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Biomedical subjects

E Okajima

Publications and source records attributed to E Okajima.

At least 19 recordsLinked to original sources

Initiation of hepatocarcinogenesis by endogenously formed N-nitrosobis(2-hydroxypropyl)amine, N-nitrosodiethanolamine and N-nitroso-2,6-dimethylmorpholine in rats.

Initiation activities of endogenously formed N-nitrosobis(2-hydroxypropyl)amine (NBHPA), N-nitrosodiethanolamine (NDELA) and N-nitroso-2,6-dimethylmorpholine (NDMM) were investigated in a modified short-term assay for rat hepatocarcinogenesis. Male Wistar rats were fed 1% bis(2-hydroxypropyl)amine, 0.5% diethanolamine or 0.25% 2,6-dimethylmorpholine in the diet plus 0.3% sodium nitrite in the drinking water. Two weeks after starting the experimental regimen they underwent 2/3 partial hepatectomy and were then maintained on the respective diets for a further week. Following a 2 week recovery period on basal diet rats were subjected to a resistant hepatocyte regimen consisting of 0.02% 2-acetylaminofluorene in the diet for 2 weeks and 1 mg carbon tetrachloride/kg body wt by gavage at the midpoint. Initiation activity was assayed by measuring hepatic foci positive for gamma-glutamyltranspeptidase. Numbers of such foci per cm2 were significantly increased in the groups given the secondary amines together with nitrite compared with values for groups given each precursor or nitrite alone. Further, the numbers of lesions were essentially similar to those found in rats given carcinogenic doses of NBHPA, NDELA and NDMM. The results clearly of demonstrate hepatocyte initiation activities of endogenously formed carcinogens, presumably NBHPA, NDELA and NDMM.

Animals

Basic fibroblast growth factor as a candidate tumor marker for renal cell carcinoma.

The present investigation was conducted to determine serum levels of basic fibroblast growth factor (FGF) by enzyme immunoassay in patients with various urogenital tumors. Renal cell carcinoma had a higher tendency (28 of 52, 53.8%) toward increased serum levels of basic FGF than any of the other urogenital tumors, and increased serum basic FGF was detected more frequently in patients with advanced renal cell carcinoma. Analysis of histological pattern indicated that renal cell carcinoma with a solid or tubular component is more likely to produce basic FGF. However, no significant difference was seen between the percentage of clear cell type tumor patients with increased serum basic FGF (50.0%) and the percentage of granular cell type tumor patients with increased serum basic FGF (66.7%). Five of 8 patients with renal cell carcinoma who underwent selective renal venous sampling before nephrectomy showed increased serum basic FGF in the renal vein from the affected kidney. After resection of the affected kidney to remove the cancer, serum basic FGF disappeared within 2 weeks. However, residual huge tumor or postoperative disease prolonged the increased levels of basic FGF in 2 patients, indicating that basic FGF is produced from and secreted by tumor tissue itself. These findings suggest that serum basic FGF can be useful in the diagnosis, and in evaluating the prognosis, of patients with renal cell carcinoma.

Biomarkers, Tumor

[A study on international prostate symptom score in the assessment of therapeutic effects and severity of symptoms due to benign prostatic hyperplasia].

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease among elderly men in Japan. Recently, various non-invasive treatment modalities have been developed, however the criteria for the diagnosis and therapeutic effects of BPH have not been established yet. World Health Organization sponsored International Prostate Symptom Score (I-PSS) was devised. The criteria, however, were limited to evaluate the frequency of the subjective symptoms of BPH. In addition, this criteria did not include the quality of life (QOL) score. PATIENTS AND METHODS: We examined I-PSS and a new by modified symptom score for patients who underwent TUR-P. RESULTS: The efficacy of TUR-P could be confirmed by I-PSS, however the criteria proposed in I-PSS and in our modified symptom score were shown to be inadequate to evaluate QOL, and to be not specific scale for BPH. It was demonstrated that objective findings such as peak flow rate, residual urine volume and prostate volume did not correlate with the QOL score, however each objective and subjective significantly improved after TUR-P. CONCLUSION: These results suggested that further effort should be made to establish reliable criteria for the diagnosis and evaluation of therapeutic efficacy considering QOL in BPH patients.

