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Biomedical subjects

J Shimazaki

Publications and source records attributed to J Shimazaki.

At least 19 recordsLinked to original sources

Ocular surface changes and discomfort in patients with meibomian gland dysfunction.

OBJECTIVE: To determine the importance of meibomian gland dysfunction (MGD) on the ocular surface. DESIGN: Prospective study. SETTING: A university-based referral practice. PATIENTS: Patients with ocular discomfort (147 eyes) and without ocular discomfort (54 eyes) were examined. In the total 201 eyes, MGD was defined as the presence of an obstruction of the meibomian orifices (obstruction group [n = 54]) or the absence of a gland structure (gland dropout group [n = 36]), or both of these findings (combined group [n = 38]). There were not any findings of MGD in 73 eyes (non-MGD group). MAIN OUTCOME MEASURES: Scores that were obtained from fluorescein and rose bengal staining, the breakup time of the tear film, the rates of tear evaporation and tear production, and meibography. RESULTS: Of the 147 eyes with ocular discomfort, 95 (64.6%) had either an obstruction of an orifice or gland dropout, or both. The combined group had higher scores for staining with fluorescein (P = .002) and rose bengal (P = .021) compared with that in the non-MGD group. The rate of tear production was increased more in the gland dropout group than in the non-MGD group (P = .002). The rate of tear evaporation was significantly increased in the gland dropout group (P = .017). CONCLUSION: Meibomian gland dysfunction is a major cause of ocular surface abnormalities and ocular discomfort.

Adult

Localization of a tumor suppressor gene associated with progression of human prostate cancer within a 1.2 Mb region of 8p22-p21.3.

Human prostate cancers frequently show loss of heterozygosity at loci on the short arm of chromosome 8. In order to take a step toward isolation of the putative tumor suppressor gene(s) on 8p via positional cloning, we performed high-resolution deletion mapping in 46 prostate cancers (stage B, 20 cases; stage C, 8 cases; endocrine therapy-resistant cancer death, 18 cases) using new 12 restriction fragment length polymorphism markers for this chromosomal region. Allelic losses were observed in 25 of the 44 cases (57%) that were informative with at least one locus. Detailed deletion mapping defined a 1.2 Mb commonly deleted region at 8p22-p21.3 flanked by markers cMSR-32 and C18-1051. A second region of common deletion was identified between C18-1312 and C18-494 at 8p21-8p11.22, suggesting that at least two tumor suppressor genes associated with prostate cancer are present on chromosome arm 8p. Allelic losses on 8p were observed more frequently in the cancer death cases (14/17, 82%) than in early-stage tumors (11/27, 40%; P < 0.01, Fisher's exact test). In two out of 7 patients for whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 8p, but the metastatic tumors showed loss of heterozygosity. These results suggest that inactivation of tumor suppressor genes on 8p plays an important role in the progression of prostate cancer.

Adenocarcinoma

Increased comfort and decreased inflammation of the eye by cooling after cataract surgery.

PURPOSE: Cooling can reduce clinical symptoms and pain caused by traumatic swelling or fracture of extremities. We obtained subjective and objective measures of the effects of cooling of the eyes after cataract surgery. METHODS: Twenty patients with bilateral cataracts were enrolled in this study. For each patient, an ice-cold eye mask was applied over gauze to one operated-on eye for two hours after the operation and was not applied after operation on the other eye. After each operation, the patient rated comfort on a five-point scale. The severity of inflammation associated with each procedure was evaluated by using an infrared radiation thermometer to determine the central corneal temperature and a laser flare-cell meter to determine the cell and flare count, at intervals up to 28 days after surgery. RESULTS: Cooling, applied after the first operation in ten patients and after the second operation in ten patients, statistically significantly increased the patients' comfort level and was associated with a significant decrease in central corneal temperature on days 0, 1, and 3; in cell counts on days 1, 3, 7, and 14; and in flare counts on days 1, 14, and 28. CONCLUSIONS: Cooling increased the comfort level and reduced inflammation after cataract surgery, with no adverse effects.

Aged

Antiandrogen withdrawal syndrome in prostate cancer after treatment with steroidal antiandrogen chlormadinone acetate.

