Antiviral activity of natural and recombinant human leukocyte interferons in tobacco protoplasts

Several purified species of human leukocyte interferon, including recombinant interferons, inhibit the multiplication of tobacco mosaic virus (TMV) in tobacco protoplasts derived from various cultivars. Viral RNA accumulation was determined by dot-blot hybridization to specific cDNA probes, and virus antigen was determined serologically. Interferon apparently inhibited both TMV-RNA replication and its expression into coat protein. However, these effects were of limited duration. Maximum effect was obtained when interferon was applied to the cells either prior to inoculation or within the first hour after inoculation. Antibodies to interferon abolished its antiviral activity in protoplasts. Tobacco protoplasts were about 1000 times more responsive to interferon than the reference animal viral-cell system and showed an "antiviral state" at a ratio of 1 molecule of interferon per cell.     

Deletion of 20p 11.23----pter with normal growth hormone-releasing hormone genes

Using a molecular analysis of the DNA from a patient with a deletion of chromosome 20 [46,XX,del(20)(p 11.23)], we have excluded the growth hormone-releasing hormone (GHRH) gene from the region 20p11.23----pter. The patient had minor facial anomalies. Rieger eye anomaly, a congenital heart defect, severe failure to thrive, and a neurosecretory problem in growth hormone (GH) secretion. Since the GHRH gene was previously mapped to chromosome 20, we used molecular genetic methods to determine whether the growth abnormalities were due to the deletion of this gene. DNAs of the patient and 2 normal control subjects were analyzed by quantitative Southern blotting using a DNA probe for the GHRH gene and 2 reference DNA probes mapping to chromosome 21. The GHRH gene was found to be present in 2 copies in the patient. This indicates that the gene for GHRH maps to the region outside the patient's deletion, in 20p11.23----qter. Furthermore, our results suggest that genes other than GHRH on 20p are important for developmental steps leading to normal neurosecretory function of GH and may also be involved in generating Rieger eye anomaly. Finally, GH deficiency and Rieger eye anomaly should be sought in other patients with deletions of 20p.     

Deletion of 20p 11.23→pter with normal growth hormone-releasing hormone genes

Using a molecular analysis of the DNA from a patient with a deletion of chromosome 20 [46,XX,del(20)(p11.23)], we have excluded the growth hormone-releasing hormone (GHRH) gene from the region 20p11.23→pter. The patient had minor facial anomalies, Rieger eye anomaly, a congenital heart defect, severe failure to thrive, and a neurosecretory problem in growth hormone (GH) secretion. Since the GHRH gene was previously mapped to chromosome 20, we used molecular genetic methods to determine whether the growth abnormalities were due to the deletion of this gene. DNAs of the patient and 2 normal control subjects were analyzed by quantitative Southern blotting using a DNA probe for the GHRH gene and 2 reference DNA probes mapping to chromosome 21. The GHRH gene was found to be present in 2 copies in the patient. This indicates that the gene for GHRH maps to the region outside the patient's deletion, in 20p11.23→qter. Furthermore, our results suggest that genes other than GHRH on 20p are important for developmental steps leading to normal neurosecretory function of GH and may also be involved in generating Rieger eye anomaly. Finally, GH deficiency and Rieger eye anomaly should be sought in other patients with deletions of 20p.     

Maternal pre‐pregnancy body mass index is not associated with infant and young child feeding in low‐income Mexican children 1–24 months old

