Variability analysis of HIV-1 gp120 V3 region: IV. Distribution functions for intra- and inter-subtype amino acid hamming distances

Distribution functions for intra- and inter- HIV-1 V3-loop subtypes amino acid Hamming distances were calculated (850 V3-loop sequences from the Los Alamos HIV-1 Database (1996) were used). These functions have pronounced bell-like shape. Such shapes of the histograms for HIV-1 V3 intra- and inter-subtype distriutions are discussed to confirm the applicability of different hierarchical cluster procedures for HIV-1 V3 classification. Two-mode distribution for the subtype E could sertificate that this subtype includes two thinner taxons.     

Carbon monoxide poisoning: easy to treat but difficult to recognise

Carbon monoxide (CO) poisoning is a common medical emergency and a frequent cause of deliberate or accidental death. It can cause acute and chronic central nervous system damage which may be minimised by prompt treatment with 100% oxygen or hyperbaric oxygen therapy. However, recognition of this intoxication can be difficult. Failure to diagnose it may have disastrous effects on the patient, and other members of the household who could subsequently become intoxicated. Guidance on the correct diagnosis of this condition is provided in the light of a number of studies screening emergency room populations. Guidelines for treatment with hyperbaric oxygen therapy are also reviewed.     

Vaccine-associated polio: a case and its lessons

A case of viral transmission to the father of a newly vaccinated infant shows how the virtual disappearance of a once terrifying illness can obscure its recognition and how perplexing public health issues may arise when an invaluable vaccine is anything less than perfect.     

Effects of low density lipoprotein on cytosolic [Ca++] in cultured rat mesangial cells

BACKGROUND: Recently, a low density lipoprotein (LDL) receptor has been identified in mesangial cells. However, the nature of intracellular signals in mesangial cells after exposure to LDL is unclear. METHODS: We studied the effect of LDL on cultured rat mesangial cell [Ca++]i using spectrofluorometry. RESULTS: Addition of LDL (15 micrograms/mL) produced a rapid, transient, and dose-dependent rise in [Ca++]i within seconds, returning to baseline in 6 minutes. No further rise was observed at higher LDL concentrations. No significant rise in [Ca++]i was observed with LDL in cells placed in a Ca(++)-free medium. The [Ca++]i rise was greatly attenuated in magnitude and duration when lanthanum was used. In contrast, verapamil failed to block the LDL-induced rise in [Ca++]i. Addition of LDL did not alter production of inositol 1,4,5-triphosphate (IP3) by mesangial cells. CONCLUSIONS: Low density lipoprotein caused a transient rise in [Ca++]i in cultured rat mesangial cells. The observed rise in [Ca++]i was largely caused by influx of extracellular Ca++ through receptor-gated channels. Mobilization from intracellular stores and activation of IP3 were not involved. The rise in [Ca++]i may mediate the effects of LDL on mesangial cell function.     

Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene

BACKGROUND: To evaluate the role of kinins in the regulation of cardiovascular function, we studied the phenotype of a mouse strain with disruption of the bradykinin B2-receptor gene (Bk 2r-/-). METHODS AND RESULTS: Under basal conditions, tail-cuff blood pressure was higher in Bk2r-/- than in wild-type Bk2r+/+ and heterozygous Bk2r+/- mice (124+/-1 versus 109+/-1 and 111+/-2 mm Hg, respectively; P<.01 for both comparisons), a difference that was confirmed by measurements of intra-arterial blood pressure in unanesthetized mice. Heart weight was greater in Bk2r-/- than in Bk2r+/+ and Bk2r+/- mice (505+/-10 versus 449+/-12 and 477+/-10 mg/100 g body wt, P<.05). Chronic blockade of B2-receptors by Icatibant (50 nmol/100 g body wt twice a day S.C.) or inhibition of nitric oxide synthase by nitro-L-arginine-methyl ester (0.14 mmol/100 g body wt orally) increased the blood pressure of Bk2r+/+ to the levels of Bk2r-/- mice. Compared with the wild-type strain, both Bk2r-/- and Bk2r+/- mice showed exaggerated vasopressor responses to angiotensin II. In addition, chronic administration of an angiotensin AT1-receptor antagonist reduced the basal blood pressure of Bk2r-/- by 21+/-3 mmHg (P<.05) to the levels of Bk2r+/+. No difference was detected between strains as far as plasma renin activity and the expression of renin and AT1-receptor genes are concerned. Chronic salt loading (0.84 mmol/g chow for 15 days) increased the blood pressure of Bk2r-/- and Bk2r+/- by 34+/-3 and 14+/-6 mm Hg, respectively, whereas it was ineffective in Bk2r+/+. CONCLUSIONS: Our results suggest that a normally functioning B2-receptor is essential for the maintenance of cardiovascular homeostasis in mice. Dysfunction of the kallikrein-kinin system could contribute to increase blood pressure levels by leaving the activity of vasoconstrictor agents unbalanced.     