OBJECTIVES: A case report is presented of 2 patients whose levels of serum prostate-specific antigen (PSA) improved after the withdrawal of a steroidal antiandrogen. METHODS: Two cases with prostate cancer had been treated with surgical castration and the steroidal antiandrogen chlormadinone acetate (CMA), and, on disease progression, the administration of CMA was terminated. RESULTS: Following withdrawal of CMA, a fall in PSA levels and remarkable clinical improvement were observed in both cases. One patient revealed a decrease and the other an increase in serum prostate acid phosphatase after the discontinuation of CMA. Serum levels of testosterone, prolactin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione were not significantly elevated after CMA withdrawal. CONCLUSIONS: Withdrawal of the steroidal antiandrogen CMA resulted in a decline in PSA levels and clinical improvement in prostate cancer patients with disease progression. Changes in testosterone, prolactin, or adrenal androgens were not a cause of the antiandrogen withdrawal syndrome.

Aged

Dry eye with only decreased tear break-up time is sometimes associated with allergic conjunctivitis.

PURPOSE: The authors' clinical experience has suggested that there is a form of dry eye with only decreased tear break-up time, which is associated with allergic conjunctivitis. The current study was performed to verify this hypothesis. METHOD: The authors recruited patients with two types of dry eye syndrome, those with only decreased tear break-up (BUT type) and those with positive vital staining (staining type). Individuals without any symptoms or signs served as controls. All subjects were compared regarding symptoms, Schirmer and tear clearance test results, conjunctival papillary formation, antigen-specific serum-IgE level (s-IgE), and goblet cell density of the palpebral conjunctiva. Antigen-induced allergic conjunctivitis was produced in guinea pigs, and histopathologic changes of the conjunctiva were examined. RESULTS: Patients with the BUT-type dry eye syndrome were younger and their symptoms were as severe as the staining type. The Schirmer and tear clearance test results were better, and the papillary formation and s-IgE were observed more than in the BUT type. The average goblet cell density in the BUT-type syndrome was 625.4 +/- 193.2/mm2, which was significantly less than 1005.6 +/- 294.5/mm2 in the controls (P < 0.01). The average goblet cell density was significantly decreased in the allergic animals (10.40 +/- 1.11/0.2 mm) compared with that of the controls (16.21 +/- 0.26/0.2 mm) or the anti-allergic drug-treated group (13.69 +/- 0.30/0.2 mm) (P < 0.01). CONCLUSION: These results support the authors' hypothesis that decreased break-up time is in part associated with the decreased goblet cell density caused by allergic conjunctivitis.

Adult

Long-term follow-up of patients with familial subepithelial amyloidosis of the cornea.

PURPOSE: To investigate the clinical course of patients with familial subepithelial amyloidosis of the cornea (FSA). METHODS: The authors retrospectively investigated the clinical course of seven Japanese patients with FSA. Corneal specimens obtained at the time of keratoplasty were examined histopathologically. RESULTS: The mean follow-up period was 20.6 years, including four patients followed for more than 25 years. In all patients, the initial symptoms of photophobia and epiphora started in the first decade of life. All except one patient had their first keratoplasty before 30 years of age. The seven Japanese patients with FSA had a total of 35 keratoplasties, each of which was followed by a severe recurrence of disease. In each patient, subepithelial haziness developed in the graft within 1 year of keratoplasty (mean, 7.9 months). Amyloid deposition typically recurred within a few years (mean, 26.6 months) followed by a deterioration of vision. There was a high incidence of postkeratoplasty complications such as wound dehiscence, glaucoma, and cataract. Histopathologic findings demonstrated that, in the early phase of recurrence, amyloid was deposited between the basal cell of the epithelium and Bowman's layer. CONCLUSION: Patients with FSA have ocular symptoms with a deterioration in vision from an early decade of life. Conventional surgical approaches were complicated by subepithelial haziness in the first postoperative year, which was followed by a severe recurrence in each patient. New surgical approaches may be indicated in FSA.

Adult

Microsatellite instability in human prostate cancer.

