Identification of a putative membrane-interacting domain of CTP:phosphocholine cytidylyltransferase from rat liver

A putative membrane-interacting domain of CTP:phosphocholine cytidylyltransferase (CT) was identified using two peptide-specific antibodies. One antibody (SA2) was raised against the N-terminus of CT (amino acid residues 1-17) and the other antibody (SA209) against an alpha-helical domain of the enzyme (amino acid residues 247-257). Both antibodies quantitatively immunoprecipitated CT from rat liver cytosol and showed specificity towards CT when octylglucoside extracts of rat liver cytosol were assessed by Western blot analysis. However, further experiments revealed that the antibodies had different characteristics. Whereas the antibody directed against the N-terminus of CT (SA2) did not influence CT/membrane interaction, the new antibody (SA209) against the alpha-helical domain of the enzyme interfered with this interaction. Our results provide experimental evidence that the alpha-helical domain (amino acid residues 228-287) of CT may serve as a membrane-interacting domain.     

Review of teenage health: time for a new direction

Teenagers represent a large proportion of the population and have the potential for considerable morbidity because of high smoking rates and unwanted teenage pregnancy. The government intends to reduce the incidence of this important morbidity, but there is no coherent strategy for attaining these improvements. Research in this area is limited in the United Kingdom, but research from elsewhere has clarified teenagers' attitudes. There have also been some intervention studies resulting in improvements in specific aspects of teenage health. A worrying theme which emerges from this research is of a new inverse care law. Teenagers with low self-esteem and less hope for their own future are more likely to lead lifestyles which put them at risk and are less likely to ask for advice in relation to their health or lifestyle. Thus, it may be more difficult to alter behaviour in these patients; overall population based improvements may be difficult to achieve. Teenagers' own concerns appear to be at variance with the goals dictated by government and health professionals. It is suggested that the only method of meeting the needs of teenagers and at the same time aiming to reduce morbidity in this age group is to foster an atmosphere of patient centredness in dealings with adolescent patients and for further ther research in this important health gain area.     

Importance of heart failure as a cause of death. Changing contribution to overall mortality and coronary heart disease mortality in Scotland 1979-1992

AIMS: As heart failure is a syndrome arising from another condition, such as coronary heart disease, it is rarely officially coded as the underlying cause of death regardless of the cause recorded by the physician at the time of certification. We sought to assess the true contribution of heart failure to overall mortality and coronary heart disease mortality and to examine how this contribution has changed over time. METHODS AND RESULTS: We carried out a retrospective analysis of all death certificates in Scotland between 1979 and 1992 for which heart failure was coded as the underlying or a contributory cause of death. From a total of 833622 deaths in Scotland between 1979 and 1992, heart failure was coded as the underlying cause in only 1.5% (13695), but as a contributory cause in a further 14.3% (126073). In 1979, 28.5% of male and 40.4% of female deaths attributed to coronary heart disease (coded as the underlying cause of death) also had a coding for heart failure. In 1992 these percentages had risen significantly to 34.1% and 44.8%, respectively (both P<0.001). Mortality rates for heart failure as the underlying or contributory cause of death, standardized by age and sex, fell significantly over the period studied in all ages and in both sexes: by 31% in men and 41% in women <65 years and 15.8% in men and 5.1% in women > or =65 years, respectively (P<0.01 for all changes). CONCLUSIONS: Death from heart failure is substantially underestimated by official statistics. Furthermore, one third or more of deaths currently attributed to coronary heart disease may be related to heart failure and this proportion appears to be increasing. While the absolute numbers of deaths caused by heart failure remains constant, this study is the first to show that standardized mortality rates are declining.     

Patterns of growth deficiency in rats exposed in utero to undernutrition, ethanol, or the neuroteratogen methylazoxymethanol (MAM)

Children and experimental animals exposed to ethanol (EtOH) in utero commonly have low birthweights, and many remain small at maturity. Low body weight or small stature in adulthood may reflect an inability to recover from in utero growth retardation, or it may reflect a separate, postnatal growth deficiency. In this study, daily body weights (postnatal days 1 to 60) were compared among the offspring of the following groups of Long Evans rats: dams fed liquid diet containing 35% EtOH-derived calories; their pair-fed and chow-fed controls; and dams exposed to methylazoxymethanol (MAM) in two previous studies, in which offspring exhibited reduced numbers of growth hormone releasing factor (GRF) neurons. All treatments produced a number of offspring with weight deficits beginning after birth and persisting into maturity. Three distinct patterns of growth deficiency were observed: (1) weight loss relative to controls in the first weeks of life, seen in offspring exposed to EtOH, pair feeding, or MAM on gestation day 13 (G13); (2) a delay in the onset of the prepubertal growth spurt, seen in all EtOH-exposed offspring and in G13 MAM-exposed dwarfs; and (3) failure to sustain the prepubertal growth spurt, seen only after exposure to MAM on G14. The results of this study support the view that prenatal EtOH exposure is capable of affecting postnatal growth specifically; moreover, the pattern of growth deficiency seen in EtOH-exposed offspring was distinct from that of the undernourished offspring of pair-fed dams.     

