bluuebunny/crossref_metadata_2025 huggingface dataset:
Immobilization Stress Rapidly and Differentially Modulates BDNF and TrkB mRNA Expression in the Pituitary Gland of Adult Male Rats
Authors: Givalois Laurent , Marmigère Frédéric , Rage Florence , Ixart Guy , Arancibia Sandor , Tapia-Arancibia Lucia
Published: April 2003

Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neuronal survival and plasticity that binds to high-affinity receptors named TrkB. In the central nervous system, brain insults, including stress, induce modifications in BDNF messenger RNA (mRNA) expression. The present study attempted to determine in the adult rat pituitary, a peripheral structure relevant for the stress response: (1) whether BDNF and TrkB mRNA expression is influenced by different durations (15, 30, 60, 180 and 300 min) of single immobilization stress; (2) the expression of BDNF transcripts containing the different exons and their possible variations after stress exposure. Plasma corticotropin (ACTH) and corticosterone concentrations were strongly and significantly increased as early as 5 min after the stress stimulus. Using RNAse protection assay and in situ hybridization, a rapid increase in BDNF mRNA occurred at 15 min. This was accompanied by an increase in BDNF protein at 60 min, and by a rapid and significant decrease in TrkB mRNA expression observed at 15 and 30 min after stress application. RT-PCR analysis of BNDF transcripts showed strong basal expression of exons III and IV, whereas transcripts containing exons I and II seemed weakly expressed. After stress application, transcripts containing exons III and IV were rapidly and significantly increased at 30 min, whereas transcripts containing exons I and II remained unchanged. These results show that pituitary BDNF transcripts expression is differentially affected by immobilization stress.
Differential Responses of Thyrotropin-Releasing Hormone (TRH) Neurons to Cold Exposure or Suckling Indicate Functional Heterogeneity of the TRH System in the Paraventricular Nucleus of the Rat Hypothalamus
Authors: Sánchez Edith , Uribe Rosa María , Corkidi Gabriel , Zoeller R. Thomas , Cisneros Miguel , Zacarias Magali , Morales-Chapa Claudia , Charli Jean-Louis , Joseph-Bravo Patricia
Published: April 2003

Thyrotropin-releasing hormone (TRH) is released from the median eminence upon neural stimulation such as cold or suckling exposure. Concomitant with the cold- or suckling-induced release of TRH is a rapid and transient increase in the expression of proTRH mRNA in the paraventricular nucleus (PVN) of the hypothalamus. We employed two strategies to determine whether TRH neurons responding to cold exposure are different from those responding to suckling. First, we attempted to identify a marker of cellular activation in TRH neurons of the PVN. Cold induced c-fos expression in about 25% of TRH neurons of the PVN, but no induction was observed by suckling. Moreover, we explored the expression of a variety of immediate early genes including NGFI-A, fra-1 and c-jun, or CREB phosphorylation but found none to be induced by suckling. The number of cells expressing high levels of proTRH mRNA was counted and compared to total expressing cells. An increased number of cells expressing high levels of proTRH mRNA was observed when both stimuli were applied to the same animal, suggesting that different cells respond separately to each stimulus. We therefore analyzed the distribution of responsive TRH neurons as defined by the cellular level of proTRH mRNA. The proTRH mRNA signal was analyzed within three rostrocaudal zones of the PVN and within six mediolateral columns. Results showed that in response to cold, all areas of the PVN of the lactating rat present increased proTRH mRNA levels, including the anterior zone where few hypophysiotropic TRHergic cells are believed to reside. The distribution of the proTRH mRNA expressing cells in response to cold was quite comparable in female and in male rats. In contrast, the response after suckling was confined to the middle and caudal zones. Our results provide evidence of a functional specialization of TRH cells in the PVN.
Glomerular Cell Replication and Cell Loss through Apoptosis in Experimental Diabetes mellitus
Authors: Pesce Carlo , Menini Stefano , Pricci Flavia , Favre Anna , Leto Gaetano , DiMario Umberto , Pugliese Giuseppe
Published: April 2003

Aim: To evaluate changes in the glomerular cell balance between replication and apoptosis in experimental diabetes mellitus (DM) in relation to morphometric data. Methods: Adult Sprague-Dowley rats with streptozotocin-induced DM and controls of the same age and strain were sacrificed 4 and 8 weeks and 6 months after disease onset. Cell replication was demonstrated with MIB-5, and apoptosis with the terminal uridine nick end labeling technique. Glomerular size and glomerular cell population were estimated morphologically. Results: Diabetic and control rats showed irrelevant MIB-5 positivity at all time points. Glomerular apoptosis was minimal in rats with 4 and 8 weeks of DM and in controls. Rats with 6 months of DM showed significantly higher glomerular apoptosis values than controls (2.49 ± 0.25 vs. 0.65 ± 0.16%; p < 0.001). The mean cell count per glomerular profile was significantly lower in these diabetic rats (64.02 ± 1.93 vs. 78.27 ± 0.99; p < 0.001), a change that correlated with that in apoptosis. The glomerular cell density was further decreased in diabetic rats because of the diabetic increase in mean glomerular volume (1.598 vs. 0.927 106 µm). Conclusions: Apoptosis is associated with loss of glomerular cells in rats with long-term, streptozotocin-induced DM and – to a considerably lower degree – in controls of the same age and strain. These changes could be relevant to glomerulosclerosis associated with long-term, streptozotocin-induced DM.
Prehospital and In-Hospital Delays in Acute Stroke Care
Authors: Evenson Kelly R. , Rosamond Wayne D. , Morris Dexter L.
Published: April 2003