Microsatellite instability (MSI) was examined at 36 loci, and found in 9 (43%) of the 21 prostatic cancers. A loss of heterozygosity had occurred in five cases (24%). MSI did not correlate with clinical stage, but might play a role in the development of a subset of prostate cancers.

Adult

Mutational analysis of CDKN2 (CDK4I/MTS1) gene in tissues and cell lines of human prostate cancer.

To study mutation of the CDKN2 gene in prostate cancer, samples from 51 Japanese patients and four human prostate cancer cell lines were examined by single-strand conformation polymorphism analysis and direct sequencing. Only one out of 51 (2%) patients revealed a mutation, which was a 24 bp deletion from the 5'-untranslated region to codon 3, resulting in loss of the initiation site. One of the four cell lines revealed a missense mutation, a GAC-->TAC (Asp-->Tyr) at codon 84. These results indicate that mutation of the CDKN2 gene is rare in prostate cancer and thus does not contribute significantly to the pathogenesis of human prostate cancer. Prostate cancer cell lines may acquire more frequent abnormality of the CDKN2 gene than tumor tissues.

Base Sequence

p53 mutations occur in clinical, but not latent, human prostate carcinoma.

To elucidate the role of the p53 tumor suppressor gene in prostate tumorigenesis, we probed for mutations in latent and clinical prostate cancers using single strand conformation polymorphism (SSCP) and restriction fragment length polymorphism (RFLP) analysis in combination with direct gene sequencing and immunohistochemical methodologies. Fifteen cases of subclinical and 32 cases of clinical carcinoma, the latter graded in stages A through D, were available for study. While p53 point mutations were detected in only 5 of 32 (16%) clinical cancers, no mutations were detected in latent disease. Of the carcinomas in stages B, C and D, 15% (2/13), 29% (2/7) and 9% (1/11) were positive for p53 mutations, respectively. Although no specific mutational patterns were observed, the aberrations found were predominantly single base missense substitutions. The data suggest not only an association of p53 mutation and progression of clinical prostate cancer, but also imply that some other mechanism(s) are at work in latent carcinoma.

Base Sequence

Microsatellite instability and other molecular abnormalities in human prostate cancer.

Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed throughout the genome. Instability of these repeat sequences at multiple genetic loci may result from mismatch repair errors, and occurs in hereditary nonpolyposis colorectal carcinoma and certain sporadic cancers. To examine microsatellite instability during the pathogenesis of human prostate cancer, we screened 48 prostate cancer cases (20 stage B, 10 stage C and 18 endocrine therapy-resistant cancer-death cases) for replication error at 17 microsatellite marker loci on 9 chromosomes. Microsatellite instabilities were found in 7 of 48 cases (14.6%), and all 7 cases showing the instability were poorly differentiated adenocarcinomas. Moreover, microsatellite instabilities were more frequently observed in cancer-death cases (6/18, 33%) than in stage B + C cases (1/30, 3.3%). These data suggest that microsatellite instability is an important genetic change related to the progression of a subset of human prostate cancer cases. It is suggested to be associated with extensive, concurrent molecular changes including androgen receptor gene mutations, as well as frequent loss of heterozygosity at chromosomal regions 8p, 10q, and 16q.

Adenocarcinoma

Disease progression in stage A prostate cancer.

To study the disease progression in stage A prostate cancer, 212 patients with stage A from a group of 3370 patients who underwent transurethral resection of the prostate, or subcapsular prostatectomy during the period 1972-1991 were followed. The stage A cases were subdivided into 103 A1 patients and 109 A2 patients and their subsequent course was followed for an average of 41.7 months (6-174 months). Progression to clinical cancer was found in 12 patients, 2 from A1 and 10 from A2 groups. This progression was evident 40.5 months (14-130 months) after prostatectomy. Eight (67%) of these cases responded to endocrine therapy. The rate of expression of ras p21, and the number of argyrophilic nucleolar organizer regions in stage A cancer cells were greater in progressing than in non-progressing cases. These results indicate that stage A cancer with progression arises mainly from the A2 subgroup and exhibits a distinctly proliferative potential even at small foci.

Adult

A case of one eye with gelatinous drop-like corneal dystrophy and the other eye with band-shaped spheroidal corneal degeneration.

