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Biomedical subjects

J Shimazaki

Publications and source records attributed to J Shimazaki.

At least 163 records · Page 9Linked to original sources

Persistent epithelial defect following penetrating keratoplasty: an adverse effect of diclofenac eyedrops.

Association between the use of diclofenac sodium (DfNa) eyedrops and the development of a postkeratoplasty persistent epithelial defect (PED) of the cornea were studied. In 100 consecutive patients undergoing penetrating keratoplasty who had no limbal or conjunctival epithelial abnormalities, 12 (12.0%) developed PED (persistence of epithelial defect for > 8 days after keratoplasty) postoperatively. The use of DfNa eyedrops correlated significantly with the development of PED (p = 0.0001, chi-square test). DfNa eyedrops were used in 19 eyes postoperatively, eight of which (42.1%) showed signs of PED. The type of preservation media, preservation time, indications for keratoplasty, or the surgical procedures performed did not correlate with the development of PED. These results indicate that DfNa eyedrops are toxic to the corneal epithelium postkeratoplasty. The eyedrops should be used with great care in patients with disorders of the corneal epithelium.

Adult↗

Allergic conjunctivitis caused by sugi (Cryptomeria japonica D. Don) pollen out of season.

Allergic conjunctivitis caused by sugi pollen is considered to be strictly a "spring disease". However, a recent report indicated that sugi pollen is scattered not only in spring but in all seasons, especially in the autumn. We retrospectively determined the number of patients with allergic conjunctivitis caused by sugi pollen during each month for 3 consecutive years, and also investigated the growth of sugi male cones in November for four years. Diagnosis of allergic conjunctivitis was based on symptomatic complaints, clinical findings, and serum sugi pollen specific IgE measured by the Multiple Antigen Simultaneous Test 16. The annual incidence of allergic conjunctivitis peaked twice, once in spring and again in autumn. Scattering of sugi pollen occurred mostly in March and October, whilst the growth of sugi male cones was highest in November. Thus, allergy to sugi pollen can cause allergic conjunctivitis both in the spring and late autumn.

Adolescent↗

Abnormalities of the adenomatous polyposis coli gene in human oral squamous-cell carcinoma.

Recent studies have suggested that abnormalities in the adenomatous polyposis coli gene (APC gene) are associated with the development not only of familial adenomatous polyposis coli (FAP) but also of cancers in digestive organs. In order to elucidate whether abnormalities of the APC gene could contribute to the development of oral squamous-cell carcinoma (SCC), genomic DNAs from tumors and normal tissues of 24 unrelated Japanese patients were examined by using PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) and sequence analyses. Five novel nucleotide substitutions of the APC gene in tumor tissues were identified in 3 patients with oral SCC (12.5%), resulting in 3 amino-acid replacements or a truncation of the APC gene product. We also examined 24 tumor and 24 normal tissue samples for loss of heterozygosity (LOH) at exon 11 of the APC gene by PCR-LOH assay. In this analysis, 45.8% of samples were informative and LOH was detected in 72.7% of informative cases. The frequency of LOH in oral SCC was similar to that previously reported in esophageal SCC. These results suggest that abnormalities in the APC gene are associated with the development of human oral SCC.

Base Sequence↗

Suppression of metastasis of rat prostatic cancer by introducing human chromosome 8.

In previous allelotype analyses of human prostatic cancer specimens, allelic loss on the short arm of chromosome 8 is frequently observed. However, it is still unclear whether this allelic loss is an initial event or a later one in development of prostatic cancer. Our previous studies demonstrate that introduction of human chromosome 11 into highly metastatic rat prostatic cancer cells results in suppression of metastatic ability without suppression of the in vivo growth rate or tumorigenicity of the hybrid cells (T. Ichikawa et al. Cancer Res., 52: 3486-3490, 1992). To clarify the role of human chromosome 8 in prostatic cancer, this chromosome was introduced into highly metastatic rat prostatic cancer cells using microcell-mediated chromosome transfer. Introduction of human chromosome 8 resulted in suppression of metastatic ability of the microcell hybrids, whereas no suppression of the in vivo growth rate or tumorigenicity was observed. These results demonstrate that human chromosome 8 contains metastasis suppressor gene(s) for prostatic cancer derived from a rat. These also suggest that human chromosome 8 has an important role in development of prostatic cancer.