Seasonal pattern of inhibition of Ostertagia ostertagi in calves in northeast Mississippi

The composition of, and seasonal changes in, populations of gastrointestinal parasites of calves in northeast Mississippi were determined for 10 months post-weaning. After weaning on 15 October, 20 mixed breed beef steers were grazed together on a 4 ha fescue/bermudagrass pasture. From November through August of the following year, two of the calves were removed each month for necropsy and counting of gastrointestinal nematodes. Eight species of worms were found: Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Bunostomum phlebotomum, Cooperia spp., Trichostrongylus colubriformis, Oesophagostomum spp., and Trichuris ovis. During all months, Ostertagia ostertagi and Cooperia spp. combined comprised at least 89% of gastrointestinal nematode burdens. Cooperia spp. represented 92.6% of the total worm burden of calves in November but declined to about 56% in January and February. From March through August, Ostertagia ostertagi comprised at least 79% of the worms from calves. Numbers of inhibited Ostertagia ostertagi increased markedly from February to March and remained at high levels prior to resumption of development in August. The proportion of Trichostrongylus axei remained about 4% throughout the year, but the highest numbers were recorded in the summer months. Other species were minor components of the worm population. These data indicate that with respect to Ostertagia ostertagi, northeast Mississippi can be considered a summer inhibition zone.     

Breakdown of blood pressure and body fluid homeostasis in heart transplant recipients

OBJECTIVES: This study was designed to investigate disturbances in arterial blood pressure and body fluid homeostasis in stable heart transplant recipients. BACKGROUND: Hypertension and fluid retention frequently complicate heart transplantation. METHODS: Blood pressure, renal and endocrine responses to acute volume expansion were compared in 10 heart transplant recipients (57 +/- 9 years old [mean +/- SD]) 20 +/- 5 months after transplantation, 6 liver transplant recipients receiving similar doses of cyclosporine (cyclosporine control group) and 7 normal volunteers (normal control subjects). After 3 days of a constant diet containing 87 mEq/24 h of sodium, 0.154 mol/liter saline was infused at 8 ml/kg per h for 4 h. Blood pressure and plasma vasopressin, angiotensin II, aldosterone, atrial natiuretic peptide and renin activity levels were determined before and at 30, 60, 120 and 240 min during the infusion. Urine was collected at 2 and 4 h. Blood pressure, fluid balance hormones and renal function were monitored for 48 h after the infusion. RESULTS: Blood pressure did not change in the two control groups but increased in the heart transplant recipients (+15 +/- 8/8 +/- 5 mm Hg) and remained elevated for 48 h (p < or = 0.05). Urine flow and urinary sodium excretion increased abruptly in the control groups sufficient to account for elimination of 86 +/- 9% of the sodium load by 48 h; the increases were blunted (p < or = 0.05) and delayed in the heart transplant recipients, resulting in elimination of only 51 +/- 13% of the sodium load. Saline infusion suppressed vasopressin, renin activity, angiotensin II and aldosterone in the two control groups (p < or = 0.05) but not in the heart transplant recipients. Heart transplant recipients had elevated atrial natriuretic peptide levels at baseline (p < or = 0.05), but relative increases during the infusion were similar to those in both control groups. CONCLUSIONS: Blood pressure in heart transplant recipients is salt sensitive. These patients have a blunted diuretic and natriuretic response to volume expansion that may be mediated by a failure to reflexly suppress fluid regulatory hormones. These defects in blood pressure and fluid homeostasis were not seen in liver transplant recipients receiving cyclosporine and therefore cannot be attributed to cyclosporine alone. Abnormal cardiorenal neuroendocrine reflexes, secondary to cardiac denervation, may contribute to salt-sensitive hypertension and fluid retention in heart transplant recipients.     

Structural characterization of novel inositol phosphosphingolipids of Tritrichomonas foetus and Trichomonas vaginalis

Two major ethanolamine phosphate-substituted inositol phosphosphingolipids have been identified in the unsaponifiable acidic lipid fractions of Tritrichomonas foetus and Trichomonas vaginalis. The compounds were radiolabelled and purified by high-performance thin-layer chromatography followed by high-performance liquid chromatography. The structures were determined by a combination of tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR) experiments, and gas-liquid chromatography of components obtained by degradation and derivatization. Inositol in the T. foetus component was 1-linked to the phosphosphingolipid, had the phosphoethanolamine group at the 3-position and a fucosyl residue at the 4-position. The T. vaginalis component lacked the fucosyl moiety. Both organisms also produced inositol phosphosphingolipids having the same long-chain base (sphingosine or dihydrosphingosine) and the same fatty acyl distribution as the inositol diphosphate compounds. These glycosphingolipids may represent metabolic intermediates for new types of membrane anchors for surface glycopeptides or glycolipids that mediate the host-parasite relationship of these trichomonads. The MS/MS and NMR spectroscopic data should provide reference information for structural determinations of other phosphorylated inositol derivatives.