Current guidelines emphasize the need for early stroke care. However, significant delays occur during both the prehospital and in-hospital phases of care, making many patients ineligible for stroke therapies. The purpose of this study was to systematically review and summarize the existing scientific literature reporting prehospital and in-hospital stroke delay times in order to assist future delivery of effective interventions to reduce delay time and to raise several key issues which future studies should consider. A comprehensive search was performed to find all published journal articles which reported on the prehospital or in-hospital delay time for stroke, including intervention studies. Since 1981, at least 48 unique reports of prehospital delay time for patients with stroke, transient ischemic attack, or stroke-like symptoms were published from 17 different countries. In the majority of studies which reported median delay times, the median time from symptom onset to arrival in the emergency department was between 3 and 6 h. The in-hospital times from emergency department arrival to being seen by an emergency department physician, initiation and interpretation of a computed tomography (CT) scan, and being seen by a neurologist were consistently longer than recommended. However, prehospital delay comprised the majority of time from symptom onset to potential treatment. Definitions and methodologies differed across studies, making direct comparisons difficult. This review suggests that the majority of stroke patients are unlikely to arrive at the emergency department and receive a diagnostic evaluation in under 3 h. Further studies of stroke delay and corresponding interventions are needed, with careful attention to definitions and methodologies.
Problems and Issues with Door-To-Door, Two-Phase Surveys: An Illustration from Central Spain
Authors: Bermejo F. , Gabriel R. , Vega S. , Morales J.M. , Rocca W.A. , Anderson D.W.
Published: April 2003

In 1994–1995, a screening and examination survey was conducted to ascertain the prevalence of dementia, Parkinson’s disease and stroke in two urban communities and one rural community of central Spain. We use this survey to illustrate many nonclinical aspects of conducting two-phase prevalence surveys. Special emphasis is given to two common weaknesses in such surveys: screening nonparticipation and screening validation.
Trends in Hospitalized Stroke for Blacks and Whites in the United States, 1980–1999
Authors: Kennedy Byron S. , Kasl Stanislav V. , Brass Lawrence M. , Vaccarino Viola
Published: April 2003

Background: Racial differences in stroke mortality are widely recognized, but it is unclear whether or not these differences are due mainly to blacks having a greater stroke incidence or higher case fatality rates compared to those of whites. Objectives: The aim of this study was to describe the race-specific US trends in hospital discharge rates and in-hospital mortality among stroke patients for the period 1980–1999. It was hypothesized that the hospital discharge rates and in-hospital mortality among stroke patients would be greater for blacks than for whites. Methods: Data from the National Hospital Discharge Survey for the period 1980–1999 were used to identify stroke subjects according to the codes of the International Classification of Diseases, ninth revision (codes 430–434 and 436). Direct standardization and Poisson regression were used to compare hospitalized stroke morbidity and mortality rates between blacks and whites. The main outcome measures were the number of stroke discharges and in-hospital deaths for black and white stroke patients. Results: Between the years 1980 and 1999, the hospital discharge rates for stroke increased for blacks (n = 8,700) and decreased for whites (n = 46,154); the in-hospital mortality rates decreased for both black and white stroke patients. Generally, the risk of a stroke hospitalization was greater for blacks than for whites by more than 70%, whereas both groups were similar in terms of in-hospital mortality rates among stroke patients. Conclusions: Differences between blacks and whites in terms of stroke mortality are more likely due to differences in stroke incidence rather than case fatality. These data imply that greater attention should be given to primary/secondary prevention and that additional research is needed to understand the reasons for these patterns.
Hormonal Responses to Exercise in Chronic Fatigue Syndrome
Authors: Ottenweller John E. , Sisto Sue A. , McCarty Richard C. , Natelson Benjamin H.
Published: April 2003

Chronic fatigue syndrome (CFS) is a debilitating disease characterized by severe, unexplained fatigue and postexertional exacerbation of symptoms. We examined basal endocrine function in a group of CFS patients and a carefully matched group of sedentary controls. The subjects then completed a graded, maximal exercise test on a treadmill, and additional blood samples were drawn 4 min and a day after the end of exercise. There were no differences in basal hormone levels before exercise. Plasma adrenocorticotropin, epinephrine, prolactin and thyrotropin responses 4 min after exercise were lower in the CFS group, but the growth hormone response may have been exaggerated, and the plasma norepinephrine response was similar to that in controls. The next day, there were no differences in hormone levels between the groups, which suggests that long-term changes in endocrine function are unlikely to be a cause of the prolonged fatigue that occurs in CFS patients after a bout of exertion.
Antidepressive Response to Sleep Deprivation in Unipolar Depression Is Not Associated with Dopamine D3 Receptor Genotype
Authors: Schumann Gunter , Benedetti Francesco , Voderholzer Ulrich , Kammerer Norbert , Hemmeter Ulrich , Travers Heinz-Werner , Fiebich Bernd , Holsboer-Trachsler Edith , Berger Mathias , Seifritz Erich , Ebert Dieter
Published: April 2003

