bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Handling of Information in Patients Suffering from Restrictive Anorexia in an Emotional Stroop Test and a Word Recognition Test
Authors: Mendlewicz L. , Nef F. , Simon Y.
Published: April 2003

Several studies have been carried out using the Stroop test in eating disorders. Some of these studies have brought to light the existence of cognitive and attention deficits linked principally to weight and to food in anorexic and bulimic patients. The aim of the current study is to replicate and to clarify the existence of cognitive and attention deficits in anorexic patients using the Stroop test and a word recognition test. The recognition test is made up of 160 words; 80 words from the previous Stroop experiment mixed at random and matched from a semantic point of view to 80 distractions. The recognition word test is carried out 2 or 3 days after the Stroop test. Thirty-two subjects took part in the study: 16 female patients hospitalised for anorexia nervosa and 16 normal females as controls. Our results do not enable us to confirm the existence of specific cognitive deficits in anorexic patients.
Alpha-2-Adrenoreceptors in Depressed Suicide Attempters: Relationship with Medical Lethality of the Attempt
Authors: Pitchot William , Hansenne Michel , Pinto Emmanuel , Reggers Jean , Fuchs Sonia , Ansseau Marc
Published: April 2003

Several lines of evidence tend to suggest a role for noradrenaline, and more specifically alpha-2-adrenoreceptors, in the biology of suicidal behavior. The purpose of this study was to assess the growth hormone (GH) response to clonidine, an alpha-2-adrenergic agonist, in majorly depressed inpatients with a history of highly lethal suicide attempt compared to depressed patients with a history of low lethal suicide attempt and nonattempters. Our sample included 20 male depressed inpatients with a history of suicide attempt compared to 20 male depressed nonattempters. We did not observe any significant difference between suicide attempters and nonattempters for GH peak values (2.4 ± 2.9 vs. 4.1 ± 3.7 ng/ml; F = 2.52, d.f. = 1, 38, p = 0.12). Moreover, GH peak responses to clonidine were not related to the degree of lethality of the attempt. The results of the present study do not support a major role for noradrenaline in the biology of suicidal behavior.
Chronic Treatment with Clozapine, but Not Haloperidol, Increases Striatal Ecto-5′-Nucleotidase Activity in Rats
Authors: Lara Diogo R. , Vianna Mônica R.M. , de Paris Fernanda , Quevedo João , Oses Jean P. , Battastini Ana M.O. , Sarkis João J.F. , Souza Diogo O.
Published: April 2003

In the search for differential mechanisms underlying clozapine’s superior antipsychotic efficacy, the purinergic system has been considered, since an antagonist of the adenosine receptor A2A was shown to block clozapine acute effects on c-fos expression in rat striatum. Further investigating the interaction of clozapine with the purinergic system, we studied the effects of chronic treatment (28 days, intraperitoneal) with clozapine (25 mg/kg) and haloperidol (1.5 mg/kg) on the activity of ectonucleotidases in the striatum and hippocampus of rats. Clozapine selectively increased striatal 5′-nucleotidase activity (22%) compared to control and haloperidol groups. In vitro, neither drug affected enzyme activities. These results reinforce the differential effects of clozapine compared to haloperidol on the purinergic system.
Possible Relationship between Combined Plasma Concentrations of Risperidone plus 9-Hydroxyrisperidone and Extrapyramidal Symptoms
Authors: Yoshimura Reiji , Ueda Nobuhisa , Nakamura Jun
Published: April 2003

We investigated the relationships between extrapyramidal symptoms (EPS) induced by risperidone, the dosage of risperidone and the combined plasma concentrations of risperidone plus its active metabolite, 9-hydroxyrisperidone, in 20 schizophrenic patients. There was a positive correlation between the scores on the Simpson and Angus Scale and both the dosage of risperidone and the sum of the plasma levels of risperidone and 9-hydroxyrisperidone. These results suggest that EPS induced by risperidone increase in conjunction with both the dosage of risperidone and the total plasma concentrations of the parent compound and its active metabolite.
Insomnia Related to Dysthymia: Polysomnographic and Psychometric Comparison with Normal Controls and Acute Therapeutic Trials with Trazodone
Authors: Saletu-Zyhlarz Gerda Maria , Abu-Bakr Manal Hassan , Anderer Peter , Semler Brigitte , Decker Kathrin , Parapatics Silvia , Tschida Ulrike , Winkler Astrid , Saletu Bernd
Published: April 2003

Utilizing polysomnography (PSG) and psychometry, objective and subjective sleep and awakening quality was investigated in 11 patients (mean age 50 ± 14) with nonorganic insomnia (F 51.0) related to dysthymia (F 34.1) as compared with 11 age- and sex-matched normal controls. Patients demonstrated decreased sleep efficiency and sleep stage S2 as well as increased sleep latency to S1, S2 and S3, wakefulness within the total sleep period, number of awakenings, S1 and REM sleep. There was no intergroup difference in REM latency. Subjective sleep quality and the total score of the Self-Assessment Scale for Sleep and Awakening Quality (SSA) were deteriorated as were evening and morning well-being, mood, affectivity and drowsiness. Noopsychic measures showed deteriorated numerical memory, fine motor activity and reaction time variability. In a placebo-controlled crossover design study, the acute effects of 100 mg trazodone1, a serotonin reuptake inhibitor with a sedative action due to 5HT2 and α1 receptor blockade, were investigated in the patients. As compared with placebo, trazodone induced an increase in slow-wave sleep (S3 + 4), a lengthening of REM latency, a decrease in REM sleep and a normalization of the periodic leg movement (PLM) index. In the morning, there was a minimal increase in somatic complaints and a decrease in critical flicker frequency and systolic blood pressure. In conclusion, our study demonstrated that dysthymia induced significant changes in objective and subjective sleep and awakening quality, which were counteracted by 100 mg trazodone, thus suggesting a key-lock principle in the treatment of nonorganic insomnia related to dysthymia with this drug.
Concomitant Endocrine and Immune Alterations during Alcohol Intoxication and Acute Withdrawal in Alcohol-Dependent Subjects
Authors: Kutscher Sven , Heise Dirk J. , Banger Markus , Saller Bernhard , Michel Martin C. , Gastpar Markus , Schedlowski Manfred , Exton Michael S.
Published: April 2003