The first case of gelatinous drop-like corneal dystrophy in one eye and band-shaped spheroidal corneal degeneration in the other eye was reported. She was a member of Japanese family with gelatinous drop-like corneal dystrophy. A close association between gelatinous drop-like corneal dystrophy and band-shaped spheroidal corneal degeneration was suggested.

Adult

Tumor marker doubling time in patients with prostate cancer: determination of prostate-specific antigen and prostatic acid phosphatase doubling time.

To estimate the growth rate of prostate cancer, the doubling times of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 51 patients: 44 were refractory to endocrine therapy, and 7 were in an untreated state. Since an exponential increase in PSA and PAP was observed in all patients, the doubling time was calculated from a semilogarithmic plot of the respective markers. PSA doubling time was almost identical with that of PAP. The tumor marker doubling time in untreated patients was approximately 10 times greater than that in the patients who were refractory to endocrine therapy. In endocrine refractory patients, the tumor marker doubling time in patients who showed deterioration of bone lesions was less than that in patients with local regrowth and/or lymph node metastasis. The prognosis of endocrine refractory patients from the time showing tumor marker failure was examined. The group showing the longest time (> 80 days) had better prognosis than that shown by the other groups with shorter doubling times. It is concluded that the determination of tumor marker doubling time is of value for measuring the growth rates of prostate cancer, and for assessing prognosis after relapse.

Acid Phosphatase

[Neoadjuvant endocrine therapy prior to nerve-sparing radical prostatectomy in patients with stage T2 prostatic cancer].

Radical prostatectomy is the effective treatment for clinical T2 prostatic cancer. However, clinical T2 stage is often understaged preoperatively. The objective of neoadjuvant therapy is to increase the curability of surgery to understaged patients. The present study was based on patients who had had neoadjuvant endocrine therapy (LH-RH agonist) prior to radical nerve-sparing prostatectomy for T2 prostatic cancer. Sexual function were estimated before and after surgery. Ten patients with a mean age of 64.6 years (range 57-71 years) and biopsy-proven cancer received this treatment modality. No patients had evidence of lymph node metastasis by the pelvic computerized tomography and their bone scan was negative for metastasis. Clinical stage was T2a in 3 patients and T2b in 7. The grade of these tumors as assessed on prostatic biopsy before neoadjuvant endocrine treatment was well differentiated in 3 and moderately differentiated in 7. The duration of neoadjuvant endocrine therapy was 3.6 months (range 2-5 months) in average. Serum levels of prostatic specific antigen (PSA) were examined monthly and prostate volume was measured by transrectal ultrasonography before and after neoadjuvant treatment. Decrease in serum PSA values was observed from an average level of 8.6 ng/ml (range 3.1-17.5 ng/ml) determined prior to neoadjuvant treatment to an average of 1.1 ng/ml (range 0.6-3.3 ng/ml) determined after neoadjuvant treatment. An average reduction of prostatic volume was 25.3% (range 7.4-56.7%) after neoadjuvant therapy. Pathological effects of the neoadjuvant therapy by the criteria proposed by Japanese Urological Association were Grade (G) 0a in 3 patients, G0b in 4, G1 in 2 and G2 in 1. Of patients who had 10 stage T2 cancer before treatment, 4 had pT2 and 6 pT3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

[Usefulness of hyper sensitive PSA assay kits for determination on low range of prostate specific antigen in prostate cancer].