The psychostimulant theory of antidepressive sleep deprivation (SD) proposes a contribution of dopamine D3 receptors (DRD3) in the limbic system to the antidepressant effects of SD. Neuroendocrinological studies suggest a positive correlation of clinical response to SD and cortisol secretion. We hypothesized that the clinical response to SD and amount of cortisol secretion upon SD is associated with the 1-1 genotype of the Bal1 polymorphism of DRD3 on exon 1. In this study, aiming at evaluating the feasibility of screening large patient samples, 52 inpatients (19 males/33 females) with unipolar depression and a score of 18 or more on the 21-item Hamilton Depression Rating Scale were treated with 1 night of total SD. We found that 31% of our patients responded to SD. There was no association between response to SD and the genotype of the DRD3 Bal1 polymorphism (p < 0.879). There was also no association between increase in cortisol secretion after SD and DRD3 genotypes (p < 1.000) in a subgroup of patients. Statistical power analysis ruled out a major effect of the DRD3 Bal1 polymorphism on clinical response to SD. These results suggest that the DRD3 Bal1 polymorphism is not a promising lead to be followed up in larger patient samples.
First Experiences in Combination Therapy Using Olanzapine with SSRIs (Citalopram, Paroxetine) in Delusional Depression
Authors: König F. , v. Hippel C. , Petersdorff T. , Neuhöffer-Weiss M. , Wolfersdorf M. , Kaschka W.P.
Published: April 2003

In an open prospective study, 26 patients with delusional depression (mood-congruent psychotic features: DSM-IV 296.4) were treated over 5 weeks with a combination of SSRI (citalopram, n = 22, or paroxetine, n = 4) and the neuroleptic olanzapine. The course of therapy was evaluated with the Hamilton depression scale (HAMD). Not only the total HAMD score, but also the subscores for affectivity and delusional symptoms decreased significantly. After the end of the 5-week combination therapy, 18 out of 26 patients (69%) could be discharged as responders to outpatient treatment. The course of treatment was characterized by excellent tolerance.
Subjective Ratings of Pain Correlate with Subcortical-Limbic Blood Flow: An fMRI Study
Authors: Schneider Frank , Habel Ute , Holthusen Holger , Kessler Christoph , Posse Stefan , Müller-Gärtner Hans-Wilhelm , Arndt Joachim O.
Published: April 2003

Studies investigating the cerebral representations of pain using functional imaging techniques failed to elucidate the affective aspects of pain. This investigation used functional magnetic resonance imaging to measure pain-related changes in cerebral activity during painful stimulation with a strong affective component. Vascular pain was induced via balloon dilatation of a dorsal foot vein of healthy volunteers. The subjects rated their perceived pain uninterruptedly during imaging, allowing cerebral activity to be correlated with both stimulus function (boxcar) and, more importantly, subjective ratings reflecting individual pain experience. The findings indicated signal increases in subcortical-limbic regions, particularly in the amygdala. This region is suggested to be involved in the affective dimension of pain.
Polymorphisms in the Dopamine, Serotonin, and Norepinephrine Transporter Genes and Their Relationship to Temperamental Dimensions Measured by the Temperament and Character Inventory in Healthy Volunteers
Authors: Samochowiec Jerzy , Rybakowski Filip , Czerski Piotr , Zakrzewska Marzena , Stepień Genowefa , Pełka-Wysiecka Justyna , Horodnicki Jan , Rybakowski Janusz K. , Hauser Joanna
Published: April 2003

There is evidence for an association between polymorphisms of monoamine transporter genes and temperamental personality traits. Recent findings have shown that interaction of allelic variants of the different genes may contribute to the personality factors. We studied the association between temperamental personality dimensions measured with the Temperament and Character Inventory (TCI) and polymorphisms of the dopamine (DAT), norepinephrine (NET) and serotonin (5-HTT) transporter genes in 127 healthy Polish volunteers. There were no significant differences between means of TCI temperamental dimensions (novelty seeking, reward dependence, persistence and harm avoidance) and the transporter genes compared by ANOVA. There were some significant associations between genotypes and TCI subdimensions. Individuals carrying the A9/A9 DAT genotype have lower RD4 scores (dependence vs. independence) than A10/A10 individuals (3.0 ± 1.4 vs. 3.5 ± 1.3); p = 0.01. Examining 5-HTT gene promoter polymorphism, heterozygous individuals (l/s) and individuals with 44-bp deletion (s/s) scored significantly lower in the HA1 subdimension (anticipatory worry and pessimism vs. uninhibited optimism; 4.3 ± 2.3 vs. 5.5 ± 2.6) in comparison with individuals without deletion (l/l); p = 0.021. The NET transporter gene polymorphism showed no significant association with any of the temperamental TCI subdimensions.
Reduced Regional [14C]2-Deoxyglucose Uptake in Response to Long-Term Clozapine Administration in Rats
Authors: Tsai Shih-Jen , Huang Yn-Ho , Huang Hei-Jen , Sim Cho-Boon
Published: April 2003

Clozapine has superior effects in treating negative symptoms of schizophrenia and causes less extrapyramidal side effects than traditional antipsychotics. In this study, we investigated the effects of acute and long-term clozapine administration on [14C]2-deoxyglucose uptake (2-DG uptake) in rats, as measured using the [14C]2-deoxy-D-glucose method. The 2-DG uptake was reduced in fewer regions after chronic clozapine (46%) than after acute clozapine (97%). After chronic clozapine treatment, the 2-DG uptake was reduced in the shell, but not the core, of the nucleus accumbens. In addition, long-term clozapine treatment remained affecting 2-DG uptake in several regions of the extrapyramidal system and the thalamus. The pattern of 2-DG uptake changes after long-term clozapine administration may provide information for the regions related to the therapeutic effect of clozapine.
EEG Effects of Smoking: Is There Tachyphylaxis?
Authors: Houlihan Michael , Pritchard Walter , Robinson John
Published: April 2003

