Folate, vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men

Deficient levels of folic acid and vitamin B12 are associated with elevated chromosome damage rate and high concentrations of homocysteine in the blood. We have therefore performed a study to determine the prevalence of folate deficiency, vitamin B12 deficiency and hyperhomocysteinemia in 64 healthy men aged between 50 and 70 years, and evaluate the relationship of these micronutrient levels in the blood with the micronucleus frequency in peripheral blood lymphocytes. We also performed a placebo-controlled, double-blind intervention study to determine whether supplementation of the diet with a daily dose of 0.7 mg (as a supplement in cereal) or 2.0 mg (in a tablet) over a period of 4 months resulted in a significant alteration of folate status, homocysteine status and the micronucleus index. Twenty-three per cent of the men were serum folate deficient (<6.8 nmol/l), 16% were red blood cell folate deficient (<317 nmol/l), 4.7% were vitamin B12 deficient (<150 pmol/l) and 37% has plasma homocysteine levels >10 micromol/l. In total, 56% of the men had one or more abnormal blood values for folate, vitamin B12 or homocysteine. The micronucleus index of these men (n = 34) in cytokinesis-blocked binucleated cells (19.2 +/- 1.1) was significantly elevated (P = 0.02) when compared to the micronucleus index of the rest of the men who had normal levels of folate, vitamin B12 and homocysteine (16.3 +/- 1.3, n = 30). Interestingly, the micronucleus index in men with normal folate and vitamin B12, but homocysteine levels >10 micromol/l (19.4 +/- 1.7, n = 15) was also significantly higher (P = 0.05) when compared to those with normal folate, vitamin B12 and homocysteine. This novel result was also supported by the observation that the micronucleus index and plasma homocysteine were significantly (P = 0.0086) and positively correlated (r2 = 0.172) in those subjects who were not deficient in folate or vitamin B12. The micronucleus index was not significantly correlated with folate indices, but there was a significant (P = 0.013) negative correlation with serum vitamin B12 (r2 = 0.099). Daily supplementation of the diet with 0.7 mg free folic acid in cereal for 2 months followed by 2.0 mg free folic acid via a tablet produced a 4- fold increase in plasma folate, a 2.6-fold increase in red blood cell folate and a 11% reduction in plasma homocysteine; however, these changes were not accompanied by a reduction in the micronucleus index. In conclusion, it is apparent that elevated homocysteine status, in the absence of vitamin deficiency and low, but not deficient, vitamin B12 status are important risk factors for increased chromosome damage in lymphocytes.      

Functional differences between two Fc receptor ITAM signaling motifs

Most Ig receptors exist as multi-subunit complexes with a unique ligand binding alpha chain and a common signaling FcR gamma-chain. The myeloid Fc gamma RIIa (CD32) appears unique among FcR because both ligand- binding and signaling capacity are found in the alpha chain. Within the cytoplasmic tails of Fc gamma RIIa and FcR gamma-chain similar, but not identical, activatory motifs (ITAMs) have been defined, in which tyrosines play an important role. Previously, Fc gamma RIIa-ITAM was shown to be critical for both proximal and distal activatory functions in IIA1.6 B-cell transfectants. Triggering of interleukin-2 (IL-2) release and antigen presentation was absent in Fc gamma RIIa, but not in FcR gamma-chain receptor complexes. We now assessed the capacity of Fc gamma RIIa wild-type and Fc gamma RIIa/gamma chimeric molecules to trigger IL-2 production and antigen presentation by B cells. Both of these functions could solely be triggered by receptors containing the FcRIIa was capable of functional interaction with FcR gamma-chain, thus reconstituting the capacity to trigger IL-2 release and antigen presentation. These data document qualitative differences between Fc receptor ITAMs.     

Oestrogen receptor gene polymorphisms and ovarian stimulation for in- vitro fertilization

Experimental evidence has shown that mice lacking the oestrogen receptor (ESR) gene are infertile with cystic ovaries and follicular arrest. In humans, several polymorphisms and mutations in the ESR gene have been identified. In this study we have analysed a common PvuII and a rare BstUI polymorphism in the ESR gene. Analysis was carried out on DNA samples from women undergoing ovarian stimulation for in-vitro fertilization (IVF) and embryo transfer and controls having at least one pregnancy. Comparisons were done between the three PvuII genotypes, concerning the mean numbers of follicles and oocytes and the mean ratios of follicles to oocytes harvested in two consecutive cycles. Significantly lower ratios were identified in the group lacking the PvuII polymorphism, compared with the groups with heterozygous or homozygous PvuII polymorphisms (P > 0.05 and P > 0.01 respectively). The rare haplotype having both PvuII and BstUI restriction sites on one chromosome was present only in the IVF group. Pregnancies from IVF were significantly rarer in patients who were homozygous for the PvuII polymorphism (P > 0.05). Our results suggest that genetic variability in the ESR has a role in the quality of the ovarian follicles as judged by the ovarian response to stimulation and may also affect implantation.      

