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Biomedical subjects

P Kaiser

Publications and source records attributed to P Kaiser.

At least 37 records · Page 2Linked to original sources
PubMed2000

Development and use of monoclonal antibodies to chicken fibronectin to show that the chicken hepatocellular carcinoma cell line, LMH, constitutively expresses fibronectin.

Fibronectin (Fn) is a high molecular weight glycoprotein and acute phase reactant that contributes to a variety of cellular activities including proliferation and wound healing. Production of Fn is influenced by cytokines such as IL-1alpha, IL-6 and TNF -alpha, and in serum Fn levels can function as an indicator of sepsis and reticulo-endothelial function. Here we describe the production of a panel of mAb to chicken Fn and give evidence that a chicken hepatocellular carcinoma cell line, LMH, constitutively expresses Fn. A capture ELISA to measure chicken Fn was developed using an IgG1 mAb (AV62) as the capture Ab, and biotinylated AV63 (IgG2b) as the detecting Ab. This study identified a single commercially available mAb directed against human Fn that also recognised chicken Fn. By contrast, the anti-chicken Fn mAbs did not cross-react with either human or bovine Fn.

Animals↗
PubMed2000

Turkey and chicken interleukin-2 cross-react in in vitro proliferation assays despite limited amino acid sequence identity.

We cloned the cDNA of turkey interleukin-2 (IL-2), initially using oligonucleotide primers based on the sequence of the chicken IL-2 gene. Compared with the only other cytokines available for comparison, the interferons (IFN), the coding regions of the turkey and chicken IL-2 genes are much less conserved (86.24% nucleotide identical and 69.93% amino acid identical). The lack of nucleotide conservation was spread across the entire length of the coding region. In comparison, the promoters of the two avian IL-2 genes shared a high degree of identity (95.71% identical over 380 nucleotides). Phylogenetic analysis shows that turkey and chicken IL-2 have diverged to a greater extent than IL-2 from closely related mammalian species. Surprisingly, considering the low level of amino acid identity, including residues known to be important in binding the IL-2 receptor in mammalian species, both turkey and chicken IL-2 cross-react in functional assays.

Amino Acid Sequence↗
PubMed2000

Cold agglutinin disease in a patient with uterine sarcoma.

Cold agglutinin disease is a rare clinical scenario. It is usually associated with infection, drug reaction, and hematologic malignancy, such as non-Hodgkin lymphoma or lymphocytic leukemia. We report a case of cold agglutinin disease in a patient with solid-tumor uterine sarcoma. Immunological dysregulation has been proposed as the pathogenesis for this disease. We also summarize recently reported cases of cold agglutinin disease, the underlying conditions, and advances in the management of cold agglutinin disease.

Adrenal Cortex Hormones↗
PubMed2000

Injuries in child care centers: gender-environment interactions.

OBJECTIVES: To examine child characteristics (age, gender) and child care center environments (socioemotional quality, physical safety) that jointly predict injuries for preschool children. METHODS: A two year prospective study of 360 preschool children, ages 2-6 years, was conducted in four urban child care centers. Composite scores for center quality and physical safety were derived from on-site observations, and injury rates were based on teacher reports. Poisson regression analyses examined age, gender, center quality, center safety, and the interactions of gender with quality and safety as predictors of injury incidence over one child year. RESULTS: Age was significantly associated with injury rates, with younger children sustaining higher rates. An interaction between gender and center quality also significantly predicted injury incidence: girls in low quality centers experienced more injuries, while girls in high quality centers sustained fewer injuries than their male peers. Finally, an interaction between gender and center safety showed that girls in high safety centers sustained more injuries than boys, while girls in low safety centers sustained fewer injuries. CONCLUSIONS: Injuries occur even in relatively safe environments, suggesting that in child care settings, the socioemotional context may contribute, along with physical safety, to the incidence of injury events. Further, gender specific differences in susceptibility to environmental influences may also affect children's vulnerability and risks of injuries. The prevention of injuries among preschool children may thus require attention to and modifications of both the physical and socioemotional environments of child care.

