Biomedical subjects

E Okajima

Publications and source records attributed to E Okajima.

At least 37 records · Page 2Linked to original sources

PubMed1998

Inhibitory effect of tomato juice on rat urinary bladder carcinogenesis after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation.

The effects of tomato juice on urinary bladder carcinogenesis were studied in male Fischer 344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. The animals (6 weeks old) were given 0.05% BBN in their drinking water for 8 weeks, followed by diluted tomato juice for 12 weeks, and killed at 20 weeks after the beginning of the experiment. Lycopene concentrations in the livers of rats given tomato juice were elevated. Histopathological analysis of urinary bladder lesions revealed the numbers, but not incidences, of urinary bladder transitional cell carcinomas (TCCs) to be decreased in the group given tomato juice. No influence on the incidence of simple and nodullopapillary hyperplasias, invasion or differentiation of TCC was noted. These results indicate that tomato juice, presumably the contained lycopene and other anti-oxidants in combination, exerts an inhibitory effect on the development of TCCs in the rat urinary bladder.

Animals↗

PubMed1998

[Nuclear matrix protein 22 levels in patients with renal transplantation].

BACKGROUND: Nuclear matrix protein 22 (NMP22) is a parameter of cell death including apoptosis. To evaluate the clinical efficacy of NMP22 as a marker for rejection after renal transplantation, we measured serum and urinary NMP22. PATIENTS AND METHODS: We measured the concentrations of serum NMP22 by Konica-Matritech NMP22 kit, and CD3, 4, 8 which are surface markers of lymphocyte, in 11 patients with renal transplantation. The patients consisted of 10 males and 1 females whose serum creatinine ranged 1.0 to 2.7 mg/dl. Additionally, 9 healthy adults were employed as control subjects. And serum and urinary NMP22 were measured after transplantation sequentially in 5 of the patients. RESULTS: 1) In the patients, serum NMP22 values were higher than those in control subjects, statistically (p < 0.01). 2) There were not significant correlations between serum NMP22 and CD3, 4, 8, 3) At the periods of acute tubular necrosis and acute rejection, serum NMP22 values were higher than those at the stable periods. CONCLUSIONS: These results suggest that serum NMP22 is useful parameter of rejection in renal transplantation patients.

Adult↗

PubMed1998

[Results of clinical study with epirubicin hydrochloride injectable solution for superficial bladder cancer. IMI28 Injectable Solution Study Group for Superficial Bladder Cancer].

A 7-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with superficial bladder carcinoma. Epirubicin-RTU at the dose of 60 mg/30 ml was administered by intravesical instillation once daily for three (3) consecutive days and a 4-day drug-free interval followed; then the above intravesical instillation of Epirubicin-RTU was repeated for three consecutive days. All 20 registered cases were eligible, and 18 cases completed the whole course of the study. In 18 completers, CR was observed in 12 cases and PR was observed in one (1) case, for an efficacy rate of 72.2%. The primary adverse reaction was bladder irritation including pollakiuria 85.0% (17/20), miction pain 85.0% (17/20), and hematuria 80.0% (16/20), which were all reversible and tolerable. In urinalysis, urinary sediment showed leukocytes and erythrocytes, and proteinuria was observed. All were reversible. From the above results, this new formulation of Epirubicin-RTU was considered useful for the treatment of superficial bladder carcinoma.

Administration, Intravesical↗

PubMed1997

p53 mutation and absence of mdm2 amplification and Ki-ras mutation in 4-hydroxyamino quinoline 1-oxide induced transplantable osteosarcomas in rats.

