Absorption of isomeric, palmitic acid-containing triacylglycerols resembling human milk fat in the adult rat

The effect of the positional distribution of palmitic acid (16:0) in triacylglycerols (TAG) on 16:0 apparent absorption in adult rats was investigated. The rats were fed two diets which contained 30 energy % as fat with identical total fatty acid compositions, both containing 30% 16:0. The Betapol diet contained TAG with 73% of total 16:0 in the sn-2 position, the control diet contained TAG with 6% of total 16:0 in the sn-2 position. After six weeks on these diets, the rats were killed two or six hours after the last meal, and the small intestine was removed, cut into 10-cm segments, and the fatty acid composition of the segment's contents was determined. At both time points the amount of 16:0 in the intestinal segments starting at 40 cm from the stomach was much lower in the animals fed Betapol than in the animals fed the control diet. Overall absorption of 16:0 and stearic acid was significantly greater in the Betapol group. Absorption of oleic and linoleic acid from the small intestine was similar in both groups, although the overall absorption was significantly greater in the animals fed Betapol. Total fat absorption was significantly higher in the Betapol-fed rats than in the control-fed rats. No effect on calcium and nitrogen absorption, on plasma total cholesterol and TAG levels, and on bodyweights (growth) was seen. The data demonstrate that the positional distribution of the fatty acids in the TAG molecule affects the site of absorption in the small intestine and particularly the net absorption of saturated fatty acids.     

Inhibitors of branched-chain amino acid biosynthesis as potential antituberculosis agents

Previous studies have shown that rheumatoid arthritis aggregates within families. However, no formal genetic analysis of rheumatoid arthritis in pedigrees together with other autoimmune diseases has been reported. We hypothesized that there are genetic factors in common in rheumatoid arthritis and other autoimmune diseases. Results of odds-ratio regression and complex segregation analysis in a sample of 43 Caucasian pedigrees ascertained through a rheumatoid arthritis proband or matched control proband, revealed a very strong genetic influence on the occurrence of both rheumatoid arthritis and other autoimmune diseases. In an analysis of rheumatoid arthritis alone, only one inter-class measure, parent-sibling, resulted in positive evidence of aggregation. However, three inter-class measures (parent-sibling, sibling-offspring, and parent-offspring pairs) showed significant evidence of familial aggregation with odds-ratio regression analysis of rheumatoid arthritis together with all other autoimmune diseases. Segregation analysis of rheumatoid arthritis alone revealed that the mixed model, including both polygenic and major gene components, was the most parsimonious. Similarly, segregation analysis of rheumatoid arthritis together with other autoimmune diseases revealed that a mixed model fitted the data significantly better than either major gene or polygenic models. These results were consistent with a previous study which concluded that several genes, including one with a major effect, is responsible for rheumatoid arthritis in families. Our data showed that this conclusion also held when the phenotype was defined as rheumatoid arthritis and/or other autoimmune diseases, suggesting that several major autoimmune diseases result from pleiotropic effects of a single major gene on a polygenic background.     

Induction of Bax-alpha precedes apoptosis in a human B lymphoma cell line: potential role of the bcl-2 gene family in surface IgM-mediated apoptosis

The members of the bcl-2 gene family are major regulators of programmed cell death, but their role in sIg-triggered apoptosis remains unclear. Using sensitive and resistant variants of the human B cell line BL-41, we studied the expression of the bcl-2 gene family during surface IgM-mediated apoptosis. We found constitutive Bcl-2 and Bcl-x expression, which remained unaltered after sIg cross-linking, in both resistant and sensitive cells. This and other experiments suggest that constitutive expression of Bcl-2 or Bcl-x alone is not sufficient to protect from activation-induced cell death in B cells. We therefore investigated Bax-alpha, the death-promoting splice variant of Bax, and found strong induction of both mRNA and protein upon sIg stimulation in sensitive cells. However, resistant subclones showed only weak expression, which was not inducible by sIg cross-linking. We provide evidence that up-regulation of Bax-alpha and the resulting imbalance of Bcl-2/Bax might be a major regulator of sIg-mediated apoptosis. Additionally, we found strong constitutive expression of Bcl-xs, the death promoting variant of Bcl-x, in sensitive cells, whereas resistant cells showed only weak Bcl-xs expression. Thus, we observed a much stronger expression of the death-promoting proteins Bax-alpha (inducible) and Bcl-xs (constitutive) in sensitive cells than in resistant cells. We therefore propose a potential role of the novel bcl-2 gene family members bcl-x and bax in surface IgM-triggered apoptosis.     