Although both alcohol intoxication and withdrawal have been demonstrated to produce significant endocrine alterations, no data exist on the effects of acute withdrawal on immune functions. Therefore, the current study investigated the effect of alcohol intoxication and acute withdrawal on plasma cortisol, prolactin and catecholamines, and blood leukocyte subset distribution in alcohol-dependent subjects. Nine male alcoholics admitted to the university clinic for alcohol dependence and 9 age-matched controls participated in the study. Blood was drawn from the alcohol-dependent subjects at 10:30 a.m. on day 0 (chronic alcohol intoxication), at the same time during acute alcohol withdrawal (day 1) and following the resolution of acute withdrawal (day 7). Blood was drawn from age- and gender-matched healthy control subjects at the corresponding time points. Plasma was then analyzed for hormone concentrations and blood examined for leukocyte subsets by flow cytometry. Alcohol-dependent patients displayed significantly elevated plasma cortisol during intoxication and withdrawal, which decreased to control levels following resolution of acute withdrawal. Small elevations of plasma prolactin and catecholamines were also observed during intoxication. Furthermore, alcohol-dependent subjects showed reduced absolute numbers of CD4+ and CD8+ T cells and natural killer cells compared with healthy controls across all time points. In contrast, although monocyte numbers were lower in alcohol-dependent patients during intoxication, acute alcohol withdrawal increased the number of monocytes in patients. Thus, alcohol dependence produces a general suppression of leukocyte subset populations in blood. However, resolution of acute alcohol withdrawal is associated with a return of plasma cortisol to control levels, and a concomitant increase in peripheral blood monocyte numbers.
A Pure Antiestrogen, ICI 182,780, Stimulates the Growth of Tamoxifen-Resistant KPL-1 Human Breast Cancer Cells in vivo but not in vitro
Authors: Kurebayashi Jun-ichi , Otsuki Takemi , Yamamoto Shigeru , Kurosumi Masafumi , Nakata Taisuke , Akinaga Shiro , Sonoo Hiroshi
Published: April 2003

The critical mechanisms responsible for antiestrogen resistance have not yet been elucidated. We previously established a breast cancer cell line, KPL-1, derived from a patient with recurrent disease which appeared under tamoxifenadministration. In a previous study, we suggested that this cell line is estrogen receptor (ER)-positive but tamoxifen-resistant. In the present study, the effects of a pure antiestrogen, ICI 182,780, on this cell line were investigated. Although tamoxifen inhibited neither cell growth nor estradiol-stimulated transcriptional activity in vitro, ICI 182,780, significantly inhibited both of them. Tamoxifen and ICI 182,780 were then administered to female nude mice bearing KPL-1 tumors. Tamoxifen had no effect on tumor growth, but ICI 182,780 unexpectedly stimulated it (p = 0.022). Estradiol tended to inhibit tumor growth (p = 0.198). Immunohistochemical analysis revealed that ICI 182,780 significantly increased the Ki6-labeling index (p<0.001) but estradiol decreased it (p = 0.035). To explore the possible mechanisms of these phenotypes, the mRNA levels of ER-α,ER-β, transforming growth factor-β1, fibroblast growth factor (FGF)-1 and FGF-4 in KPL-1 cells were compared with those in other ER-positive human breast cancer cell lines by reverse-transcription polymerase chain reaction. FGF-1 was overexpressed only in KPL-1 cells. This cell line is the first breast cancer cell line to be growth-stimulated by ICI 182,780 in vivo. Paracrine interaction between tumor cells and stromal cells mediated by growth factors, such as FGF-1, might be a key factor to explain the unique hormone responsiveness of KPL-1 cells.
Thiazolidinedione Induces Apoptosis and Monocytic Differentiation in the Promyelocytic Leukemia Cell Line HL60
Authors: Hirase Nobuhisa , Yanase Toshihiko , Mu Yi-ming , Muta Koichiro , Umemura Tsukuru , Takayanagi Ryoichi , Nawata Hajime
Published: April 2003

Thiazolidinedione (TZD) is known to be a potent activator of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor that constitutes a heterodimer with retinoid X receptor (RXR). Since a considerable amount of PPARγ is expressed in various hematopoietic cells, the present study was undertaken to examine the effect of TZD in the absence or presence of LG100268, an RXR-selective ligand, on a cultured promyelocytic leukemia cell line, HL60. Treatment with TZD (25–50 µM troglitazone or pioglitazone) markedly suppressed cell proliferation of HL60. A cell cycle analysis revealed that the suppressive effect of troglitazone on HL60 cell proliferations was caused by G0/G1 cell cycle arrest as well as by an apoptotic effect. Treatment with the same concentration of troglitazone also induced the monocytic differentiation of HL60 cells. The apoptotic or the differentiating effect of TZD on HL60 cells was synergistically enhanced by the combined treatment with 1 µM LG100268, while LG100268 alone neither had an apoptotic nor a differentiating effect on HL60 cells. These results suggest that these actions are mediated through the nuclear receptor system constituted by the PPARγ: RXR heterodimer.
Progestin Regulation in Tumor Growth of Female Genital Tract Cancers
Authors: Fujimoto Jiro , Sakaguchi Hideki , Misao Ryo , Hirose Reiko , Wen Hongwu , Tamaya Teruhiko
Published: April 2003

