Mechanism of Ba(2+) block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues.

1. The block of the IRK1/Kir2.1 inwardly rectifying K+ channel by a Ba(2+) ion is highly voltage dependent, where the ion binds approximately half-way within the membrane electrical field. The mechanism by which two distinct mutations, E125N and T141A, affect Ba(2+) block of Kir2.1 was investigated using heterologous expression in Xenopus oocytes. 2. Analysis of the blocking kinetics showed that E125 and T141 affect the entry and binding of Ba(2+) to the channel, respectively. Replacing the glutamate at position 125 with an asparagine greatly decreased the rate at which the Ba(2+) ions enter and leave the pore. In contrast, replacing the polar threonine at position 141 with an alanine affected the entry rate of the Ba(2+) ions while leaving the exit rate unchanged. 3. Acidification of the extracellular solution slowed the exit rate of the Ba(2+) from the wild-type channel, but had no such effect on the Kir2.1(E125N) mutant. 4. These results thus reveal two unique roles for the amino acids at positions 125 and 141 in aiding the interaction of Ba(2+) with the channel. Their possible roles in K+ permeation are discussed.

Computerized system to enhance the clinical diagnosis of pigmented cutaneous malignancies.

BACKGROUND: An increase in the incidence of cutaneous malignant melanoma in recent years has not been accompanied by satisfactory progress in diagnostic methods. This study was carried out to evaluate a specially designed computerized image analysis system, called Derma Vision, to aid in the differentiation between malignant and benign cutaneous pigmented lesions. METHODS: Seventy-one lesions were photographed with a digital camera and the data were analyzed by the Derma Vision system. The system assessed the variation of hues in each image, calculated the mean standard deviation of the hues, and produced a value that expressed the range of hues in the lesion. The lesions were then excised and examined histologically. The computer-assisted clinical diagnosis was correlated with the histologic diagnosis to determine the accuracy of the former. RESULTS: Derma Vision predicted the malignant character of a lesion with 92% precision, compared with 87% accuracy based only on the clinical features. CONCLUSIONS: This simple, inexpensive device can boost the accuracy of clinical diagnosis and provide a useful tool to the physician faced increasingly with having to determine whether pigmented lesions are malignant or benign.

Congenital contractural arachnodactyly in two double second cousins: possible homozygosity.

A Bedouin family with two girls affected by severe congenital contractural arachnodactyly (CCA) is described. The girls were double second cousins. One of the girls also had ambiguous genitalia, an anomaly not generally associated with this disorder. The two children were both the product of first-cousin Bedouin parents from the same family. It is possible that both sets of parents were heterozygous for CCA; thus the infants may have been homozygous for CCA, which is usually an autosomal dominant condition. No instance of homozygous CCA has previously been reported. This family suggests genetic heterogeneity in CCA and that, in some rare families, the mode of inheritance may be autosomal recessive.

Umbilical ascorbic acid levels in fetal distress.

Umbilical arterial and venous blood samples were obtained at birth immediately after clamping the cord in 38 infants. Simultaneously, maternal arterial samples were collected. Arterial blood samples were analyzed for acid-base blood gas content and venous blood samples were analyzed for plasma ascorbic acid levels. The umbilical plasma ascorbic acid level was significantly higher when compared with maternal plasma levels (172.9 +/- 39.2 vs. 57.8 +/- 21.0 mumol/liter, p < 0.0001). Correlations between maternal ascorbic acid levels and umbilical cord levels proved to be insignificant. Umbilical ascorbic acid levels in the 2 groups of infants characterized by the presence or absence of fetal distress showed significantly higher levels in the fetal distressed group (17 infants) when compared to the non-distressed group (21 infants)--191.9 +/- 36.0 vs. 157.4 +/- 34.6 mumol/liter, p < 0.005. The use of an umbilical cord ascorbic acid cut-off point of 95.8 mumol/liter gave a sensitivity of 76% and a specificity of 67% as predictors for the presence or absence of fetal distress (p < 0.025). The results of the present study demonstrate a substantial increase in ascorbic acid levels in infants exposed to intrapartum fetal distress, without any clinical sign of such insult at or after birth.

Platelet counts in maternal and umbilical venous blood at the time of delivery.

Platelet count in 38 paired maternal venous and umbilical venous specimens were determined at delivery. Umbilical values were significantly higher than simultaneous maternal values (p = 0.004), and a significant relationship was demonstrated between umbilical values and maternal values (r = 0.54, p = 0.0004). Associations between platelet counts and acid-base variables were found to be insignificant in the mother and the umbilical cord.

Heredofamilial syndrome of mesodermal hamartomas, macrocephaly, and pseudopapilledema.

A 4 1/2-year-old boy with macrocephaly, pseudopapilledema, lipoangiomatosis, macropenia, and spotted pigmentations of the glans is reported. Lipoid masses were found in the subcutaneous tissue, tonsils, and probably the left lung. Some of these findings are consistent with features already reported by Riley and Smith, later by Bannayan, and recently by Ruvalcaba et al. We propose to unify the features of this syndrome and name it macrocephaly, hamartomas, and papilledema syndrome. The inheritance in our described case seems to be autosomal dominant.

The caprine arthritis-encephalitis virus is a distinct virus within the Lentivirus group.

The genetic relatedness among viral genomes of caprine arthritis-encephalitis virus, visna virus, and progressive pneumonia virus, was determined. Whereas the genomic RNAs of two strains of visna virus are indistinguishable as reflected both by their annealing kinetics as well as by the thermal stability of the hybrids, the caprine arthritis-encephalitis virus and visna virus have only 30% of their nucleic acid sequences in common. Furthermore, within the homologous regions of the two viral genomes, there is a significant level (approximately 10%) of mismatched base pairs. This limited homology that exists between caprine arthritis-encephalitis virus and visna virus was lower than the sequence homology observed between the genomes of visna virus and progressive pneumonia virus, or between the genomes of caprine arthritis-encephalitis virus and progressive pneumonia virus. All this indicates that caprine arthritis-encephalitis virus is an additional distinct member of the Lentivirus group of the Retroviridae family.