Animals↗

Effect of early exposure of flutamide on subsequent growth of transplantable rat prostatic tumor (dunning R-3327).

Rat transplantable prostatic tumors (Dunning R-3327) were treated with flutamide before tumors grew palpable, in order to examine the effect of short term treatment of antiandrogen for prostatic cancer in latent period on the growth after appearance of tumor. Flutamide delayed an appearance of the tumor nodule and retarded the growth rate in proportion as treatment began earlier. Flutamide also reduced final tumor volume. Flutamide-treated tumors histologically consisted of small or dilated glandular structure with an increase in stromal area, but androgen receptors were preserved. Flutamide-treated tumor showed slow growth with androgen sensitivity when transplanted to intact rats, showing prolonged influences of antiandrogen on tumor growth. There was no significant difference between flutamide-treated and control groups in weight of accessory sex organs and serum androgen or estrogen levels. In conclusion, flutamide treatment may retard an appearance of prostatic cancer concomitant in benign prostatic hyperplasia.

Animals↗

Natural course of human benign prostatic hyperplasia with relation to urinary disturbance.

To examine the natural course of human benign prostatic hyperplasia (BPH), cases in health care examination with or without slight urinary symptoms were examined by echography. In comparison with these cases, the size of the prostate was examined in patients who received prostatectomy. Prostatic sizes of health care cases varied widely along with increasing age, but could be divided into two groups: increasing or no-change. According to serial determinations of prostatic sizes in the increasing group, the annual growth rate of the prostate was calculated as 1.65 +/- 1.13 and 0.85 +/- 0.44 g in men < 65 years old and in men > or = 65 years old, respectively. Distribution of prostatic sizes as a function of age in health care cases was similar to that in operated patients, showing that the size was not correlated with urinary symptoms or surgical indication. Since uroflow rates decreased along with increasing age in the no-change group of operated patients, aging was a factor in deterioration of uroflow. Between the increasing and the no-change groups in health care cases, differences were found in total cholesterol and neutral fat in serum, in addition to gamma-seminoprotein; the latter may be due to differences in the size of the prostate. In conclusion, natural course of the prostatic hyperplasia is separated into two groups, increasing and no-change. Occurrence of urinary symptoms does not simply relate to an increase in prostatic weight but, at least in part, to the aging process.

Adult↗

Effect of naftopidil on urethral obstruction in benign prostatic hyperplasia: assessment by urodynamic studies.

Thirty-two patients with voiding dysfunction attributable to symptomatic benign prostatic hyperplasia were treated with naftopidil, an alpha 1-blocker, at doses of 25-75 mg/day for 4-6 weeks. The efficacy of the drug was assessed from the changes in urinary symptoms and urodynamic data. Total symptom scores were significantly reduced after treatment (P < 0.001). Average flow rate and maximum flow rate were significantly increased (P < 0.001 and P < 0.001, respectively), and residual urine volume, residual urine rate (ratio of residual urine volume/sum of voided volume and residual urine volume), and maximum urethral closure pressure were significantly (P < 0.05, P < 0.01, and P < 0.05, respectively) reduced, and at bladder capacity, the first desire to void was significantly (P < 0.05) increased. The pressure/flow study demonstrated no changes in intravesical pressure at maximum flow, but a significant (P < 0.05) reduction in minimum urethral resistance. A mild side effect (dizziness) was noted in one patient (3.3%), which soon disappeared after the dose was decreased. The efficacy was good or excellent in 21 of 30 patients (70.0%). The drug was evaluated to be promising in the treatment of bladder outlet obstruction due to benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗

Inhibition of growth and increase of acid phosphatase by testosterone on androgen-independent murine prostatic cancer cells transfected with androgen receptor cDNA.