The irregular response to progestins directly in tumor growth might be caused by dominant negative progesterone receptor (PR) mutants and the damage to PR-A expression. Progestin treatment as an anti-angiogenic therapy would be less effective in the PR-mutated tumors. Therefore, various anti-angiogenic inhibitors must be used in progestin-refractory and progestin-dependent tumors.
Scattered Fat Invasion: An Indicator for Poor Prognosis in Premenopausal, and for Positive Estrogen Receptor in Postmenopausal Breast Cancer Patients
Authors: Kimijima I. , Ohtake T. , Sagara H. , Watanabe T. , Takenoshita S.
Published: April 2003

Background: Intracrine mechanisms which accelerate cancer cell growth are becoming well known in breast cancer research. In this study, microscopic invasive patterns of breast cancer cells into surrounding stromal tissues were evaluated. Patients and Methods: 174 patients (110 patients ≤50, and 64 ≧60 years) underwent total or partial mastectomy from 1985 to 1993. In these patients the microscopic invasive pattern (especially scattered invasion into fat, SIF), influence on hormone receptor status, survival, and adjuvant therapy effectiveness were studied. Results: A correlation was shown between being SIF- and estrogen receptor-positive only in older (≧60 years) patients (χ2 test, p = 0.058). In younger patients, SIF was also related to a poorer prognosis (log rank test, p = 0.0004). These results were also confirmed by multivariate analysis. Adjuvant therapy activity was influenced by SIF status in premenopausal patients. Conclusion: In older patients, SIF may be related to an intracrine supply of estrogen. In younger patients, SIF seems to work by a different mechanism for survival. These results also suggest some influence of SIF on adjuvant chemo-endocrine therapy results.
Postirradiation Angiosarcoma of the Chest Wall and Breast: Issues of Radiogenic Origin, Diagnosis and Treatment in Two Cases
Authors: Polgár C. , Orosz Z. , Szerdahelyi A. , Fodor J. , Major T. , Mágori A. , Czeyda-Pommersheim F. , Vámosi Nagy I. , Szakolczai I. , Fejös Z. , Németh G.
Published: April 2003

The authors report two cases of postradiation angiosarcoma (AS) among 5,100 breast cancer patients treated in the period 1980–1994 at the National Institute of Oncology, Budapest. Relevant data in the literature is also reviewed to analyze the questions of radiogenic origin, diagnosis and treatment. Secondary AS occurred in these cases in a previously irradiated field after a 6- and 8-year latency period, respectively. Detailed histopathological and immunohistochemical examinations from the biopsy specimens confirmed the diagnosis as AS. The first patient was treated successfully with radical surgery. The second patient, with unresectable AS, died of rapid local progression within 4 months. The incidence of chest wall and breast AS after radiotherapy was found to be 0.46 per 1,000 in our patient population, which means an estimated odds ratio of 2.9 for secondary AS. Patients treated with radiotherapy for primary breast cancer are at higher risk for developing secondary AS compared to the healthy population. An etiological relationship between radiotherapy and subsequent AS of the chest wall and breast is likely, but still controversial. Initial radical surgery is the only effective treatment for achieving long-term survival. These very rare cases deserve special attention due to the atypical clinical appearance, difficulties of differential diagnosis and poor prognosis.
A Dose-Finding Study of Irinotecan (CPT-11) plus a Four-Day Continuous 5-Fluorouracil Infusion in Advanced Colorectal Cancer
Authors: Kakolyris S. , Souglakos J. , Kouroussis C. , Androulakis N. , Mavroudis D. , Kalbakis K. , Kotsakis A. , Vardakis N. , Koukourakis M. , Romanos J. , Georgoulias V.
Published: April 2003

Objective: Irinotecan (CPT-11) has shown considerable activity in colorectal cancer, and its combination with 5-fluorouracil (5-FU) represents an attractive approach. A phase I study was conducted to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of CPT-11 in combination with a continuous infusion of 5-FU for 4 days. Methods: Forty-two patients with histologically confirmed metastatic colorectal cancer who had not received prior treatment for advanced disease were enrolled. The patients’ median age was 64 years; 26 (62%) patients were men, and the performance status (WHO) was 0 in 26 (62%) patients, 1 in 15 (36%) and 2 in 1 (2%). Twenty-two (52%) patients had 2 or more metastatic sites. CPT-11 (starting dose 200 mg/m2) was administered as a 30-min intravenous infusion with increments of 50 mg/m2 on day 4. 5-FU (starting dose 400 mg/m2) was administered as a 4-day continuous intravenous infusion with increments of 50 mg/m2 on days 1–4. Treatment was repeated every 4 weeks. Results: The MTD of the combination was found to be 600 mg/m2 for 5-FU and 350 mg/m2 for CPT-11. Neutropenia, febrile neutropenia and delayed diarrhea were the DLTs. Grade 3/4 neutropenia was observed in 22 (13%) out of 169 administered treatment cycles, febrile neutropenia in 7 (4%) and grade 3/4 diarrhea in 20 (12%). Other toxicities were mild. Among 36 patients evaluable for response, partial response was achieved in 8 (22%), stable disease in 12 (33%) and progressive disease in 16 (44%) patients. Responses were mostly seen at the higher dose levels. Conclusions: The combination of a 4-day continuous infusion of 5-FU followed by CPT-11 represents an active and well-tolerated regimen for patients with colorectal cancer. This regimen merits further evaluation in phase II studies.
Three-Year Results of the First Educational and Early Detection Program for Testicular Cancer in Hungary
Authors: Géczi Lajos , Gomez Frederic , Horváth Zsolt , Bak Mihály , Kisbenedek László , Bodrogi István
Published: April 2003