Age Distribution↗
PubMed2000

A second case of inv(4)pat with both recombinants in the offspring: rec dup(4q) in a girl with Wolf-Hirschhorn syndrome and rec dup(4p).

In a girl presenting with features of Wolf-Hirschhorn syndrome, cytogenetic and molecular cytogenetic analysis revealed a rearranged chromosome 4 with monosomy of the distal bands 4pter-->4p16.2 and trisomy of the distal bands 4q35.1-->4qter [rec dup(4q)] due to a large, paternal pericentric inversion. In the following two pregnancies, prenatal diagnosis showed the same imbalance in one fetus and a reverse segmental imbalance [rec dup(4p)] in the other. We discuss the recombination risk of the given inversion with respect to the size of the inverted segment and the viability of the recombinants. The high frequency of recombinants in this family and others suggests a high recurrence risk in similar cases with large pericentric inversions comprising almost entire chromosomes.

Abnormalities, Multiple↗
PubMed1999

Cyclin-dependent kinase and Cks/Suc1 interact with the proteasome in yeast to control proteolysis of M-phase targets.

Cell cycle-specific proteolysis is critical for proper execution of mitosis in all eukaryotes. Ubiquitination and subsequent proteolysis of the mitotic regulators Clb2 and Pds1 depend on the cyclosome/APC and the 26S proteasome. We report here that components of the cell cycle machinery in yeast, specifically the cell cycle regulatory cyclin-dependent kinase Cdc28 and a conserved associated protein Cks1/Suc1, interact genetically, physically, and functionally with components of the 26S proteasome. A mutation in Cdc28 (cdc28-1N) that interferes with Cks1 binding, or inactivation of Cks1 itself, confers stabilization of Clb2, the principal mitotic B-type cyclin in budding yeast. Surprisingly, Clb2-ubiquitination in vivo and in vitro is not affected by mutations in cks1, indicating that Cks1 is not essential for cyclosome/APC activity. However, mutant Cks1 proteins no longer physically interact with the proteasome, suggesting that Cks1 is required for some aspect of proteasome function during M-phase-specific proteolysis. We further provide evidence that Cks1 function is required for degradation of the anaphase inhibitor Pds1. Stabilization of Pds1 is partially responsible for the metaphase arrest phenotype of cks1 mutants because deletion of PDS1 partially relieves the metaphase block in these mutants.

Adaptor Proteins, Signal Transducing↗
PubMed1999

The epidemiology of injuries in 4 child care centers.

OBJECTIVES: (1) To describe the pattern of injury in preschool-aged children in 4 child care centers as compared with the results of other studies; (2) to compare injury rates by sex, age, and child care center; and (3) to examine environmental and child factors contributing to injury severity. DESIGN: A 2-year cohort study of 362 preschool-aged children attending 4 urban child care centers. Teachers completed standardized injury forms on the type of injury, body location, site of injury, and contributing factors. RESULTS: During the 2 years of the study, 1886 injuries were reported. The mean and median child injury rate was 6 and 4 injuries per 2000 exposure hours (equivalent to 1 full-time child care year), respectively. The majority of injuries (87%) were minor, occurred during free play (81%) and on the playground (74%), and were precipitated by child-related factors (59%), such as being pushed. Boys had significantly higher median injury rates than girls. Age-adjusted injury rates for each child care center were significantly different by center (F3 = 61, P<.001). While moderate to severe injuries were more often precipitated by combinations of child and environmental factors (chi2(4) = 20, P<.001), minor injuries were usually precipitated by child-related factors. CONCLUSIONS: Injury data from child care centers are important for identifying common risk factors for frequent or severe injury events and for designing injury prevention programs. More research is needed to identify factors contributing to injuries, such as children's behavior and the child care centers' physical and socioemotional environments.

Age Distribution↗
PubMed1999

Promoter sequence, exon:intron structure, and synteny of genetic location show that a chicken cytokine with T-cell proliferative activity is IL2 and not IL15.

