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Biomedical subjects

P Kaiser

Publications and source records attributed to P Kaiser.

At least 55 records · Page 3Linked to original sources

Structure of the chicken interferon-gamma gene, and comparison to mammalian homologues.

The sequence of the chicken interferon-gamma (ifn-gamma) gene was determined, one of the first non-mammalian cytokine gene structures to be elucidated. Initial genomic clones were amplified from chicken genomic DNA and were used to isolate a cosmid clone covering the entire gene for sequencing. The exon:intron structure of chicken ifn-gamma is very similar to those of its mammalian homologues, with the exception of the third intron, which is markedly shorter in the chicken. The first exon contains both 5' UTR and signal sequence and the first 22 aa of the mature protein. The remainder of the coding region lies in exons 2-4. Exon 4 also encodes the stop codon and the 3' UTR, including two possible polyadenylation signals. A number of potential regulatory sequences similar to those found in mammals have been identified, in the promoter, in each intron and in the 3' UTR. In the promoter, these include the TATAATA- and CCAT-boxes, a consensus GATA motif in the reverse orientation and a potential NF-kappa B binding site. Other regulatory elements identified in the promoters of mammalian ifn-gamma genes are absent. Internal to the gene structure, regulatory sequences identified include elements found in the DNase I hypersensitivity region of the first intron of the human ifn-gamma gene and several potential NF-kappa B binding sites. The 3' UTR contains an AT-rich sequence, including nine repeats of the 'instability' motif ATTTA. As in mammals, chicken ifn-gamma is a single copy gene. The gene is highly conserved, with no polymorphisms yet identified using either RFLP or SSCP in the coding region. However, promoter sequence polymorphisms between different inbred lines of chickens have been identified, with possible links to disease resistance.

Animals↗

Avian IFN-gamma genes: sequence analysis suggests probable cross-species reactivity among galliforms.

Little is known about the evolution of cytokines in non-mammalian systems. To address this problem, we attempted to clone the gene for interferon-gamma (IFN-gamma) from a variety of avian species using oligonucleotide primers based on the sequence of the chicken IFN-gamma gene. The coding sequence and partial intron sequences were determined for four species, namely guinea fowl, ring-necked pheasant, Japanese quail, and turkey. To obtain sequence information on the gene extremities, a modified 5' and 3' RACE protocol was used. The sequence information showed that the coding regions of the IFN-gamma gene are highly conserved among the species studied (93.5%-96.7% and 87.8%-97.6% at the nucleotide and peptide levels, respectively) and are more conserved at the amino-terminal region (exons 1 and 2) than the carboxyl-terminal (exons 3 and 4). This high degree of overall identity at the predicted primary amino acid sequence level of the protein, including the deduced IFN-gamma receptor binding motifs, suggests that IFN-gamma may be cross-reactive among these species. Phylogenetic analysis shows that the similarity of the avian IFN-gamma sequences parallels the presumed evolutionary relationships between the species.

Amino Acid Sequence↗

Molecular and cytogenetic [correction of cytogenate] analysis of an X/autosomal translocation: 45,X,dic(X;17)(p22.2;p13)

We present an unusual case of monosomy 17p13-pter and monosomy Xp22.2-pter due to a dicentric translocation chromosome X/17 in a female newborn with severe anomalies. The karyotype was identified as 45,X,dic(X;17)(p22.2;p13) by high resolution GTG banding in lymphocytes. R banding showed the translocational X-chromosome to be late replicating, and there was no spreading of X-inactivation onto the autosomal segment. Furthermore, it could be demonstrated by C banding that the X-centromere in the translocation chromosome was inactive. The results of short tandem repeat (STR) typing confirmed the partial monosomy X and 17 as well as the paternal origin of the two chromosomes X and 17 which were involved in the translocation chromosome formation. The cell stage of the structural rearrangement was consistent with paternal meiosis as well as with postzygotic mitosis. The monosomy was confirmed in lymphocytes and fibroblasts, and mosaicism was not detected.

Chromosome Banding↗

Paternally inherited deletion of CSH1 in a patient with Silver-Russell syndrome.