Aged

[Fine needle aspiration cytology in screening of prostatic cancer].

Between October 1990 and June 1993, 112 patients underwent fine needle aspiration cytology and core needle biopsy of the prostate under transrectal ultrasonographic guidance. They were suspected of having prostatic cancer from the prostatic antigen level, digital rectal examination and/or transrectal ultrasonography. Twenty seven of the 112 cases (24%) were diagnosed with prostatic cancer. Their cytological diagnoses showed 22 class IV or V, 2 class III, and 3 class I or II. Efficiency, false negative rate and false positive rate were 86%, 11% and 0% in fine needle aspiration cytology. We could obtain sufficient samples for fine needle aspiration cytology in all cases. No severe complication was observed. However, we missed 3 patients, in fine needle aspiration cytology, who were strongly suspected of having prostatic cancer, and reexamination or additional core needle biopsy would have been necessary on 15 of the 112 patients (13%) who showed false negative or class III cytological results, if we had screened prostatic cancer only by fine needle aspiration cytology. In conclusion, fine needle aspiration cytology may not be as useful as core needle biopsy to screen prostatic cancer.

Adenocarcinoma

[A case of patent urachus].

A case of congenital patent urachus is reported. A 12-month-old boy was referred to our outpatient clinic with the complaint of watery discharge from the navel. A cystography revealed the communication between the dome of the urinary bladder and the umbilicus. Excretion from the umbilicus of indigocarmine solution instilled into the urinary bladder was recognized. There were no complicated abnormalities in other organs. The patient underwent radical operation. Herein, we collected 164 cases of urachal disorders reported in Japan and reviewed the incidence, clinical symptoms, diagnosis and treatment. The classifications of the disease were briefly discussed.

Humans

[Measurement and clinical significance of serum concentrations of pyridinium cross-links in patients with renal osteodystrophy].

Serum concentration of the pyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), which are markers of bone resorption, was measured by high-performance liquid chromatography in 56 patients on maintenance hemodialysis. The following analyses were conducted: 1) correlation with known markers of bone metabolism, 2) correlation with findings on bone changes on plain X-ray film, 3) elimination rates by hemodialysis, and 4) increment per day in pyridinoline after hemodialysis (delta Pyr/day). There was a very close correlation found between serum Pyr and Dpyr (r = 0.861). Both serum Pyr and Dpyr showed correlations with known markers of bone metabolism: C-PTH (r = 0.806 and r = 0.747, respectively), M-PTH (r = 0.766 and r = 0.749), osteocalcin (r = 0.717 and r = 0.693), Alp-3 (r = 0.523 and r = 0.441) and tartrateresistant acid phosphatase (r = 0.549 and r = 0.548). In addition, a correlation between the duration of hemodialysis and serum Pyr and Dpyr was observed (r = 0.426 and r = 0.318, respectively). When comparing the mean values of serum Pyr or Dpyr in three groups of patients divided according to bone changes seen on plain X-ray film, there were statistically significant differences between the group without bone changes and the remaining two groups with some bone changes (p < 0.05). A mean of 45.3% of serum Pyr was removed by hemodialysis. The serum Pyr level returned almost to the original concentration by the following hemodialysis. delta Pyr/day showed a close correlation with C-PTH (r = 0.656).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Current practice and controversies in urinary diversion--the selection of the operation method of urinary diversion and postoperative care].

Since Kock et al. reported a low pressure continent reservoir using detubularized ileal segment as urinary diversion following cystectomy, continent urinary diversion including neobladder has been focused upon. On the other hand, ureterocutaneostomy, or ileal conduit as an incontinent urinary diversion is still commonly used, and especially the latter form is usually performed in many hospitals. These facts suggest that it is difficult to conclude that continent urinary diversion regarded as an excellent operation with good quality of life (QOL) is a generally acceptable method and that there are still some problems to decide the indication for urinary diversion. We discuss the problems about the postoperative complications and care of urinary diversion after cystectomy and our opinion about the selection of these operations.

Humans

[Complications and quality of life in patients with ileal conduit diversion].

