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Biomedical subjects

K Sperling

Publications and source records attributed to K Sperling.

At least 55 records · Page 3Linked to original sources
PubMed1996

Possible autosomal recessive inheritance of progressive hearing loss with stapes fixation.

Four sibs with progressive, bilateral conductive hearing loss are presented. Symmetrical hearing loss averaging 30-60 dB (0.125-8 kHz) became apparent between 8 and 24 years of age. Tympanotomy showed a fixed stapes either through ossified stapedius tendon or through ossified stapedius tendon or through a bony bridge from the stapes to the pyramidal eminence in all patients. After surgical removal of the bony tendon hearing was normal. Both parents, four other sibs, and all grandparents had normal hearing. This family and a further published case suggest a possibly recessive inheritance of this form of conductive hearing loss.

Adult↗
PubMed1996

Evolution of the gonosomal heterochromatin of Microtus agrestis: rapid amplification of a large, multimeric, repeat unit containing a 3.0-kb (GATA)11-positive, middle repetitive element.

The sex chromosomes of Microtus agrestis are extremely large due to the accumulation of constitutive heterochromatin. We have cloned and characterized a 2,999-bp (GATA)n-positive sequence, following HaeIII digestion, that is confined to the noncentromeric heterochromatin of the X chromosome. The cloned element exhibits an accumulation of certain oligomers, which are scattered throughout its entire length, and several copies of Chi-related sequence motifs, which are thought to be implicated in recombination. The latter might have been responsible for the extensive amplification of homologous genomic elements. The sequence has been amplified to a copy number of 1-2 x 10(4) within the genome of M. agrestis. In contrast to many satellite DNAs, which are thought to be an inevitable constituent of constitutive heterochromatin, the sequence exhibits a tissue-specific methylation pattern and is organized, not as a simple tandem array, but as a component of an extremely large, multimeric, higher-order repeat unit with a length of over 20 kb. This higher-order repeat accounts for at least 15-30% of the gonosomal heterochromatin in M. agrestis. Sequences homologous to pMAHAE2 are abundant in the genomes of all Microtus species. The copy number varies from approximately 100 per diploid genome in M. arvalis, M. oeconomus, and M. cabrerae to approximately 500 per diploid genome in M. guentheri and up to 1-2 x 10(4) in M. agrestis. Our molecular data indicate that the sequences of the pMAHAE2 family probably arose during the evolution of the common ancestor of Microtus and have subsequently been amplified extensively in the X chromosomes of M. agrestis in the phylogenetically very short period of less than 1 million years.

Animals↗
PubMed1995

Irreversible repression of DNA synthesis in Fanconi anemia cells is alleviated by the product of a novel cyclin-related gene.

Primary fibroblasts from patients with the genetic disease Fanconi anemia, which are hypersensitive to cross-linking agents, were used to screen a cDNA library for sequences involved in their abnormal cellular response to a cross-linking challenge. By using library partition and microinjection of in vitro-transcribed RNA, a cDNA clone, pSPHAR (S-phase response), which is able to correct the permanent repression of semiconservative DNA synthesis rates characteristic of these cells, was isolated. Wild-type SPHAR mRNA is expressed in all fibroblasts so far analyzed, including those of Fanconi anemia patients. Correction of the abnormal response in these cells appears therefore to be due to overexpression after cDNA transfer rather than to genetic complementation. The cDNA contains an open reading frame coding for a polypeptide of 7.5 kDa. Rabbit antiserum directed against a SPHAR peptide detects a protein of 7.9 kDa in Western blots (immunoblots) of whole-cell extracts from proliferating, but not resting, fibroblasts. The deduced amino acid sequence of SPHAR contains a motif found in the cyclins, and it is proposed that SPHAR acts within the injected cell by interfering with the cyclin-controlled maintenance of S phase. In agreement with this proposal, normal cells transfected with an antisense SPHAR expression vector have a significantly reduced rate of DNA synthesis during S phase and a prolonged G2 phase, reflecting the need for postreplicative DNA processing before entry into mitosis.

Amino Acid Sequence↗
PubMed1995

Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity.