Smoking generally affects the human EEG by reducing low-frequency activity and increasing higher-frequency activity. Using a double-blind design, we sought to determine if acute tolerance (tachyphylaxis) to this effect can be observed. EEG was recorded in overnight-abstaining participants before and after smoking three cigarettes at 40-min intervals in two separate sessions. In one session (‘short interval’), all three cigarettes had ‘typical’ nicotine yields (1.1 mg, FTC method). In the other session (‘long interval’), the second cigarette had a very low nicotine yield (0.05 mg; thus making the interval between 1.1-mg cigarettes 80 min). Eyes-closed alpha power decreased and eyes-open beta-2 power increased following smoking each of the ‘typical-yield’ cigarettes but not the low-yield cigarettes. The decrease in alpha power after smoking the ‘typical-yield’ cigarette at the 40- and 80-min intervals was less than that following the first cigarette of the day, indicating tachyphylaxis. In contrast, the increase in eyes-open beta-2 power did not differ among cigarettes regardless of the order or interval between ‘typical-yield’ cigarettes. EEG changes in other frequency bands produced by smoking the first cigarette of the day were not consistent across sessions, making interpretation in terms of tachyphylaxis somewhat problematic. Overall, lower-frequency alpha activity displayed patterns consistent with tachyphylaxis while beta-2 did not.
Plasma Concentrations of Amino Acids in Chronic Schizophrenics Treated with Clozapine
Authors: Tortorella A. , Monteleone P. , Fabrazzo M. , Viggiano A. , De Luca B. , Maj M.
Published: April 2003

Peripheral amino acid changes have been reported in schizophrenia, but results are not consistent. We measured serum levels of different amino acids in 11 neuroleptic-resistant schizophrenic patients before and after clozapine treatment and in 11 age- and sex-matched healthy subjects. The schizophrenic patients exhibited significantly higher levels of serum aspartate, glutamate, isoleucine, histidine and tyrosine and significantly lower concentrations of serum asparagine, tryptophan and serine. In patients, the ratio between tryptophan and large neutral amino acids (LNAA) was significantly lower than in matched controls, whereas the tyrosine/LNAA ratio did not differ significantly. Moreover, 12 weeks of clozapine administration significantly reduced serum levels of glutamate but did not restore the values observed in normal controls, nor did it affect other amino acid concentrations. These data show changes in serum amino acids that may influence central serotonergic, dopaminergic and glutamatergic transmission in neuroleptic-resistant schizophrenics.
Review: Gonadotropins and Development of Ovarian Cancer
Authors: Konishi Ikuo , Kuroda Hideki , Mandai Masaki
Published: April 2003

An epidemiological correlation between infertility therapy and ovarian cancer development has been reported in 1992; consequently, the possible role of gonadotropins in ovarian carcinogenesis has received much attention. Here, we review the effect of gonadotropins on epithelial ovarian carcinoma and ovarian surface epithelium (OSE), which is the histogenetic origin of carcinomas. Recent studies have demonstrated that gonadotropin receptors are expressed in OSE and in approximately half of the ovarian carcinomas. Gonadotropins have also been reported to stimulate cell proliferation and to inhibit apoptosis in OSE and ovarian cancer cells. These data suggest that gonadotropins play an important role in the development, progression, and/or chemoresistance of ovarian carcinomas. Hormonal therapy against gonadotropins may be applicable for patients with ovarian carcinoma.
Molecular Bases for the Actions of Ovarian Sex Steroids in the Regulation of Proliferation and Apoptosis of Human Uterine Leiomyoma
Authors: Matsuo Hiroya , Kurachi Osamu , Shimomura Yosuke , Samoto Takashi , Maruo Takeshi
Published: April 2003

Uterine leiomyomas appear during the reproductive years and regress after menopause, indicating the ovarian steroid-dependent growth potential. In order to characterize the molecular mechanism of sex steroidal regulation of leiomyoma growth, we examined whether sex steroids could influence the proliferation of leiomyoma cells. As epidermal growth factor (EGF) has been shown to mediate estrogen action and play a crucial role in regulating leiomyoma growth, we also investigated the effects of sex steroids on EGF and EGF receptor (EGF-R) expression in leiomyoma cells. In cultures of leiomyoma cells, the addition of either estradiol (E2; 10 ng/ml) or progesterone (P4; 100 ng/ml) resulted in an increase in proliferating cell nuclear antigen (PCNA) expression in the cells, whereas in cultures of normal myometrial cells, the addition of E2 augmented PCNA expression in the cells, but P4 did not. Immunoblot analysis revealed that leiomyoma cells contained immunoreactive EGF and that P4 treatment resulted in an increase in EGF expression in the cells, whereas E2 treatment resulted in a lower EGF expression in the cells. By contrast, E2 treatment augmented EGF-R expression in cultured leiomyoma cells, but P4 did not. These results indicate that P4 upregulates the expression of PCNA and EGF in leiomyoma cells, whereas E2 upregulates the expression of PCNA and EGF-R in those cells. It is, therefore, conceivable that P4 and E2 act in combination to stimulate the proliferative potential of leiomyoma cells through the induction of EGF and EGF-R expression. We also found that Bcl-2 protein, an apoptosis-inhibiting gene product, was abundantly expressed in leiomyoma relative to that in normal myometrium and that Bcl-2 protein expression in leiomyoma cells was upregulated by P4, but downregulated by E2. It seems, therefore, likely that P4 may also participate in leiomyoma growth through the induction of Bcl-2 protein in leiomyoma cells. The abundant expression of Bcl-2 protein in leiomyoma cells may be one of the molecular bases for the enhanced growth of a leiomyoma relative to that of normal myometrium in the uterus.
Inhibition of Human Epithelial Ovarian Cancer Cell Growth in vitro by Somatostatin Analog RC-160
Authors: Yano Tetsu , Radulovic Sinisa , Osuga Yutaka , Kugu Koji , Yoshikawa Hiroyuki , Taketani Yuji , Schally Andrew V.
Published: April 2003

