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Biomedical subjects

A Read

Publications and source records attributed to A Read.

At least 37 records · Page 2Linked to original sources
PubMed1995

Hearing loss and pigmentary disturbances in Waardenburg syndrome with reference to WS type II.

Thirty families in which there were 149 individuals affected by the Waardenburg syndrome (WS) were investigated for penetrance of hearing loss and pigmentary abnormalities. Twenty two families contained 89 individuals affected by WS Type II and eight families with 60 individuals affected by Type I. A bilateral symmetrical sensorineural hearing loss was found to be the most common type of hearing loss. The most frequent degree of hearing loss category was a hearing loss of > 100dB HL with no difference between syndrome types. Although there was no significant difference in the frequency of pigmentation disorders between Type I and II, considering these abnormalities as a whole, heterochromia irides was more common in Type II than Type I and other pigmentation disorders were more frequent in Type I: 62 per cent of Type I patients had more than one pigmentary defect, but only 28 per cent of Type II. Pigmentary disturbances were not significantly more frequent in the hearing impaired group than in the normally hearing group in either Type I or II when taking into account the occurrence of only one pigmentation disorder. There was a significantly higher proportion of pigmentary defects in the hearing impaired group with Type I when only those having more than one pigmentary abnormality were compared: 93.3 per cent of Type I patients and 88.5 per cent of Type II patients with a profound hearing loss had pigmentary defects. The frequency of pigmentation disorders was not greater when the hearing loss was more severe in either type. Penetrance for hearing loss and pigmentary abnormalities showed marked intrafamilial and interfamilial variation.

Adolescent↗
PubMed1994

Molecular basis of splotch and Waardenburg Pax-3 mutations.

Pax genes control certain aspects of development, as mutations result in (semi)dominant defects apparent during embryogenesis. Pax-3 has been associated with the mouse mutant splotch (Sp) and the human Waardenburg syndrome type 1 (WS1). We have examined the molecular basis of splotch and WS1 by studying the effect of mutations on DNA binding, using a defined target sequence. Pax-3 contains two different types of functional DNA-binding domains, a paired domain and a homeodomain. Mutational analysis of Pax-3 reveals different modes of DNA binding depending on the presence of these domains. A segment of Pax-3 located between the two DNA-binding domains, including a conserved octapeptide, participates in protein homodimerization. Pax-3 mutations found in splotch alleles and WS1 individuals change DNA binding and, in the case of a protein product of the Sp allele, dimerization. These findings were taken as a basis to define the molecular nature of the mutants.

Animals↗
PubMed1994

Refining the genetic map for the region flanking the X-linked hypophosphataemic rickets locus (Xp22.1-22.2).

We have screened fourteen kindreds with X-linked hypophosphataemic rickets with four microsatellite markers, viz AFM163yh2, DXS999 (AFM234yf12), DXS443 and DXS365, in order to refine the genetic map flanking the gene, and to define a close flanking interval for the construction of a yeast artificial chromosome (YAC) and cosmid contig. The genetic data were enhanced after the isolation of a large 1.2-megabase YAC derived from AFM163yh2, in which marker DXS274 was present but not DXS365 or DXS443. Against HYP, DXS365, AFM163yh2 and DXS443 showed no recombinants (Zmax = 18.1, Zmax = 9.9, and Zmax = 16.0 respectively). DXS999 gave Zmax = 9.6 at 4% recombination and lies distal to HYP but proximal to DXS197 and DXS43. The disease gene and markers AFM163yh2 and DXS365 are flanked by DXS443 and DXS274. Combining the genetic and physical data, we are able to propose the following gene marker order: Xptel-DXS43-DXS197-DXS999-DXS443-[(DXS3 65-AFM163yh2), HYP]-DXS274-DXS41-Xcen.

Base Sequence↗
PubMed1994

Fine structure mapping of the human X-linked hypophosphatemic rickets gene locus.

X-linked hypophosphatemic rickets (HYP) is an X-linked dominant disorder characterized by decreased renal tubular phosphate reabsorption and consequent hypophosphatemia. Renal cross-transplantation studies in Hyp mice indicate that the disorder is secondary to the elaboration of an as yet unidentified humoral factor. A full understanding of the pathophysiology of the disease and the nature of this factor will be facilitated by identification of the HYP gene. Efforts to isolate the HYP gene have been deterred by limited precision in the map of the Xp22.1 region and the consequent distance between DXS365 and DXS274, the previously discovered flanking markers for the HYP gene. To map the HYP region precisely, HYP family resources from two groups of investigators were combined, and several newly available microsatellite repeat probes were tested for linkage to HYP. Our data indicate that DXS365, DXS3424, DXS443, DXS1052, DXS274, and DXS1683 are tightly linked to the HYP gene and suggest a locus order of: Xtel-DXS315-(GLR/DXS43)-DXS257-(DXS443+ ++-DXS3424)-DXS365-HYP-DXS1683-DXS1052-DXS 274-(DXS41/DXS92)-DXS451-Xcen. The HYP gene is located in the 350- to 650-kilobase region between DXS365 and DXS1683. These results will provide a basis for the isolation of candidate genes from the region.