A series of 180 patients treated with ileal conduit urinary diversion at Nara Medical University and its affiliated hospitals were reviewed. The patients ages at the time of operation ranged from 21 to 79 years old with an average of 60.9 years old and the average postoperative follow-up period was 44.2 months. Early complications occurred in 60 patients (33.3%) and 9 (5.0%) of them resulted in post-operative deaths. Late complications were noticed in 54 (31.6%) of the 171 patients. Frequent late complications included peristomal dermatitis (37.3%), ureteroileal stenosis (17.9%) and urolithiasis (11.9%), for the latter two of which endourological treatments seemed to be effective. To be emphasized is that more attentive care should be paid to the condition of the peristomal skin during follow-up.

Adult

Immunization with anti-idiotype monoclonal antibodies bearing the internal image of the renal-cell carcinoma-associated antigen G250 induces specific cellular immune responses.

We have previously isolated and characterized 6 anti-idiotype antibodies (Ab2s) directed against monoclonal antibody G250 (MAbG250) which reacts with a tumor-associated antigen (TAA) expressed in a large proportion of human renal-cell carcinomas (RCC). These 6 Ab2s (NUH31, 51, 71, 82, 91: IgG1, NUH44: IgG2a) showed MAbG250 binding site specificity and induction of anti-TAA antibody resembling MAbG250 (so-called AbI') in rabbits, indicating that they are internal image antibodies. To investigate whether these Ab2s could induce G250-TAA-specific cell-mediated immunity, delayed-type hypersensitivity (DTH) tests were carried out with G250 antigen-positive and/or -negative cells in the ears of BALB/c mice. Mice primed with Ab2 showed antigen-specific DTH responses, whereas no significant DTH response was observed with G250-negative cells. This antigen-specific DTH could be transferred to naive mice by lymphocytes harvested from Ab2-sensitized mice. In addition to the classical DTH responses observed 24 and 48 hr after tumor challenge, an early-phase antigen-specific hypersensitivity response was seen 2 hr after challenge. This early component of the specific hypersensitivity reaction but not the classical DTH could be transferred to naive mice by serum from Ab2-sensitized mice, indicating that the early reaction was due to serum factors. These findings demonstrate that all Ab2s induced tumor-specific cellular immune responses directed against human RCC, and suggest that they may be useful as RCC-TAA surrogates, i.e., as tumor vaccines for RCC patients.

Animals

Vaccination with anti-idiotype antibodies mimicking a renal cell carcinoma-associated antigen induces tumor immunity.

We have previously isolated and characterized 6 different internal image mouse monoclonal anti-idiotype antibodies (Ab2) directed against the paratope of mouse monoclonal antibody G250 (MAbG250, Ab1), which specifically reacts with human renal cell carcinoma (RCC). These Ab2s (NUH31, 44, 51, 71, 82 and 91) demonstrated specificity for the combining site of Ab1, and appeared to recognize 2 partly overlapping idiotopes on Ab1. In this study, we further characterize the fine specificity of the Ab2, investigate whether the immunogenicity of Ab2 could be enhanced by conjugation to a carrier and investigate the anti-tumor efficacy of Ab3 sera in mice challenged with RCC. Immunization of animals with Ab2 conjugated to keyhole limpet hemocyanin as carrier protein resulted in a 2-fold increase in antigen-specific anti-anti-idiotype antibodies (Ab3) as compared with immunization using Ab2 alone. Specific reactivity was observed with antigen-positive cell lysates, and all Ab3 sera contained immunoglobulin resembling Ab1 (Ab1'), as shown by competitive Ab1-antigen binding assays. Fine-specificity studies of Ab3 sera revealed that the Ab2s can be divided into 4 mutually exclusive groups, showing that the 6 Ab2s recognize 4 slightly different idiotopes in the Ab1 binding pocket. Treatment of RCC-challenged mice with Ab3 sera resulted in significant tumor growth inhibition and lower tumor take rates as compared with control groups. Ab3 sera obtained from NUH-91-immunized animals showed superior characteristics as compared to the other Ab3 sera: no tumors remained after 5 weeks of Ab3-NUH91 treatment. Our findings indicate that the Ab2 elicit powerful anti-tumor effects in immune-competent animals.

Adjuvants, Immunologic

Internal image anti-idiotype antibodies related to renal-cell carcinoma-associated antigen G250.