The polymorphic arylamine N-acetyltransferase (NAT2; EC 2.3.1.5) is supposed to be a susceptibility factor for several drug side effects and certain malignancies. A group of 844 unrelated German subjects was genotyped for their acetylation type, and 563 of them were also phenotyped. Seven mutations of the NAT2 gene were evaluated by allele-specific PCR (mutation 341C to T) and PCR-RFLP for mutations at nt positions 191, 282, 481, 590, 803, and 857. From the mutation pattern eight different alleles, including the wild type coding for rapid acetylation and seven alleles coding for slow phenotype, were determined. Four hundred ninety-seven subjects had a genotype of slow acetylation (58.9%; 95% confidence limits 55.5%-62.2%). Phenotypic acetylation capacity was expressed as the ratio of 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine after caffeine intake. Some 6.7% of the cases deviated in genotype and phenotype, but sequencing DNA of these probands revealed no new mutations. Furthermore, linkage pattern of the mutations was always confirmed, as tested in 533 subjects. In vivo acetylation capacity of homozygous wild-type subjects (NAT2*4/*4) was significantly higher than in heterozygous genotypes (P = .001). All mutant alleles showed low in vivo acetylation capacities, including the previously not-yet-defined alleles *5A, *5C, and *13. Moreover, distinct slow genotypes differed significantly among each other, as reflected in lower acetylation capacity of *6A, *7B, and *13 alleles than the group of *5 alleles. The study demonstrated differential phenotypic activity of various NAT2 genes and gives a solid basis for clinical and molecular-epidemiological investigations.

Alleles↗
PubMed1994

Significant increase in trisomy 21 in Berlin nine months after the Chernobyl reactor accident: temporal correlation or causal relation?

OBJECTIVE: To assess whether the increased prevalence of trisomy 21 in West Berlin in January 1987 might have been causally related to exposure to ionising radiation as a result of the Chernobyl reactor accident or was merely a chance event. DESIGN: Analysis of monthly prevalence of trisomy 21 in West Berlin from January 1980 to December 1989. SETTING: Confines of West Berlin. RESULTS: Owing to the former "island" situation of West Berlin and its well organised health services, ascertainment of trisomy 21 was thought to be almost complete. A cluster of 12 cases occurred in January 1987 as compared with two or three expected. After exclusion of factors that might have explained the increase, including maternal age distribution, only exposure to radiation as a result of the Chernobyl reactor accident remained. In six of seven cases that could be studied cytogenetically the extra chromosome was of maternal origin, confirming that nondisjunction had occurred at about the time of conception. CONCLUSION: On the basis of two assumptions--(a) that maternal meiosis is an error prone process susceptible to exogenous factors at the time of conception; (b) that owing to the high prevalence of iodine deficiency in Berlin a large amount of iodine-131 would have been accumulated over a short period--it is concluded that the increased prevalence of trisomy 21 in West Berlin in January 1987 was causally related to a short period of exposure to ionising radiation as a result of the Chernobyl reactor accident.

Accidents↗
PubMed1994

Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK).

We have isolated the gene for human type I keratin 9 (KRT9) and localised it to chromosome 17q21. Patients with epidermolytic palmoplantar keratoderma (EPPK), an autosomal dominant skin disease, were investigated. Three KRT9 mutations, N160K, R162Q, and R162W, were identified. All the mutations are in the highly conserved coil 1A of the rod domain, thought to be important for heterodimerisation. R162W was detected in five unrelated families and affects the corresponding residue in the keratin 14 and keratin 10 genes that is also altered in cases of epidermolysis bullosa simplex and generalised epidermolytic hyperkeratosis, respectively. These findings provide further evidence that mutations in keratin genes may cause epidermolysis and hyperkeratosis and that hyperkeratosis of palms and soles may be caused by different mutations in the KRT9 gene.

Amino Acid Sequence↗
PubMed1994

PAX3 gene structure and mutations: close analogies between Waardenburg syndrome and the Splotch mouse.

The human PAX3 gene contains a paired box and a paired-type homeobox, and is believed to play a role in pattern formation in the embryo. We describe the exon-intron structure of the homeobox-containing part of PAX3, complementing earlier descriptions of the 5' part of the gene. Mutations in PAX3 have been described in patients with Type 1 Waardenburg syndrome, who have hearing loss and pigmentary abnormalities, while Splotch mice have mutations in the homologous mouse Pax-3 gene. We describe a series of patients who have previously unidentified PAX3 mutations. These include a chromosomal deletion, a splice-site mutation and an amino acid substitution which closely correspond to the molecular changes seen in the Splotch-retarded, Splotch and Splotch-delayed mouse mutants respectively. These mutations confirm that Waardenburg syndrome is produced by gene dosage effects and show that the phenotypic differences between Splotch mice and humans with Waardenburg syndrome are caused by differences in genetic background rather than different primary effects of the mutations.

Animals↗
PubMed1994

Preoperative infiltration of the surgical area enhances postoperative analgesia of a combined low-dose epidural bupivacaine and morphine regimen after upper abdominal surgery.