Most androgen-unresponsive prostatic cancer cells are found to lack androgen receptor (AR). To clarify the role of AR in the process of the progression from androgen-dependent to androgen-unresponsive tumor, the AR gene was transfected into an AR-negative rat prostatic cancer cell line CUB-II. AR-transfectant cells expressed AR mRNA and showed binding to R1881. AR was found in nuclei of AR-transfectant cells by histochemical examination. Therefore, AR-transfectant cells were considered to contain functional AR. The growth of AR-transfectant cells was markedly inhibited in culture in the presence of testosterone, and the effect of testosterone was reduced by simultaneous addition of flutamide. Moreover, tumors inoculated with AR-transfectant cells in male mice showed much slower growth than those in females. The tumors of AR-transfectant cells in mice consisted of slightly larger spindle-shaped cells when compared to those of CUB-II cells. Moreover, AR-transfectant cells contained a few polynuclear giant cells. Since CUB-II cells contained acid phosphatase (AcP) activity, the addition of testosterone in culture increased AcP activity of AR-transfectant cells. It is concluded that resumption of androgen-dependent processes reduces the growth rate accompanying changes of phenotype.

Acid Phosphatase↗

Chemotherapy for endocrine-therapy-refractory prostate cancer.

The effects of various chemotherapy regimens on endocrine-therapy-refractory prostate cancer were examined in 64 patients. Chemotherapy was started from the first evidence of relapse. The regimens of the initial chemotherapy were as follows: cisplatin (CDDP, 4 cases) and ifosfamide (4 cases) were given as single agents and vincristine, ifosfamide, and peplomycin (VIP, 8 cases); cyclophosphamide, doxorubicin, and CDDP (CAP, 14 cases); ifosfamide, doxorubicin, and CDDP (IAP, 24 cases); and etoposide, doxorubicin, and CDDP (EAP, 10 cases) were given as combinations. On the basis of the results, the patients were divided into two groups: single agents plus VIP and other combinations. In the CAP, IAP, and EAP groups, the cause-specific survival was similar, and the survival of these groups was longer than that of the single agents plus VIP group. Since patients with a long duration between the start of endocrine therapy and the start of chemotherapy were contained in the CAP, IAP, and EAP groups, comparison was performed without these cases. No difference was found between the two groups, suggesting that no superior regimen was found. The short-term effect was evaluated on the basis of the changes observed in prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels at 3 months after the start of chemotherapy, and patients showing a complete response, partial response, or no change on any of the regimens exhibited longer survival than did those with progressive disease. Since the PSA doubling time estimated before the chemotherapy correlated with the change in the PSA values due to the chemotherapy, the rate of proliferation of the tumor influenced the effect of the chemotherapy. Thus, this finding suggests that slowly growing cancers show a better response to chemotherapy than do rapidly proliferating ones.

Acid Phosphatase↗

Relationship between diurnal rhythm of serum testosterone and two prostatic markers (PSA and PAP) in untreated prostate cancer.