The potential usefulness of internal-image anti-idiotype antibodies (Ab2s) in modulating hosts' immune responses to tumor-associated antigen (TAA) have stimulated considerable interest in the development and characterization of Ab2s. Six different mouse monoclonal Ab2s (NUH31, 44, 51, 71, 82 and 91) were generated against murine monoclonal antibody G250 (MAbG250) which recognizes a human renal-cell carcinoma-associated antigen. All 6 Ab2s showed specificity for the MAbG250 paratope in Western-blot analysis. In inhibition assays, all Ab2s were able to compete with the nominal antigen, albeit with differing efficiency. Based on cross-blocking studies for idiotope mapping, the Ab2s could be divided into 2 groups (group I; NUH31, 51, 71, group 2; NUH44, 82, 91). However, cross-reactivity between these 2 groups was observed, indicating that they recognized partly overlapping epitopes on the paratope of MAbG250. Sera from rabbits immunized with Ab2s showed reactivity with G250 antigen-positive cell lysates, but not with antigen-negative cell lysates. Additional studies revealed that all Ab2s were able to induce anti-anti-idiotype antibodies resembling MAbG250 (Ab1'). These findings suggest that the Ab2s functionally mimic the original G250 antigen and may be of use in the immunotherapy of human renal-cell carcinoma.

Animals

Prospective randomized study of prophylaxis of superficial bladder cancer with epirubicin: the role of a central pathology laboratory. Nara Uro-oncology Research Group. (NUORG).

The preliminary results of a multi-institutional prospective randomized study of the prophylaxis of superficial bladder cancer using epirubicin (protocol NUORG SBT-003) are reported. The subjects were 129 patients with untreated superficial bladder cancer (< or = T1b, < or = G2) who were randomized into 2 groups: a transurethral resection (TUR)-alone group (63 patients) and a TUR + intravesical epirubicin (20 mg/40 ml, 30 times/2 years) group (66 patients). The nonrecurrence rate observed in the epirubicin group was significantly higher than that seen in the control group. To unify the pathological diagnosis, a central pathology laboratory (CPL) was set up for extramural review. The correspondence of the pathological diagnosis of TUR-Bt specimens between the CPL and the local pathology laboratory (LPL) was 70.5% in grading and 51.9% in staging. There was a tendency for overdiagnosis by the LPL for both the grade and the stage of tumors. However, differing interpretations by pathologists seem to exert little influence on the nonrecurrence rate at interim analysis. Further observation will be necessary to clarify the prophylactic efficacy of low-dose, long-term periodic intravesical epirubicin instillation and the influence of the disagreement in pathological findings between the CPL and the LPL on the analysis of the results.

Administration, Intravesical

[Urethral opening pressure as a parameter for introduction of the proper voiding modality in myelodysplastic patients].

To introduce the proper voiding modality to patients with myelodysplasty, urethral opening pressure (UOP), an intravesical pressure just at the beginning urine flows out beyond the external urethral sphincter, was measured in 63 myelodysplastic patients. Among 45 renal units with any morphological or functional changes at the first UOP measurement, 37 units (82.2%) were included in the high UOP group (> or = 35 cmH2O). And among 41 ureters with VUR of more than grade 2, 32 (78.0%) were in the high UOP group. In addition, deformity of the urinary bladder was observed in 36 patients, and 26 (72.2%) of these bladders showed high UOP values. Therefore, all the patients could be divided into two groups: high UOP group (> or = 35 cmH2O, 28 cases) and low UOP group (< 35 cmH2O, 35 cases). Twenty-three patients (82.1%) with high UOP values had been mainly treated with clean intermittent catheterization (CIC). In contrast, 24 patients (68.6%) with low UOP values had been allowed to urinate by Credè' or Valsalva's method. In the followup study for 40 to 44 months, patients in the CIC group obtained good prognosis as for morphological or functional changes of the urinary tract. On the other hand, patients in the Credè' or Valsalva's method group showed a significantly higher deterioration rate in the high UOP group (80.0%) than that in the low UOP group (9.1%) (p < 0.005). From these results, hopely that in myelodysplastic patients with the underactive detrusor, CIC may be introduced for low pressure voiding to those who show high UOP values as early as possible. On the other hand, those who show low UOP values may be managed with Credè' or Valsalva's method as well as CIC. Thus, UOP is considered a possible prognostic factor for the morphological and functional changes of the urinary tract, which may be a useful parameter in decision of voiding modalities in myelodysplastic patients.