Base Sequence↗
PubMed1993

True telomeric translocation in a baby with the Prader-Willi phenotype.

We report on a baby with a nonreciprocal de novo unbalanced translocation between chromosomes 12 and 15. Her karyotype was 45,XX, -12, -15, +der(12)t(12;15)(pter-->qter::q13-->qter). The paternal origin of the 15q11-13 region was shown by DNA marker studies and, consistent with this, the baby had the Prader-Willi (PWS) phenotype. The breakpoint on 12q was distal to D12S11 (lambda MS43) which maps to 12q24.3-qter. Fluorescent in situ hybridization using the oligonucleotides (TTAGGG)7 and (AATCCC)7 showed that the 12q telomere was still present within the translocated chromosome. Thus, the translocation was within or onto the end of the telomere of 12q. This unusual translocation is further evidence of an unexplained instability of the 15q11-13 region.

Chromosome Banding↗
PubMed1993

New markers for linkage analysis of X-linked hypophosphataemic rickets.

Three polymorphic markers have been used to improve the genetic map of the region Xp22.1-p22.2, which contains the HYP (hypophosphataemic rickets) locus. DXS365 gave no recombinants with HYP, with a peak Lod score of 5.4 at theta = 0.0. A microsatellite marker mPA274 was derived for the DXS274 locus; it detects five alleles with a polymorphism information content of 0.55. Combining information from this microsatellite and the original DXS274 marker, probe CRI-L1391, the peak Lod score for DXS274 against HYP was 9.6 at theta = 0.02. A microsatellite associated with the DXS207 locus (mPA207) gave a peak lod score against HYP of 4.7 at theta = 0.14. A consideration of key recombinants and multilocus analysis suggests the gene order. Xpter-DXS207-DXS43-DXS197-(DXS365,HYP)- DXS274-DXS41-Xcen.

Base Sequence↗
PubMed1993

Immunogenicity of two recombinant hepatitis B vaccines in older individuals.

PURPOSE: Currently available hepatitis B vaccines are recombinant, yeast-derived preparations given in 10-micrograms or 20-micrograms doses. The optimum dose remains controversial. We sought to assess the relative immunogenicity of two hepatitis B vaccines, given in different doses, in older individuals. PATIENTS AND METHODS: In a multicenter, double-blind, randomized clinical trial, a total of 460 healthy subjects between 39 and 70 years of age were screened and immunized with either Engerix-B 20 micrograms or Recombivax HB 10 micrograms in standard, intramuscular, 3-dose regimens. Of these, 397 subjects were eligible to continue vaccination. Immunogenicity was measured by determination of antibody to hepatitis B surface antigen (anti-HBs). Seroconversion and seroprotection rates, and geometric mean titers of anti-HBs were calculated at 1, 3, 6, and 8 months after the initial dose of vaccine. RESULTS: Seroprotection rates for subjects receiving the 20-micrograms dose of vaccine were slightly, but not significantly, greater than for subjects receiving the 10-micrograms dose, at each time point. However, at 3 months, males receiving the higher dose had significantly higher seroprotection rates than males receiving the lower dose: 63% versus 37% (p < 0.001). At 8 months, geometric mean titers for the group receiving Engerix-B 20 micrograms were significantly greater than that for the group receiving Recombivax HB 10 micrograms: 840 mIU/mL versus 340 mIU/mL (p = 0.001). CONCLUSIONS: Immunization with the 20-micrograms dose of recombinant hepatitis B virus vaccine appeared to result in more rapid development of seroprotective anti-HBs titers in older men and in higher titers of anti-HBs at the completion of vaccination when compared to the 10-micrograms dose. The latter data suggest that the 20-micrograms dose may result in a longer duration of seroprotective anti-HBs titers.

Adult↗
PubMed1993

Helicobacter pylori infection in elderly people: correlation between histology and serology.

A hundred elderly dyspeptic patients were studied to assess the prevalence of Helicobacter pylori infection and the correlation between histological and serological findings. Eighty-one per cent of the patients with gastritis and 63% with gastric ulcer were H. pylori positive. All patients who had H. pylori negative gastritis and gastric ulcers were on nonsteroidal anti-inflammatory drugs (NSAIDs). There were 24 patients who had evidence of H. pylori infection and were on NSAIDs. H. pylori positive patients had more dyspeptic symptoms in comparison with those who were H. pylori negative. In patients who were taking NSAIDs, the presence of severe active gastritis seemed to correlate with the presence of H. pylori but not with the use of NSAIDs. Serology had a sensitivity of 90% and a specificity of 93% with a negative predictive value of 86%. There was a significant correlation between IgG titre and the degree of inflammation and H. pylori infection. We conclude that H. pylori gastritis is the commonest histopathological finding in elderly dyspeptic patients. H. pylori infection may be an important risk factor in elderly patients who take NSAIDs, increasing their risk of gastric ulcer. H. pylori serology in elderly people has a high sensitivity and specificity comparable with those in young age groups.