In this study, we investigated the effects of somatostatin analog RC-160 on the growth of the OV-1063 human epithelial ovarian cancer cell line in vitro. RC-160 inhibited cell proliferation, as measured by cell number, and [3H]thymidine incorporation into DNA at 10–9–10–5M. In OV-1063 cells, 125I-labeled RC-160 was bound to one class of specific, saturable binding sites with high affinity (Kd = 0.2 ± 0.03 nM) and low capacity (5,500 binding sites per cell). 125I-labeled RC-160 could be displaced by unlabeled RC-160. Ligand binding was dependent on time and temperature. Receptor internalization assay showed that the ligand-receptor complex was internalized at 37°C, which indicates the presence of biologically active somatostatin receptors on OV-1063 cells. These results suggest that somatostatin analog RC-160 can suppress the growth of OV-1063 human epithelial ovarian cancer cells by a direct action and that the inhibitory effect of somatostatin analog is mediated through the high-affinity somatostatin receptors.
Expression of Cell-Cycle Regulator p27 Is Correlated to the Prognosis and ER Expression in Breast Carcinoma Patients
Authors: Nohara Takehiro , Ryo Toshio , Iwamoto Shinji , Gon Goki , Tanigawa Nobuhiko
Published: April 2003

Cell cycle inhibitor p27 is variously expressed in breast carcinoma. A possible association between the expression of p27 and the prognosis of breast carcinoma remains to be elucidated. We investigated the expression of p27 and cyclin D1 in a retrospective series of 216 breast carcinomas immunohistochemically. Expression of p27 (p27 LI) ranged from 0 to 93.6% (median 62.4%). There was a positive association between p27 LI and cyclin D1 (p < 0.01) and between p27 LI and ER (p < 0.0001). In the combination study of p27 LI and cyclin D1 expression, the patients classified as low p27 LI/cyclin D1 negative had a poorer prognosis than those in other categories. p27 was identified as an independent prognostic factor by the multivariate Cox proportional hazard model with a relative risk of death of disease of 4.1 (p < 0.05; vs. high p27 LI compared to the median). Assessment of p27 expression and examination of both p27 LI and cyclin D1 expression may identify breast carcinoma patients who would benefit from adjuvant therapy.
Association between HLA-A/-B Antigens and -DRB1 Alleles and Nasopharyngeal Carcinoma in Tunisia
Authors: Mokni-Baizig Nehla , Ayed Khaled , Ayed Farhat Ben , Ayed Saloua , Sassi Faiçal , Ladgham Abderrahmen , Bel Hadj Omrane , El May Ahmed
Published: April 2003

Using serologic and molecular methods, 45 nasopharyngeal carcinoma (NPC) patients were typed for HLA class I and class II and were compared to 100 unrelated normal Tunisians. Our results showed that the antigen frequency of HLA-B13 and allelic frequencies of DRB1*03, DRB1*15 were significantly higher in the NPC patients than in the control group (15.5 vs. 4; 26.4 vs. 11.5, and 14.4 vs. 6.5%, respectively) probably indicating a positive association with NPC. Moreover, we observed that HLA-A23 was absent in our NPC sample and was present in 18% of normal controls, and HLA-DRB1*11 was less frequent among the patients compared to the controls (5.5 vs. 14%) suggesting a protective effect of this association with NPC.
Immunoreactivity of Monoclonal Antibody BW835 Represents a Marker of Progression and Prognosis in Early Gastric Cancer
Authors: Baldus Stephan E. , Zirbes Thomas K. , Glossmann Jan , Fromm Susanne , Hanisch Franz-Georg , Mönig Stefan P. , Schröder Wolfgang , Schneider Paul M. , Flucke Uta , Karsten Uwe , Thiele Jürgen , Hölscher Arnulf H. , Dienes Hans P.
Published: April 2003