Objective: To determine whether a testicular self-examination-based early-detection program may help in the early diagnosis of testicular cancer. Methods: Advertisements were placed in the media describing the early signs of testicular cancer, the risk factors, the correct method of self-examination and the importance of early detection. Between April 1995 and April 1998, 5,056 men underwent physical and ultrasound examination of the testicles, and in case of suspicious findings tumor markers were checked. Results: Testicular tumors were found in 1.28% of the men with symptoms. No tumors were found in men without symptoms or in men with pain, sensitivity to palpation, or complaints unrelated to the testicle. Of those with a palpable lump or swollen testicle, 4.5 and 3.9% were found to have a tumor. In total, 28 testicular cancers (15 seminomas and 13 nonseminomas) in 26 volunteers and 4 benign tumors were detected. The occurrence of cancer was most frequent in the age group of 15–40 years (1.6%). Conclusion: The rate of cancer detection and the detected seminoma rate in the program are not sufficient to justify a widespread early detection program for testicular cancer (examination of men who reveal testicular abnormalities by self-examination) despite the increased tumor incidence. Early diagnosis should be based on an educational program for the population at risk, the training of staff engaged in the health care of the young, and the use of early ultrasound examination in men with palpable lumps and swollen testicles, especially in young men.
Effects of Octreotide on Liver Metastasis and Intrametastatic Lipid Peroxidation in Experimental Pancreatic Cancer
Authors: Wenger F.A. , Kilian M. , Jacobi C.A. , Mautsch I. , Peter F.J. , Guski H. , Schimke I. , Müller J.M.
Published: April 2003

Objectives: In prospective clinical trials, octreotide improved the quality of life and survival time in patients with pancreatic cancer. In this study, we analyzed whether octreotide modulates the intrametastatic oxygen radical metabolism and might decrease liver metastasis in a model of pancreatic cancer. Methods: Syrian hamsters received 0.9% NaCl or N-nitrosobis(2-oxopropyl)amine for 3 months. Therapy was performed for 12 weeks by 0.9% NaCl or octreotide. Hamsters received a standard diet or were fed a high-fat diet. In the 25th week, pancreas and liver were examined macroscopically and histologically. The level of lipid peroxidation and the activity of glutathione peroxidase and superoxide dismutase were determined intrahepatically and intrametastatically. Results: The number and size of liver metastases per animal were increased by high-fat diet and decreased by octreotide. While high-fat diet increased intrahepatic extrametastatic lipid peroxidation, octreotide decreased intrahepatic extrametastatic lipid peroxidation and increased intrametastatic lipid peroxidation. Conclusions: Octreotide decreases the number and size of liver metastases in chemically induced pancreatic cancer in Syrian hamsters. Possible mechanisms are the prevention of high lipid peroxidation in non-metastatic liver as well as the increase in intrametastatic lipid peroxidation, leading to loss of integrity of spread tumor cells.
Application of Classification Tree and Neural Network Algorithms to the Identification of Serological Liver Marker Profiles for the Diagnosis of Hepatocellular Carcinoma
Authors: Poon Terence Chuen-Wai , Chan Anthony Tak-Cheung , Zee Benny , Ho Stephen King-Wah , Mok Tony Shu-Kam , Leung Thomas Wai-Tong , Johnson Philip James
Published: April 2003

Objective: Although many attempts have been made to identify tumour-specific α-fetoprotein (AFP) glycoforms or other serological markers for the diagnosis of hepatocellular carcinoma (HCC), none of the available markers has, so far, shown satisfactory sensitivity and specificity. Here we aimed to apply classification tree and neural network algorithms to interpret the levels of multiple serological liver markers to improve overall specificity and sensitivity, particularly with a view to discriminating between liver cirrhosis with and without HCC. Methods: We developed classification trees and neural networks that identified serological liver marker profiles comprising AFP, α1-antitrypsin (A1AT), α2-macroglobulin (A2MG), thyroxine-binding globulin (TBG), transferrin and albumin as well as sex and age, which might permit the diagnosis of HCC. Data were collected from 65 HCC patients, 51 patients with liver cirrhosis alone (LC) and 51 normal healthy subjects. Results: The generated classification trees and neural networks showed similar diagnostic values in differentiating HCC from LC. The classification trees identified AFP, A1AT and albumin as the most important classification parameters, whereas the neural networks identified A2MG, AFP, A1AT and albumin as the predominant factors. The classification logic of the classification trees indicated that more HCC cases could be identified among cases with slightly elevated AFP levels by using the serum levels of A1AT and albumin. The neural networks were also useful for the identification of the HCC cases when the AFP levels were below 500 ng/ml (p < 0.005). The neural networks could identify HCC cases with AFP levels within the normal range, but the classification trees could not. By combining the conventional AFP test and the neural networks, the overall diagnostic sensitivity for HCC was significantly increased from 60.0 to 73.8% (p < 0.05) while maintaining a high specificity (88.2%). The sensitivities for tumors of different sizes were similar. Conclusion: The neural network algorithm appeared to be more powerful than the classification tree algorithm in the identification of the distinctive serological liver marker profiles for the diagnosis of the HCC subgroup without significant elevation in serum AFP levels. By incorporating serological levels of other liver markers and including data from a large number of patients and control subjects, it should prove possible to develop a versatile neural network for early diagnosis of HCC.
Future Role of Topotecan in the Treatment of Lung Cancer
Authors: Schiller Joan H.
Published: April 2003

