Biomedical subjects

J Shimazaki

Publications and source records attributed to J Shimazaki.

At least 109 records · Page 6Linked to original sources

PubMed1996

Mapping of metastasis suppressor gene(s) for rat prostate cancer on the short arm of human chromosome 8 by irradiated microcell-mediated chromosome transfer.

Our previous studies demonstrated that human chromosome 8 contains metastasis suppressor gene(s) for rat prostate cancer. However, it is still unknown which portion of human chromosome 8 is associated with suppression of metastatic ability, because all of the clones in which metastatic ability is suppressed contain at least one copy of intact human chromosome 8. In the present study, we used the irradiated microcell-mediated chromosome transfer technique to enrich for specific chromosomal arm deletions of selected chromosomes. The resultant series of human chromosomes 8 with a variety of chromosomal deletions was introduced into highly metastatic Dunning rat prostate cancer cells. All of the resultant microcell hybrids showed reduced metastatic ability. To obtain a smaller size of human chromosome 8 and to locate further the region of metastasis suppressor gene(s), the most reduced size of human chromosome 8 that was generated with the initial irradiated chromosome transfer was retransferred into the Dunning cancer cells without irradiation. The resultant microcell hybrids were analyzed to determine which portion of human chromosome 8 suppressed the metastatic ability of the recipient cells. This analysis demonstrates that the portion of human chromosome 8 containing metastasis suppressor gene(s) for rat prostate cancer cells lies on human chromosome segment 8p21-p12, where frequent allelic losses have been detected in allelotype analyses of human prostate cancer. This suggests that one of the metastasis suppressor genes for rat prostate cancer on human chromosome 8 may also play an important role in the progression of human prostate cancer.

Animals↗

PubMed1996

Codon 877 mutation in the androgen receptor gene in advanced prostate cancer: relation to antiandrogen withdrawal syndrome.

The growth of prostate cancer is androgen responsive, and androgen receptor (AR) is thought to play an important role in the development of this cancer. Recently, some reports demonstrated that AR gene mutations were detected in human prostate cancer tissues. We have previously reported that one of eight endocrine therapy-resistant prostate cancer cases showed AR gene mutation [Suzuki et al: J Steroid Biochem Mol Biol 46:759-765, 1993]. To further investigate structural abnormality of the AR in a large number of human prostate cancers, exons B-H encoding DNA-and hormone-binding domains were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products and direct sequencing. Tissues surgically removed from 30 cases of stage B or C prostate cancer and from 22 cases of endocrine therapy-resistant cancers obtained at autopsy were used in the study. Three out of 22 cancer death cases (14%) revealed AR gene mutations, one of which contained two different mutations-exon D in cancerous prostate and exon H in metastatic tissues. In the other two cases, AR gene mutations in exon H were found in metastatic tissues. All three cases in metastatic tissues showed the same mutation at codon 877 (877Thr-->Ala). In stage B or C cancer tissues and the other cancer death samples, no AR mutation was detected. The mutation in exon H was identical to that reported in a human prostate cancer cell line, LNCaP. These results indicate that AR gene mutation scarcely occurs in the early stage of prostate cancer and that the mutation is found in relation to endocrine therapy resistance. Two patients with an AR gene mutation at codon 877 revealed a remarkable fall in prostate-specific antigen after withdrawal of antiandrogen. Data on the other case were not available. These results indicate that a codon 877 mutation in the AR gene in advanced prostate cancer evokes the antiandrogen withdrawal syndrome. To our knowledge, this report is the first description of relationship between an AR mutation at codon 877 and the antiandrogen withdrawal syndrome.

Aged↗

PubMed1996

Pain caused by bone metastasis in endocrine-therapy-refractory prostate cancer.

