A genome-wide allelotype study of primary and corresponding recurrent glioblastoma multiforme in one patient

Glioblastoma multiforme (GBM) is the most common type of primary malignant brain tumor. Although comprehensive therapeutic measures are available, recurrence is very frequent and the prognosis of GBM remains dismal. To date, little is known about the molecular pathogenesis associated with GBM recurrence. According to Knudson ' s two-hit hypothesis of tumor suppressor gene (TSG) inactivation,1 deletion of a chromosomal region, as revealed by loss of heterozygosity (LOH), is often indicative of the presence of a potential TSG. Allelotype studies involving a comprehensive LOH analysis of the whole genome can provide more detailed and thorough information for detecting genetic anomalies than traditional LOH analysis. The present study is designed to conduct a genome-wide allelotype analysis of one patient ' s primary and corresponding recurrent GBM tumors in an effort to reveal molecular genetic alterations associated with the recurrence of this malignancy.     

Effect of shunt surgery on spleen size, portal pressure and oesophageal varices in patients with non-cirrhotic portal hypertension

Shunt surgery is considered to be the treatment of choice in patients with non-cirrhotic portal hypertension. There is little data on the effect of side-to-side lieno-renal (SSLR) shunt on oesophageal variceal size, splenic size and splenic pulp pressure (SPP) in patients with non-cirrhotic portal hypertension. We evaluated pre- and postoperatively endoscopic grading of varices, splenic size and SPP for predicting shunt patency in 86 patients with non-cirrhotic portal hypertension: 56 with extrahepatic portal venous obstruction (EHPVO) and 30 with non-cirrhotic portal fibrosis (NCPF). The EHPVO patients with patent shunts (n= 47) showed significant reduction in SPP (pre-operative 43.56±7.9 vs postoperative 29.96±7.7 cm of saline), splenic size (6.5±2.8 vs 4.00±2.6 cm below costal margin) and varices grades (2.96±0.5 vs 0.92±0.8). Patients with blocked shunt (n= 9) did not show significant reduction in SPP and varices grades. However, there was reduction in spleen size (8.6±3.0 vs 6.3±4.3). In the NCPF group, 28 had patent shunts and showed significant reduction in SPP (46.3±13.5 vs 33.8±7.6 cm of saline), splenic size (9.1±3.3 vs 6.8±4.6 cm below costal margin) and varices grades (2.8±0.7 vs 1.05±0.96). As only two patients with NCPF had blocked shunts, no statistical comparison between patients with patent and patients with blocked shunts could be done. In conclusion, following SSLR, there is a significant reduction in SPP and varices grades in patients with patent shunts. Endoscopic grading of varices can be used to predict shunt patency. However, spleen size is not a good criteria for predicting shunt patency.     

Sertoli-Leydig cell tumour in an infertile patient after stimulated ovulation

A 36 year-old infertile female developed a stage IV (FIGO) ovarian carcinoma consisting of a poorly differentiated Sertoli-Leydig cell tumour after receiving one course of ovulation induction with follicle stimulating hormone (FSH), human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG) followed by gonadotrophin-releasing hormone analogue (GnRHa). The patient died of liver metastasis and hepatic failure 4 1/2 months after first diagnosis, despite aggressive treatment consisting of debulking surgery and aggressive adjuvant chemotherapy.      

A Clinico-Pathological Analysis of Seventeen Cases of Non-Hodgkin'S Lymphoma Involving the Orbit

Seventeen patients with non-Hodgkin's lymphoma involving the orbit were studied. There were 12 males and 5 females and their median age was 53 years. Three cases were classified as stage I, two as stage II and 12 as stage IV. the histology was small lymphocytic type in 4 of the 5 stage I and II cases, and immunophenotyping, confirming their B-cell origin, was performed in two of these cases. All stage I and II patients responded favourably to local radiotherapy alone. the 12 stage IV patients had a marked male predominance and more commonly an intermediate grade histology and T-immunophenotype. Several of the orbital lesions seemed to represent extension of nasal lymphomas. the stage IV patients had a poorer survival than the stage I and II patients but the difference was not statistically significant, probably due to the small number of patients.     

PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells

PD-L1 and PD-L2 are ligands for PD-1, a costimulatory molecule that plays an inhibitory role in regulating T cell activation in the periphery. We find that PD-L1 is highly expressed on inflammatory macrophages as compared with resident peritoneal macrophages but can be induced on resident macrophages by classical activation stimuli such as lipopolysaccharide, IFN-gamma, and polyinosinic-polycytidylic acid. Further up-regulation of PD-L1 on inflammatory macrophages can also be induced by subsequent exposure to lipopolysaccharide and IFN-gamma. In contrast, PD-L2 is not expressed on inflammatory macrophages but can be induced by alternative activation via IL-4. Although PD-L1 is highly inducible on a variety of antigen-presenting cell lines as well as resident macrophages, PD-L2 is most significantly inducible only on inflammatory macrophages. PD-L1 up-regulation depends on TLR4 and STAT1, whereas PD-L2 expression depends on IL-4R alpha and STAT6. Consistent with these results, T helper 1T helper 2 (Th1/Th2) cells also differentially up-regulate PD-L1 and PD-L2 expression on inflammatory macrophages. Hence, Th1 cells as well as microbial products can enhance PD-L1 expression on many different macrophage populations, whereas Th2 cells instruct only inflammatory macrophages to up-regulate PD-L2. These results suggest that PD-L1 and PD-L2 might have different functions in regulating type 1 and type 2 responses.     

Endogenous endothelial nitric oxide synthase-derived nitric oxide is a physiological regulator of myocardial oxygen consumption

Our objective was to determine the precise role of endothelial nitric oxide synthase (eNOS) as a modulator of cardiac O2 consumption and to further examine the role of nitric oxide (NO) in the control of mitochondrial respiration. Left ventricle O2 consumption in mice with defects in the expression of eNOS [eNOS (-/-)] and inducible NOS [iNOS (-/-)] was measured with a Clark-type O2 electrode. The rate of decreases in O2 concentration was expressed as a percentage of the baseline. Baseline O2 consumption was not significantly different between groups of mice. Bradykinin (10(-4) mol/L) induced significant decreases in O2 consumption in tissues taken from iNOS (-/-) (-28+/-4%), wild-type eNOS (+/+) (-22+/-4%), and heterozygous eNOS(+/-) (-22+/-5%) but not homozygous eNOS (-/-) (-3+/-4%) mice. Responses to bradykinin in iNOS (-/-) and both wild-type and heterozygous eNOS mice were attenuated after NOS blockade with N-nitro-L-arginine methyl ester (L-NAME) (-2+/-5%, -3+/-2%, and -6+/-5%, respectively, P<0.05). In contrast, S-nitroso-N-acetyl-penicillamine (SNAP, 10(-4) mol/L), which releases NO spontaneously, induced decreases in myocardial O2 consumption in all groups of mice, and such responses were not affected by L-NAME. In addition, pretreatment with bacterial endotoxin elicited a reduction in basal O2 consumption in tissues taken from normal but not iNOS (-/-)-deficient mice. Our results indicate that the pivotal role of eNOS in the control of myocardial O2 consumption and modulation of mitochondrial respiration by NO may have an important role in pathological conditions such as endotoxemia in which the production of NO is altered.     