Previously, we reported the establishment of two transplantable osteosarcomas, one induced by local application of a carcinogen, 4-hydroxyamino quinoline 1-oxide(4-HAQO), and another which developed spontaneously in rats, and their subdivision into four lines with high and low metastatic potential to the lung. In the present study, mutations of p53 and Ki-ras genes were investigated by PCR and SSCP followed by direct sequencing, and the amplification of the mdm2 gene was assessed by Southern blot analysis. Mutations of p53 in exon 7 were detected in 4-HAQO-induced transplantable osteosarcomas, but not their spontaneous counterparts, irrespective of the metastatic potentials. Direct sequencing revealed a CGC to CAC transition with an amino acid change of Arg to His, at codon 246. Neither Ki-ras mutations nor mdm2 amplification were detected in any of the transplantable tumors. The results suggest that while p53 mutations occurred during osteosarcoma development by 4-HAQO without mdm2 amplification and Ki-ras mutation does not contribute to osteosarcoma development in rats.

4-Hydroxyaminoquinoline-1-oxide↗

PubMed1997

Cripto expression in human urological tumors.

The expression of cripto, a novel transforming gene of the epidermal growth factor superfamily, was immunohistochemically examined in 20 cases of urinary bladder, one ureter, three renal pelvic, 18 kidney, nine prostate, three adrenal and four testicular tumors. Three cases of urinary bladder carcinomas, two of grade 2 and one of grade 3 transitional cell carcinoma which were T1a and T3b, and INF beta and INF gamma, respectively, showed positive binding of specific antibody, along with one cortical carcinoma of the adrenal gland positive staining. None of the ureter, renal pelvic, kidney, prostate or testicular tumors showed positive staining. These results indicate that cripto is not frequently expressed in urological tumors.

Adrenal Gland Neoplasms↗

PubMed1997

Shortened telomere length and increased telomerase activity in hamster pancreatic duct adenocarcinomas and cell lines.

Recently, shortened telomere length and increased telomerase activity have been demonstrated in various human cancers. In the study reported here, we ascertained whether gene changes are characteristic of pancreatic cancers. Hamster duct carcinomas and cell lines were investigated by Southern blot analysis for telomere restriction fragment (TRF) length and by the telomeric repeat amplification protocol (TRAP) assay for telomerase activity. Comparison with normal pancreas and spleen revealed shortened TRF length and markedly increased telomerase activity in primary pancreatic duct carcinomas induced by the rapid-production model as well as in a transplantable carcinoma and the cell lines. The enzyme level was 86.0-215.7 times the low levels found in control pancreas and spleen tissues. Late-passage Syrian hamster embryo cells, known to be immortalized and tumorigenic, had shorter TRFs than the original cells in primary culture did. These results indicate that hamster pancreatic duct carcinoma cells are immortalized, with the potential for proliferation ad infinitum, and provide a model for basic therapeutic research into the substances targeting telomerase.

Adenocarcinoma↗

PubMed1997

A histopathological mapping study of the urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in dogs.

Bladder tumors were induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in five Beagles and four mongrel dogs. The tumors were observed for long periods and the tumor progression was traced using histopathological mapping. The results indicated (1) that low-dose BBN over a long period induced multiple low-grade (G1-2) and low-stage (pTa-1) papillary tumors, resembling superficial bladder cancer in humans; (2) that high-dose BBN over a short period induced high-grade (G2-3) and high-stage (pT3b) nonpapillary tumors and carcinoma in situ (CIS) resembling invasive cancer and CIS in humans; (3) that beagle dogs required longer periods and higher total doses of BBN as compared with mongrel dogs; (4) that the tumors induced by low-dose BBN in beagles were observed without BBN as long as the animals lived, and neither increasing numbers of tumors nor malignant features such as deep infiltration and metastasis was observed; and (5) that low-dose BBN seems to induce mild dysplasia, which is followed by Brunn's nest-like proliferation in the lamina propria and nodular change, eventually leading to the development of papillary noninvasive transitional cell carcinoma (TCC); and that high-dose BBN seems to induce severe dysplasia which leads to CIS and nonpapillary invasive TCC. These results may contribute to clarifying the natural history of human bladder cancer.

Animals↗

PubMed1997

Inhibition by piroxicam of oxidative DNA damage, liver cirrhosis and development of enzyme-altered nodules caused by a choline-deficient, L-amino acid-defined diet in rats.