In a randomized, blinded trial we assessed the value of adding preoperative infiltration of the surgical area with bupivacaine to a low dose epidural regimen for postoperative pain treatment. Forty-nine patients scheduled for major upper abdominal surgery during combined thoracic epidural (bupivacaine + morphine) and general anaesthesia were studied. Postoperative analgesia was epidural bupivacaine 10 mg/hr-1 + morphine 0.2 mg/hr-1 for 72 h. The patients randomly received preoperative infiltration of the surgical area with bupivacaine 0.25%, 40 ml (group I); or no infiltration (group II). Pain was evaluated at rest, during cough and during mobilization six and eight h after start of surgery, and at 8 a.m. and 4 p.m. on the following days until 72 h after start of surgery. The sensory level of analgesia was evaluated by pin prick. We found no difference between the two groups during rest and cough. However, during mobilization group I had lower pain scores compared to group II (P < 0.05). There was a significant reduction in the need for supplemental intramuscular morphine in the treatment group compared to the control group (P < 0.05). Thus an enhanced analgesic effect was demonstrated by adding preoperative infiltration of the surgical area with local anaesthetic to a low dose epidural bupivacaine/morphine regimen after upper abdominal surgery.

Abdomen↗
PubMed1994

Postoperative Tc-scintimetry in femoral neck fracture. A prospective study of 46 cases.

13 men and 33 women with 8 undisplaced and 38 displaced fractures of the femoral neck treated with internal fixation were included in a prospective study of Tc-scintimetry performed early (1-3 weeks), as well as after 2 and 12 months. 9 fractures redisplaced and 5 had late segmental collapse. Healing complications were associated with decreased uptake in early and 2-month scintimetry, but the specificity was only 50 percent. With normal or increased uptake, uncomplicated healing of the fracture was predictable with 90-100 percent sensitivity.

Aged↗
PubMed1993

Environmental trichlorfon and cluster of congenital abnormalities.

Of 15 live births in one Hungarian village in 1989-90, 11 (73%) were affected by congenital abnormalities and 6 were twins. Of the 11, 4 had Down syndrome. Likely causes of such clusters (known teratogenic factors, familial inheritance, consanguinity) were excluded. A case-control study and environmental investigations pointed the finger of suspicion at the excessive use of trichlorfon at local fish farms. The content of this chemical was very high in fish (100 mg/kg) and several pregnant women, including all mothers of babies with Down syndrome, had consumed contaminated fish in the critical period for the congenital abnormalities observed.

Abnormalities, Drug-Induced↗
PubMed1993

Oocytes from pachytene to dictyotene can easily be analysed in neonatal rodents.

We have investigated the dynamics of meiotic prophase I in neonatal ovaries from different wild rodent species, from a laboratory strain of Mus musculus and from Mus musculus x Mus spretus F1 hybrids. We found that almost all stages of prophase I were regularly present in neonatal ovaries from these species and that their transcriptional activity can be assessed by [3H]-uridine incorporation, indicating that postnatal analysis of meiotic chromosomes and synapsis may be conducted as an alternative to the investigation of foetal ovaries.

Animals↗
PubMed1991

Frequency of trisomy 21 in Germany before and after the Chernobyl accident.

For Berlin (West) the rate of trisomy 21 among newborn and all prenatally diagnosed cases can be almost completely recorded, including the maternal age distribution. During the 9-year-period from 1980 and 1988 the average number of trisomy 21 per month was about 2, following a Poisson distribution. A significant increase (P less than 0.01) was observed in January 1987, exactly 9 months after the Chernobyl accident. In a supraregional study based on greater than 30,000 prenatal diagnoses performed in 1986, no significant effect could be observed. However, the highest rates of trisomy 21 were observed in the more heavily contaminated, southern part of Germany. The majority of these fetuses were conceived during the period of greatest radioactive exposure. The data are discussed with respect to the effect of low-dose radiation around the time of conception on the induction of non-disjunction in man.

Abnormalities, Radiation-Induced↗
PubMed1991

Routine applications of DNA fingerprinting with the oligonucleotide probe (CAC)5/(GTG)5.

The use of DNA fingerprinting with synthetic oligonucleotides is illustrated for practical applications familiar in clinical diagnostics: pre- and postnatal zygosity determination and the monitoring of bone marrow transplantation. A simple method for non-radioactive detection is described which may be interesting for many diagnostic laboratories.

Bone Marrow Transplantation↗
PubMed1990

Frequency of the delta F508 mutation and flanking marker haplotypes at the CF locus from 167 Czech families.

This study analyses distribution patterns of the delta F508 mutation of the cystic fibrosis transmembrane conductance regulator gene (CFTR) gene and the cystic fibrosis (CF)-linked marker loci MET, D7S23, D7S399, and D7S8 in a sample of 167 (116 complete) CF families from Bohemia and Moravia (Czechoslovakia). DNA typing was performed by polymerase chain reaction amplification, restriction analysis, and agarose or polyacrylamide gel electrophoresis. The frequency of the delta F508 mutation in this sample is 67% and the frequency of the B haplotype is 77.6% on CF chromosomes. Linkage disequilibrium was found between delta F508 and all markers tested.

Chromosome Deletion↗