Pre‐pregnancy overweight and obesity is associated with shorter breastfeeding (BF) duration. Whether pre‐pregnancy overweight and obesity is associated with other aspects of infant and young child feeding (IYCF) has not been investigated. We used data from 370 children born January 1999–September 2001 in a semi‐urban community in Morelos, Mexico, where information on how they were fed was available at 1, 3, 6, 9, 12, 18 and 24 months of age. We modified the World Health Organization's dietary diversity indicator to assess the quality of the complementary foods. An index that included BF, quality of complementary foods and other behaviours was constructed to measure IYCF. We used survival analysis to examine the association of pre‐pregnancy body mass index (pBMI) category and BF duration and mixed models for quality of complementary food and IYCF index. Mean maternal pBMI was 24.4 ± 4.1; 31% were overweight, and 9% were obese. pBMI was not associated with BF duration. Quality of complementary food improved over time (6 months, 1.3 ± 1.3; 24 months, 3.8 ± 1.04). Compared with normal‐weight women, overweight and obese women were more likely to feed from more food groups (0.24 ± 0.11 point, P = 0.03), but this did not improve diet diversity from 6 to 24 months. IYCF index decreased throughout follow‐up (1 month, 7.8 ± 2.4; 24 months, 5.5 ± 1.8), and pBMI was not associated with IYCF (?0.11 ± 0.13 point, P = 0.4). We conclude that heavier women were not engaging in IYCF behaviours that were distinct from those of normal‐weight women from 1 to 24 months post‐partum.     

Characterization of a murine high-affinity thiamine transporter, Slc19a2

Thiamine-responsive megaloblastic anemia with deafness and diabetes (TRMA) is a rare autosomal recessive disorder of thiamine transport. Previous studies have demonstrated that the disease is caused by mutations in the SLC19A2 gene encoding a high-affinity thiamine transporter. We hypothesize that thiamine transport, mediated by SLC19A2, plays a role in the development and or maintenance of several organ systems, in particular the erythropoietic, auditory, and glucose homeostasis systems. To investigate the transporter further, we cloned the murine Slc19a2 locus and characterized the resulting protein. Murine Slc19a2 is a 498 amino acid protein, with 12 predicted transmembrane domains. The gene spans approximately 13kb with 6 exons, structurally identical to that of the human homolog. We localized the Slc19a2 gene to mouse chromosome 1, a region syntenic to human chromosome 1q23 that contains the TRMA locus. Transient expression of Slc19a2 in HEK293T cells resulted in specific uptake of [3H] thiamine, confirming a thiamine transporter function. Western blot analysis of mouse tissues reveals a wide distribution of Slc19a2 protein. Immunohistochemistry studies indicate that Slc19a2 is expressed on the cell surface and intracellularly, and is specifically localized to a subpopulation of cells in cochlea, small intestine, and pancreas.     

Pharmacologic neuroprotection with an inhibitor of nitric oxide synthase for the treatment of glaucoma

Excessive nitric oxide, generated by inducible NOS-2 in astrocytes and microglia in the optic nerve head of patients with glaucoma, may contribute to the optic neuropathy associated with the disease. A rat model of glaucoma, in which there is chronic, moderately elevated IOP and slow loss of retinal ganglion cells, has been established to study pharmacological agents that have the potential to be neuroprotective. In this model, the pharmacological use of an inhibitor of NOS-2, aminoguanidine, significantly prevents the loss of retinal ganglion cells. A well-tolerated pharmacological inhibitor of NOS-2, perhaps orally or locally delivered, is a reasonable candidate for a neuroprotective agent for treating glaucoma.     

Comparative study of proton and phosphorus magnetic resonance spectroscopy in schizophrenia at 4 Tesla

This study used high-field magnetic resonance spectroscopy to examine the correlation of 1H and 31P metabolite levels in patients with schizophrenia and normal controls. 1H and 31P in vivo spectra were acquired successively from the left anterior cingulate and left thalamus of nine chronic schizophrenic patients and eight comparable healthy controls. A significant positive correlation between glutamine (Gln) and phosphoethanolamine (PEtn) was found in the left anterior cingulate of patients. In the left thalamus of patients, a significant negative correlation between N-acetylaspartate (NAA) and glycerophosphocholine (GroPCho) was found. No significant correlations were found in controls. The correlation between glutamine and phosphoethanolamine may reflect a link between neurotransmission alterations and membrane phospholipid metabolism alterations. The negative correlation between N-acetylaspartate and glycerophosphocholine may reflect the presence of neurodegeneration.