The gene encoding a chicken cytokine with T-cell proliferative activity was cloned, sequenced, and mapped. The results show that this cytokine is chicken IL2 and not IL15. The exon:intron structure of chicken IL2 corresponds almost exactly to those of mammalian IL2s with the exceptions of exon 2 and introns 2 and 3 which are shorter. Chicken IL2 contains five repeats of the "instability" motif ATTTA in the 3'untranslated region in exon 4. It is a single-copy gene, with neither structural (amino acid) nor promoter sequence polymorphisms identified. Analysis of the predicted amino acid sequence suggests that overall protein structure is conserved, but the receptor binding sites are not. A number of potential regulatory sequences similar to those found in mammals have been identified in the promoter. These include (5'-3') a composite NF-AT/ "AP-1" element, a CD28 response element, an AP-1 element, an NF-AT element, and the AP-1 part of an AP-1/octamer composite element. The mammalian NF-kappaB and octamer binding sites seem to be absent, although there are alternative potential NF-kappaB and octamer-binding elements in the chicken IL2 promoter, in close proximity to their mammalian homologues. Sequence comparisons also predict other potential transcription factor binding sites as yet undescribed in mammalian IL2 promoters. A Taq I polymorphism was identified which enabled chicken IL2 to be mapped to chromosome 4, linked to ANX5, with synteny with mouse chromosome 3 and human chromosome 4. This is the first non-mammalian cytokine gene to be mapped.

Amino Acid Sequence↗
PubMed1999

The chicken 9E3/CEF4 CXC chemokine is the avian orthologue of IL8 and maps to chicken chromosome 4 syntenic with genes flanking the mammalian chemokine cluster.

The gene encoding the chicken chemokine 9E3/CEF4 was cloned, sequenced, and mapped; 9E3/CEF4 was the first nonmammalian cytokine cDNA to be cloned and has significant amino acid identity with both human IL8 and human GROalpha. These results show that this cytokine is chicken IL8 and not GROalpha. The exon:intron structure of chicken IL8 corresponds almost exactly to that of human IL8 and differs from those of other known mammalian CXC chemokine genes. Analysis of the predicted amino acid sequence suggests that overall protein structure is conserved between human and chicken IL8, but that the receptor binding sites are not. Genetic distance analysis also suggests that this gene encodes chicken IL8. A number of potential regulatory sequences similar to those found in human IL8 have been identified in the promoter. These include (5'-3') a hepatocyte NF-1 binding site, an NF-kappaB binding site, and a TATAAA box. The human AP-1 binding site and CCAT box are poorly conserved in the promoter of the chicken gene, but there are other potential AP-1 binding sites and a potential CCAT box. The human IRF-1 and octamer binding sites seem to be absent. However, the chicken gene promoter contains a GATA motif not present in the promoter of human IL8. Sequence comparisons also identify conserved regions in the promoter that may function as transcription factor binding sites as yet undescribed in the human IL8 promoter. Promoter sequence polymorphisms have been identified in chicken lines C and 61, but neither lie in any of the regulatory regions mentioned above. Chicken IL8 contains nine repeats of the "instability" motif ATTTA in the 3' untranslated region (UTR) in exon 4. A multiple restriction single-stranded conformational polymorphism was identified which enabled chicken IL8 to be genetically mapped to Chromosome (Chr) 4, linked to SPP1 and ALB1, and thus showing conserved synteny with mouse Chr 5 and human Chr 4. This is the first nonmammalian chemokine gene to be genetically mapped.

Amino Acid Sequence↗
PubMed1999

[Threshold value retinopathy of prematurity. Visual outcome of 2-year-old children after cryocoagulation].

BACKGROUND: The results of the Cryo-ROP group showed that cryotherapy significantly reduces the rate of adverse morphological and functional outcome of eyes with threshold retinopathy of prematurity. Structural status and visual acuity of 48 eyes which consecutively underwent cryocoagulation in our hospital between 1990 and 1994 were examined at 2 years corrected gestational age. METHOD: Visual acuity and fundus morphology were examined by Teller acuity-cards test, retinoscopy, orthoptic status and fundus examination. A favourable grating acuity was defined as > or = 2.2 cy/degree, a favourable morphology as no pathological or mild findings at the level of the posterior pole or stage 4 a. RESULTS: Fifty-six % of cases reached a quantifiable grating acuity between 0.32 and 13.0 cy/degree, 42% reached a favourable functional outcome, and 69% of the eyes had a morphologically favourable outcome. Fifty-five % of the measurable eyes were myopic, and 29% had a high myopia > or = -6.0 D. 47% showed a heterotropia. CONCLUSIONS: Our results show a discrepancy between morphological and functional outcome. Especially for zone 1 eyes, cryocoagulation of the avascular retina does not seem to allow a favourable morphological and functional outcome.

