years younger than the general population and the females were 9.3 years younger. The proportion of patients with colon cancer (both sexes) and cancer of the uterus and breast (females) was higher in the dialysis patients than in the general population.

Adolescent↗

Evidence for high risk of cerebral hemorrhage in chronic dialysis patients.

One-half of the total deaths in chronic dialysis patients are due to cardiovascular disease; however, the precise incidence and relative risk of those compared to normals are not known. Therefore, we sought to determine the annual incidence of cardiovascular disease and relative risk of those on chronic dialysis to the general population. Both the general population (1.2 million, Census 1990) and chronic dialysis patients (N = 1,609) in Okinawa, Japan were studied prospectively from April, 1988, to March, 1991. Diagnosis of stroke was made by symptoms and brain CT scan, and acute myocardial infarction was done by changes in electrocardiogram and serum enzymes. The relative risk (observed/expected ratio) was calculated by using the standardized morbidity rate obtained in both sexes and age-class every 10 years in the general population. Forty-one stroke (8 cerebral infarction, 31 cerebral hemorrhage, and 2 subarachnoid hemorrhage) and four acute myocardial infarction cases were registered during the study period in chronic dialysis patients. The incidence per 1,000 person-year was 11.5 in stroke, 2.2 in cerebral infarction, 8.7 in cerebral hemorrhage, 0.6 in subarachnoid hemorrhage, and 1.1 in acute myocardial infarction. The relative risk compared to normals was 5.2 in stroke, 2.0 in cerebral infarction, 10.7 in cerebral hemorrhage, 4.0 in subarachnoid hemorrhage, and 2.1 in acute myocardial infarction. Cerebral hemorrhage occurred at 10 years younger than that of the general population (P < 0.001) and was associated with high prevalence of hypertension and low levels of serum albumin and cholesterol. Our results confirm the importance of blood pressure control and nutritional status in chronic dialysis patients.

Adolescent↗

Survival analysis of dialysis patients in Okinawa, Japan (1971-1990).

We analyzed longitudinal data obtained from the initiation of chronic dialysis in Okinawa, Japan. A total of 1,982 patients (824 females and 1,158 males) were registered in the Okinawa Dialysis Study (OKIDS) up to the end of 1990. The number of patients dying, undergoing renal transplantation, or being transferred was 605 (30.5%), 75 (3.8%), and 23 (1.2%), respectively. The mean acceptance rate per million population increased from 19.7 in 1971 to 1975 to 157.4 in 1986 to 1990. The percentage of diabetic patients and the annual gross mortality rate were, respectively 0% and 0.52 (1971 to 1975), 7.3% and 0.12 (1976 to 1980), 14.4% and 0.06 (1981 to 1985), and 24.6% and 0.07 (1986 to 1990). Cox proportional hazard analysis was used to determine the relative risk (RR) for sex, primary renal disease, age at entry, and the year of starting dialysis. The RR for males was 1.09 (1.00 for females) and the 95% confidence interval (CI) was 0.93 to 1.28. The RR for diabetics was 1.88 (95% CI; 1.55 to 2.28) when that for nondiabetics was set at 1.00. The RR (95% CI) for starting dialysis in 1976 to 1980, 1981 to 1985, and 1986 to 1990 was 0.65 (0.59 to 0.72), 0.43 (0.35 to 0.52), and 0.28 (0.20 to 0.38), respectively, when the RR in 1971 to 1975 was taken as 1.00. During the last two decades, the survival of chronic dialysis patients in Okinawa has continued to improve despite the large increase in acceptance rate, the older age of the new patients, and the increase in diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