Selective employment of chemokine receptors as human immunodeficiency virus type 1 coreceptors determined by individual amino acids within the envelope V3 loop

The chemokine receptor CCR5 acts as an essential cofactor for cell entry by macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains, whereas CXCR4 acts as an essential cofactor for T-cell-line-adapted strains. We demonstrated that the specific amino acids in the V3 loop of the HIV-1 envelope protein that determine cellular tropism also regulate chemokine coreceptor preference for cell entry by the virus. Further, a strong correlation was found between HIV-1 strains classified as syncytium inducing in standard assays and those using CXCR4 as a coreceptor. These data support the hypothesis that progressive adaptation to additional coreceptors is a key molecular basis for HIV-1 phenotypic evolution in vivo.     

Metastatic parathyroid carcinoma in the MEN2A syndrome

We report a patient with a metastatic parathyroid carcinoma and medullary carcinoma of the thyroid. This patient represents a variation of the multiple endocrine neoplasia syndrome (MEN) type 2A. There was no evidence of a phaeochromocytoma. The case illustrates the difficulties that may be encountered in localising the source of PTH secretion; the patient underwent four unsuccessful exploratory operations of the neck and mediastinum before further investigations revealed a single metastatic deposit of parathyroid carcinoma involving the first thoracic vertebra. PCR amplification and sequencing of the RET oncogene from the metastatic parathyroid carcinoma and genomic DNA revealed a heterozygous mutation (Cys634Tyr) in exon 11, as has previously been described to occur in MEN 2A. In addition, loss of tumour heterozygosity was demonstrated at loci from chromosomes 1, 2, 3p, 13q and 16p. This represents the first report of a parathyroid carcinoma in a MEN2A patient, in which the multiple allelic deletions are consistent with the generalised losses observed in aggressive tumours.     

Comparison of two methods of surfactant administration and the effect on dosing-associated hypoxemia

OBJECTIVE: The purpose of our study was to test the hypothesis that surfactant dosing through a proximal sideport adapter on an endotracheal tube leads to more dosing-associated hypoxemia compared with a method of dosing that uses a double-lumen endotracheal tube. STUDY DESIGN: Using adequate sample size to compare significant changes in O2 saturation (power > 0.8, alpha < 0.05) we enrolled 36 infants with respiratory distress syndrome in this randomized trial. A 10% change in O2 saturation was considered clinically significant. Nineteen infants received 38 doses of surfactant through the sideport adapter. Seventeen infants received 31 doses of surfactant through the nonventilation lumen of a double-lumen endotracheal tube. Two main outcome measures were assessed: time-averaged O2 saturation values 30 minutes after dosing and the largest absolute fall in O2 saturation for each patient. RESULTS AND CONCLUSIONS: Time-averaged O2 saturation measures were higher in the proximal sideport group (p = 0.02), but the magnitude of difference was probably not clinically significant. No significant difference was detected between groups when we compared largest absolute drop in O2 saturation. Secondary analyses found no effect of birth weight or dose number (second vs third dose) on either outcome measure.     

Red-green colour blindness in the Tormes-Alberche Valley (Avila-Central Spain)

A population from a Central Spanish region (Tormes-Alberche Valley) has been investigated for the presence of red-green colour vision defects. A sample of 998 subjects (469 male and 529 female) was analyzed. To identify colour vision defects, Ishihara test plates were used. The red-green colour blindness percentage obtained was 4.69 +/- 0.976% for males (2.13% protan and 2.56% deutan types) and none of the females tested were found to be colour blind. These results are within the variation range of Mediterranean populations and lower than the usual frequencies among non-Mediterranean European samples.     

Antihyperglycemic activity of phenolics from Pterocarpus marsupium

Glucose levels in rats with hyperglycemia induced by streptozotocin were determined after i.p. administration of marsupsin (1), pterosupin (2), and pterostilbene (3), three important phenolic constituents of the heartwood of Pterocarpus marsupium. Marsupsin and pterostilbene significantly lowered the blood glucose level of hyperglycemic rats, and the effect was comparable to that of 1,1-dimethylbiguanide (metformin).     

BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer

BACKGROUND: To define the incidence of BRCA1 mutations among patients seen in clinics that evaluate the risk of breast cancer, we analyzed DNA samples from women seen in this setting and constructed probability tables to provide estimates of the likelihood of finding a BRCA1 mutation in individual families. METHODS: Clinical information, family histories, and blood for DNA analysis were obtained from 263 women with breast cancer. Conformation-sensitive gel electrophoresis and DNA sequencing were used to identify BRCA1 mutations. RESULTS: BRCA1 mutations were identified in 16 percent of women with a family history of breast cancer. Only 7 percent of women from families with a history of breast cancer but not ovarian cancer had BRCA1 mutations. The rates were higher among women from families with a history of both breast and ovarian cancer. Among family members, an average age of less than 55 years at the diagnosis of breast cancer, the presence of ovarian cancer, the presence of breast and ovarian cancer in the same woman, and Ashkenazi Jewish ancestry were all associated with an increased risk of detecting a BRCA1 mutation. No association was found between the presence of bilateral breast cancer or the number of breast cancers in a family and the detection of a BRCA1 mutation, or between the position of the mutation in the BRCA1 gene and the presence of ovarian cancer in a family. CONCLUSIONS: Among women with breast cancer and a family history of the disease, the percentage with BRCA1 coding-region mutations is less than the 45 percent predicted by genetic-linkage analysis. These results suggest that even in a referral clinic specializing in screening women from high-risk families, the majority of tests for BRCA1 mutations will be negative and therefore uninformative.     

Antimutagenic activity of casein against MNNG in the E. coli DNA repair host-mediated assay

The effect of caseinate and soy protein in the diet on the mutagenicity induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was assessed in-vivo and ex-vivo in the DNA-repair host-mediated assay and liquid suspension assay, respectively. Of the two proteins only casein showed a strong antimutagenic activity over the whole digestive tract, except in the stomach. It is suggested that the molecular structure of a protein determines its protective effect against mutagens: casein lacks secondary and tertiary structure so that amino acids are more readily available for interaction with the mutagen than with the amino acids in soy protein which is a globular protein.     

Expression of matrix metalloproteinases and their inhibitors in aneurysms and normal aorta

BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by degradation of collagen and elastin resulting from increases in matrix metalloproteinase (MMP) activity. Previous authors have identified isolated increases in expression of specific MMPs in AAAs, but none have compared relative levels of expression of particular MMPs to one another or to those of their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). This study proposes to quantify relative mRNA levels for interstitial collagenase (MMP-1), 72 kd type IV collagenase (MMP-2), 92 kd type IV collagenase (MMP-9), TIMP-1, and TIMP-2 in normal aorta (NA) and AAA to provide insight as to the relative importance of each in aneurysm formation. METHODS: Competitive polymerase chain reactions (PCRs) with gene-specific external standards and cDNA derived from AAAs (n = 8; mean age, 67.4 years) and NA (n = 5; mean age, 40.6 years) were used to quantify mRNA levels. Results were normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels, determined by means of competitive PCR, and compared by means of Mann-Whitney statistics. RESULTS: Significant increases in MMP mRNA expression in AAA over NA were observed for MMP-1 (3.64 versus 0.3, p = 0.007), MMP-9 (78.03 versus 3.35, p = 0.003), TIMP-1 (835.32 versus 477.2, p = 0.027), and TIMP-2 (18.09 versus 4.14, p = 0.003). The ratio of MMP to TIMP mRNA levels was higher in AAA than NA (0.135 versus 0.045, p = 0.018). CONCLUSIONS: Increases in expression of MMP-1, MMP-9, and MMP/TIMP ratios may result in increased proteolysis and matrix degradation, which characterize AAAs. MMP-9 appears to be the predominant metalloproteinase expressed in AAA, because its mRNA levels were more than 20 times and 2 times higher than those of MMP-1 and MMP-2, respectively. TIMP-1 mRNA levels were in molar excess to those of any of the metalloproteinases studied.