Child, Preschool↗
PubMed1999

Mutations in the SLC3A1 gene in cystinuric patients: frequencies and identification of a novel mutation.

Cystinuria is a frequent autosomal recessive transport disorder characterized by defective renal resorption of cystine and other dibasic amino acids. Biochemically, three types of cystinuria can be defined. Here we present our results of screening for mutations in the SLC3A1 gene, which codes for a dibasic amino acid transporter protein and appears to be involved in the pathogenesis of cystinuria type I. Our study population consists of 5 Italian cystinuria type I patients and 10 cystinuric patients as yet unclassified as to clinical type. The latter were of different ethnic origin. In total, we found 13 point mutations and 8 genomic rearrangements in 15 cystinuric patients, i.e., our detection rate was 70% (23/30 chromosomes). Remarkably, in patients known to be suffering from cystinuria type I, the mutation detection rate was only 50%, whereas in patients unselected as to cystinuria type, we found 80% of mutations. Additionally, our results, as with those published in the literature, indicate a possible population specific distribution of mutations: Each of the 4 Greek patients analyzed here showed homozygosity for mutation T216M in exon 3. Analysis of a Yugoslavian patient showed homozygosity for a novel mutation, R365L, in exon 6 (nt1094G > T). Findings from molecular genetic studies, as well as physiological investigations, suggest that there are further genes that play a role in the etiology of cystinuria. Nevertheless, our results show that screening for mutations in the SLC3A1 gene can be a meaningful step toward molecular genetic diagnosis of cystinuria in patients without biochemical classification. As with cystic fibrosis, the finding of specific mutations in particular ethnic populations, suggest that the diagnostic approach should take into consideration a patient's ethnic origins.

Amino Acid Transport Systems, Basic↗
PubMed1999

Screening for mutations in the promoter and the coding region of the IGFBP1 and IGFBP3 genes in Silver-Russell syndrome patients.

In the present study we sought to identify genetic variation in genes for insulin-like growth factor binding proteins 1 and 3 (IGFBP1, IGFBP3) in 7p12-13 which through alteration of protein function or level of expression might contribute to the manifestation of Silver-Russell syndrome. Genomic DNA samples from 49 Silver-Russell syndrome (SRS) patients and from unaffected controls were investigated by single-strand conformation analysis. Overlapping polymerase chain reaction fragments covered the whole coding sequences as well as the 5' untranslated region of the IGFBP1 and IGFBP3 genes. We detected 3 new polymorphisms in the transcribed sequence of IGFBP1, one amino acid polymorphism in exon 1 of IGFBP3 and four variants in its promotor region and in intron 1. They all occurred in similar frequencies in SRS patients and in controls. Thus, paternally inherited mutations in the promoter and coding regions of IGFBP1 and IGFBP3 genes play neither a major nor a minor role in the etiology of SRS. The newly detected polymorphisms in the coding region are powerful tools for analysis of imprinting status and for detection of possible changes in the imprinting patterns of the two genes.

Alleles↗
PubMed1999

Biparental expression of IGFBP1 and IGFBP3 renders their involvement in the etiology of Silver-Russell syndrome unlikely.

Maternal uniparental disomy (UPD) of chromosome 7 has recently been reported in about 10% of Silver-Russell (SRS) patients. It can therefore be concluded that at least one gene on chromosome 7 is imprinted and mutations in this gene/these genes might contribute to the phenotype of the disease. Two genes which are involved in growth and localised in 7p12-13 are the insulin-like growth factor binding proteins 1 and 3 (IGFBP1; IGFBP3). Comparison to the mouse genome shows that the syntenic region on mouse chromosome 11 is imprinted, UPD of this region leads to deviations in growth in mice. In the present study we investigated whether the genes for IGFBP1 and IGFBP3 might be involved in the etiology of SRS: after exclusion of SRS specific mutations we could demonstrate biparental expression of both genes in lymphocytes of an SRS patient without UPD7 as well as expression in a patient with maternal UPD7. Our results as well as those from other groups show biparental expression of IGFBP1 in fetal tissues and expression of IGFBP3 in nearly every tissue during puberty and adult life. Thus, no evidence is given for an involvement of the two genes in SRS.