The Thomsen-Friedenreich (TF) antigen is a well-known human pan-carcinoma antigen. It represents a carbohydrate core disaccharide (Galβ1-3GalNAc) which is predominantly bound to mucin peptide cores. Its immunoreactivity depends on changes in glycosylation which lead to a reduction in the carbohydrate chain length and the exposure of core carbohydrates. In the present study, we investigated 208 gastric adenocarcinomas with respect to their immunohistochemical reactivity applying two monoclonal antibodies (MAbs). MAb specifically detecting TF antigen (A78-G/A7) and MAb BW835 were included. The latter reacts with a certain glycoform of the MUC1 peptide core, characterized by core-type glycans like TF. A78-G/A7 epitopes were detected in 68.8% and BW835 epitopes in 57.7% of the carcinomas. BW835 immunoreactivity correlated with the presence of lymph node metastases. Both A78-G/A7 and BW835 staining were significantly stronger in tubular/papillary cancer (WHO classification) and intestinal-type cancer according to Laurén. In univariate survival analyses of all patients studied, BW835 immunoreactivity was a marker of an unfavorable prognosis (p < 0.05). The presence of A78-G/A7 and BW835 epitopes exerted a negative effect on the subgroup of pTNM stage I carcinomas. These results indicate that TF and MUC1-TF immunoreactivity defines a ‘high-risk’ subgroup of stage I patients in gastric cancer.
Evaluation of Polysaccharopeptide Effects against C6 Glioma in Combination with Radiation
Authors: Mao Xiao Wen , Green Lora M. , Gridley Daila S.
Published: April 2003

Long-term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. The major goal of this study was to determine whether polysaccharopeptide (PSP), a crude polysaccharide peptide extract derived from Coriolus versicolor, a fungus, could enhance the effects of radiation against glioma cells in culture and in xenografted tumors in vivo. PSP significantly augmented radiation-induced damage to C6 rat glioma cells in vitro. Nude mice injected subcutaneously with the C6 cells were treated with PSP (injected intraperitoneally at 2 mg/injection) and radiation (2 Gy/fraction, 8 Gy in total) using three different time-dose protocols. Tumor volumes were consistently smaller in all treated groups compared to the non-treated tumor-bearing controls except in one group which received PSP prior to tumor implantation. The administration of radiation alone resulted in the slowest tumor progression, whereas PSP alone had no effect. Furthermore, PSP in combination with radiation treatment did not increase radiation efficacy. Natural killer cell, lymphocyte and granulocyte counts in blood and spleen were significantly higher in PSP-treated animals, demonstrating that PSP has protective effects on immunological function. Collectively, these results warrant further investigation to determine if PSP can be effectively utilized to upregulate immune responsiveness in case of neoplasia and other diseases in which immunosuppression is a prominent feature.
Testing for HER2 Status
Authors: Hanna Wedad
Published: April 2003

Incorporation of a new biological marker such as HER2 into routine clinical practice requires proof that it provides reproducible information independent of, and better than, conventional pathologic criteria, and that it influences treatment decisions. In breast cancer, HER2 amplification/overexpression predicts for a poor clinical outcome and an enhanced survival benefit from the HER2-targeted therapy, Herceptin®, and may predict for resistance to some conventional therapies. Thus, HER2 is considered to be a clinically important molecule and testing for HER2 abnormalities is already part of routine patient assessment in many parts of the world. There is currently no gold standard for HER2 testing. The main challenge is to standardize and technically validate HER2 testing methodologies. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the most common HER2 tests used, and show a high level of concordance. HER2 testing approaches based on the polymerase chain reaction (PCR) are under extensive investigation and appear promising. A Canadian HER2 testing algorithm designed to increase the validity and reproducibility of HER2 testing has been compiled. HER2-positive cases are defined as those with >10% of tumor cells with moderate/strong, complete membrane staining in the invasive component, by IHC. Confirmatory HER2 testing using either FISH or quantitative PCR is recommended for indeterminate cases. Additional studies are required to calibrate HER2 testing results to clinical outcome.
Keratoconus Staging with Ultrasound Biomicroscopy
Authors: Avitabile T. , Marano F. , Castiglione F. , Reibaldi A.
Published: April 2003

The diagnosis of keratoconus is based on slip-lamp and keratometric findings, and its classification includes 4 different stages. In this study, we compare the ultrasound biomicroscopy (UBM) findings and the keratoconus index (KI) determined using UBM with the severity of the disease. By means of UBM (Humphrey Instruments system model 840) using a 50-MHz probe, we studied 49 eyes affected with different forms of keratoconus. Using a method previously described, we calculated the KI and compared these data with the findings obtained using videokeratography. The mean thickness at the corneal apex in keratoconic eyes was 0.369 mm, while the mean peripheral corneal thickness was 0.568 mm. The mean KI was 1.449 in keratoconic eyes. The KI increased according to the severity of the disease. The mean central keratometry power was 56.95, while the mean amount of steepening of the inferior cornea compared with that of the superior cornea was 8.16. UBM can be considered a useful tool in the study of keratoconus. Using high-frequency ultrasound, it is also possible to obtain reliable measurements of corneal thickness related to the severity of the disease determined by videokeratography.
Corneal Oedemas: Diagnosis and Surgical Planning with Ultrasound Biomicroscopy
Authors: Avitabile T. , Russo V. , Ghirlanda R. , Castiglione F. , Marino A. , Reibaldi A.
Published: April 2003

We used the Humphrey Ultrasound Biomicroscope (UBM System 840 by Zeiss-Humprey Instruments, San Leandro, Calif. USA) to study various corneal oedemas and leucomas. This UBM system, using a high-resolution probe of 50 Mhz, has an axial and lateral resolution of about 50 µm. We analysed 36 eyes divided into two groups, 27 (group A) affected by corneal oedema caused by traumatic-mechanic or phlogistic-toxic lesions, 9 (group B) affected by postsurgery oedema. Thanks to its high-resolution power, we could study their pathogenesis and their clinical evolution and so arrange a suitable therapy and perform an accurate follow-up of these pathologies.
Echobiometry of the Ocular Layers at the Posterior Pole
Authors: Colangelo L. , Mancini A. , Lobefalo L. , Attimonelli P. , Zuppardi E. , Falconio G. , Mastropasqua L.
Published: April 2003