It is of clinical importance to control pain in the management of patients with endocrine-therapy-refractory prostate cancer. To evaluate factors influencing the manifestation of pain and the relationship between characteristics of pain and prognosis, patients with pain from bone metastasis were analyzed. A total of 48 patients with endocrine-therapy-refractory prostate cancer, who showed progression of bone metastasis and were followed-up until death, comprised the present study. The patients were divided into three groups according to the grade of pain: no need for analgesics, a need for non-opioid analgesics, and a need for opioid analgesics. The time interval between the diagnosis of the endocrine-therapy-refractory state and the requirement for analgesics was estimated. Survivals from the endocrine-therapy-refractory state were calculated according to the grade of pain or the time interval to requirement for analgesics. In addition, the extent of disease, the doubling time of tumor markers at the refractory state, any change of alkaline phosphatase, and other prognostic factors were examined in relation to pain. All 22 endocrine-therapy-resistant cases at initial treatment and 18 of 26 (69%) relapsed cases required analgesics during the clinical course until death. No difference in survival was observed between the grades of pain. The patients who needed analgesics within 1 year after becoming refractory to endocrine therapy showed significantly shorter survival than those without or with analgesics more than 1 year later. Although the time elapsing before analgesics were needed was not related to the extent of disease, the patients who showed a shorter doubling time for tumor markers and/or an exponential increase in alkaline phosphatase tended to require analgesics within 1 year. In endocrine-therapy-refractory prostate cancer, the early requirement for analgesics suggests poor prognosis, and the onset of pain may be attributable not to the extent of the disease but rather to the rapid expansion of bone metastasis.

Aged↗

PubMed1996

Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome.

PURPOSE: Ocular cicatricial pemphigoid and Stevens-Johnson syndrome often cause ocular damage and blindness not amenable to surgical correction. We present a new surgical technique for reconstructing affected eyes. METHODS: Fourteen eyes of 11 patients with cicatricial keratoconjunctivitis (seven patients with cicatricial pemphigoid and four with Stevens-Johnson syndrome; average age +/- S.D., 55.5 +/- 25.4 years) were treated with a combination of allograft limbal transplantation, amniotic membrane transplantation, and tarsorrhaphy, followed every 15 minutes by artificial tears derived from the patient's blood serum. Eight eyes required concomitant penetrating or lamellar keratoplasty because of corneal opacity. RESULTS: With a mean follow-up of 143 days (range, 10 to 608 days), we achieved successful ocular surface reconstruction in 12 eyes, with minimal recurrence of symblepharon. Failure occurred in two eyes (one each in 9- and 10-year-old boys) that developed corneal infiltration and vascularization. CONCLUSIONS: A combination of allograft limbal transplantation, amniotic membrane transplantation, and tarsorrhaphy, followed by the use of serum-derived tears, can reconstruct the ocular surface in most cases. Although in this study the follow-up period was short and relatively few patients were studied, this approach appears to offer an alternative to keratoprosthesis for treating severe cicatricial keratoconjunctivitis with dry eye.

Adult↗

PubMed1996

Effects of diclofenac eye drops on corneal epithelial structure and function after small-incision cataract surgery.

PURPOSE: To investigate prospectively the effect of diclofenac sodium (DfNa) eye drops on corneal epithelial structure and function. METHODS: Seventeen patients with bilateral age-related cataract undergoing phacoemulsification combined with intraocular lens implantation were studied prospectively. After the surgery on both eyes, one eye each of these patients was assigned randomly to receive 0.1% DfNa eye drops three time daily (DfNa group), and the other eye served as control (control group). Vital stainings, tear function test, corneal sensitivity measurement, specular microscopy for corneal epithelium and endothelium, pachymetry, anterior fluorometry to measure epithelial barrier function, and laser flare-cell-metry were performed before and after surgery. RESULTS: There were no statistically significant differences between the DfNa and control groups in any measurement examined except for laser cell-flare-metry, in which the DfNa group demonstrated a significantly lower flare value at day 7 postoperatively (compare with the preoperative level of 73% +/- 41% in the DfNa group, and 130% +/- 98% in the control group, P=0.035). Epithelial cells in the DfNa group showed slight elongation and increased permeability postoperatively; however, there were no statistically significant differences with the control group. CONCLUSIONS: Administration of DfNa eye drops did not cause significant abnormalities in the corneal epithelial structure or function of patients who had undergone small-incision cataract surgery. Their safety for use in procedures such as excimer laser photorefractive keratectomy remains to be established.

