Biomedical subjects

J Shimazaki

Publications and source records attributed to J Shimazaki.

At least 37 records · Page 2Linked to original sources

PubMed2000

Association of preoperative tear function with surgical outcome in severe Stevens-Johnson syndrome.

OBJECTIVE: To retrospectively study the surgical outcome in severe Stevens-Johnson syndrome (SJS). DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Twenty-nine eyes of patients with severe SJS associated with total conjunctivalization were examined. INTERVENTION: Preserved human amniotic membrane grafting and keratolimbal allograft transplantation was performed. Intensive immunosuppression and epithelial management were continued postoperatively. MAIN OUTCOME MEASURES: Successful ocular surface reconstruction was determined by epithelialization with corneal epithelium. The association between surgical outcome and preoperative tear function was studied. RESULTS: The ocular surface was successfully covered by corneal epithelium in 13 eyes (44.8%). The mean corrected visual acuity recovered from 0.0039 to 0.017. Persistent epithelial defect was the most common complication. Eyes with successful ocular surface reconstruction had significantly better preoperative Schirmer's test values (P = 0.025) and tear clearance rates (P = 0.043) than those that failed. CONCLUSIONS: In patients with severe SJS, preoperative tear function significantly influenced surgical outcome. Eyes with Schirmer's test value of >10 mm have a greater chance of successful ocular surface reconstruction.

Adolescent↗

PubMed2000

Overexpression of mitogen-activated protein kinase superfamily proteins unrelated to Ras and AF-1 of estrogen receptor alpha mutation in advanced stage human breast cancer.

Transactivation of the activation function-1 (AF-1) region of the estrogen receptor alpha (ER-alpha) gene is regulated by pathway "cross-talk" from Ras mitogen-activated protein kinase (MAPK). An analysis of this system is important for solving the problem of resistance to anti-estrogen agents used in the treatment of human breast cancer. We investigated the ER-alpha and Ras gene mutations and the MAPK-related protein status in 103 cases of breast carcinoma. None of the cases showed mutations in the AF-1 region of the ER-alpha gene. Despite the extremely low frequency of K- and H-Ras mutations in codon 12 (2/103 and 0/103), Ras p21 overexpression was identified in 29.1% (30/103), suggesting that the Ras activation in almost all cases we studied was not caused by point mutations but by enhanced expression. Our immunohistochemical analysis showed that the cases with overexpression of Ras and MAPK proteins (Ras p21, ERK-1, JNK-1, and p38) had a progressive tendency towards invasive growth, advanced-stage cancer, and decreased levels of ER-alpha protein. These results suggest that enhanced MAPK activity could be one of the characteristics of advanced breast cancer and that it could be involved in the transformation into estrogen-independent growth.

Breast Neoplasms↗

PubMed2000

Alternatively spliced MDM2 transcripts in human breast cancer in relation to tumor necrosis and lymph node involvement.

Several short forms of alternatively spliced Murine double minute 2 (MDM2) transcripts have recently been shown to correlate with high-grade malignancy in a number of human tumors. We examined the frequency of splice variants and their correlation with clinicopathological features in 60 cases of human breast cancer. Seven short forms coexpressed with wild-type mRNA were detected by nested RT-PCR. Sequencing of all the MDM2 variants demonstrated mRNA splicing which disrupted not only the conserved p53-binding domain but also, further towards the carboxy-terminus, the conserved nuclear localization sequence and/or the acidic and zinc finger domains. There was no significant correlation between the coexpression of splice variants and tumor size, histologic type or hormone (estrogen and progesterone) receptor status. However, cases with spliced MDM2 transcripts tended to be of a more aggressive type with axillary lymph node involvement and extensive necrosis in the tumors. Although the functional significance of MDM2 variants remains obscure, we anticipate that these variants will be confirmed as a novel prognostic marker in human breast cancer.

Adenocarcinoma↗

PubMed2000

Change in the ratio of free-to-total prostate-specific antigen during progression of advanced prostate cancer.

