Investigations of the lipid metabolism of the white matter in multiple sclerosis Changes in glycero-phosphatides and lipid-splitting enzymes

Phospho- and galacto- lipids and lipidhydrolyzing enzymes have been determined in the white matter of a young patient with a subacute course of multiple sclerosis (MS). Significant changes were observed for the concentration of glycerophosphatides and the fatty acid pattern of the normal appearing with matter surrounding MS-plaques. Among the individual glycerophosphatides a significant decrease of phosphatidylserine and phosphatidylinositol was found, whereas the ethanolamine containing phosphatides showed lower figures (non significant).The fatty acid pattern of the ethanolamine-phosphatide-fraction of the diseased tissue showed a decrease of the 181 and the sum of 201 and 183 fatty acids as compared to the normal control, whereas the highly unsaturated, long-chained fatty acids 204 (arachidonic acid) and 226 (docosahexaenic acid) were elevated. The measurement of lipidhydrolyzing enzymes resulted in an increased phospholipase A₁ activity in the diseased tissue. The experimental data point to a decreased activity of the fatty acid elongation system in the course of MS. The decrease of the acidic glycerophosphatides might be due to the increased phospholipase A₁ activity.The impaired interaction of the lipids with the basic myelin protein, as described in the present paper, might be involved in the pathogenesis of the demyelinating process.     

Leukocyte selenium, zinc, and copper concentrations in preeclamptic and normotensive pregnant women

Preeclampsia is an important cause of maternal and perinatal mortality worldwide. The etiology of this relatively common medical complication of pregnancy, however, remains unknown. We studied the relationship between maternal leukocyte selenium, zinc, and copper concentrations and the risk of preeclampsia in a large hospital-based case-control study. One hundred seventy-one women with proteinuric pregnancy-induced hypertension (with or without seizures) comprised the case group. Controls were 184 normotensive pregnant women. Leukocytes were separated from blood samples collected during the patients’ postpartum labor and delivery admission. Leukocyte concentrations for the three cations were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Concentrations for each cation were reported as micrograms per gram of total protein. Women with preeclampsia had significantly higher median leukocyte selenium concentrations than normotensive controls (3.23 vs 2.80 μg/g total protein, p<0.0001). Median leukocyte zinc concentrations were 31% higher in preeclamptics as compared with controls (179.15 vs 136.44 μg/g total protein, p<0.0001). Although median leukocyte copper concentrations were slightly higher for cases than controls, this difference did not reach statistical significance (17.72 vs 17.00 μg/g total protein, p=0.468). There was evidence of a linear increase in risk of preeclampsia with increasing concentrations of selenium and zinc. The relative risk for preeclampsia was 3.38 (adjusted odds ratio [OR]=3.38, 95% confidence interval [CI]=1.53–7.54) among women in the highest quartile of the control selenium distribution compared with women in the lowest quartile. The corresponding relative risk and 95% CI for preeclampsia was 5.30 (2.45–11.44) for women in the highest quartile of the control zinc distribution compared with women in the lowest quartile. There was no clear pattern of a linear trend in risk with increasing concentration of leukocyte copper concentrations (adjusted for linear trend in risk =0.299). Our results are consistent with some previous reports. Prospective studies are needed to determine whether observed alterations in selenium and zinc concentrations precede preeclampsia or whether the differences may be attributed to preeclampsia-related alterations in maternal and fetal-placental trace metal metabolism.     

Influence of Storage on Monodispersed Cells of Mycobacterium terrae Used for Quantitative Carrier Test prEN 14563

The degree of cell clumping increased with time of storage (1% cell clumps immediately after homogenization and 3 and 6.5% after 48 and 96 h of storage, respectively), and the number of living single cells decreased. Quantitative carrier tests were carried out with these cells using ortho-phthaldialdehyde (OPA) and coco fatty aminoxethylate as biocides. In contrast to OPA, with coco fatty aminoxethylate the reductions obtained with freshly homogenized mycobacteria were significantly higher (P = 0.02) than those obtained with mycobacteria kept in the refrigerator for 4 days. Therefore, it is advisable to prepare the test suspension freshly for each test.     

Gender-Dependent Differences in Plasma Matrix Metalloproteinase-8 Elevated in Pulmonary Tuberculosis

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers.     

Risk Factors for Low Birthweight in Zimbabwean Women: A Secondary Data Analysis

Background

Low birth weight (LBW) remains the main cause of mortality and morbidity in infants, and a problem in the care of pregnant women world-wide particularly in developing countries. The purpose of this study was to describe the socio-demographic, nutritional, reproductive, medical and obstetrical risk factors for delivering a live LBW infant at Harare Maternity Hospital, Zimbabwe.

Methods

A secondary data analysis from data obtained through a questionnaire and delivery records was conducted. Linear regression models with a complimentary log-log link function were used to estimate the relative risks for all LBW, term LBW and preterm LBW.