Aged↗
PubMed1993

Role of serology in monitoring treatment for Helicobacter pylori infection in elderly patients.

Fifteen elderly patients with type B gastritis caused by Helicobacter pylori infection were treated with triple therapy consisting of colloidal bismuth subcitrate, amoxycillin and metronidazole. All were followed up every 6 weeks for 3 months. After triple therapy, eradication of the infection was confirmed in 12 patients (85%) by histology and bacteriology. In this group, a significant reduction in IgG antibody levels against H. pylori was detected (p < 0.001). In a control group of 15 patients with type B gastritis who received no antibacterial treatment, the specific IgG antibody titre remained unchanged during 3 months of follow-up. We conclude that this simple and noninvasive serological test would be suitable for follow-up after treatment of H. pylori infection in elderly patients.

Aged↗
PubMed1993

Percutaneous endoscopic gastrostomy: the Heidelberg Repatriation Hospital experience.

Percutaneous endoscopic gastrostomy (PEG) was performed on 32 patients (mean age 75 years) who were dysphagic but enteral alimentation was possible. Seventeen patients were recovering from a stroke; the interval between the onset of stroke and PEG averaged 44 days. The procedure was successful and well tolerated by 16 of these 17 patients. Ten patients (31%) still had a functioning PEG, a median of 30 weeks after placement. Seven patients whose swallowing recovered had their tubes removed an average of 3 months after their insertion. Fifteen patients (47%) subsequently died from their underlying disease, a mean of 126 days following PEG. There were no deaths directly related to catheter placement. Percutaneous endoscopic gastrostomy is a useful alternative to surgical gastrostomy in elderly patients with long-term oral feeding problems.

Adult↗
PubMed1991

Rifampicin as cytotoxic agent for cholangiocarcinoma: preliminary report of seven cases.

Seven consecutive patients with unresectable cholangiocarcinoma of the major bile ducts, referred to one surgical department with a hepatobiliary interest, were treated by biliary decompression and with the antibiotic rifampicin in an uncontrolled preliminary study. Three patients were also given tamoxifen. Five of the seven are dead, the mean survival being 26 months (expected mean survival 8 months), and two are alive and well in May 1991, 48 and 30 months respectively from the time of presentation. A controlled study of rifampicin with and without tamoxifen is indicated in unresectable cholangiocarcinoma.

Adenoma, Bile Duct↗
PubMed1991

Colorectal polyps, diet, alcohol, and family history of colorectal cancer: a case-control study.

A case-control study was conducted in Melbourne, Australia. Cases (n = 49) were patients who had one or more histologically confirmed adenomatous polyps larger than 1 cm in diameter previously removed by endoscopy. In both the cases and the community controls (n = 727), previous diet, alcohol consumption, and family history of colorectal cancer in near relatives were investigated. The family history rate of colorectal cancer was similar in the two groups. Those with adenomatous polyps were found to have a low fiber/vegetable intake (p = 0.04); in males, there was a high intake of beef (p = 0.04), milk drinks (p = 0.01), and beer (p = 0.05). This study provides further evidence for the hypothesis that dietary factors and alcohol consumption may play a role in the development of adenomatous colorectal polyps and that these factors are similar to dietary risk factors for colorectal cancer.

Aged↗
PubMed1989

Molecular genetics in the National Health Service in Britain.

A recent report from the Departments of Health draws attention to the value of DNA diagnosis for inherited diseases and the need for planning these services in the National Health Service. There is great potential for preventive medicine, but a major immediate benefit is the newfound ability to exclude the carrier state in many people at risk and to protect fetuses from abortion when, as in most cases, they are shown to be normal by DNA tests. However, the widespread application of these new techniques requires prior evaluation and general acceptance. This will only be obtained after public debate, education of professionals and the population, and the establishment of adequate non-directive genetic counselling services. Some of the points to be considered in setting up molecular genetics laboratories are described.

Cystic Fibrosis↗
PubMed1987

Immunoglobulin lambda light chain genes in rheumatoid arthritis.

Restriction fragment length polymorphisms (RFLPs) obtained by hybridisation of an immunoglobulin lambda constant region probe to Eco RI digests of genomic deoxyribonucleic acid (DNA) obtained from rheumatoid arthritis (RA) and control subjects have been compared. Polymorphic bands of 8, 13, 18, and 23 kb (kilobases) were shown. The 8/8 genotype and 8 kb allele were increased and the 8/18 genotype and 18 kb allele decreased in the RA group. This effect was independent of HLA and Gm. These findings suggest that genes linked to the loci for the immunoglobulin lambda constant region may influence susceptibility to RA.

Arthritis, Rheumatoid↗