BACKGROUND: The ratio of free-to-total prostate-specific antigen (PSA) is different in benign prostatic hyperplasia and in the early stage of prostate cancer. The present study was undertaken to examine the ratio of free-to-total PSA in the advanced stage of this cancer and its subsequent change during course of the disease. METHODS: Free and total PSA were measured in sera collected from the following patients with benign and cancerous prostatic diseases: 47 cases of benign prostatic hypertrophy, nine in TIC with less than 10 ng/mL of total PSA, 11 in stage C, 16 in D2, 22 in remission under endocrine therapy, and 12 in relapse. In addition, PSA was measured sequentially in four other patients who were also in relapse. RESULTS: The ratio of free-to-total PSA was similar in early and advanced stages of untreated prostate cancer and was lower than that in benign prostatic hyperplasia. The ratio increased to the level of benign prostatic hyperplasia during remission from stages C and D2 under endocrine therapy. There was no correlation with the intervals from the start of the therapy to examination. Following relapse, the ratio came down gradually to the level obtained in untreated prostate cancer. CONCLUSION: The ratio of free-to-total PSA was similar in all stages of untreated prostate cancer. Response and relapse to endocrine therapy were associated with increase and decrease in ratio, respectively.

Disease Progression↗

PubMed2000

Complications with one-piece lamellar keratolimbal grafts for simultaneous limbal and corneal pathologies.

PURPOSE: To determine the efficacy of a one-piece lamellar keratolimbal graft for the treatment of ocular surface disorders involving the limbus and cornea. METHODS: A retrospective study of a case series including eight patients with either Stevens-Johnson syndrome (four patients), ocular cicatricial pemphigoid (three patients), or familial subepithelial amyloidosis of the cornea (one case) was performed with a mean follow-up period of 18 months after surgery. RESULTS: Of the eight cases, three patients retained a corneal epithelial appearance upon their latest visit. No statistically significant difference was observed between preoperative visual acuity (0.013) and postoperative acuity (0.082). Stromal neovascularization was observed in all cases. Seven of eight cases experienced persistent epithelial defects (PED), four of which evolved secondary infectious ulcers. Two cases required further surgical intervention to treat PED or infectious ulcers. None of the cases developed glaucoma. CONCLUSION: A one-piece keratolimbal graft does not seem to offer any advantage over a two-piece limbal and corneal graft in the treatment of severe ocular surface disorders involving the limbus and cornea.

Adolescent↗

PubMed2000

The evolution of lamellar keratoplasty.

Recent advancements in lamellar keratoplasty have two aspects: the refinement in surgical technique, which has improved postoperative visual outcomes and the transplantation of specific tissues of the donor cornea, such as limbal stem cells. Stem cell transplantation has expanded dramatically as a method of ocular surface reconstruction. Long-term prognosis for limbal allograft transplantation has recently been reported, and postoperative treatments including epithelial management and immunosuppression are now major topics to be studied.

Cell Transplantation↗

PubMed2000

Changes in ocular surface caused by antiglaucomatous eyedrops: prospective, randomised study for the comparison of 0.5% timolol v 0. 12% unoprostone.

AIM: To study changes induced in ocular surface epithelia and the tear film by antiglaucomatous eyedrops. A beta blocker (0.5% timolol) and a novel prostaglandin F(2alpha) metabolite related drug (0.12% unoprostone) were examined in a prospective, randomised fashion. METHODS: 40 patients were randomly assigned to use either 0. 5% timolol (timolol group) or 0.12% unoprostone eyedrops (unoprostone group) twice a day for 24 weeks. In addition to routine ocular examinations, corneal epithelial integrity (vital staining tests, tear film break up time (BUT), anterior fluorometry, specular microscopy) and tear function (Schirmer's test, cotton thread test, tear clearance test (TCT)) were examined before and after the treatment. RESULTS: Both eyedrops caused significant reduction in intraocular pressure from the baseline levels. No significant changes were noted in corneal integrity in both groups, except a decrease in BUT at 20 weeks in the timolol group. The timolol group demonstrated significant decreases in Schirmer's test, tear clearance test, and tear function index (Schirmer's test value multiplied by clearance test); however, no such changes were noted in the unoprostone group. CONCLUSION: While unoprostone eyedrops caused no adverse effects on the corneal epithelial integrity and tear function, timolol caused significant impairments in tear production and turnover.

Adrenergic beta-Antagonists↗

PubMed2000

Trabeculectomy with mitomycin C for post-keratoplasty glaucoma.