Abnormalities, Multiple↗
PubMed1998

Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1.

Ubiquitin-mediated proteolysis controls the abundance of many cell cycle regulatory proteins. Recent work in Saccharomyces cerevisiae suggests that a complex consisting of Cdc53, Skp1, and a third component known as an F-box protein (termed SCF) in combination with Cdc34 specifically targets regulatory proteins for degradation, and that substrate specificity is likely to be mediated by the F-box subunit. A screen for genetic interactions with a cdc34 mutation yielded MET30, which encodes an F-box protein. MET30 is an essential gene required for cell cycle progression and met30 mutations interact genetically with mutations in SCF components. Furthermore, physical interactions between Met30, Cdc53, Cdc34, and Skp1 in vivo provide evidence for an SCFMet30 complex. We demonstrate the involvement of Met30 in the degradation of the Cdk-inhibitory kinase Swe1. Swe1 is stabilized in met30 mutants and GST-Met30 pull-down experiments reveal that Met30 specifically binds Swe1 in vivo. Furthermore, extracts prepared from cdc34 or met30 mutants are defective in polyubiquitination of Swe1. Taken together, these data suggest that SCF-mediated proteolysis may contribute to the regulation of entry into mitosis. Our data, in combination with previously published results, also provide evidence for distinct SCF complexes in vivo and support the idea that their F-box subunits mediate SCF substrate specificity.

Amino Acid Sequence↗
PubMed1998

[Possibilities and risks of genetic diagnosis].

In the recent past, cytogenetic and molecular genetic methods led to an enormous increase in knowledge on genetic information. It reveals a correlation between the genetic information and the phenotype of an individual. Therefore, new starting points concerning the origin of diseases arise. A new nosology will develop. It will force researchers to emphasize more and more on the contribution of the--disturbed--genetic information system to the development of diseases. They will routinely carry out genome analyses on the following four already established levels: 1. phenotype level, 2. biochemical level, 3. chromosomal level, 4. molecular genetic level. Practicians mustn't close their mind to these new possibilities and methods: The three classical tasks of medicine--diagnosis, prevention and therapy--will be supplemented considerably by an earlier (presymptomatic) and more precise diagnosis that is furthermore independent of the organ. Moreover, there is the increasing possibility to predict the risk to develop a disease for descendants in certain partnerships more precisely and, if necessary, to diagnose prenatally. From the medical point of view, these advances are predominantly positive and to the patient's benefit. But it is pointed out that the diagnostic progress also raises new problems which were previously unknown. The answers will have to be given by society as a whole.

Chromosome Mapping↗
PubMed1998

New case of mosaic tetrasomy 9p with additional neurometabolic findings.

Tetrasomy 9p is a rare chromosomal aberration that was described in 28 previous patients. Here we report on a newborn girl who was referred for genetic evaluation because of developmental delay, hypertonicity, microcephaly, minor anomalies, and neurometabolic findings. She had an isochromosome 9p (pter --> p10 --> pter) in 32% of blood cells. The extra chromosome was not found in amniocytes. Examination of fibroblasts from different skin biopsies also showed mosaicism in this tissue. In a first biopsy from the abdominal wall, the cells (n = 50) had a normal chromosomal complement. Further analysis of fibroblasts from the left forearm showed the isochromosome 9p in 5 out of 8 mitoses. Fluorescence in situ hybridization (FISH), using a whole chromosome 9 probe, confirmed that the extra marker was 9 in origin. Molecular studies showed that the isochromosome was of maternal origin. Meiotic nondisjunction was followed by centromeric misdivision and postzygotic loss of the marker.

Centromere↗