In a continuing study on the aetiology of Silver-Russell syndrome (SRS), we detected a patient with a heterozygous deletion in the growth hormone gene cluster (17q22-q24). The deletion of the chorionic somatomammotrophin hormone 1 (CSH1) gene was inherited from the patient's father. The patient shows typical symptoms of SRS. Though deletions of CSH1 have been reported without any phenotypic consequences, the heterozygous deletion might be involved in the aetiology of SRS in the case presented here. Apart from other observations in SRS, like maternal uniparental disomy 7, changes in the genomic region 17q22-qter might be responsible for the expression of this syndrome for at least some of the patients, leading to the heterogeneity of SRS.

Child↗

Restrictive dermopathy: report and review.

Restrictive dermopathy (RD) is a lethal autosomal recessive genodermatosis (MIM No. 275210) in which tautness of the skin causes fetal akinesia or hypokinesia deformation sequence (FADS). Polyhydramnios with reduced fetal movements is followed by premature delivery at around 31 weeks gestation. Manifestations include a tightly adherent, thin, translucent skin with prominent vessels, typical facial changes, generalized joint contractures, enlarged fontanelles, dysplasia of clavicles, respiratory insufficiency, and an enlarged placenta with short umbilical cord. Histologic abnormalities of the skin include thin dermis with paucity and hypoplasia of the appendages and abnormally arranged collagen bundles. Elastic fibers are nearly missing. The subcutaneous fat is slightly increased. These skin findings usually appear after 22 or 24 weeks of gestation, which is why prenatal diagnosis with skin biopsy may fail. This disease is easily differentiated from other congenital FADS, such as Pena-Shokeir syndrome, COFS syndrome, Parana hard-skin syndrome, etc. We report on an affected boy of consanguineous parents and 30 previous cases are reviewed.

Calcification, Physiologic↗

[Corneal topography after cataract surgery with tunnel incision on a steeper meridian in inverse and oblique astigmatism].

Scleral tunnel incision at the 12 o'clock-position for no-stitch cataract surgery can increase preexisting against-the-rule astigmatism by flattening the vertical corneal meridian. An oblique axis can change by operative induction. We investigated, in a prospective study, whether reduction of such a preoperative astigmatism could be induced by locating the tunnel incision on the steeper meridian. Eighteen eyes with senile cataract and against-the-rule or oblique astigmatism of at least 0.7 diopters were operated with a standardized 5 x 6 mm scleral tunnel incision and a 6 mm PMMA posterior chamber lens. We evaluated the astigmatism with a videokeratoscopy TMS-I preoperatively and about 6 months after the surgery. The mean corneal astigmatism was 1.8 diopters pre- and 1.5 diopters postoperatively. A reduction of keratometric astigmatism was reached in 72% of cases; 17% remained unchanged. The surgically induced astigmatism calculated by Jaffer's and Clayman's vector analysis was 0.68 diopters. The technique of scleral tunnel incision with lateral or oblique approach can reduce a preexisting against-the-rule or oblique astigmatism.

Astigmatism↗

Molecular studies in 37 Silver-Russell syndrome patients: frequency and etiology of uniparental disomy.

We report studies on the etiology of uniparental disomy (UPD) in Silver-Russell syndrome (SRS) patients. Thirty-seven SRS families were typed with short tandem repeat markers from chromosomes 2, 7, 9, 14, and 16. UPD for these chromosomes has either been described in association with growth retardation or has been observed in confined placental mosaicism, a mechanism that may result in UPD. Maternal UPD7 was detected in three SRS patients, accounting for approximately 10% of the tested SRS patients. These results agree with previously published studies. The allelic distribution in one of the three families indicates complete isodisomy, whereas allelic patterns in the other two families are consistent with partial and complete heterodisomy, respectively, suggesting that, in the latter cases, UPD originates from maternal meiosis, whereas in the first case, it seems to be of mitotic origin. STR typing for UPD of chromosomes 2, 9, 14, and 16 showed no abnormalities. Our results demonstrate the necessity of screening SRS patients for UPD7, although the effect of UPD7 cannot be correlated with the SRS phenotype as yet. An association between UPD for the other investigated chromosomes and SRS seems to be negligible.