The thickness of the retina, choroid and sclera in relation to macular oedema (ME) can be measured using A scan echography. Ninety diabetic patients (180 eyes) divided into two groups with and without ME, respectively, were studied compared to a third group of 73 healthy controls (146 eyes). Statistical analysis of results showed good specificity (80%) and reasonable sensitivity (70%) of the echographic method in showing the presence of ME confirmed by fluorescein angiography.
Biometric Pre-Operative Evaluation of Ocular Axial Length in Patients Subjected to Corneal Transplantation
Authors: Sabetti L. , Specchia G. , Toscano A. , Balestrazzi E.
Published: April 2003

In cases of keratoconus and consequent penetrating keratoplasty, the refractive requirements of the patient determine the dimensions of the donor button and the receiving wound size. The pre-operative biometric evaluation of the axial parameters may induce the surgeon to choose an oversized button to obtain the right curvature of the cornea and avoid hypermetropia. In this study we present 20 patients transplanted between 1993 and 1995, 13 female, 7 male, aged between 23 and 45 years. These cases demonstrate the utility of this easy and economic technique.
Echographic Evaluation of Choroidal Melanomas Treated with Ruthenium-106 Plaques: The Treatment Failures
Authors: Perri Paolo , Police Gianpiero , Pastena Bruno , Ravalli Luca , Grande Lorenzo , Rossi Antonio
Published: April 2003

From July 1990 to October 1995 we treated 45 patients with choroidal melanomas using ruthenium-106 plaques. The population mean age was 59.2±10.4 years. In this paper, the authors describe in detail their clinical management and follow-up timing. They also report on the echographic pattern change after treatment and the clinical history of some failure cases.
Rapidly Growing Choroidal Metastasis: Case Report
Authors: Police Gianpiero , Perri Paolo , Pastena Bruno , Ravalli Luca , Grande Lorenzo , Rossi Antonio
Published: April 2003

A rapidly growing choroidal metastasis from an occult carcinoma is described. The patient was first seen with a loss of visual acuity. The fundus examination showed a non-pigmented solid mass located at the posterior pole. Clinical history, echographic characteristics and tumour growth kinetics are described in detail.
Ultrasonographic and Angiographic Follow-Up of Primary Choroidal Malignant Melanoma after Proton Beam Irradiation Therapy
Authors: Romani A. , Baldeschi L. , Genovesi-Ebert F. , Rizzo S. , Nardi M.
Published: April 2003

The aim of this study is to evaluate the reliability of the ultrasonographic and angiographic follow-up of primary choroidal malignant melanoma (PCMM) after proton beam irradiation therapy in a series of 14 patients. All patients underwent standardized A and B scan ultrasonography, fluorescein and indocyanine green videoangiography (FV, ICGV) before and after treatment with proton beam irradiation. The follow-up was carried out at 1, 3, 5, 8 months and then every 6 months. The mean follow-up was 26 months (range 6–46 months). The thickness of the tumors was demonstrated to be decreased and the internal reflectivity to be enhanced in 12 out of 14 cases from 8 months after treatment till the end of the follow-up period. In 2 eyes which were enucleated 5 months after treatment, histopathology confirmed that medium-low internal reflectivity corresponded to several areas of high cellularity and cellular mitosis. FV and ICGV were impossible because of opacities of dioptric media in 2 cases. From 8 months after treatment till the end of the follow-up period, in all the examined patients, FV demonstrated large hypofluorescent zones of the lesions which represented the destruction of the vascular tree of the tumor. From 8 months after treatment till the end of the follow-up period, ICGV demonstrated hypofluorescence of the lesions in 8 cases; mild hyperfluorescence and zones of colorant staining were present in late angiograms in 2 cases. The results of our study seem to confirm the reliability of standardized A and B scan ultrasonography in the follow-up of PCMM treated with proton beam irradiation; if ultrasonography is used together with FV and ICGV, the reliability of this combination is surely higher.
Epidemiology of Cataract in India: Combating Plans and Strategies
Authors: Vajpayee R.B. , Joshi Sujata , Saxena Rohit , Gupta S.K.
Published: April 2003

Blindness due to cataract presents an enormous problem in India not only in terms of human morbidity but also in terms of economic loss and social burden. The WHO/NPCB (National Programme for Control of Blindness) survey has shown that there is a backlog of over 22 million blind eyes (12 million blind people) in India, and 80.1% of these are blind due to cataract. The annual incidence of cataract blindness is about 3.8 million. The present annual level of performance is in the order of about 1.6–1.9 million cataract operations. To clear the backlog of cataract cases by the year 2000 and to tackle the rising incidence, 5–6 million cataract operations annually will have to be performed as against the present rate of 1.7 million per year. India is undertaking a new long-term initiative to expand the capability of cataract surgery and service levels with financial assistance from the World Bank. An important feature of this initiative is the attention given to spread the cataract blindness programme in rural and tribal areas. The second feature is the emphasis placed on modern extracapsular cataract extraction with intra-ocular lens implantation as the preferred surgical technique. Another noteworthy feature is developing institutional capacity and appropriate co-ordination mechanisms for collaboration between the non-government organization and the public sector to expand coverage to the most disadvantaged populations. The fourth and the most important strategy is to carry out intensive campaigns at the state and national levels against cataract blindness in order to substantially increase the demand for cataract services. A country like India has more significance for such a plan in view of the fact that various social, economic and environmental factors contribute to cataract blindness in populations at a much younger age.
Scheimpflug Records without Distortion – A Mythos?
Authors: Huebscher H.-J. , Fink W. , Steinbrück D. , Seiler T.
Published: April 2003