Aged↗

PubMed1996

Changes in histologic grade and argyrophilic nucleolar organizer regions during progression of prostate cancer.

To determine the changes in histologic features during the course of prostate cancer under long-term endocrine therapy, histologic grade and argyrophilic nucleolar organizer regions (AgNORs) were examined in specimens before treatment, at relapse, and at cancer death. A total of 29 patients who had received therapy and died of prostate cancer were evaluated. Among the 29 cases, biopsy tissues before treatment (25 cases) and during progression from endocrine therapy (10 cases) were compared with autopsy specimens. Histologic grade was determined by the method of Gleason, and the number of AgNORs in cancer cells was counted. Survival of the patients was compared with the histologic features. There was a tendency for a higher grade of cancer during the clinical course. Moreover, a statistically significant increase in the number of AgNORs was observed from pretreatment biopsy to autopsy. Upon comparison of metastatic sites with local cancer at autopsy, no significant difference was noticed in terms of histologic grade or AgNOR count. Although there was no correlation between the number of AgNORs and survival after initial treatment, an inverse relationship was demonstrated between the number of AgNORs and survival in patients with systemic progression after endocrine therapy. In conclusion, prostate cancer shows an increase of malignant potential, as assessed by histologic grade and the number of AgNORs. Patients with cancer of high proliferative ability showing high grade and greater numbers of AgNORs have poorer prognosis from progression.

Biopsy↗

PubMed1996

Clinical usefulness of serum carboxyterminal propeptide of type I procollagen and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen in patients with prostate cancer.

A study was undertaken to evaluate the clinical usefulness of measurements of serum concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as parameters of bone metastasis in patients with prostate cancer. Serum PICP, ICTP, prostate-specific antigen (PSA), and alkaline phosphatase (ALP) were evaluated in 82 patients with prostate cancer and 26 patients with benign prostatic hyperplasia (BPH). These markers were measured serially in 16 prostate cancer patients during treatment. The serum levels of PICP, ICTP, ALP, and PSA were significantly higher in prostate cancer patients with bone metastasis than in patients with either BPH or prostate cancer without bone metastasis. Although the rate of detection of bone metastasis with PICP and ICTP was slightly lower than that with PSA determined by the receiver operating characteristic curve, the correlation between both PICP and ICTP and the extent of disease was much higher than that of PSA. PICP and ICTP levels varied with ALP and PSA levels, the patient's clinical course after the start of endocrine therapy and the progression of bone metastasis. The levels of PICP and ICTP did not change substantially in patients who developed local regrowth or lymph node metastasis, and decreased as bone metastases responded to radiotherapy. PICP and ICTP thus reflect the metastatic burden in bone and are useful for monitoring the response of bone metastasis to therapy.

Aged↗

PubMed1996

Improvement of corneal sensation and tear dynamics in diabetic patients by oral aldose reductase inhibitor, ONO-2235: a preliminary study.

The mechanism in the pathogenesis of diabetic corneal disease is unclear, but aldose reductase may be involved in the corneal disease. We studied the effects of an aldose reductase inhibitor (ARI) on the ocular surface of diabetic patients. Fourteen aphakic or pseudophakic patients with diabetes were treated with orally administered ONO-2235 (150 mg/day). Corneal sensation, vital staining of ocular surface, and tear production were examined before and 3 months after the administration. After a 3-month period of oral ARI, corneal sensation recovered significantly (from 4.1 +/- 4.8 to 3.0 +/- 3.1 g/mm2; p = 0.015), with parallel improvements in rose bengal and fluorescein staining scores (p < 0.05). Tear break-up time had also improved (p = 0.003). Results of Schirmer's test (p = 0.03) and the cotton-thread test (p = 0.0001) showed significant improvement in tear production. Improvement in the dynamics of tear production may be due to an improvement in corneal sensitivity. An oral ARI can improve corneal epithelial changes caused by diabetes, probably through recovery of corneal sensation and tear production.

Administration, Oral↗

PubMed1996

Relationship between grade of varicocele and the response to varicocelectomy.