Previously, we have reported that aspirin, a cyclooxygenase (COX) inhibitor, can prevent the fibrosis, cirrhosis and generation of oxidative DNA damage, and the associated development of glutathione-S-transferase placental form (GST-P)-positive preneoplastic liver nodules, caused by a choline-deficient, L-amino acid-defined (CDAA) diet in rats. In the present study, in order to elucidate the role of COX pathway in liver lesion-induction by a CDAA diet, the modulatory effects of other distinct chemical classes of COX inhibitors were examined. A long-acting example, piroxicam (PIRO) (at doses of 0.01, 0.02, 0.04 and 0.06%) and the short-acting ibuprofen (IBU) (at doses of 0.02, 0.04 and 0.06%) and indomethacin (IND) (at doses of 0.005 and 0.008%) were administered in the CDAA diet to male F344 rats, and animals were killed after 12 and 30 weeks. In another experiment, IND was given in drinking water at doses of 0.001, 0.002 and 0.004%. None of the inhibitors affected the development of fatty liver caused by a CDAA diet, but PIRO at doses higher than 0.04%, strongly inhibited the development of GST-P-positive and neoplastic nodules as well as fibrosis, cirrhosis and formation of 8-hydroxydeoxyguanosine (8-OHdG) adducts. IBU at the highest dose also exhibited similar but much less pronounced inhibitory effects. With IND, there was only a tendency for inhibition with no clear dose-dependence. The results together with our previous findings, indicate that relatively strong COX inhibitors, acting irreversibly like aspirin or for extended periods like PIRO, can prevent the endogenous hepatocarcinogenesis associated with a CDAA diet, although not the development of a fatty liver, suggesting that an augmented COX pathway might play key roles in the causation of liver lesions in this model.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1997

Sequential changes of urinary pyridinoline and deoxypyridinoline as markers of metastatic bone tumor in patients with prostate cancer: a preliminary study.

Urinary concentration of pyridinoline and deoxypyridinoline, novel markers of bone resorption, was measured serially in patients with prostate cancer as markers of metastatic bone tumor. In 11 patients, five without bone metastasis and six with bone metastasis, pyridinoline and deoxypyridinoline were serially monitored for between 6 and 24 months. All patients received some hormonal therapy with or without radical prostatectomy. Pyridinoline and deoxypyridinoline were measured by ion-paired high-performance liquid chromatography and were adjusted according to urinary creatinine concentration. The sequential changes of pyridinoline and deoxypyridinoline were compared with those of prostatic specific antigen and alkaline phosphatase as well as with the findings of bone scintigrams. During the observation periods, no metastatic bone lesion developed and no significant changes in pyridinoline and deoxypyridinoline occurred in the five patients without bone metastasis. In the six patients with bone metastasis, the levels of prostatic-specific antigen showed relatively rapid decreases after starting therapy. In contrast, the levels of pyridinoline, deoxypyridinoline and alkaline phosphatase showed transient increases followed by gradual decreases in most cases. Correlations were observed between the changes of pyridinoline and deoxypyridinoline and the findings of bone scintigrams. The data suggest that serial monitoring of pyridinoline and deoxypyridinoline could be clinically useful as markers of metastatic bone tumors and may allow less frequent bone scintigrams during patient followup.

Aged↗

PubMed1997

Chemopreventive efficacy of piroxicam administered alone or in combination with lycopene and beta-carotene on the development of rat urinary bladder carcinoma after N-butyl-N-(4-hydroxybutyl)nitrosamine treatment.

