Absence of vitamin D deficiency in young Nigerian children

OBJECTIVE: To determine the prevalence of vitamin D deficiency in young Nigerian children residing in an area where nutritional rickets is common. Study design: A randomized cluster sample of children aged 6 to 35 months in Jos, Nigeria. RESULTS: Of 218 children evaluated, no child in the study had a 25-hydroxyvitamin D (25-OHD) concentration <10 ng/mL (the generally held definition of vitamin D deficiency). Children spent an average of 8.3 hours per day outside of the home. Twenty children (9.2%) had clinical findings of rickets. Children with clinical signs of rickets were more likely to be not currently breast fed and have significantly lower serum calcium concentrations than those without signs of rickets (9.1 vs 9.4 mg/dL, respectively, P =.01). Yet, 25-OHD levels were not significantly different between those children with clinical signs of rickets and those without such clinical signs. CONCLUSION: Vitamin D deficiency was not found in this population of young children in whom clinical rickets is common. This is consistent with the hypothesis that dietary calcium insufficiency, without preexisting vitamin D deficiency, accounts for the development of clinical rickets in Nigerian children.     

Differential activation of NAD kinase by plant calmodulin isoforms. The critical role of domain I

NAD kinase is a Ca2+/calmodulin (CaM)-dependent enzyme capable of converting cellular NAD to NADP. The enzyme purified from pea seedlings can be activated by highly conserved soybean CaM, SCaM-1, but not by the divergent soybean CaM isoform, SCaM-4 (Lee, S. H., Kim, J. C., Lee, M. S., Heo, W. D., Seo, H. Y., Yoon, H. W., Hong, J. C., Lee, S. Y., Bahk, J. D., Hwang, I., and Cho, M. J. (1995) J. Biol. Chem. 270, 21806-21812). To determine which domains were responsible for this differential activation of NAD kinase, a series of chimeric SCaMs were generated by exchanging functional domains between SCaM-4 and SCaM-1. SCaM-4111, a chimeric SCaM-1 that contains the first domain of SCaM-4, was severely impaired (only 40% of maximal) in its ability to activate NAD kinase. SCaM-1444, a chimeric SCaM-4 that contains the first domain of SCaM-1 exhibited nearly full ( approximately 70%) activation of NAD kinase. Only chimeras containing domain I of SCaM-1 produced greater than half-maximal activation of NAD kinase. To define the amino acid residue(s) in domain I that were responsible for this differential activation, seven single residue substitution mutants of SCaM-1 were generated and tested for NAD kinase activation. Among these mutants, only K30E and G40D showed greatly reduced NAD kinase activation. Also a double residue substitution mutant, K30E/G40D, containing these two mutations in combination was severely impaired in its NAD kinase-activating potential, reaching only 20% of maximal activation. Furthermore, a triple mutation, K30E/M36I/G40D, completely abolished NAD kinase activation. Thus, our data suggest that domain I of CaM plays a key role in the differential activation of NAD kinase exhibited by SCaM-1 and SCaM-4. Further, the residues Lys30 and Glu40 of SCaM-1 are critical for this function.     

Regulation of protein synthesis in ventricular myocytes by vasopressin. The role of sarcoplasmic/endoplasmic reticulum Ca2+ stores

Protein synthesis in H9c2 ventricular myocytes was subject to rapid inhibition by agents that release Ca2+ from the sarcoplasmic/endoplasmic reticulum, including thapsigargin, ionomycin, caffeine, and arginine vasopressin. Inhibitions were attributable to the suppression of translational initiation and were coupled to the mobilization of cell-associated Ca2+ and the phosphorylation of eIF2alpha. Ionomycin and thapsigargin produced relatively stringent degrees of Ca2+ mobilization that produced an endoplasmic reticulum (ER) stress response. Translational recovery was associated with the induction of ER chaperones and resistance to translational inhibition by Ca2+-mobilizing agents. Vasopressin at physiologic concentrations mobilized 60% of cell-associated Ca2+ and decreased protein synthesis by 50% within 20-30 min. The inhibition of protein synthesis was exerted through an interaction at the V1 vascular receptor, was imposed at physiologic extracellular Ca2+ concentrations, and became refractory to hormonal washout within 10 min of treatment. Inhibition was found to attenuate after 30 min, with full recovery occurring in 2 h. Translational recovery did not involve an ER stress response but rather was derived from the partial repletion of intracellular Ca2+ stores. Longer exposures to vasopressin were invariably accompanied by increased rates of protein synthesis. Translational inhibition by vasopressin, but not by Ca2+-mobilizing drugs, was both preventable and reversible by treatment with phorbol ester, which reduced the extent of Ca2+ mobilization occurring in response to the hormone. Larger and more prolonged translational inhibitions occurred after down-regulation of protein kinase C. This report provides the first compelling evidence that hormonally induced mobilization of sarcoplasmic/endoplasmic reticulum Ca2+ stores is regulatory upon mRNA translation.     