Topotecan (HYCAMTIN®; GlaxoSmithKline, Brentford, Middlesex, UK) is a novel topoisomerase I inhibitor with potentially broad applicability in the treatment of solid and hematologic malignancies. In addition to its use in relapsed small-cell lung cancer (SCLC), topotecan is under investigation in numerous studies for first-line therapy in SCLC and for first- and second-line treatment of non-small-cell lung cancer (NSCLC). Preliminary evidence presented in this supplement demonstrates that single-agent topotecan and topotecan-based combination regimens are active in these settings. In addition to its potential use in SCLC and NSCLC, the feasibility and antitumor activity of topotecan as single-agent therapy and in combination therapy are under active investigation in a variety of other solid and hematologic tumors. Other important avenues of investigation include the feasibility and tumor activity of a more convenient oral formulation, as well as the investigation of alternate regimens (e.g., 3-day, weekly), with high priority given to regimen toxicity, patient convenience, and quality of life. Preliminary results of some of these trials are presented in this summary. The results of other clinical experience trials are eagerly anticipated.
HER2 as a Prognostic Factor in Breast Cancer
Authors: Ménard Sylvie , Fortis Stefania , Castiglioni Fabio , Agresti Roberto , Balsari Andrea
Published: April 2003

HER2 amplification/overexpression is a marker of poor prognosis in breast cancer. The prognostic impact of HER2 positivity is lower in node-negative compared with node-positive women. The only significant, independent prognostic factors in breast cancer are node status, HER2 status and menopausal status. HER2-positive tumors also contain p53 abnormalities, tend to be hormone receptor and bcl-2 negative, have lymphoid infiltration (LI) and a high mitotic index. Patients with LI who are HER2 positive have a better prognosis than those who are HER2 negative, whereas HER2-positive patients without LI have a significantly worse prognosis than HER2-negative patients. Morphological and biological alterations appear to identify two categories of breast tumor. Two hypotheses may explain the progression to two tumor types: (1) atypical ductal hyperplasia (ADH) is a precursor of ductal carcinoma in situ (DCIS), which is a precursor of invasive ductal carcinoma (IDC); or (2) ADH is a precursor of HER2-negative IDC whereas DCIS is a precursor of HER2-positive IDC. The second theory fits well with two breast cancer subsets and the characteristics of ADH and DCIS. The first type of IDC occurs in older patients, progresses slowly due to estrogen dependency but is aggressive long term. The other type progresses rapidly, is HER2 positive and is more likely to occur in young patients.
Analysis of Tears in Patients with Atopic Keratoconjunctivitis, Using Flow Cytometry
Authors: Murat Avunduk Avni , Cihat Avunduk Mustafa , Tekelioglu Yavuz
Published: April 2003

Atopic keratoconjunctivitis (AKC) is a chronic allergic eye disease. Although the pathogenesis is not fully understood, some impairment in cell-mediated immunity was suggested by histopathological findings in conjunctival specimens obtained from affected individuals. T-cell infiltration and an enhanced T-helper/T-suppressor cell ratio in conjunctival biopsy specimens were observed previously by immunofluorescence procedures. We analyzed the cells in tears of patients with AKC using flow cytometry (FCM) and compared the results to those of normal subjects to identify the role of T lymphocytes in the pathogenesis of the disease. The tear samples of the patients and normal subjects were collected with capillary tubes, and the surface receptors of cells were detected with FCM. Statistical analyses were performed with Student’s t test. The percentages of T cells, activated B cells, and T-helper/T-suppressor cell ratios were found to be higher in the tears of patients with AKC than in controls. We propose that a decreased T-suppressor cell concentration in tears may enhance immunoglobulin-E production of B cells, and the signs and symptoms are provoked by inflammatory mediators liberated from mast cell degranulation.
Gene Expression of the Phosducin-Like Protein in the Retina
Authors: Abe Toshiaki , Tomita Hiroshi , Tamai Makoto
Published: April 2003

Phosducin, which is expressed abundantly in the retina, mediates phototransduction or signal transduction cascades by interacting with transducin or G-protein βγ-subunits. We have reported on the possibility that phosducin is expressed from a multiple gene family and that each phosducin may mediate G-protein-coupled signal transduction cascades. To elucidate new genes that may mediate signal transduction cascades in the retina and that may form a gene family with phosducin, we screened a bovine retinal cDNA library. During the screening, we identified a cDNA that looked the same as the phosducin-like protein of the rat, as reported by other investigators. We examined the gene expression in rat retina using semiquantitative polymerase chain reaction and compared it to that of other organs. One form generated by alternative splicing expressed in the retina was the same as in other tissues, but, interestingly, another form had differing tissue distribution and was expressed abundantly in the retina.
Retinal Cytokine Response in Mouse Alkali-Burned Eye
Authors: Miyamoto Fumi , Sotozono Chie , Ikeda Tsunehiko , Kinoshita Shigeru
Published: April 2003