AIM: To investigate the effect of trabeculectomy with and without mitomycin C in post-keratoplasty glaucoma. METHODS: A retrospective study was performed on patients who underwent trabeculectomy for glaucoma after penetrating keratoplasty. 34 eyes of 32 patients were included in this study. 26 eyes received trabeculectomy with mitomycin C and eight eyes without mitomycin C. The procedure was deemed successful if the intraocular pressure was maintained below 21 mm Hg with or without use of additional antiglaucoma medication (mean follow up time 22.3 (SD 10.3) months). RESULTS: At the last examination trabeculectomy was successful in 19 of 26 eyes (73.0%) with mitomycin C (+) and two of eight (25.0%) without (p=0.0219). When the prognosis was analysed by Kaplan-Meier curve, the mitomycin C (+) group showed a better prognosis (p=0.0182). Mean intraocular pressure and average number of glaucoma medications improved in the group with mitomycin C without severe side effects on the graft. Graft rejection after trabeculectomy was seen in two eyes in the mitomycin C group. Final graft clarity rate was 69.2% (18/26) in the mitomycin C (+) group and 37.5% (3/8) in the mitomycin C (-) group. Complications such as persistent epithelial defect, cystoid macular oedema, choroidal detachment, leakage from bleb were seen in four eyes in the mitomycin C (+) group and in one eye in the mitomycin C (-) group. CONCLUSIONS: Trabeculectomy with mitomycin C showed better results for glaucoma following keratoplasty.

Adult↗

PubMed2000

[Endocrine therapy of stage D2 prostate cancer--comparison of drugs used for total androgen blockade].

Patients with Stage D2 prostate cancer were treated with surgical or medical (LHRH analog) castration combined with either estrogen, chlormadinone acetate or flutamide as initial therapy. The effect of each medication was compared. The overall survival, cause-specific survival and relapse-free survival were not different among the three medications. Patients given each medication were divided into two groups each according to grade, extent of diseases on bone metastases, and levels of tumor marker. Survivals of the corresponding two groups were compared with each other among different medications. No differences were revealed with any medication. There were no serious side effects in whole patients, except that grade 2 liver dysfunction was accompanied in 12% of flutamide-treated group. It is concluded that the three drugs used with castration did not make any difference in the survival of stage D2 patients, and differences between medications were seen in the frequency of side effects.

Aged↗

PubMed2000

Telomerase activity and p53 expression in pterygia.

PURPOSE: To investigate tolomerase activity and p53 expression in pterygial tissue. METHODS: Pterygia tissue was obtained during excisional surgery fr om 35 eyes of 35 patients, and superior bulbar conjunctival tissue from the same eye was also sampled as control when possible. Fluorescence telomeric repeat amplification protocol was used to measure telomerase activity in whole pterygium samples from 9 cases and in the epithelium and stroma of pterygium from another 10 cases. p53 protein content was measured by enzyme-linked immunosorbent assay (ELISA) in tissues obtained from 7 eyes, as well as in epithelial cell suspensions collected by brush cytology in 8 eyes. Six samples were also analyzed for UV-specific mutations in the p53 gene by the single-strand conformation polymorphism technique and DNA sequencing. A conjunctival epithelial cell line was irradiated with sublethal levels of UV-B to investigate whether telomerase activity can be induced in vitro. RESULTS: In all, 63% of pterygia samples demonstrated telomerase activity, whereas all 10 paired conjunctival control samples were negative (P = 0.05, chi-square test). Of the 10 samples in which telomerase activity was measured separately in the epithelium and stroma of pterygia, 5 samples were positive in the epithelium, only 1 of which had activity in the stroma. Average telomerase activity in positive samples was 18.44 +/- 8.77 U/microg protein, compared with telomerase activity measured in a carcinoma in situ patient (33.73 U/microg), and in an immortalized conjunctival epithelial cell line (50.72 +/- 15.55 U/microg). Telomerase activity was not upregulated in this cell line by UV-B exposure. All 6 pterygia samples tested for p53 mutations did not reveal the UV-specific mutations in exons 5, 6, 7, or 8. No statistical significance was observed in the pterygium or conjunctiva p53 protein levels in epithelial cells collected by brush cytology, while p53 protein level was lower in pterygia when measured in whole tissue samples. CONCLUSIONS: Telomerase activity was detected in some pterygia, mostly in the epithelium. Pterygia was not associated with an increase in epithelial p53 protein content measured by ELISA.

Cell Line↗

PubMed1999

Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation.