Results

The frequency of LBW was 16.7%. Lack of prenatal care (adjusted relative risk [ARR] 1.69, 95% CI 1.44, 1.98), mother’s mid-arm circumference below 28.5 cm, (ARR 1.35, 95% CI 1.19, 1.54) and rural residence (ARR 1.22, 95% CI 1.04, 1.40) increased the risk of LBW. Eclampsia, anemia, and ante-partum hemorrhage, were associated with LBW (ARR 2.64, 95% CI 1.30, 5.35; ARR = 2.63, 95% CI 1.16, 5.97; and ARR = 2.39, 95% CI 1.55, 3.68), respectively. Malaria increased the risk of LBW (ARR = 1.89, 95% CI 1.21, 2.96). Prenatal care, infant sex, anemia, antepartum hemorrhage, premature rapture of membranes and preterm labor were associated with the three LBW categories. History of abortion or stillbirth, history of LBW, malaria, eclampsia, and placenta Previa, were associated with all LBW and preterm LBW, while pregnancy induced hypertension, and number of children alive were associated with all LBW and term LBW.

Conclusions

LBW frequency remains high and is associated with nutritive, reproductive, medical and obstetrical factors. Preterm LBW and term LBW have similar and also different risk factors. Understanding the role of different risk factors in these different LBW categories is important if the goal is to reduce LBW frequency, and its complications, in Zimbabwe.     

Occurrence and Properties of Phospholipases A1 of Plasma Membranes Prepared from Neuronal- and Glial-Enriched Fractions of the Rabbit Cerebral Cortex

Abstract: Exogenously added glycerophosphatides, specifically radioactively labelled either in the 1 or in the 2 position, were used to investigate the occurrence and properties of phospholipase A₁ in plasma membranes prepared from neuronal- and glial-enriched fractions of rabbit brain. Phospholipase A₁ activity was maximal at pH values ranging between 8.0 and 9.0 for the plasma membranes of both cell types. The enzyme activity was most abundant in the microsomal fraction, with a neurondglial ratio of about 2. The plasma membranes displayed about half the enzymic activity of the microsomal fraction, whereas only small amounts of phospholipase A₁ were present in the neuronal and glial mitochondria. Investigations on the substrate specificity showed a different pattern for the enzyme of neuronal and glial origin. The release of labelled fatty acids from phosphatidylcholine by the neuronal plasma membrane phospholipase A₁ decreased with increasing degree of unsaturation of the fatty acids at the 1 position. The presence of plasmalogens and plasmalogen precursors in the incubation mixture appreciably inhibited the hydrolysis of the corresponding diacyl compounds.     

Calcium control of waveform in isolated flagellar axonemes of chlamydomonas

The effect of Ca(++) on the waveform of reactivated, isolated axonemes of chlamydomonas flagella was investigated. Flagella were detached and isolated by the dibucaine procedure and demembranated by treatment with the detergent Nonidet; the resulting axomenes lack the flagellar membrane and basal bodies. In Ca(++)-buffered reactivation solutions containing 10(-6) M or less free Ca(++), the axonemes beat with a highly asymmetrical, predominantly planar waveform that closely resembled that of in situ flagella of forward swimming cells. In solutions containing 10(-4) M Ca(++), the axonemes beat with a symmetrical waveform that was very similar to that of in situ flagella during backward swimming. In 10(-5) M Ca(++), the axonemes were predominantly quiescent, a state that appears to be closely associated with changes in axomenal waveform or direction of beat in many organisms. Experiments in which the concentrations of free Ca(++), not CaATP(--) complex were independently varied suggested that free Ca(++), not CaATP(--), was responsible for the observed changes. Analysis of the flagellar ATPases associated with the isolated axonemes and the nonidet- soluble membrane-matrix fraction obtained during preparation of the axonemes showed that the axonemes lacked the 3.0S Ca(++)-activated ATPase, almost all of which was recovered in the membrane-matrix fraction. These results indicate that free Ca(++) binds directly to an axonemal component to alter flagellar waveform, and that neither the 3.0S CaATPase nor the basal bodies are directly involved in this change.     

The mosaic nature of the eukaryotic nucleus

The phylogenies for each of the protein-coding genes from the Methanococcus jannaschii genome were surveyed to determine the history of the major groups of life. For each gene, homologous sequences from other archaea, eucarya, and Gram-positive and Gram-negative bacteria were collected and aligned, and a phylogeny was reconstructed with a maximum-likelihood algorithm. The majority of significant phylogenies favor the eucarya and the archaca as sister groups. A smaller, but still substantial, portion of these significant phylogenies favor an eucarya/Gram-negative clade. These results indicate that support for the early history of life is not unequivocal. A chimeric origin of eukaryotes or an ancient, massive horizontal transfer of genes from Gram-negative bacteria to eucarya can explain many of the observed phylogenies.      

Protein-based phylogenies support a chimeric origin for the eukaryotic genome

The phylogenetic position of the archaebacteria and the place of eukaryotes in the history of life remain a question of debate. Recent studies based on some protein-sequence data have obtained unusual phylogenies for these organisms. We therefore collected the protein sequences that were available with representatives from each of the major forms of life: the gram-negative bacteria, gram-positive bacteria, archaebacteria, and eukaryotes. Monophyletic, unrooted phylogenies based on these sequence data show that seven of 24 proteins yield a significant gram-positive-archaebacteria clade/gram-negative- eukaryotic clade. The phylogenies for these seven proteins cannot be explained by the traditional three-way split of the eukaryotes, archaebacteria, and eubacteria. Nine of the 24 proteins yield the traditional gram-positive-gram-negative clade/archaebacteria-eukaryotic clade. The remaining eight proteins give phylogenies that cannot be statistically distinguished. These results support the hypothesis of a chimeric origin for the eukaryotic cell nucleus formed from the fusion of an archaebacteria and a gram-negative bacteria.