The kinetics of inflammatory cytokines in sensory retina of mice with corneal alkali-burned eyes were examined. Retinal samples were collected from ICR mice with unburned and alkali-burned eyes from day 3 to day 14. Enzyme-linked immunosorbent assay was used to quantitate the expression levels of interleukin-1α (IL-1α), IL-1β and IL-6. Concentrations of IL-1β and IL-6 were significantly elevated at day 3 after alkali burn, and reduced to normal level by day 7. The concentration of IL-1α was below assay sensitivity at all times. A significant elevation of IL-1β and IL-6 in the sensory retina may contribute to the retinal inflammatory response in the alkali-burned eyes. This is the first report suggesting that the retina is involved in the damage process of alkali burn.
A Morphological and Morphometrical Study of the Retina in Aging SAM Mice
Authors: Shoji Masato , Okada Morio , Ohta Akira , Higuchi Keiichi , Hosokawa Masanori , Honda Yoshihito
Published: April 2003

We investigated whether neuronal cell loss occurred as a part of normal aging of the retina in the Senescence-Accelerated Mouse, strains SAMP1 and SAMR1, and in the BALB/c mouse. All three strains showed age-related atrophy of the retina after histologically normal development. Morphometrical study revealed the following facts. The rate of loss of photoreceptor cells in the peripheral retina was greater than in the central retina in all three strains. In the central retina, the rate of loss of photoreceptor cells was greater in the SAMP1 and SAMR1 mice than in the BALB/c mice. In the peripheral retina, the SAMR1 and SAMP1 strains had fewer cells than the BALB/c strain at all ages, but the rate of loss of these cells did not differ among the three strains. The rate of loss of ganglion cells did not differ between the peripheral and central retinas in the three strains. The SAMR1 and SAMP1 strains had fewer ganglion cells in the peripheral retina than the BALB/c strain at all ages. Because the rate of age-related loss of these cells in SAMP1 mice was not accelerated, and they were short-lived, SAMP1 mice did not show marked age-related loss. On the contrary, the SAMR1 mice showed a marked loss of photoreceptor cells and ganglion cells late in life because of their longer life span, and we propose that this strain is a suitable animal model for the study of mechanisms of age-related loss of neuronal cells in the retina.
Automatic Static Threshold Perimetry Is Useful for Estimating the Effects of Laser Photocoagulation on Diabetic Maculopathy
Authors: Okuyama Michiko , Okisaka Shigekuni
Published: April 2003

Focal photocoagulation was performed on 18 eyes in 18 diabetes patients; a visual acuity test, fluorescein angiography and automated static threshold perimetry by Octopus automated static perimetry (program 31) were conducted before and 1, 3 and 6 months after krypton laser photocoagulation. Central field sensitivity and total loss were measured by automated static threshold perimetry. Group A (13 eyes) had a total loss of less than 150 dB. In these subjects, mild fluorescein leakage was detected within the area of the vascular arcade. In group B (5 eyes) with a total loss of greater than 150 dB, diffuse fluorescein leakage was also detected outside the vascular arcade. The central field sensitivity was reduced in 2 eyes of group B. The total loss worsened in 8 eyes of group A (61.5%) and 5 eyes of group B (100%). Inspection of photographs gave the impression that the degree of fluorescein leakage and the area of the avascular zone on fluorescein angiography accorded with total loss, thus suggesting that total loss reflects visual functions better than visual acuity or central field sensitivity. Therefore, automated static threshold perimetry appears to be a useful method for estimating visual functions after photocoagulation in diabetic maculopathy patients.
Expression of Cytokine Genes in a Patient with Conjunctival Melanoma Compared with Other Pigment Cells
Authors: Abe Toshiaki , Ohashi Toshifumi , Tamai Makoto
Published: April 2003

Conjunctival melanomas, which have a relatively good prognosis as compared to other mucosal melanomas, have been investigated morphologically and pathologically. We examined the gene expression of several cytokines in a patient with conjunctival melanoma and compared them to those of other pigment cells of the eye, because no reports have discussed cytokine expression in melanoma of the eye. Samples were collected from a 64-year-old woman with conjunctival melanoma and mRNAs were extracted and reverse-transcriptase polymerase chain reaction was performed. We found that potent inhibitors of tumor cell growth such as interleukin 2, 4, 6 and γ-interferon were expressed in the tumor. These inhibitors were not expressed in other pigment cells of the eye, in blood, in conjunctival melanosis or in choroidal melanomas. The basic fibroblast growth factor gene, which has also been known to stimulate melanoma cell growth, was not expressed in the conjunctival melanoma, and it showed +/– or weak expression in choroidal melanomas, but it was expressed in the pigment cells in the eye and in conjunctival melanosis. Although only limited cytokine expression was examined here, these results may suggest an influence of these cytokines to the growth of conjunctival melanoma.
Visual Function and Gene Analysis in a Family with Oguchi’s Disease
Authors: Yoshii Masaru , Murakami Akira , Akeo Kiyoshi , Nakamura Atsuo , Shimoyama Masaru , Ikeda Yoko , Kikuchi Yasuhiro , Okisaka Shigekuni , Yanashima Kenji , Oguchi Yoshihisa
Published: April 2003