BACKGROUND: Conditions that destroy the limbal area of the peripheral cornea, such as the Stevens-Johnson syndrome, ocular pemphigoid, and chemical and thermal injuries, can deplete stem cells of the corneal epithelium. The result is scarring and opacification of the normally clear cornea. Standard corneal transplantation cannot treat this form of functional blindness. METHODS: We performed and evaluated 70 transplantations of corneal epithelial stem cells from cadaveric eyes into 43 eyes of 39 patients with severe ocular-surface disorders and limbal dysfunction. Medical treatment had failed in all patients. The patients had a mean preoperative visual acuity of 0.004 (only being able to count the number of fingers presented by the examiner) in the affected eyes, which satisfies the criteria for legal blindness in most countries. In 28 eyes, we also performed standard corneal transplantation. Stem-cell transplantations were performed as many as four times on 1 eye if the initial results were not satisfactory; 19 eyes had multiple transplantations. Patients were followed for at least one year after transplantation. RESULTS: A mean of 1163 days after stem-cell transplantation, 22 of the 43 eyes (51 percent) had corneal epithelialization; of the 22 eyes, 7 eyes had corneal stromal edema and 15 eyes had clear corneas. Mean visual acuity improved from 0.004 to 0.02 (vision sufficient to distinguish the largest symbol on the visual-acuity chart from a distance of 1 m) (P<0.001). The 15 eyes in which the cornea remained clear had a final mean visual acuity of 0.11 (the ability to distinguish the largest symbol from a distance of 5 m). Complications of the first transplantation included persistent defects in the corneal epithelium in 26 eyes, ocular hypertension in 16 eyes, and rejection of the corneal graft in 13 of 28 eyes. The epithelial defects eventually healed in all but two of the eyes. CONCLUSIONS: Transplantation of corneal epithelial stem cells can restore useful vision in some patients with severe ocular-surface disorders.

Adult↗

PubMed1999

Inability of bone turnover marker as a strong prognostic indicator in prostate cancer patients with bone metastasis: comparison with the extent of disease (EOD) grade.

BACKGROUND: Although clinical investigations of bone turnover markers in prostate cancer patients have been conducted, the relationships of pretreatment levels of the markers to the prognosis of patients with bone metastasis has not been fully examined. METHODS: The serum levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP), alkaline phosphatase (ALP), and prostate-specific antigen (PSA) were examined in 48 untreated prostate cancer patients with bone metastasis, and the prognoses of the patients were evaluated using univariate and multivariate analyses. RESULTS: The patients with low PICP or ALP values had significantly better outcomes in terms of cause-specific survival compared to the patients with high PICP or ALP values. There was no significant difference in survival between patients with high and low ICTP or PSA values. The multivariate analysis of PICP, ICTP, ALP, PSA, and extent of disease (EOD) grade revealed that only the EOD grade was an important prognostic indicator for survival. CONCLUSIONS: These results demonstrate that the extent of bone metastasis evaluated by bone scintigrams is a more important prognostic indicator than are the serum biochemical markers of bone turnover.

Aged↗

PubMed1999

Surgical treatment of children blinded by Stevens-Johnson syndrome.

PURPOSE: The surgical treatment of severe Stevens-Johnson syndrome is considered to be very difficult, especially in children. However, ocular surface reconstruction is possible in certain cases. METHODS: We have performed ocular surface reconstruction by allogeneic corneal epithelial stem cell transplantation in four children blinded by Stevens-Johnson syndrome. RESULTS: Two cases failed, and the other two had excellent results. The successful cases had good lacrimal function and conjunctival epithelium, with clear corneal stroma and pathology limited to the superficial ocular tissue, whereas the failures did not. CONCLUSIONS: The successful ocular surface reconstruction has been stable for more than 1 year in two cases, suggesting that some patients with Stevens-Johnson syndrome are very good candidates for ocular surface reconstruction, especially when the patients have good tear function and healthy conjunctival epithelium.

Amnion↗

PubMed1999

Long-term results of a randomized trial for the treatment of Stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities.

OBJECTIVES: To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. METHODS: One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. RESULTS: The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates (P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. CONCLUSIONS: Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

Adenocarcinoma↗

PubMed1999

Treatment of persistent corneal epithelial defect by autologous serum application.