Pollutant transport during a regional O3-episode in the mid-Atlantic states

Ozone (O3) concentrations in the Baltimore-Washington (B-W) metropolitan area frequently exceed the National Ambient Air Quality Standard (NAAQS) in the summer months. The most extreme O3 events occur in multi-day high O3 episodes. These events can be regional in scale, with O3 concentrations exceeding the NAAQS at numerous locations along the eastern U.S. seaboard, and are typically associated with slow-moving or stagnant high pressure systems. In the B-W region, the most extreme events typically occur with surface high pressure overhead or just west of the region and an upper air high-pressure area (ridge) to the west or northwest. Besides providing conditions conductive to local O3 production (subsidence and strong low-level inversions, weak horizontal winds, little cloud cover), this weather pattern may also result in transport of O3 and its precursors from heavily industrialized areas west and north of the B-W region. In this paper, observations and back trajectories made during the severe regional O3 event of July 12-15, 1995, are used to confirm the hypothesis that significant regional-scale transport of O3 and its precursors occur during extreme O3 events of the standard type in the B-W area.     

Activation of protein phosphatase 5 by limited proteolysis or the binding of polyunsaturated fatty acids to the TPR domain

In the urine of patients with bladder cancer, levels of the angiogenio peptide basic fibroblast growth factor (bFGF) may be elevated 100-fold. To date, levels of expression of bFGF in bladder tumor tissue have not been determined, nor has the cellular source of the urinary bFGF been identified. bFGF mRNA expression was quantified using RNase protection analysis in 32 primary bladder tumors and 8 normal bladder specimens. In addition, bFGF protein expression in the tumor cytosol was determined using a Quantikine ELISA, and bFGF protein expression was localized with immunohistochemistry. bFGF mRNA expression was absent in 28 of 32 (87%) bladder cancers despite detectable expression in 7 of 8 (87%) normal bladder specimens (P = 0.0001). In only one tumor was bFGF mRNA expression higher than in normal bladder tissue. Median bFGF protein expression was also higher in the normal bladder specimens than in the superficial tumors (3800 pg/g protein versus 1140 pg/g protein; P < 0.02), but there was no statistically significant difference between protein expression in normal bladder and invasive cancers (3800 pg/g versus 3600 pg/g). Median bFGF protein expression was higher in invasive cancers than in superficial tumors (P < 0.05). Intense bFGF immunoreactivity was seen in the basal lamina of normal transitional epithelium, in normal human detrusor muscle, and in vessels within tumors. Tumor cell immunoreactivity was rare and was usually weak. Only in the tumor which strongly overexpressed bFGF mRNA and protein was cytoplasmic staining detectable in the neoplastic cells. There are two mechanisms of bFGF-induced angiogenesis in bladder cancer. Rarely, neoplastic cells synthesize bFGF but more commonly bFGF is released by degradation of epithelial basement membranes and detrusor muscle, from where it can diffuse into the tumor microenvironment and bind to blood vessels. Mechanisms of extracellular matrix degradation may be important in bladder cancer angiogenesis and progression and as such are potential therapeutic targets.     

Self monitoring of blood glucose in blind diabetic patients

Blind diabetic patients face particular difficulties in blood glucose self monitoring (BGSM). We investigated the quality of BGSM in blind and severely visually impaired diabetic patients and assessed the effects of training in BGSM using a blood glucose meter with voice edition of values and a modified test strip holder for easier placement of blood samples on the strip (One Touch II talk (OT II)). Twenty-six insulin-treated diabetic patients (23 IDDM and 3 NIDDM) participated. At baseline the quality of BGSM was checked in 14 patients who already regularly performed BGSM without external help. Thereafter all 26 patients received an extensive instruction in BGSM for blind patients. At re-examination, after a mean period of 41 days, the quality of BGSM performed by the patients without assistance was checked in three different blood samples. Blood glucose was measured in the same sample by a routine laboratory method. At baseline the mean absolute difference between BGSM and the reference method was -0.3 mmol l(-1) (range; +/- SD) (-7.7-4.8; +/- 2.6 mmol l(-1)); 74% of BGSM measurements deviated by more than 10% from the reference values and 43% by more than 20%. At follow-up all 26 patients reported daily BGSM without external help. The mean absolute difference between BGSM and the reference method was -0.1 (-2.7-2.8; +/- 0.9 mmol l(-1)); 25% of BGSM measurements deviated by more than 10 % from the laboratory reference values and 5% by more than 20%. The results of this study suggest that a substantial number of blind diabetic patients do not perform BGSM on their own at all and in those who do the reliability of the results is poor. However, after extensive instruction, the majority of blind diabetic patients should be able to perform BGSM and to obtain reliable results.     