The effects of the non-steroidal anti-inflammatory drug (NSAID) piroxicam and the carotenoids lycopene and beta-carotene, alone or in combination, on the development of rat superficial urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Male Fischer 344 rats, 6 weeks old, were given 0.05% BBN in the drinking water for 8 weeks followed by administration of piroxicam (0.0075% in the diet), lycopene (0.0025% in the drinking water) and/or beta-carotene (0.0025% in the drinking water) for 12 weeks, then killed for histological analysis of urinary bladder lesions. Cell proliferation potential was analyzed by immunohistochemical staining of the proliferative cell nuclear antigen (PCNA). Piroxicam alone, piroxicam+lycopene, and piroxicam +lycopene+ beta-carotene all significantly decreased the incidences and numbers of transitional cell carcinomas (TCCs), but the combination of piroxicam with carotenoids did not result in a clear improvement in the preventive potential of piroxicam. Piroxicam+ beta-carotene also caused a significant reduction and lycopene alone a slight but not significant reduction in the number of TCCs. In contrast, beta-carotene alone and lycopene+ beta-carotene were without inhibitory influence on any of the lesion categories examined, and the latter significantly increased the proportion of high-grade TCCs. Nevertheless, all of the chemopreventive agents, either alone or in combination, significantly decreased the TCC PCNA index, the effect extending to the surrounding epithelium in the piroxicam+lycopene and piroxicam+lycopene+beta-carotene groups. These results indicate that the NSAID piroxicam may be a more effective chemopreventive agent than lycopene and beta-carotene for superficial urinary bladder carcinogenesis.

Animals↗

PubMed1997

Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score.

BACKGROUND: The prevalence of lower urinary tract symptoms was determined by survey as an initial step in estimating the significance of benign prostatic hyperplasia (BPH) in Asia and Australia. METHODS: The symptom index (0 to 35) and quality-of-life (QOL) index (0 to 6) of the international prostate symptom score were measured in 7588 men in 9 Asian countries and 146 men in Australia. RESULTS: The percentages of Asian men considered to be symptomatic (symptom index > or = 8) were 18%, 29%, 40%, and 56% in the age groups of 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, respectively. For Australian men, these figures were 36%, 33%, and 37% in the 50 to 59, 60 to 69, and 70 to 79 year age groups, respectively. CONCLUSIONS: Our estimates indicate that the prevalences of symptomatic men in Asia and Australia are similar to or greater than those in Europe and America, and suggest BPH is similarly common in these areas.

Adult↗

PubMed1997

[Electroejaculation and assisted reproductive techniques in the patients with spinal cord injury].

BACKGROUND: Most of the patients with spinal cord injury (SCI) have fertility problems by an ejaculation and a poor fertility of the ejaculate. The objective of this paper is to evaluate the clinical effectiveness of electroejaculation (EE) and combined use of EE and assisted reproductive techniques for the patients with SCI. PATIENTS AND METHODS: Using a Seager Model, EE was attempted on 69 patients with SCI. Of the 69 patients 14 (20%) had cervical, 49 (71%) thoracic and 6 (9%) lumbar paraplegia. Mean patient age was 30 years (range 19 to 47 years) and the mean interval from spinal injury to the first EE was 9 years (range 1 to 38 years). Artificial insemination of husband (AIH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) were used to achieve a pregnancy. RESULTS: Antegrade ejaculation was obtained in 60 patients (86.9%). Patients with under-active bladder showed low induction rate (58.3%). Volume of ejaculate was ranged from 0.05 to 5.2 ml (average 1.0 ml) and sperm concentration was ranged from 0 to 546 x 10(6)/ml (average 40.3 x 10(6)/ml), but sperm motility was poor (range 0 to 70%, average 9.4%). Assisted reproductive techniques was attempted on 87 occasions (AIH 80, IVF 2, ICSI 5) on 15 couples. To date, there have been 4 pregnancies (AIH 2, ICSI 2) resulting in 3 healthy live births. CONCLUSION: Combined use of EE and assisted reproductive techniques is excellent management for the patients with SCI who wish to father children.

Adult↗

PubMed1997

[Long-term follow up of patients with spina bifida--a review of 228 cases].