OBJECTIVE: To evaluate the efficacy of autologous serum application for the treatment of persistent epithelial defect. DESIGN: Prospective, clinical, noncomparative case series. PARTICIPANTS: A total of 16 eyes were studied. INTERVENTION: Autologous serum was prepared from the patients and diluted to 20% by saline. The patients were instructed to use the autologous serum six to ten times a day. The concentration of vitamin A, epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta) was measured at 1 week and 1 month stored in the refrigerator and 1 month and 3 months in the freezer. MAIN OUTCOME MEASURES: Time to closure of epithelial defect. RESULTS: Vitamin A, EGF, and TGF-beta were stable during the 1 month in the refrigerator and 3 months in the freezer. Among 16 persistent epithelial defects, 7 (43.8%) healed within 2 weeks, 3 (18.8%) healed within 1 month, and the remaining 6 (37.5%) did not respond within 1 month. No apparent side effect of autologous serum application was observed. CONCLUSIONS: Autologous serum application healed 43.8% of persistent defect within 2 weeks and 62.5% within 1 month.

Adult↗

PubMed1999

Immunohistochemical finding of alpha-1-antichymotrypsin in tissues of benign prostatic hyperplasia and prostate cancer.

BACKGROUND: Ratio of free to total (F/T) prostate-specific antigen (PSA) is higher in the blood of patients with benign prostatic hyperplasia than those with prostate cancer. To clarify the difference between ratios in these two, alpha-1-antichymotrypsin, the major component of the bound PSA in the blood, was immunohistochemically examined. METHODS: Tissues were obtained surgically via a retropubic approach from patients with benign prostatic hyperplasia (nine cases) and prostate cancer (27 cases). These samples were processed in paraffin blocks, cut into 5 mm sections and stained with antibodies against alpha-1-antichymotrypsin and PSA. RESULTS: The percentage of alpha-1-antichymotrypsin-stained cells in prostate cancer was higher than that in benign prostatic hyperplasia (P<0.05). Almost all of glandular and cancer cells were stained with PSA antibody. The percentage of alpha-1-antichymotrypsin-stained cells in prostate cancer did not correlate to histologic grade, although alpha-1-antichymotrypsin-stained cells were more widely scattered in high grade tissues. No correlation was found between alpha-1-antichymotrypsin-stained cells and ratio of F/T in the blood of cancer patients. In about 20% of cancer tissues, histiocytes with positive alpha-1-antichymotrypsin staining were found in stroma but not in that of benign prostatic hyperplasia. CONCLUSIONS: Prostate cancer tissues are shown to have a richer environment of alpha-1-antichymotrypsin than those of benign prostatic hyperplasia. Some cancer tissues contained alpha-1-antichymotrypsin-stained histiocytes. These local events may correlate to a high amount of the bound form among total PSA in the blood of prostate cancer patients.

Aged↗

PubMed1999

Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer: a multicenter, randomized, controlled trial in Japan. Zoladex Study Group.

OBJECTIVE: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade. METHODS: Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate). RESULTS: There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone. CONCLUSIONS: Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

Aged↗

PubMed1999

Efficacy and safety of infrared warming of the eyelids.

PURPOSE: To evaluate our newly developed infrared heater (IRH) and compare it to a broad-spectrum heater (BSH) for warming the eyelids. MATERIALS AND METHODS: Ten normal subjects were enrolled in this study. All measurements were recorded in a room with temperature 23 degrees C, 40% humidity, and no wind. The IRH is composed of two hard eye patches that have light-emitting diodes (LEDs) emitting near-infrared radiation. We first compared the temperature rises in the cornea, lacrimal gland, and eyelids after warming through closed eyelids with the IRH for 5 and 10 min. Next, we compared warming with the IRH or BSH for 30 min. We then used the IRH for 5 min with the eyes open to confirm its safety. Finally, we determined subjective feeling after warming the eyes. RESULTS: Direct comparison of 5 versus 10 min of warming with the IRH showed no significant differences in temperature rises in the upper eyelid (p = 0.09). The IRH caused significantly more heating (p < 0.05) than did the BSH everywhere except the cornea. The temperatures never rose above 37.7 degrees C for either heater during 30 min or with the IRH with the eyes open for 5 min. The subjects' comfort level rose significantly (p < 0.05) after treatment with the IRH. CONCLUSIONS: Our study showed the efficacy and safety of warming the eyelids with a newly developed IRH. Only 5 min is necessary to increase ocular temperature and enhance comfort.

Adult↗