A family with 1 case of retinitis pigmentosa (III-1) and 2 cases of Oguchi’s disease (III-2, 3) was examined in terms of electrophysiology as well as molecular biology. The proband (III-3), a 42-year-old female, and 2 older brothers (III-1, 2, aged 52 and 45 years) and 2 unaffected members in the same family participated in this study. Corrected visual acuities of the individuals with Oguchi’s disease (III-2, 3) were 1.2. On funduscopy, blood vessels stood out in relief against a metallic-appearing background and a Mizuo-Nakamura phenomenon was evident. Full-field electroretinograms (ERGs) recorded from the proband were indicative of rod dystrophy, but results of other electrophysiological examinations (multifocal ERG, pattern ERG and visual-evoked cortical potential recordings) were within normal limits. Patient III-1 had corrected visual acuities of RE 20 cm/m.m. and LE 30 cm/n.d., severe chorioretinal atrophy in both fundi, and full-field ERG revealed rod-cone dystrophy. Mutation of the arrestin gene (1147de1A) was detected in all 3 cases, but no mutation was observed for the rhodopsin gene. A homozygous deletion 1147 (1147de1A) in codon 309 of the arrestin gene was commonly observed in all 3 patients. Visual function in each patient coincides with that of retinitis pigmentosa or Oguchi’s disease, respectively.
A Standard Strain of Human Ocular Keratocytes
Authors: Dropcova Simona , Denyer StevenP. , Lloyd AndrewW. , Gard PaulR. , Hanlon GeoffW. , Mikhalovsky SergeiV. , Sandeman Susan , Olliff Cedric J. , Faragher RichardG.A.
Published: April 2003

The ability of an injured cornea to regenerate from deep tissue trauma is largely due to wound healing processes mediated by the surviving stromal keratocytes. Despite the importance of the wound healing process, and the ease with which keratocytes can be grown in tissue culture, a standardised strain of the cells has never been made available. Accordingly, this study reports a strain of human embryonic keratocytes, designated EK1.BR as a research tool for the ophthalmic community. EK1.BR has been characterised with respect to life-span, fraction of dividing cells and maintenance of a keratocyte phenotype in culture. It is hoped that these cells will prove useful in the in vitro study of stromal wound healing and the characterisation of keratocyte gene expression.
An Index for Human Lens Transparency Related to Age and Lens Layer: Comparison between Normal Volunteers and Diabetic Patients with Still Clear Lenses
Authors: Sasaki Hiroshi , Hockwin Otto , Kasuga Takabumi , Nagai Kouta , Sakamoto Yasuo , Sasaki Kazuyuki
Published: April 2003

Objective: The light scattering intensity of normal, clear lenses varies with age and with the localization within the lens. Realizing the biometry of single lens areas together with their relevant light scattering intensity one should be able to calculate an index to express the lens transparency properties of normal human lenses in dependence on age. Performing the same procedure in cases of diabetic patients with still clear lenses it should become possible to obtain an index for the lens transparency properties of lenses under the ‘risk factor’ diabetes. Methods: 748 eyes with transparent lenses in 383 healthy individuals and 134 eyes with clear lenses in 70 subjects with diabetes were examined. Scheimpflug slit images of the lens were documented by a Nidek EAS-1000 instrument. Biometry for measuring the distance of the single lens layers from the anterior capsule and densitometry for determining the light scattering intensity of six defined lens layers along the (theoretical) optical axis were performed. The index of the lens transparency properties was calculated using the light scattering intensity of a defined lens layer and its distance from the anterior capsule. Results: Lens thickness and light scattering intensities increased linearly with increasing age in the normal population as well as in the diabetic patients. The densitogram pattern of the light scattering intensities in the defined representative six points was similar in both populations, but in the diabetic group the lens thickness was larger and the light scattering intensities were higher at all ages. Conclusion: The index of lens transparency properties calculated with the light scattering intensities of a certain lens area and its distance from the anterior capsule is a useful measure of lens clarity in dependence on age. ‘Clear’ lenses of the diabetic population show significantly higher indices for the lens transparency properties in all age groups.
Comparison of Clinical and Digital Assessment of Nuclear Optical Density
Authors: Robman L.D. , McCarty C.A. , Garrett S.K.M. , Stephenson H. , Thomas A.P. , McNeil J.J. , Taylor H.R.
Published: April 2003

To compare the standardised Nidek EAS-1000 densitometric analysis of the lens with clinical assessment of the nucleus at an early stage of cataract development, 1,200 eyes of 1,204 participants of the VECAT study were assessed at the baseline using both subjective and objective lens grading. Standardisation of the automatic slit image analysis was achieved using a custom-designed EAS-1000 Software version 3.01c. Among 6 measurements of nuclear optical density, the mean pixel luminescence of integrated anterior nuclear density correlated best with clinical assessment (R = 0.662, p < 0.001). Variance components that interfere with the assessment are defined.
Blood-Aqueous Barrier Disruptionin Expe rimental Anterior Segment Ischemia in Rabbit Eyes
Authors: Ino-ue Masanori , Shirabe Hisamitsu , Yamamoto Misao
Published: April 2003

The blood-aqueous barrier (BAB) in experimentally induced anterior segment ischemia (ASI) following strabismus or retinal detachment surgery in pigmented rabbits was evaluated by laser flare photometry. Four simultaneous rectus tenotomies produced a significantly higher flare value on the 1st postoperative day. Obstruction of one or two vortex veins produced significantly high flare values on the 1st and 3rd postoperative days. Scleral buckling with interference of one vortex vein produced a higher flare value than that with buckling alone. Interference of three vortex veins by diathermy and the encircling procedure produced serious ASI. Disruption of BAB in ASI can be detected quantitatively with laser flare photometry. Introduction of prostaglandin synthetase inhibitor resulted in a significant reduction of flare values following surgery. Prostaglandin synthetase inhibitor can partly ameliorate BAB disruption.
Development of a Simple Dry Eye Model in the Albino Rabbit and Evaluation of Some Tear Substitutes
Authors: Burgalassi Susi , Panichi Luana , Chetoni Patrizia , Saettone M. Fabrizio , Boldrini Enrico
Published: April 2003

