Imaging spectrum of thrombo-occlusive vascular disease associated with antiphospholipid antibodies

The association of antiphospholipid antibodies with unexplained thrombo-occlusive vascular disease is well known but often remains unrecognized. The most well-studied clinical manifestation is venous thrombosis, but arterial occlusive disease involving multiple sites is also well documented. Twenty-six cases of thrombo-occlusive disease were observed in 22 patients over a 3-year period. Magnetic resonance imaging and angiography were used to make the diagnoses. None of the patients who underwent angiography or venography developed thrombolytic disease related to the puncture site. This group of patients with antiphospholipid antibody syndrome had a wide distribution of arterial and venous thrombotic disease. Radiologists should consider antiphospholipid antibody syndrome in the differential diagnosis when evaluating thrombo-occlusive vascular disease that is unexpected or occurs without risk factors. Knowledge of antiphospholipid antibody status has important implications for prognosis and therapy.     

Congenital pulmonary lymphangiectasis with chylothorax: a heterogeneous lymphatic vessel abnormality

We describe the generation of a new antipeptide antibody that binds to the centromeric region of human mitotic chromosomes. This antibody was raised against a synthetic peptide corresponding to the 481-493 amino acid sequence of the human CENP-B autoantigen. Immunofluorescence analysis revealed that this anti-CENP-B serum showed an identical pattern to the human CREST anticentromere autoantibody in both mitotic cells and interphase nuclei. Immunoblotting showed that this antibody reacts with the recombinant human CENP-B autoantigen, indicating that it is directed to the 80-kDa centromere polypeptide. We have used this serum to determine, by indirect immunofluorescence, whether CENP-B is conserved in different mammalian species. Surprisingly, the human antipeptide antibody does not react with the centromeric proteins of cultured mouse, hamster, or Indian muntjac cells. Because the CENP-B gene has been cloned in human and mouse, our results suggest that the CENP-B epitope used as an immunogen in this study is not ubiquitous in mammalian cells, and that we have most probably established a monospecific antibody to the human centromere.     

Taking enzyme kinetics out of control; putting control into regulation

The matrix formulation of metabolic control analysis, which states that multiplying the elasticity matrix for any system by the corresponding control matrix yields an identity matrix, can be transformed into a statement that multiplying a matrix expressing internal regulatory properties by a matrix expressing external regulatory properties also yields an identity matrix. This transformation supplies the formal basis for metabolic regulation analysis, and provides the key to determining the control structure of a system without the need to know the exact changes in enzyme activities that are made to measure control coefficients.     

Erythrocyte sodium lithium countertransport in normal and hypertensive pregnancy: relation to haemodynamic changes

OBJECTIVE: To establish the changes in erythrocyte sodium lithium countertransport (SLC) with advancing normal pregnancy and to determine if these changes were different in pregnancy induced hypertension (PIH). The changes in both groups were assessed in relation to haemodynamic changes. DESIGN: SLC, mean arterial pressure (MAP), cardiac output (CO) and total peripheral vascular resistance (TPVR) were determined serially during normal pregnancy and cross-sectionally in PIH. Women were studied again 20 weeks after delivery where possible. SETTING: Routine antenatal clinic and antenatal ward of a regional reference centre. SUBJECTS: Fifty-one normal primigravid women were studied serially and 41 primigravid women with PIH were studied at time of diagnosis. RESULTS: During normal pregnancy SLC (mmol Li/h/l cells) increased from a nonpregnant value of 0.24 +/- 0.02 (mean +/- SEM) to 0.32 +/- 0.02 at 14 weeks, and 0.37 +/- 0.02 at 20 weeks gestation. This was maintained until 38 weeks (0.40 +/- 0.02). The increase until 20 weeks occurred at the time of greatest change in CO (5.10 +/- 0.18 to 6.79 +/- 0.20 l/min) and TPVR (1327 +/- 58 to 969 +/- 33 dyn/s/cm-5). The decrease in TPVR with a rise in SLC is opposite to the relation reported in essential hypertension so that a functional relation is unlikely. However, the changes within pregnancy were positively correlated (r = 0.43, P < 0.01). In hypertensive pregnancies TPVR was elevated compared with normotensive pregnancies (1543 +/- 100 vs 1090 +/- 37) but the SLC was not different from that found in normotensive pregnancies (0.43 +/- 0.02 vs 0.40 +/- 0.02). CONCLUSIONS: The changes in SLC activity suggest dynamic effects on erythrocyte membrane function during pregnancy. However, no differences could be found between normal and hypertensive pregnancy and SLC is unlikely to be of value as a marker of hypertensive risk during pregnancy.     