OBJECTIVE: To clarify the relation between diurnal rhythm of serum levels of testosterone and two prostatic markers, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP). METHODS: Blood was obtained every four hours during a thirty-two-hour period from fourteen men with untreated prostate cancer. RESULTS: Serum levels of PSA and PAP showed circadian rhythm in 4 and 5 patients, respectively. About half of the remaining patients, the highest or nearly highest peaks of serum levels of PSA or PAP were observed in the afternoon rather than the morning. In 3 patients, circadian rhythms were not observed in serum levels of PAP, but the fluctuation patterns were the same as those of testosterone and showed synchronous movement. In 7 patients, serum testosterone levels were followed by the same fluctuation pattern for either PSA or PAP after some time delay. Little change in serum levels of PSA was seen throughout the thirty-two-hour period despite large fluctuations of testosterone and PAP levels in 5 patients. CONCLUSIONS: Close relation between the fluctuation in serum levels of PSA and PAP, and that in serum levels of testosterone during diurnal periods could be considered. However, the relationship between serum testosterone levels and those of PSA and PAP was ambiguous because of both the difference in the time delay of PSA and PAP in relation to testosterone and the small fluctuation in PSA despite obvious fluctuations in testosterone and PAP in some cases.

Acid Phosphatase↗

Relationship between bladder neck diameter and hydraulic energy at maximum flow.

A pressure-flow study was performed with a 5-micro-tip transducer catheter in 6 normal male volunteers (bladder neck diameters 0.80 cm. or larger) and 13 male subjects suspected of having bladder neck contracture. Intraurethral pressure was measured at various sites in the urethra at maximum flow to calculate hydraulic energy at these sites using the Bernoulli equation. When the subjects were divided into 2 groups (1 group with a bladder neck diameter of 0.73 cm. or larger and 1 with a bladder neck diameter of 0.60 cm. or smaller), the relative value of energy (ratios to the initial energy generated in the bladder) at the external urethral sphincter was significantly (p < 0.01) greater in the former than in the latter group. Therefore, the "flow rate controlling zone" lies at the external urethral sphincter in the former group and at the bladder neck in the latter group.

Humans↗

Effects of beta 2-stimulants on contractility and fatigue of canine urethral sphincter.

The effects of beta 2-stimulants [clenbuterol (CB) and terbutaline (TB)] on the contractility of the urethral sphincter of female dogs were studied by measuring intraurethral pressure (IUP) during stimulation of bilateral pudendal nerves. In nine dogs 1, 10 and 100 micrograms/kg. of CB were administered, but no changes in IUP were observed. In the other 33 dogs, sphincteric fatigue was experimentally prepared by electrically stimulating the pudendal nerves at 15 V, 20 Hz for 30 to 40 minutes. In fatigued sphincters, CB (n = 17) and TB (n = 7) increased the contracting pressure (pressure difference between stimulation-generated peak level and baseline level of IUP). The inotropic effect of beta 2-stimulant (TB) on the fatigued urethral sphincter was abolished by a beta-blocker, propranolol. From the present study it was concluded that beta 2-stimulants have little effect on the total contractility of the nonfatigued urethral sphincter because it is composed of smooth and striated muscles (fast- and slow-contracting muscles). However, beta 2-stimulants enhanced the contractility of fatigued urethral sphincter. These results suggest that beta 2-stimulants act on fast-contracting fibers in the urethral sphincter because the inotropic effect of sympathomimetic amine is much greater on fatigued, fast-contracting fibers than on nonfatigued ones and its depressive effect on slow-contracting fibers is not potentiated after fatigue.

Animals↗

Improvement of urethral resistance after the administration of an alpha-adrenoceptor blocking agent, urapidil, for neuropathic voiding dysfunction.

We assessed the effect of a new alpha-blocking agent, urapidil, on neuropathic voiding dysfunction, by urodynamic studies. The residual urine volume and rate significantly decreased, whereas the average and the maximum flow rate did not increase significantly. The pressure at maximum flow and minimum urethral resistance decreased significantly. These results suggest that improvement of the voiding dysfunction in some cases could be due to the decreased micturition pressure without increasing the flow rate. The urethral resistance calculated from the pressure/flow data seemed to be a valuable index in evaluating the effects of the drug on neuropathic voiding dysfunction.

Adrenergic alpha-Antagonists↗

The urodynamic status during psychogenic erection in a patient with a conus medullaris injury. Case report.