Large paraesophageal varices on endosonography predict recurrence of esophageal varices and rebleeding

BACKGROUND & AIMS: Recurrence of varices and rebleeding after endoscopic therapy is very common. Data on the prediction of recurrent varices after initial obliteration by endoscopic therapy are few. The aim of this study was to correlate the presence and the size of paraesophageal varices (PEVs) in patients after endoscopic variceal ligation with recurrent varices and rebleeding. METHODS: Forty patients who underwent endoscopic banding ligation for esophageal variceal bleeding were studied by endosonography within 4 weeks after obliteration of varices. PEVs were classified as none, small, or large (maximum diameter, > or =0.5 cm). Esophagoscopy and endosonography were then repeated every 6 months for up to 1 year. RESULTS: Two patients (5%) were not detected to have PEVs. Small and large PEVs were identified in 24 (60%) and 14 (35%) patients, respectively. During the follow-up period of 1-year, recurrent submucosal esophageal varices were detected in 24 patients, including 13 patients (93%) with large PEVs and 11 patients (46%) with no or small PEVs (P = 0.0019). Recurrent bleeding occurred in 6 patients (43%) with large PEVs and in 3 patients (12%) with small PEVs (P = 0.044). CONCLUSIONS: Patients with large PEVs have a higher risk of developing recurrent varices and rebleeding. (Gastroenterology 1997 Jun;112(6):1811-6)     

T-cell activation and receptor downmodulation precede deletion induced by mucosally administered antigen

The fate of antigen-specific T cells was characterized in myelin basic protein (MBP) T-cell receptor (TCR) transgenic (Tg) mice after oral administration of MBP. Peripheral Th cells are immediately activated in vivo, as indicated by upregulation of CD69 and increased cytokine responses (Th1 and Th2). Concurrently, surface TCR expression diminishes and internal TCR levels increase. When challenged for experimental autoimmune encephalomyelitis during TCR downmodulation, Tg mice are protected from disease. To characterize Th cells at later times after antigen feeding, it was necessary to prevent thymic release of naive Tg cells. Therefore, adult Tg mice were thymectomized before treatment. TCR expression returns in thymectomized Tg mice 3 days after MBP feeding and then ultimately declines in conjunction with MBP-specific proliferation and cytokine responses (Th1-type and Th2-type). The decline correlates with an increase in apoptosis. Collectively, these results demonstrate that a high dose of fed antigen induces early T-cell activation and TCR downmodulation, followed by an intermediate stage of anergy and subsequent deletion.     

In vitro function and post-transfusion survival of granulocytes collected by continuous-flow centrifugation and by filtration leukapheresis

The function of granulocytes collected by continuous-flow centrifugation (CFC) and by filtration leukapheresis (FL) was studied in vitro, and the post-transfusion recovery and intravascular survival of these cells was studied by autologous transfusion in normal donors. Granulocytes collected by both FL and CFC leukapheresis (CFCL) functioned normally in the quantitative nitroblue tetrazolium, oxygen consumption, and chemotaxis assays. Bacterial killing was slightly but consistently decreased in FL but not CFCL granulocytes. The post- transfusion recovery of control granulocytes collected by ordinary phlebotomy averaged 52% in eight transfusions, compared with 34% for six CFCL granulocyte concentrates and 16% for six FL concentrates. The intravascular half-times were 3.8 hr for phlebotomy and 3.0 hr for CFCL granulocytes. FL granulocytes had survival curves which were nonlinear and a single half-life could not be calculated. The average half-time 30 min after transfusion was 1.3 hr, and 3 hr after transfusion it was 2.6 hr. Granulocytes collected by FL had a mild impairment of bacterial killing, decreased post-transfusion recovery, and altered intravascular kinetics. None of these abnormalities was found in granulocytes collected by CFCL.     

Cervical cancer in Calabar, Nigeria

Objective: To assess the prevalence of cervical cancer and histologic variants as seen in Calabar,Cross River state.Methods: This is a retrospective study involving histologically verified uterine cervix carcinoma between January,1997 and December,2006.Results: There were 1,207 malignancies diagnosed during the study period;175(14.5%) were malignancies of the genital tract while 113(9.4.0%) were carcinoma of the cervix constituting 64.6% of female genital malignancies.Cervical cancer was commonest between the ages of 40-59 years.There was no patient with carcinoma of the cervix below the age of 20 years.Squamous cell carcinoma(87.6%) of the uterine cervix was the main histological type.Conclusion:Cervical cancer is still the most common female genital tract malignancy in Calabar with most of these patients in their middle age.The use of PAS/Alcian blue stain as was used in this study eliminates most false-positive squamous cell carcinomas compared with Haematoxylin and Eosin stains used in most reports from most centres in this part of the world.Epithelial malignancies continue to be the predominant histological variant with squamous cell variety the commonest.There is also an urgent need for introduction of efficient and affordable population based cervical screening programme for early detection,use of vaccines against Human Papilloma Virus(HPV) and treatment of pre-malignant cervical lesions.