Prostate specific antigen (PSA) levels after total prostatectomy or radiation therapy to localized prostate cancer and also during endocrine therapy are within normal range. Therefore, it is necessary to use hyper sensitive PSA assay kits for early detection of relapse. The present study was undertaken to evaluate two hyper sensitive assay kits (Delfia kit, lower limit 0.1 ng/ml, Kabi Pharmacia Diagnostics Co. and Markit M kit, 0.5 ng/ml, Dainippon Pharmaceutical Co.) and to compare them with conventional PSA kit (Eiken Chemical Co., 1.0 ng/ml). Total of 291 sera were examined: patients consisted of 10 total prostatectomy+endocrine therapy, 9 radiation therapy+endocrine therapy, 5 radiation therapy alone and 44 endocrine therapy alone. Values of endocrine therapy alone were divided into two groups according to duration after start of treatment; more or less than 5 years. The following results were obtained. 1. In non-relapse patients after total prostatectomy+endocrine therapy and radiation+endocrine therapy, PSA showed under lower limit with hyper sensitive kit. On the contrary, conventional kit indicated more than 1.0 ng/ml. 2. Radiation therapy alone kept PSA in detectable range with hyper sensitive kit in spite of no sign of relapse. 3. In non-relapsed patients under endocrine therapy alone, long duration (more than 5 years after start of treatment) decreased PSA in non detectable values with hyper sensitive kits. In this case, conventional kit still showed PSA as more than 1 ng/ml. 4. Doubling time at relapse was estimated similar with Delfia kit and Markit M kit, and much longer with conventional kit. It is concluded that hyper sensitive kit is more useful to manage patients after therapy than conventional kit.

Aged

[Usefulness of fine needle aspiration cytology in the diagnosis of prostate cancer].

The efficacy of aspiration cytology, using Franzen method and echo-guided aspiration for prostate cancer was examined to 102 patients under saddle-block anesthesia in urological clinic of Chiba University Hospital. Between 1990 and 1993, 77 cases out of 102 patients were diagnosed histologically as prostate cancer by needle biopsy and 90% of them were coincidental with findings of aspiration cytology. Looking at histological grades, well differenciated cancer was shown to yield low positivity compared with moderately and poorly differentiated cancer. Positive rate showed similar when grade of specimens from needle biopsy was classified with Gleason pattern. Neither T category nor method of aspiration between Franzen and echo-guided methods influenced positive rate of aspiration cytology. On aspiration cytology, its grading revealed 60% of coincidence with that obtained by histological method. When counting more than 300 scattered cells, 90% of coincidence was achieved with histological grading. It is concluded that aspiration cytology is efficient for diagnosis of prostate cancer.

Biopsy, Needle

[Clinical evaluation of TANDEM PSA in Japanese cases and comparison with other methods].

Clinical evaluation of TANDEM PSA which is the most frequently used prostate specific antigen (PSA) assay method in the world and a comparison with other methods were performed in Japanese cases in a cooperative research fashion. The minimum detectable level of the method was found to be 0.50 ng of PSA in one ml of serum and 1.9 ng/ml was regarded as the upper normal value in Japanese males. The distribution of serum PSA showed a significant difference between the benign prostate hypertrophy (BPH) cases and patients with stage C or D prostate cancer. The sero-diagnosis prostate cancer at an early stage with the TANDEM PSA was difficult. The correlation to other methods of PSA detection was very high. Furthermore, the clinical use of the method in following-up the clinical course of prostate cancer patients was very useful. These findings suggested that the PSA detection using TANDEM PSA is applicable even in Japanese cases although the upper cut-off level is decreased.

Aged

Intratumor cellular heterogeneity and alterations in ras oncogene and p53 tumor suppressor gene in human prostate carcinoma.

To assess the potential role of ras oncogene activation and p53 tumor suppressor gene mutations in the development of human prostate carcinoma, nine cases of histologically heterogeneous prostate tumors obtained from total prostatectomies were probed for these specific events. Each tumor was divided into 5 to 10 areas according to different growth or histological patterns. Targeted DNA sequences coding for ras and p53 were amplified by the polymerase chain reaction, analyzed by single-strand conformational polymorphisms, and confirmed by direct DNA sequencing. Point mutations of the ras gene were found in three of the nine tumors. Two contained K-ras codon 13 and H-ras codon 61 mutations, found in only one and three areas of each lesion, respectively. The third tumor contained two different point mutations in K-ras codons 13 and 61 in different foci of the sample. Loss of heterozygosity at the polymorphic codon 72 in the p53 gene was detected in two of four informative cases (50%) showing fragment cleavage by restriction fragment length polymorphism analysis. Mutations in p53, missense transversions, single base insertions, and two base deletions were also detected in three tumors. The present results reveal mutated ras and p53 occasionally occurring in small foci of the tumor and that genetic mutations in p53, as opposed to those in ras, are more closely associated with invasive growth of heterogeneous prostate carcinoma.

Carcinoma