Seroepidemiology of canine leptospirosis on the island of Barbados

Previous surveillance in Barbados documented the absence of infection with Leptospira serogroup Canicola in dogs. The aim of this study was to survey the current state of canine leptospirosis in Barbados, 10 years after the last survey. Sera from 78 unwanted dogs scheduled for euthanasia and 61 dogs suspected of having acute leptospirosis were tested by microscopic agglutination (MAT) and by an ELISA method adapted for canine IgM and IgG antibodies. The seroprevalence in unwanted dogs was 62% (48/78), at an MAT titre of > or = 100. The majority of animals had low titres, suggestive of previous infection. Serogroup Autumnalis was the most common reactor (45%), followed by serogroups Icterohaemorrhagiae and Australis (each 16%) and Pomona (13%). Serogroup Ballum was uncommon in this group. The seroprevalence determined by MAT in acutely-ill dogs was 75% (46/61). The most common predominant serogroup was Icterohaemorrhagiae (36%) followed by serogroup Australis (13%), while serogroups Autumnalis and Ballum were also of little significance. Paired specimens were available from eight acutely-ill dogs. One animal was seronegative while five dogs showed evidence of seroconversion. An IgM-ELISA titre of > or = 320 was used to confirm current infection in eight of these nine animals. Previous studies in Barbados showed a higher prevalence of serogroup Icterohaemorrhagiae than of Autumnalis, but the relative frequency of these two serogroups may be changing. The high seroprevalence in dogs is of public health concern because the close contact between dogs and man may provide the link between a reservoir in the environment and susceptible humans.     

The mouse mutation sarcosinemia (sar) maps to chromosome 2 in a region homologous to human 9q33-q34

The autosomal recessive mouse mutation sarcosinemia (sar), which was discovered segregating in the progeny of a male whose premeiotic germ cells had been treated with the mutagen ethylnitrosourea, is characterized by a deficiency in sarcosine dehydrogenase activity. Using an intersubspecific cross, we mapped the sar locus to mouse chromosome 2, approximately 15-18 cM from the centromere. The genetic localization of this locus in the mouse allows the identification of a candidate region in human (9q33-q34) where the homologous disease should map.     

Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis

Intraperitoneal and intracranial inoculation of herpes simplex virus type 2 (HSV 2) into BALB/cN and C57BL/6N mice was carried out to induce experimental myelitis. The myelitis was clearly observed in C57BL/6N mice following intraperitoneal inoculation. Within 24 hours before death, the mice showed urinary and rectal incontinence and paraplegia of the hind legs. Randomly distributed, severe necrosis was demonstrated in the spinal cord, mainly at the lower cord. In BALB/cN mice the clinical symptoms were not clearly observed, as the mice died shortly after their onset. Although spinal cord necrosis was more prominent in C57BL/6N mice than BALB/cN mice, brain necrosis was only found in the latter, and not in the former. Both strains of mouse showed marked nuclear pyknosis of the nerve cells and slight nuclear pyknosis of the astrocytes in the brain where HSV 2 antigen was demonstrated immunohistochemically. The antigen was also detected in the necrotic spinal cord. In contrast, intracranial inoculation of the virus into both strains did not cause myelitis. Spinal cord necrosis was not demonstrated and virus DNA was not detected, by PCR, in spinal cord samples. In the brain, however, the virus was demonstrated by both PCR and immunohistochemistry.     

Pioneer in public health education: Roscoe Conkling Brown

In order to study the influence of ageing on the hormonal function of the endothelium in man, plasma endothelin levels were measured in 11 normal young persons (mean aged 25.7 +/- 1.8 years) and in 16 apparently healthy elderly subjects (mean 87.5 +/- 5.4 years) without anamnestic or clinical signs of symptomatic atherosclerosis. The mean plasma level +/- SD of endothelin was 2.72 +/- 0.61 pg/ml in elderly subjects and 2.09 +/- 0.66 in young subjects. The difference was statistically significant (p < 0.05). Various humoral or local age-related environmental factors may be responsible for this result. In particular increased vascular production of endothelin may be the response to endothelial cell damage caused by an asymptomatic atherosclerotic process. Studies still need to define whether enhanced plasma endothelin levels in elderly subjects not suffering from symptomatic atherosclerosis are the consequence of ageing alone or an ongoing but clinically silent atherosclerotic process.