BACKGROUND: The objective of this report is to evaluate the upper urinary tract changes of the patients with spina bifida who have been followed up for more than 10 years. METHODS: We analyzed 228 patients (97 males and 131 females) of spina bifida. Mean patient age was 18.7 years (10 to 51 years) and follow up period ranged from 10 to 27 years (mean 13.4 years). Upper urinary tract deterioration (Hydroureter and/or hydronephrosis), vesicoureteral reflux (VUR) and bladder deformity were investigated by excretory urography and voiding cystourethrography. We compared these 3 parameters in the initial and final examinations. RESULTS: In the initial examinations, upper urinary tract deterioration, VUR and bladder deformity were observed in 32.9%, 33.3% and 40.0%, respectively. During the follow up period, upper urinary tract was improved in 47.3% and VUR in 80.0%. Bladder deformity was disappeared in 14.4%. On the other hand, upper urinary tract was deteriorated in 9.3%. VUR and bladder deformity was newly developed or progressed in 8.0% and 29.3%, respectively. Finally, upper urinary tract deterioration, VUR and bladder deformity were observed in 31.3%, 18.2% and 52.0%, respectively. CONCLUSION: These results revealed that upper urinary tract and VUR were relatively controlled, however, bladder deformity was increased in its frequency. To prevent upper urinary tract deterioration, further analysis of sequential changes of urinary tract conditions should be demanded.

Adolescent↗

PubMed1997

[Bropirimine (U-54461S) late phase II clinical study for carcinoma in situ of the bladder. Japan Bropirimine Study Group].

Late Phase II clinical study with bropirimine (U-54461S), a novel oral antitumor agent that has interferon inducing and anti-proliferative activities, was conducted in patients with bladder CIS at 38 institutions nationwide. To investigate the efficacy and safety of the treatment, bropirimine was administered to the patients at the dose of 750 mg every two hours, three times a day, for three consecutive days with four-day drug withdrawal, based on the results of the preceding clinical studies up to early phase II. Among the 48 patients registered, 41 patients were evaluable for antitumor efficacy. Complete response (CR) was observed in 17 of them, no change (NC) in 18 patients, and progressive disease (PD) in 6 patients; so the efficacy rate was 41.5%. Classified by patient background, the efficacy rates were 58.3% (7/12) in patients with primary bladder CIS, 34.5% (10/29) in those with secondary bladder CIS, 45.5% (10/22) in those with Grade 3, and 23.8% (5/21) in those previously given chemotherapeutic agents or BCG by intravesical or other routes. Adverse drug reactions frequently observed were influenza-like symptoms such as fever and generalized malaise and gastrointestinal symptoms like anorexia and nausea/vomiting; these symptoms were all Grade 2 or milder. Abnormalities in laboratory tests, such as an elevation in GOT/GPT, neutropenia, and leukopenia were observed. These adverse effects were all tolerated by the patients. From the above results, bropirimine was considered to be a useful oral agent for the treatment of bladder CIS.

Administration, Oral↗

PubMed1997

[Clinical studies on lower urinary tract injury].

A total of 61 patients with lower urinary tract injuries were treated at Nara Medical University and its affiliated hospitals, between January 1985 and June 1995. There were 9 patients with bladder injuries and 52 patients with urethral injuries. The main cause of bladder injury was a traffic accident sustained in 4 patients (44.5%) and that of urethral injury was an occupational accident sustained in 27 cases (51.9%). The major associated injuries were a bone fracture seen in 45 patients (73.8%) and an intrascrotal hematoma seen in 28 patients (45.9%). Posterior urethral injuries associated with pelvic bone fractures were classified into 3 types according to the classification reported by Colapinto et al.; 8 patients (32.0%) into Type I, 8 (32.0%) into Type II and 9 (36.0%) into Type III. Of the 25 patients with posterior urethral injuries, 8 (32.0%) underwent immediate surgical treatment, 12 (48.0%) underwent initial cystostomies and delayed surgical treatment and 5 (20.0%) received indwelling of urethral catheters. Postoperative complications of urethral injury included urethral stricture in 30 patients (57.7%), incontinence in 3 (5.8%) and impotence in 3 (5.8%). A significant relationship between the duration of cystostomy and the incidence of postoperative urethral stricture was observed in our patients. Therefore at least three weeks of cystostomy will be necessary in the management of patients with complicated urethral injuries.