Predictors of Spontaneous Smoking Cessation Among Chinese Men Whose Wives are Pregnant

This is an exploratory study to identify the predictors that Chinese men will spontaneously quit smoking during their wives' pregnancy. Smoking husbands who accompanied their non-smoking pregnant wives to an antenatal clinic were invited to complete a questionnaire soliciting information regarding their smoking behaviours, perceptions of support received from their wives, and motivating factors for quitting smoking. A total of 74 men were recruited. Two-thirds (67.6%) were daily smokers, had started smoking under the age of 18 (66.2%), and smoked 6-15 cigarettes (48.6%) a day. Nearly one-third of the smoking husbands (n = 50, 67.6%) reported that their wife was the person who provided them with the necessary main support in quitting. Nearly a quarter (18 out of 74, 24.3%) of the husbands indicated that they quit smoking during their wives' pregnancy. Those more likely to quit were the 'occasional smokers' (61.1% vs. 38.9%), those who craved cigarettes a few hours after getting up (0% vs. 100%), those who were confident in their ability to quit (77.8% vs. 22.2%), and those who had previously attempted to quit (88.9% vs. 11.1%). The level of negative support from wives to quit smoking was significantly related to men's quitting (55.6% vs. 44.4%). The results of this study identified the husbands most likely to spontaneously quit smoking during their wives' pregnancy as those who were occasional smokers, were confident about smoking cessation, and reported their wives as being bothered by smoke.     

Deregulation of E-cadherin-catenin complex in precancerous lesions of gastric adenocarcinoma

BACKGROUND AND AIM: Decrease in expression of the E-cadherin-catenin complex is an important element in gastric carcinogenesis. However, the expression of the complex in gastric precancerous lesions has not been well studied. The present study aimed to examine the serial change in expression of E-cadherin-catenin complex in the precancerous lesions of gastric cancer patients. METHODS: Gastrectomy specimens of 40 patients with gastric cancer were retrieved. Areas with chronic gastritis, atrophic gastritis, intestinal metaplasia and adenocarcinoma were identified and immunostained for alpha-catenin, beta-catenin and E-cadherin. The results were scored semiquantitatively by two independent pathologists using a validated scoring system. RESULTS: A significant decrease in score was observed in 5% (1/22) of alpha-catenin, 0% (0/22) of beta-catenin and 9% (2/22) of E-cadherin in chronic atrophic gastritis patients, and in 28% (5/18) of alpha-catenin, 67% (10/15) of beta-catenin and 57% (8/14) of E-cadherin in intestinal metaplasia patients. The scoring of alpha-catenin, beta-catenin and E-cadherin correlated with each other. Forty-three percent of patients had concordant changes of scores along the gastritis-adenocarcinoma sequence. There was no association between Helicobacter pylori status and E-cadherin-catenin complex expression. CONCLUSION: Deregulation of the E-cadherin-catenin complex was observed in the majority of precancerous lesions in patients with gastric adenocarcinoma, which has potential diagnostic and therapeutic implications.     

Anti-GAD antibodies in Chinese patients with youth and adult-onset IDDM and NIDDM

Summary An autoimmune basis for the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is supported by the frequent presence of autoantibodies – islet cell antibodies (ICAs) and GAD antibodies (GADab). However, in Chinese patients with clinical IDDM, a low prevalence of ICAs was observed. In non-insulin-dependent diabetic (NIDDM) patients, it has been suggested that the presence of GADab may identify a subset of latent autoimmune diabetes in adults (LADA). We determined the frequency of GADab in a large group of 134 IDDM and 168 NIDDM Chinese patients, and assessed the relation with ICAs status. Results showed that 39.6 % IDDM and 16.1 % NIDDM patients had GADab, and 20.1 % and 4.8 %, respectively had detectable ICAs. Frequency of GADab positivity was not influenced by whether the patients had youth or adult-onset IDDM or NIDDM, or by duration of diabetes. NIDDM patients seropositive for GADab shared similar clinical characteristics and fasting C-peptide levels with those who were GADab negative. Presence of GADab therefore did not serve to identify a sub-group of patients with latent or slow-onset IDDM. Half (53 %) of our IDDM patients had neither GADab nor ICAs. The reason for this observation is unclear. One theory is that other autoantigens yet to be identified may be contributory. Alternatively, in the Chinese, autoimmunity may not be the major factor in the pathogenesis of IDDM. [Diabetologia (1997) 40: 1425–1430] Received: 11 March 1997 and in revised form: 13 May 1997