Initiation and propagation of blood coagulation at artificial surfaces studied in a capillary flow reactor

BACKGROUND: There is a potential for interaction between malaria and human immunodeficiency virus (HIV) infection. HIV infection might reduce immunity to malaria resulting in more frequent and severe infections; conversely malaria might enhance the progression of HIV infection to AIDS. In this paper we have reviewed some of the studies that have addressed this topic. METHODS: Studies identified by a MEDLINE search were systematically reviewed and the measures of association between the two infections were either abstracted or recalculated from the reported data. Inferences drawn from these studies and the biological plausibility of an interaction are discussed. RESULTS: The prevalence ratio (PR) of peripheral parasitaemia among HIV seropositive (HIVSP) individuals compared to HIV seronegative (HIVSN) individuals ranged from 0.72 to 0.94 in children and from 3.3 to 0.69 in adults. However, only one study showed a statistically significant difference between HIVSP and HIVSN groups (PR 3.3, 95% CI: 2.7-4.2). The rate ratio of non-severe malaria among HIVSP children compared to HIVSN children was 1.4 (95% CI: 0.99-2.0). Data from a trial of chemoprophylaxis during pregnancy suggested that placental malaria may predispose to perinatal transmission of HIV. Studies that have investigated the immune response to P. falciparum among HIVSP subjects have given variable results. CONCLUSION: There is no convincing evidence for an interaction between malaria and HIV with the possible exception of an interaction between placental malaria and HIV infection. Several studies, however, had potentials for bias and/or an inadequate sample size. There is a need for carefully designed studies to resolve whether mortality from severe malaria, in particular cerebral malaria, is increased in HIVSP subjects, whether malaria infection of the placenta increases the risk of vertical transmission of HIV, and whether malaria infection increases the progression of HIV infection to AIDS.     

Laser-Doppler scanning of local cerebral blood flow and reserve capacity and testing of motor and memory functions in a chronic 2-vessel occlusion model in rats

BACKGROUND AND PURPOSE: An animal model of incomplete forebrain ischemia resembling human hemodynamic insufficiency was established. The model allows examination of acute and chronic changes of local cerebral blood flow (lCBF) and reserve capacity in correlation with behavioral parameters. METHODS: Anesthetized male Wistar-Kyoto rats underwent bilateral carotid occlusion (BCO). Laser-Doppler scanning of lCBF at baseline conditions and after acetazolamide was done 30 minutes after BCO, motor and memory function tests were administered after 1 and 2 days, and both investigations were repeated after 1, 2, 4, and 6 weeks. A sham-operated and a control group without any vessel manipulation served as controls. RESULTS: lCBF dropped within 60 minutes after surgery by 62% (P<0.001) in 10 animals surviving BCO (BCOsurvival) and by 69% in 5 rats that died within 9 days (BCOlethal). Acetazolamide increased lCBF to 142.33% in controls, to 136.66% in sham-operated rats (both significant), and to 104.80% in BCOsurvival (not significant), and it decreased flow by 23.1% in BCOlethal rats (P<0.001). Baseline lCBF normalized within 4 weeks. Total motor function scores were significantly reduced from 9 points preoperatively to 5.80+/-0.65 in BCOlethal and 6.68+/-0.54 points in BCOsurvival rats 1 day after occlusion. Memory retention function remained impaired after BCO, as did the acetazolamide response, which correlated with motor score and was inversely related to maze exploration time. CONCLUSIONS: This model allows long-term follow-up of cerebral function, lCBF, and reserve capacity in a pathophysiological setting similar to hemodynamic insufficiency in humans.