BACKGROUND: Although several studies indicate that larger varicoceles are associated with greater impairment of spermatogenesis, others suggest that the response to surgery is independent of varicocele size. In order to elucidate these seeming contradictions, correlations between the preoperative evaluation of varicoceles and improvement in semen quality after varicocelectomy were investigated. METHODS: Forty men with left unilateral varicocele, followed for at least 6 months after varicocelectomy, were included in this study. The relationships between the grade of varicocele by palpation, Doppler examination, ultrasound, or scintigraphy were correlated with a postoperative improvement in sperm density or sperm motility. RESULTS: Greater improvement in sperm density was observed in the patients with a large varicocele graded by palpation or measured by ultrasound, and greater improvement in sperm motility was observed in the patients with high uptake of radioactivity in the left side by scrotal scintigraphy. CONCLUSION: An improvement in semen quality after varicocelectomy is greater in patients with a large varicocele than in the patients with a small one. The significance of surgical repair of a small varicocele should be reconsidered.

Angiography↗

PubMed1996

Characteristics of androgen-independent growth of androgen-responsive Shionogi carcinoma 115 cells.

BACKGROUND: The effects of castration on the biological features of an androgen-responsive carcinoma were examined in order to clarify the mechanism responsible for the relapse of an androgen-responsive carcinoma after androgen ablation therapy. METHODS: A well-characterized androgen-responsive mammary carcinoma, Shionogi carcinoma 115 (SC115), was used for these experiments. Male mice were examined for the effects of castration on the growth rate of the tumor, the number of androgen receptor-positive cells, and the karyotype of the SC115 tumors. Castration was performed 1 week prior to tumor transplantation, or 2 or 3 weeks after tumor transplantation. RESULTS: SC115 tumors did not develop when transplanted into castrated male mice. When castration was performed 2 weeks after transplantation, the tumor showed androgen-independent growth with temporary regression of growth rate. However, when castration was performed more than 3 weeks after transplantation, the tumor showed androgen-independent growth not associated with any temporal regression of growth rate. There were no significant differences in histological features or the number of androgen receptor-positive cells between SC115 tumors in untreated or castrated mice. To test whether SC115 tumors growing under androgen-deprived conditions became fully androgen-independent, SC115 tumors were transplanted in both male and female mice. A transplanted tumor piece grew progressively only in male mice. This indicates that the SC115 tumor maintains its androgen response in the next generation, even though growth of the tumor resumed after temporary suppression due to castration. Chromosomal analyses revealed no apparent cytogenetic changes in the SC115 tumors that resumed growth under androgen-deprived conditions. CONCLUSION: These results suggest that no gross changes in the number of androgen receptor-positive cells or karyotype are necessary for androgen-independent growth in this system once the size of tumor increased.

Androgens↗

PubMed1996

Non-invasive assessment of the donor corneal endothelium using ocular redox fluorometry.

AIMS: To investigate the usefulness of ocular redox fluorometry for evaluating donor corneal endothelial viability. METHODS: Corneas from 42 recipients of penetrating keratoplasty and four donor corneas were examined by ocular redox fluorometry. Autofluorescence from reduced pyridine nucleotides (PN) and oxidised flavoproteins (Fp) of the human corneal endothelium were measured non-invasively, and the PN/Fp ratio was used as a tissue metabolic indicator. Specular microscopy and electron microscopy were also performed. RESULTS: Both the quality of specular microscopic image and the PN/Fp ratio were significantly correlated with the degree of corneal endothelial damage determined by histological examination. Corneas with poor specular microscopic image showed significantly decreased PN/Fp ratio compared with corneas with good or fair specular images (p = 0.041 and 0.027, respectively). The PN/Fp ratio increased in corneas with mildly damaged endothelium but decreased in corneas with severely damaged endothelium determined by histological examination. Evaluation of corneal endothelium by combination of specular microscopy and ocular redox fluorometry showed excellent association with that of histopathological examination (p < 0.0001). CONCLUSION: Ocular redox fluorometry is useful for assessing donor corneal endothelial viability. Combination of ocular redox fluorometry and specular microscopy may increase the ability of donor cornea selection.

Adult↗

PubMed1996

Temporary corneal stem cell dysfunction after radiation therapy.