The Scheimpflug principle was recommended as allowing distortion-free imaging; however, a detailed analysis reveals geometrical errors as well as distortions arising from absorption of light along the optical pathway. Correction formulas and factors will be presented and applied to the biometry of the eye.
Age-Related Accumulation of Free Polyunsaturated Fatty Acids in Human Retina
Authors: Nourooz-Zadeh Jaffar , Pereira Paulo
Published: April 2003

The present study reports composition of free (nonesterified) as well as total (sum of free and esterified) fatty acids (FAs) in human retina (n = 13). For free fatty acid (FFA) analysis, retina tissue was homogenized, total lipids were partitioned with ethyl acetate and subsequently applied onto a aminopropyl (NH2) cartridge to isolate FFAs from the bulk of other lipids. FFAs were converted to methyl ester derivatives and analysed by gas chromatography using flame ionization detector. Analysis of FFAs revealed that the mean percentage composition of the major components including palmitic acid (PA), stearic acid (SA), oleic acid (OA), arachidonic acid (AA) and docosahexaenoic acid (DHA) were 17.2, 36.7, 15.6, 8.8 and 14.2%, respectively. There were significant correlations between age of the donors’ and the content of both free AA and DHA (rPearson = 0.69, p = 0.005, and rPearson = 0.64, p = 0.009). The mean percentage of total PA, SA, OA, AA and DHA were 22.6, 23.2, 17.7, 11.4 and 21.9%, respectively. There was no association between age and any of the major FAs. The present study provides the first evidence for the presence of FFAs in the human retina as well as an age-related accumulation of polyunsaturated fatty acids (PUFAs). The latter finding suggests an alteration in the metabolism of retinal PUFAs which can be due to an increase of oxidative stress and/or decrease of antioxidant defences during ageing.
Vascular Architecture of Degenerated Retina in WBN/Kob Rats: Corrosion Cast and Electron Microscopic Study
Authors: Bhutto Imran A. , Miyamura Noritake , Amemiya Tsugio
Published: April 2003

The purpose of the present study is to determine the changes of vascular architecture in the degenerated retina. We used mainly corrosion casts of the retinal vasculature and scanning electron microscopy to obtain a wide three-dimensional view. WBN/Kob rats (a spontaneously diabetic strain) were used because their outer retinas degenerate and become very thin with age. In 15-month-old rats, localized constriction and irregular caliber of the capillaries were evident in the vascular casts. Two layers of capillary network in the retina were maintained, but the capillaries were decreased in number. Numerous loop formations were present in the superficial capillary networks. Neither microaneurysms nor arteriovenous shunts were seen in young and old rats. Transmission electron microscopy revealed that capillary pericytes in the inner and outer plexiform layers had thickened basement membranes and that endothelial cells had many vesicles in their cytoplasm. Thus the retinal capillary changes in WBN/Kob rats are nondiabetic but due to hereditary retinal degeneration, although the systemic and pancreatic abnormalities in this rat strain are diabetic. Even when the retina becomes very thin, two layer capillary networks remain.
Topically Applied Water Extract of Propolis to Suppress Corneal Neovascularization in Rabbits
Authors: Hepşen İbrahim F. , Er Hamdi , Çekiç Osman
Published: April 2003

Purpose: Propolis, a natural honey bee hive product, has anti-inflammatory and antioxidative properties. We aimed to assess the possible contribution of topically applied propolis to the suppression of corneal neovascularization (CNV). Methods: The effect of a water extract of propolis (WEP) 1% drops (group 1) in comparison with dexamethasone 0.1% (group 2) and saline (group 3) on CNV was tested in rabbit corneas injured by silver nitrate cauterization. The extent of CNV was quantitated as the area of CNV and the percent area of CNV for each cornea of the three groups (12 right eyes per group) in the first week of the treatment. The mean percent CNV was used for statistical analysis. Results: The corneas treated with the topical WEP 1% had an almost equal percent CNV as compared with the corneas treated with topical dexamethasone 0.1% and had less percent CNV than the control eyes. The quantitative analysis in groups 1, 2 and 3 revealed that the mean percent CNV was 41.0 ± 14.1, 39.4 ± 11.0 and 56.9 ± 18.4, respectively. The differences between both groups 1 and 3 as well as groups 2 and 3 were statistically significant (p = 0.02 and p = 0.01, respectively), whereas the difference between groups 1 and 2 was not significant (p = 0.86). Conclusions: The topical application of a WEP 1% has an inhibitory effect on CNV in the rabbit’s cornea. The inhibitory effect of propolis was shown to be comparable to that of topical dexamethasone 0.1%, a potent inhibitor of angiogenesis. We suggest that the effect of propolis may partially be due to its inhibitory effect on the activity of both cyclo-oxygenase and lipo-oxygenase.