Accidents, Occupational↗

PubMed1997

[Urological emergency for cancer patients].

We summarized here the urological emergency status accompanied by cancer, such as urinary obstruction, bleeding and renal failure. Hydronephrosis occurs due to obstructive change and post-renal failure finally results after complete obstruction of bilateral ureters. Patients with obstructive disease are treated with percutaneous nephrostomy or indwelling double-J catheter. Bladder tamponade develops after bleeding of the urinary tract. Patients with bleeding are treated by bladder irrigation or transcatheter arterial embolization. Acute renal failure (ARF) includes pre-renal ARF, renal ARF and post-renal ARF, necessitating emergency hemodialysis. The emergency status can be often observed simultaneously, so careful examination and rapid treatment are necessary.

Emergencies↗

PubMed1997

[A comparative study of the effects of granisetron alone and a combination of granisetron plus steroids on CDDP-based combination chemotherapy-induced emesis--outcomes of a multicenter randomized comparative study using the central registration method. Nara Medical University Kytril Study Group].

The present investigation was conducted to examine the effects of granisetron alone and a combination of granisetron plus steroids on CDDP-based combination chemotherapy-induced emesis by multi-institutional randomized comparative trial using a central registration method. A total of 62 patients with urological cancer enrolled this study were randomized into two groups: granisetron (40 micrograms/kg) only group and granisetron (40 micrograms/kg) plus steroids (500 mg of methylprednisolone or 8 mg of dexamethasone) group. There were 31 patients eligible in the granisetron only group and 28 in the combination group. The same anti-emetic treatments were given in the recycling courses of chemotherapeutic regimens. Therefore, eligible patients of the second and the third cycle numbered 31 (17 in the granisetron only group, 14 in the combination group) and 21 (11 in the granisetron only group and 10 in the combination group). Significant inhibition of acute emesis in combination group was observed when compared with the granisetron only group in each cycle. Delayed emesis was also significantly inhibited in the combination group on Day 2 and 3 of the first cycle and on Day 2 of the second and third cycle. In addition, appetite loss was significantly reduced in the combination group on Day 2 and 3 of the first and second cycle. No adverse events were seen in either group. These results suggested that a combination of granisetron and steroids was useful for preventing CDDP-based combination chemotherapy-induced emesis.

Adult↗

PubMed1997

[Total androgen blockade for prostate cancer].

To evaluate the usefulness of total androgen blockade (TAB) therapy, we retrospectively studied 45 patients with prostate cancer who received TAB therapy as the first-line treatment. The clinical stage was A2 in 1 patient, B1 in 10, B2 in 9, C in 6, D1 in 3 and D2 in 16. Seven, 25 and 13 patients had well, moderately and poorly differentiated adenocarcinomas, respectively. The patients were placed on 1 of 3 TAB regimens: Luteinizing hormone-releasing hormone (LH-RH) agonist and flutamide (group 1), LH-RH agonist and chlormadinone acetate (group 2) and a surgical castration and flutamide (or chlormadinone acetate) (group 3). The therapeutic effect was evaluated at 12 weeks according to the response criteria in the general rules for clinical and pathological studies on prostatic cancer. The overall response was partial response (PR) in 35 patients (77.8%), no change (NC) in 6 (13.3%) and progressive disease (PD) in 4 (8.9%). PR was obtained in 81.3, 79.2 and 60% of the patients in groups 1, 2 and 3, respectively. One patient with PD responded briefly to flutamide withdrawal. None of the patients developed any severe adverse effects. In conclusion, the first-line TAB therapy is effective for prostate cancer with a lower risk than estrogens. Relapsed cases should be followed for flutamide withdrawal syndrome during TAB therapy.

Adenocarcinoma↗