BACKGROUND: Radiation therapy can cause corneal and conjunctival abnormalities that sometimes require surgical treatment. Corneal stem cell dysfunction is described, which recovered after the cessation of radiation. METHODS: A 44-year-old man developed a corneal epithelial abnormality associated with conjunctival and corneal inflammation following radiation therapy for maxillary cancer. He experienced ocular pain and loss of vision followed by conjunctival epithelialisation of the upper and lower parts of the cornea. RESULTS: Examination of brush cytology samples showed goblet cells in the upper and lower parts of the cornea, which showed increased fluorescein permeability, and intraepithelial lymphocytes. Impression cytology showed goblet cells in the same part of the cornea. Specular microscopy revealed spindle type epithelial cells. Patient follow up included artificial tears and an antibiotic ophthalmic ointment. The corneal abnormalities resolved after 4 months with improved visual acuity without any surgical intervention, but the disappearance of the palisades of Vogt did not recover at 1 year after radiation. CONCLUSION: Radiation therapy in this patient caused temporary stem cell dysfunction which resulted in conjunctivalisation in a part of the cornea. Although limbal stem cell function did not fully recover, this rare case suggested that medical options should be considered before surgery.

Adult↗

PubMed1996

Allergic conjunctivitis and dry eye.

AIMS: Differential diagnosis of allergic conjunctivitis or dry eye is sometimes very difficult to diagnose by symptoms and clinical examination alone, especially in older patients. It was hypothesised that clinically allergic patients who were serum antigen specific IgE negative were candidates for dry eye. METHODS: Sixty patients were studied prospectively who were clinically diagnosed with allergic conjunctivitis by their itchy sensation and papilla formation of conjunctiva. They consisted of 30 serum antigen specific IgE positive and 30 IgE negative patients, with no significant differences in age. Dry eye examination and serum total IgE were performed on these two groups. RESULTS: No significant differences were seen between the two groups with regard to age (p = 0.76) and sex ratio. The antibody negative group had lower Schirmer's test scores (p = 0.002), lower tear clearance (p = 0.0001), lower tear function index (p = 0.0001), and lower serum total IgE (p = 0.04) than the antibody positive group. CONCLUSION: This study suggests that the evaluation of serum antigen specific IgE and tear dynamics are important for the differential diagnosis of patients with allergic conjunctivitis and dry eye. Clinically diagnosed allergic conjunctivitis with negative serum antigen specific and total IgE can be one form of dry eye.

Adolescent↗

PubMed1996

Increase in corneal epithelial cell size with extended wear soft contact lenses depends on continuous wearing time.

AIM: Although 1 week of continuous wearing time (CWT) is recommended for extended wear soft contact lenses (EWSCL), there have been few studies concerning the appropriateness of this or other CWTs. The current study was undertaken to examine the effect of various CWTs on the cornea by observing the corneal epithelium. METHODS: Specular microscopy was used to evaluate corneal epithelial changes induced by EWSCL in 19 myopic patients (24.0 (SD 6.7) years), divided into four groups: CWT of 0, 1, 3, and 6 days. RESULTS: The initial mean cell area was 628.2 (13.4) micron2. After 6 months this was 629.3 (28.6) micron2 for daily wear (ns), and 660.0 (40.9) micron2, 727.7 (49.6) micron2 (p < 0.01), and 815.5 (67.2) micron2 (p < 0.01) for CWT of 1, 3, and 6 days, respectively (p < 0.01). CONCLUSION: These findings indicate that the corneal epithelium changes proportionally with the CWT; the shorter the CWT, the better the epithelial morphology. This suggests that the CWT for EWSCL be minimised, so as to reduce the potential risk of contact lens related problems.

Adult↗

PubMed1996

Retrospective survey of a link between cat and dog antigens and allergic conjuctivitis.

This retrospective 3-year study was designed to determine (a) which antigen positive patients were found in greater numbers, (b) whether the patients who were positive for cat or dog antigen-specific IgE were also positive for other antigens, and (c) whether the number of patients with allergic conjunctivitis increased during a particular time of the year. A total of 762 patients were diagnosed with allergic conjunctivitis including 107 cat-positive and/or dog-positive patients. Cat-positive patients were more prevalent than dog-positive patients, (p < 0.001). All but 2 patients were positive for other antigens, indicating a strong link between the animal antigens and other antigens. Cat and dog allergy increased in spring and early summer.