Virus-like, double-stranded RNAs in the parasitic protozoan Cryptosporidium parvum

We have discovered and analysed two novel, linear extrachromosomal double-stranded RNAs (dsRNAs) within oocysts of major north Amercian isolates of Cryptosporidium parvum, a parasitic protozoan that infects the gastrointestinal tract of a variety of mammals, including humans. These dsRNAs were found to reside within the cytoplasm of sporozoites, and were not detected in other species of the genus. cDNAs representing both dsRNA genomes were cloned and sequenced, 1786 and 1374 nt, and each encoded one large open reading frame (ORF). The deduced protein sequence of the larger dsRNA (L-dsRNA) had homology with viral RNA-dependent RNA polymerases (RDRP), with more similarity to polymerases from fungi than those from other protozoa. The deduced protein sequence from the smaller dsRNA (S-dsRNA) had limited similarity with mitogen-activated c-June NH2 terminal protein kinases (JNK) from mammalian cells. Attempts to visually identify or purify virus-like particles associated with the dsRNAs were unsuccessful. Sensitivity of the dsRNAs to RNase A also suggests that the dsRNAs may be unencapsidated. A RDRP activity was identified in crude extracts from C. parvum sporozoites and products of RNA polymerase activity derived in vitro were similar to the dsRNAs purified directly from the parasites.     

Lectin-induced apoptosis of tumour cells

The mechanisms of cytotoxic activity of Griffonia simplicifolia 1-B4 (GS1B4) and wheat germ agglutinin (WGA) lectins against various murine tumour cell lines were studied. Tumour cells that lack lectin-binding carbohydrates were resistant to lysis by these lectins. However, YAC-1 cells that expressed GS1B4 lectin-binding sites showed low sensitivity to lysis. To further analyse the relative importance of cell surface carbohydrates in lectin cytotoxicity, BL6-8 melanoma cells, which do not express the alpha 1,3 galactosyltransferase (alpha 1,3GT) gene and cell surface alpha-galactosyl epitopes reacting with GS1B4 lectin, were transfected with cDNA encoding alpha 1,3GT. After transfection, BL6-8 cells expressed high levels of GS1B4-binding alpha-galactosyl epitopes, but remained resistant to lysis by GS1B4 lectin, suggesting that the presence of lectin-binding epitopes, while essential, is not sufficient for tumour cell lysis and probably some intracellular mechanisms are involved in the regulation of lectin-mediated cytotoxicity. We found that the GS1B4 and WGA lectins induced apoptosis with DNA fragmentation of sensitive, but not resistant, tumour cell lines. DNA fragmentation, as well as tumour cell lysis, was blocked in the presence of the specific inhibitory sugar. To determine whether binding of the lectin to cell surface carbohydrates is sufficient to trigger tumour cell lysis, lectin-sensitive CL8-1 melanoma cells were incubated with GS1B4 lectin immobilized on agarose beads. Although these tumour cells bind to the immobilized lectin, it failed to trigger tumour cell death, suggesting that only soluble lectin is capable of tumour cell lysis and lectin internalization is probably required for their lysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

The surgical treatment of renal artery fibrodysplasia. The immediate and late results

Between November 1977 and April 1992, thirty patients carrying several forms of renal artery fibrodysplasia underwent surgical treatment. The series is composed of thirteen male and seventeen female, aged between 1 and 51 years (mean age 32). All patients had arterial hypertension, which was not relieved by medical therapy, consisting in the administration of an average of 2.9 antihypertensive drugs per patients. Bilateral renal artery lesions were diagnosed in ten patients (33.3%). The remaining twenty patients (66.6%) had unilateral lesions, one of which involved a congenital single kidney, making a total of forty renal arteries affected by the disease. Surgical procedures consisted in renal artery revascularization in thirty-one kidneys, in aneurysmectomy alone or associated with aorto-renal bypass in six cases, and in a nephrectomy as a single procedure in one case. Three kidneys were considered lost and were left untouched. There was no operative mortality. Evaluated between 1 and 173 months following the operation (mean 79 months/6.6 years) twenty-six patients (86.6%) were classified as either cured or improved. Only two patients (6.6%) did not get any improvement with the surgical treatment. Two patients whose condition after the operation was considered satisfactory were lost to follow-up. The results of this experience are compared with other series published in the international literature, as well as with the percutaneous transluminal angioplasty which has been regarded as an alternative to arterial reconstructive surgery.     

Comparative analysis of the informational merits of ergometric and functional indicators of work capacity

Informational merits of ergometric and routine functional indices (MPK, anaerobic threshold--AT, PWC170) were compared by testing performance of 20 young males with high levels of fitness. Criterion for work ability was maximum time of rowing ergometer with incremental loading and two tests with permanent load in the regions of submaximum (about 7 W/kg) and high (about 4 W/kg) loading. Ergometric indices, i.e. individual limits of relative power, were calculated from Muller's equation tlim = eb x W-a. Before, during, and after 5-20 minutes of test session gas exchange, pulse rate, and blood lactate were measured to calculate MPK, AT and PWC170, and oxygen demand fraction. Ergometric indices were found to be no less informative in evaluation of work ability than the common indices involving determination of gas exchange, PR and lactate. Ergometric and functional indices showed high correlation. It was stated that none of the indices can be equally informative regarding all types of work ability testing. Application of two-increment test and subsequent calculation using Muller's equation allows to get around the principle of uncertainty according to which none of the test can be at one and the same time used to assess power and capacity of energy systems of the skeletal muscles. Besides, ergometric tests provide reliable enough characteristics of work ability without resort to expensive and bulky equipment.     

The use of bioceramic materials and cryosurgery in the treatment of patients with the Gorlin-Goltz syndrome

Therapeutic response to treatment (vaginal and external cryotherapy, drugs) in 97 patients with chronic salpingo-oophoritis at reproductive age provides the conclusion on effectiveness of various cryotherapeutic regimens in this disease. Cryotherapy improves regional blood circulation, restores contractility of the uterine tubes.