Prevention of bromobenzene toxicity by N-acetylmethionine: correlation between toxicity and the impairment in O- and S-methylation of bromothiocatechols

Bromobenzene (800 mg/kg, ip) caused severe liver necrosis with massive hemorrhage in the golden Syrian hamster within the first 24 hr. Kidney injury was also observed. Treatment with N-acetylmethionine (NAM) at an ip dose of 1200 mg/kg at 5 hr after bromobenzene administration significantly protected the liver and kidney against injuries. Plasma glutamate pyruvate transaminase and blood urea nitrogen levels were substantially decreased in the NAM-treated animals. Histological evaluations confirmed these results. When the urinary neutral and phenolic metabolites of bromobenzene from NAM-treated and untreated hamsters were isolated and compared by GC and GC/MS, a striking result was observed in terms of O- and S-methylated thiol-containing metabolite formation. The NAM-treated animals showed approximately a 8- to 14-fold increase in the excretion of the four isomeric O- and S-methylated bromothiocatechols. These thiocatechols, which are now known to be the 3,4-series metabolites of bromobenzene, can undergo methylation at either the thiol or the hydroxyl functional group. The excretion of 3-S- and 4-S-methylated bromodihydrobenzene thiolols was also increased significantly in the NAM-treated hamster, but other neutral and phenolic metabolites were relatively unchanged. These results suggest that bromobenzene toxicity in the Syrian hamster may be associated with impaired methylation capabilities, an impairment that could be due to methionine and glutathione depletion.     

Cigarette smoking and submaximal exercise test duration in a biracial population of young adults: the CARDIA study

Symptom-limited, graded exercise treadmill testing was performed by 4,968 white and black adults, ages 18-30 yr, during the baseline examination for the Coronary Artery Risk Development in Young Adults (CARDIA) study. Compared with nonsmokers, the mean exercise test duration of smokers was 29-64 s shorter depending on race/gender group (all P < 0.001), but mean duration to heart rate 130 (beats.min-1) ranged from 20-50 s longer (P < 0.05). In each race/gender group, test duration to heart rates up to 150 was 15-35 s longer (P < 0.05) in smokers than in nonsmokers after adjustment for age, sum of skinfolds, hemoglobin, and physical activity score. The mean maximum heart rate was lower in smokers than in nonsmokers (difference ranging from 6.7 beats.min-1 in white men to 11.2 beats.min-1 lower in black women, P < 0.001), although maximum rating of perceived exertion was nearly identical in smokers and nonsmokers. Chronic smoking appears to blunt the heart rate response to exercise, so that exercise duration to submaximal heart rates is increased even though maximal performance is impaired. This may result from downloading of beta-receptors caused by smoking. Smoking status should be considered in the evaluation of physical fitness data utilizing submaximal test protocols, or else the fitness of smokers relative to nonsmokers is likely to be overestimated.     

Effect of furosemide and intravenous normal saline fluid load upon the renal resistive index in nonobstructed kidneys in children

Recent literature has shown that relative to baseline the renal resistive index remains unchanged in nonobstructed kidneys and increases in obstructed kidneys after administration of furosemide. To our knowledge the effect upon the renal resistive index of furosemide administered in conjunction with intravenous normal saline fluid load has not been reported. We evaluated the renal resistive index in 13 nonobstructed kidneys in 8 children 6 to 18 years old before and after furosemide and intravenous normal saline fluid load. The mean resistive index decreased from baseline (mean decrease was 0.06 +/- 0.06 standard deviation), with the observation of a resistive index decrease significant to p < 0.005). It appears likely that the combination of an intravenous normal saline fluid load and furosemide caused the resistive index decrease, since a decrease was not observed with furosemide alone; however, these results cannot exclude the possibility that the resistive index decrease was due to the intravenous normal saline fluid load alone. Nonetheless, these data are important since they may provide the foundation for the development of a pharmacologically challenged Doppler sonographic examination using furosemide and intravenous normal saline fluid load to evaluate better potentially obstructed kidneys.