Adolescent↗

PubMed1996

Interleukin-4 and IgE in seasonal allergic conjunctivitis.

We measured interleukin-4 (IL-4) and IgE to study their presence in patients with seasonal allergic conjunctivitis. Twenty patients and 10 normal subjects were enrolled in this study, and their brush cytology samples and peripheral blood lymphocytes (PBL) were cultured for 3 or 24 h. IL-4 levels were measured using ELISA in the supernatants. Measurements of serum IgE were also performed. IL-4 was detected in 4 of 40 brush cytology samples and 10 of 40 PBL samples, but not from the controls. IL-4 positivity rate of patients was significantly higher than normal in 24-hour cultured PBL (p = 0.03). Patients' serum IgE was also significantly higher (p = 0.006). IL-4 may contribute to the development of seasonal allergic conjunctivitis.

Adolescent↗

PubMed1996

[Prognostic factors in patients with non-metastatic renal cell carcinoma].

BACKGROUND: The objective of this study is to evaluate prognostic factors of non-metastatic renal cell carcinoma using univariate and multivariate statistical methods. METHODS: 390 patients who were performed radical surgery in our hospital between 1960 and 1994 were entered to this study. Kaplan-Meier method with log-rank test and Cox's proportional hazard model were used for statistical analysis. RESULTS: Chief complaints, tumor localization on kidney, tumor size, fever, hemoglobin, C-reactive protein, erythrocyte sedimentation rate, immunosuppressive acidic protein, operative method, blood loss, histologic grade, cell type, pT, pN and pV revealed to have prognostic statistical significance in the univariate analysis. Whereas, sex, age, blood type, hypertension, affected side and preoperative embolization did not. In the multivariate analysis of the preoperatively evaluable factors, CRP, tumor size and tumor localization proved to be significant prognostic predictors in this order. When the pathological factors were included to the multivariate analysis, pV, historogic grade and pN revealed to be significant prognostic predictors in this order. CONCLUSION: These results suggest that pathological factors were significant prognostic predictors for non-metastatic renal cell carcinoma.

Carcinoma, Renal Cell↗

PubMed1996

[Relationship between the quantitative morphometry and the clinical response to alpha adrenergic blocker in benign prostatic hyperplasia].

BACKGROUND: There have been few reports on the relationship between the prostatic tissue components and the effect of alpha adrenergic blocker on urination. The present study was undertaken to correlate the rates of the prostatic tissue components and the clinical response to alpha adrenergic blocker in benign prostatic hyperplasia. METHODS: 40 patients with symptomatic benign prostatic hyperplasia were treated with 0.2 mg/day tamsulosin, a alpha adrenergic blocker, for 4-8 weeks followed by transurethral resection of the prostate. The mean weight of resected prostatic tissues was 25.2 g (range 5-96 g). Specimens were stained with antibodies to muscle-specific actin and to prostate-specific antigen for the detection of the smooth muscle and the glandular epithelium, respectively. Double-immunoenzymatic stained tissue sections were divided into four groups: smooth muscle, connective tissue, glandular epithelium, and glandular lumen. The rates of the areas of respective prostatic tissue components were evaluated with computer-assisted quantitative color image analysis. RESULTS: The mean rate of the area of smooth muscle, connective tissue, glandular epithelium, and glandular lumen was 32.7%, 46.9%, 10.8%, and 9.6%, respectively. International prostatic symptom score, maximum flow rate and residual urine volume before the treatment were not related to the rates of respective prostatic tissue components. International prostatic symptom score and residual urine volume were reduced and maximum flow rate was increased after the treatment with tamsulosin. A significant relationship was proved between the rate of smooth muscle and the change in maximum flow rate. The large hyperplastic adenoma contained less smooth muscle and showed a lower sensitivity to alpha adrenergic blocker than the small one. CONCLUSION: The clinical response to alpha adrenergic blocker was related to the rate of smooth muscle in benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