Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Partial characterization of a Hantavirus isolated from a Clethrionomys glareolus captured in Belgium

A Hantavirus was isolated in Vero-E6 cells from lungs of a free living bank vole (Clethrionomys glareolus) captured in Turnhout, Province of Antwerp--Northern part of Belgium. With help of monoclonal antibodies the Belgian Hantavirus isolate could be clearly differentiated from Hantaan virus strain 76-118, Prospect Hill virus strain PH1 and SR11, a Hantavirus isolated from laboratory Wistar rat in Japan, but not from the nephropathia epidemica virus strain H?lln?s.     

The Effects of Afferent Stimulation on Neurons in Slices of the Medial Septal Area and Their Modulation by Biologically Active Substances in Hibernating and Awake Ground Squirrels

Evoked neuron activity in slices of the medial septal area and its modulation by neuropeptides and monoamines was studied in two groups of ground squirrels – hibernating and awake animals. Electrical stimulation of the medial forebrain bundle evoked predominantly inhibitory effects of different durations. In addition, responses were seen consisting of resetting of the phase of background volleys to the stimulus after initial inhibition; there were also small numbers of short-latency single-spike responses. All the neuropeptides tested, which had been identified from the brains of hibernating animals, induced differentiated reversible effects consisting of modulation of responses; changes in evoked activity were seen significantly more often than shifts in spontaneous activity. The effects depended on the state of the animal. Thus, peptide TSKYR increased the duration of inhibition in hibernating ground squirrels but shortened inhibition in awake animals. Peptide TSKY, which had little effect in hibernating animals, increased the duration of inhibition in awake animals. Dipeptide DY, which decreased the duration of inhibition and increased the amplitude of the activatory components of responses in hibernating ground squirrels, had little effect in awake animals. The effects of noradrenaline and serotonin correlated to a large extent with their effects on spontaneous activity. It is suggested that endogenous substances are involved in creating the conditions required for increasing the latent excitability and reactivity of septal neurons during hibernation. This allows the medial septal area to function as a sentry post, allowing the receipt of signals and urgent arousal during hibernation.     

Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure.

The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high-grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (+/- 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (+/-2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6-mo period.     

Effects of microbial metabolites on catalase activity and growth of Staphylococcus aureus 6538 P

The effects of cell extracts and supernatants ofLactobacillus spp. andCorynebacterium spp. on catalase activity and growth ofStaphylococcus aureus 6538 P were studied. Intra- and extracellular metabolites of lactobacilli and corynebacteria inhibited catalase activity ofS. aureus 6538 P. The growth ofS. aureus 6538 P decreased after incubation with lactobacillus metabolites. The inhibitory effect of intra- and extracellular metabolites of lactobacilli and corynebacteria on catalase activity ofS. aureus is a possible pathway of microbial interrelations responsible for the formation and/or development of microbial biocenoses. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 80–82, July, 2000