Adolescent

Sequential changes in stem cell markers in peripheral blood and leukapheresis samples after injections of recombinant human granulocyte colony-stimulating factor in patients with urogenital malignant solid tumors: a preliminary study.

In order to evaluate the mobilization effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on peripheral blood stem cells (PBSCs), rhG-CSF was given to patients with urogenital malignancy before chemotherapy. Markers for the stem cells, such as colony forming unit-granulocyte/macrophage (CFU-GM) and burst forming unit-erythrocyte (BFU-E), were sequentially monitored in peripheral blood and leukapheresis samples. Five patients, including a 13-year-old boy, were given 5 micrograms/kg rhG-CSF subcutaneously: the pediatric case for four consecutive days and the adult cases for six consecutive days (53-72 years of age). None of the patients had received chemotherapy within the four weeks prior to the start of the rhG-CSF series. PBSC collections were performed on the fifth day in the pediatric case and on the fifth and seventh days in the adult cases. Progenitor cells were monitored by methyl-cellulose cell culture techniques. CFU-GM on day 5 of the rhG-CSF series in peripheral blood increased 14- to 53-fold compared with samples taken immediately before the series. CFU-GM in the leukapheresis products on day 5 was greatest (70 x 10(3)/kg) in the pediatric case and least (14 x 10(3)/kg) in the oldest patient's case. The totals of the CFU-GM collected by two phereses in the adult cases were 21-73 x 10(3)/kg and the totals of CD34 positive cells were 0.6 to 1.4 x 10(6)/kg. The data suggest rhG-CSF to induce sufficient PBSCs for bone marrow rescue into the peripheral blood without any preceding chemotherapy. The patient's age may, however, be a contributory factor in using this method.

Adolescent

[Clinical studies of renal trauma].

A total of 70 patients with renal trauma were treated at the Department of Urology, Nara Medical University and Nara Prefectural Hospital, including Life-Saving Emergency center, from January 1982 to June 1993. They were between 3 and 79 years old (mean 30.0) and preponded to the younger generation. The main cause of injury was traffic accident in 46 cases (65.7%). According to the Classification of Renal Injury by the Japanese Association for the Surgery of Trauma in Japan, there were 31 cases (44.3%) of type I (subcapsular injury), 18 cases (25.7%) of type II (superficial injury), 15 cases (21.4%) of type III (deep injury), and 6 cases (8.6%) of type IV (pedicle injury). Surgical treatment was performed in 17 cases (24.2%). The major associated injuries were bone fracture in 32 cases (45.7%), lung injury in 17 cases (24.2%), and liver injury in 15 cases (21.4%). Furthermore, hydronephrosis and ureteral tumors were incidentally found in 4 and 1 patient during the course of treatment for renal trauma. Post-traumatic plasma renin activities (PRA) in types III and IV were significantly higher than those in types I and II. Hypertension developed in 1 case of types I and II and 4 cases of types III and IV. The mean level of PRA was significantly decreased 2 years after renal injury in both groups. We should bear in mind that renal trauma may be associated with other urological diseases such as hydronephrosis and urological malignancies, and post-traumatic PRA should be followed carefully.

Adolescent

[Asymptomatic synchronous bilateral granulomatous orchitis--a case report].

A case of asymptomatic synchronous bilateral granulomatous orchitis in a 79-year-old male patient is described. He was diagnosed with asymptomatic microhematuria, and referred to our outpatient clinic. In the physiological examination, there were stone-hard indurations in his bilateral testes. There were multiple hypoechoic areas in the scrotal ultrasonography. Bilateral testicular tumor was suspected. However, histological findings after bilateral orchidectomy revealed granulomatous orchitis. Abdominal computed tomography revealed swelling of the paraaortic lymph nodes postoperatively. However no malignant origin was detected. Differential diagnosis between testicular tumor and granulomatous orchitis is very difficult in any examination except by histological findings. Conservative therapy is usually not effective, and most cases are treated by orchidectomy. Bilateral cases of this entity are relatively rare, but in young cases, it is necessary to distinguish the granulomatous orchitis from the testicular tumor before surgical intervention.

Aged