The present paper is concerned with the development of a simple dry eye model in the rabbit, induced by daily repeated instillations of 1.0% atropine sulphate. The evolution of the dry eye syndrome in the animals was assessed by the Schirmer I test and by examination of the cornea after fluorescein staining. The model produced rapidly some typical dry eye symptoms and could be satisfactorily used for a preliminary assessment of the protective activity of some polymeric tear substitutes. These were based on hydroxypropylmethylcellulose, sodium hyaluronate, sodium polyacrylate or tamarind gum. The latter polymer showed the best overall results. Ferning tests on the formulations were also performed: their validity as predictors of the efficacy of tear substitutes is discussed.
Effects of Age, Sex, Cataract, and Cataract Surgery on Serum γ-Crystallin Concentration
Authors: Coulter, III John B. , Phinizy Jo Lynne , Hunnicutt Ruthann E. , Baumgart Mary Ann , Hise Elizabeth M. , Marr Linda K.
Published: April 2003

Purpose: To determine if measurement of lens protein in serum is a feasible means to gain information on the physiologic status of the lens in human subjects. Methods: The γ-crystallin concentration was measured by a sandwich radioimmunoassay in the sera of 280 subjects aged 25–94 years. Medical records were reviewed for diagnoses of cataract and aphakia. Results: There was no effect of age or sex on the serum γ-crystallin concentration. There were 57 subjects with cataract and 27 with aphakia. γ-Crystallin was higher in all cataract groups and lower in aphakia. The mean γ-crystallin concentrations for selected subject groups were as follows: clear lens 301 pg/ml; pure nuclear cataract 344 pg/ml; pure cortical cataract 439 pg/ml and aphakia 255 pg/ml. Conclusions: This is the first published report to show that lens protein is measurable in serum and to demonstrate the feasibility of using serum assays of lens proteins to gain information on the physiological status of the lens. Our results confirm the hypothesis that molecular and cellular events leading to cataract cause increased leakiness of lens cell membranes with release of lens proteins appearing in the blood. It is conceivable that measurement of lens proteins in serum might find future use in the evaluation of cataract risk, potentially cataractogenic and anticataractogenic agents, retained lens fragments after phacoemulsification, secondary cataract, phacolytic glaucoma, anaphylactic endophthalmitis, eye injuries, and other eye diseases.
Retinal Capillary Changes in Otsuka Long-Evans Tokushima Fatty Rats (Spontaneously Diabetic Strain)
Authors: Miyamura Noritake , Bhutto Imran Ahmed , Amemiya Tsugio
Published: April 2003

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a spontaneously diabetic strain with polyuria, polydipsia and mild obesity. The pathological features of OLETF rats closely resemble those of patients with non-insulin-dependent diabetes mellitus. The purpose of this study is to investigate the retinal capillary changes in the OLETF rat and to confirm the valuability of the OLETF rat as the model of diabetic retinal disease. One-month-old male OLETF rats and age- and sex-matched Long-Evans Tokushima Otsuka (LETO) controls were supplied by Otsuka Pharmaceutical Co. Ltd. (Tokushima, Japan). Body weight and blood sugar levels were measured monthly. Their eyes were enucleated 14 months after birth. Ultrathin sections were made and examined with a transmission electron microscope. According to their location, two kinds of retinal capillaries were differentiated: those in the nerve fiber layer (NFL) and those in the outer plexiform layer (OPL). The image of each capillary was transferred to a computed image analyzer, and basement membrane thickness and the ratio of the pericyte area to total capillary cross-section area were determined. Corrosion casts of retinal vessels were made and examined with scanning electron microscopy (SEM). OLETF rats gained more weight than LETO rats from the beginning, and the difference increased gradually with age. The blood sugar level of OLETF rats was higher than that of LETO rats after 5 months of age. In the retinal capillaries of 14-month-old OLETF rats, basement membranes were significantly thicker (OLETF: 209 ± 51 nm in NFL, 132 ± 23 nm in OPL; LETO: 118 ± 28 nm in NFL, 79 ± 14 nm in OPL), and the ratio of pericyte area to the capillary cross-section area was significantly lower than that of the controls (OLETF: 0.131 ± 0.92 in NFL, 0.111 ± 0.102 in OPL; LETO: 0.288 ± 0.142 in NFL, 0.198 ± 0.136 in OPL). The endothelial cell cytoplasm had degenerated. SEM examination of the vascular corrosion cast of a 14-month-old OLETF rat showed caliber irregularity, narrowing, tortuosity and loop formations of capillaries. The morphological changes in the retinal capillaries of OLETF rats were similar to those seen in diabetic patients. The OLETF rat may be a useful animal model for the study of ocular diabetic complications in humans.
Fetal Calf Serum Protects Cultured Porcine Corneal Endothelial Cells from Endotoxin-Mediated Cell Damage
Authors: Ventura Angela C. Sobottka , Engelmann Katrin , Böhnke Matthias
Published: April 2003

In corneal organ culture, a contamination of sterile culture media with endotoxin is frequently found. Thus, we investigated if the presence of endotoxin affects the viability of cultured porcine corneal endothelial cells. Endotoxin in high concentrations caused morphological cell changes in porcine corneal endothelial monolayer cultures, delayed proliferation and decreased cellular esterase activity of porcine corneal endothelial cells in vitro. The toxic effect of endotoxin was modulated by the fetal calf serum content of the medium, the concentration of endotoxin and the incubation time.