The urodynamic status of a 24 year old male patient with psychogenic erection who sustained a conus medullaris lesion from a burst fracture of the first lumbar vertebra is reported. During the initial measurement the external urinary sphincter pressure began to rise from the base pressure of 35 cm H2O 5 seconds after the beginning of audiovisual sexual stimulation and reached the peak of 110 cm H2O. In parallel, the bladder neck pressure gradually rose from its base pressure of 5 cm H2O to a maximal pressure of 115 cm H2O and then ejaculation occurred. The difference is no more than 5 cm H2O and this small difference in pressure inhibits retrograde ejaculation.

Adult↗

State of adenomatous polyposis coli gene and ras oncogenes in Japanese prostate cancer.

Genetic alterations of ras oncogenes (K-, H- and N-ras) and adenomatous polyposis coli (APC) gene in tissues of prostate cancer from Japanese patients were examined using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis and direct sequencing. Tissues from 8 cases of untreated stage B prostate cancer surgically removed and from 10 cases of endocrine therapy-resistant metastatic disease obtained at autopsy were used in the present study. In four out of 18 cases (22%), ras point mutations were found, two in either codon 12 or 61 of K-ras and two in either 13 or 61 of H-ras. These point mutations were detected in one of the stage B cases (13%) and in three of the autopsy cases (30%). All these cases were poorly differentiated adenocarcinoma. In autopsy cases showing ras mutation in cancerous prostate, the same alteration was observed in metastatic tissues. No APC gene mutation was detected in any sample, although polymorphism was found in some cases. These results indicate that ras oncogene mutations are related to the progression of prostate cancer, whereas APC gene alteration is not involved in tumorigenesis and development of this cancer.

Adenocarcinoma↗

p53 gene mutations in human prostate cancers in Japan: different mutation spectra between Japan and western countries.

The involvement of p53 mutations in prostate cancers in Japan was investigated. To evaluate any possible clinicopathological significance, p53 mutations in 40 samples from 36 Japanese prostate cancers of different stages (five cases of latent tumors, three of stage A cancers, 10 of stage B, five of stage C and 13 of stage D), including four lymph node metastases of stage D cases, were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and sequencing. Mutations were detected in five of 40 samples (12.5%); four were in primary cancers and the other in a lymph node metastasis from one of them. All mutation-positive cases were in stage D, and the mutation frequency in stage D cases was 31%. This result indicates that p53 mutations may play a role in the progression of a subgroup of prostate cancers in Japanese, as observed for Americans and Europeans. However, a difference was noted between Japanese and Americans in the p53 mutational spectrum (at CpG site), presumably arising from variation in the underlying etiologic factors.

Aged↗

Diurnal rhythm of serum gamma-seminoprotein in patients with untreated prostate cancer: comparison of the original and revised assay kits.

To compare levels of gamma-seminoprotein (gamma-Sm) assayed by original and revised assay systems, blood was obtained every 4 h over a 32-h period from 8 untreated prostate cancer patients. Serum levels of prostate specific antigen (PSA) were also examined. In 6 patients, the coefficient of variation (CV) of the serum levels assayed by the revised assay was significantly different from that of the intra-assay samples. In contrast, the CV of the gamma-Sm serum levels assayed by the original assay differed significantly from that of the intra-assay samples in only 2 patients. The fluctuations in gamma-Sm assayed by the revised assay were, at least in part, similar to those of the PSA serum levels in all patients. The mean CV of the gamma-Sm serum levels assayed by the revised assay was significantly larger than that for levels measured by the original assay. After treatment, the rate of decrease in gamma-Sm serum levels determined by the original assay differed from that in the serum levels of PSA and prostatic acid phosphatase. These results indicate that the original assay for gamma-Sm do not detect diurnal differences in serum gamma-Sm levels, even at levels below 20 ng/ml. These observations indicate that the analysis of data obtained using the original gamma-Sm kit should be interpreted with caution.

Acid Phosphatase↗