Abnormalities, Multiple↗

Chromosomal findings in 150 couples referred for genetic counselling prior to intracytoplasmic sperm injection.

A total of 150 infertile couples underwent chromosome analysis and genetic counselling before intracytoplasmic sperm injection (ICSI). Chromosomal abnormalities, including low-level sex chromosome mosaicism, were detected in 12% of the men and an unexpectedly high 6% of the women. Chromosomal abnormalities included gonosomal mosaicism in 13 cases, Robertsonian translocations in four males, autosomal reciprocal translocations in five cases, reciprocal translocation involving a sex chromosome in one case, inversions in three cases and a marker chromosome in one male. Chromosomal variants found in 11 women and 13 men were not included in the above percentages. Couples with a chromosomal aberration in one partner received a second counselling. The different aspects of genetic counselling in these couples are discussed. In conclusion, we recommend genetic counselling and chromosomal analysis of men and women prior to ICSI therapy.

Adult↗

Characterization of the bacterial flora isolated from a pilot-scale lagoon processing swine manure.

The bacterial flora of an experimental plant that processes liquid swine manure by an aerated compartmented (multistage) lagoon system has been studied. The total flora is characterized by a larger number of oligotrophic bacteria than eutrophic ones. Each compartment displays a specific flora, different from the flora in the manure, and consisting of a complex assembly of Gram-negative and Gram-positive ubiquitous species, such as Aeromonas spp. and Pseudomonas spp., and specialized species, such as Sphingobacterium spp. and Corynebacterium spp. The fecal indicator microorganisms have been shown to disappear in the course of the processing. A significant population of nitrifying bacteria has been observed at levels up to 10(4) bacteria.mL-1.

Animal Husbandry↗

Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5.

E6-AP, a 100-kDa cellular protein, was originally identified through its interaction with the E6 protein of the oncogenic human papillomavirus types 16 and 18. The complex of E6-AP and E6 specifically interacts with p53 and mediates ubiquitination of p53 in concert with the E1 ubiquitin-activating enzyme and the E2 ubiquitin-conjugating enzyme UbcH5. Recent results suggest that E6-AP is representative of a family of putative ubiquitin-protein ligases. Members of this family are characterized by a conserved C-terminal region, termed hect domain. In this paper, we describe the isolation of two human E2s, designated as UbcH6 and UbcH7, that in addition to UbcH5 can interact with E6-AP. UbcH6 is a novel member of an evolutionally conserved subfamily of E2s that includes UbcH5 and Saccharomyces cerevisiae UBC4. Although UbcH7 does not appear to be a member of this subfamily, UbcH7 efficiently substitutes for UbcH5 in E6-AP-dependent ubiquitination. Surprisingly, UbcH6 was only weakly active in this particular assay. In addition, UbcH5 but not UbcH6 or UbcH7 efficiently interacts with the heet protein RSP5. These results indicate that E6-AP can interact with at least two species of E2 and that different hect proteins may interact with different E2s.

Amino Acid Sequence↗

Resilience and vulnerability among preschool children: family functioning, temperament, and behavior problems.

OBJECTIVE: To examine the effects of child temperament and stressful family functioning on child behavior problems among preschool children. METHOD: One hundred forty-five preschool children, aged 2 to 5 years, were evaluated by teachers, mothers, and independent observers. Teachers reported on child temperament; from these ratings, two dimensions of temperament were derived: difficult/easy and approachability. Mothers reported on two dimensions of family functioning: conflict and expressiveness. Both teachers and independent observers rated child behavior problems. RESULTS: Children with more difficult temperaments who were in high-conflict families had the most internalizing and externalizing behavior problems, while children with easy temperaments had fewer such problems, regardless of levels of family conflict. Difficult children whose families were highly expressive engaged in the most observed aggression. CONCLUSIONS: Results suggest that temperament is involved in both protective and vulnerability processes. A difficult temperament operates as a vulnerability factor for internalizing and externalizing behavior problems and observed aggression, while an easy temperament functions as a protective mechanism for these outcomes.

Child Behavior Disorders↗

The evaluation of gonosomal mosaics: lymphocyte interphase nuclei analyzed by FISH.

The reliable evaluation of chromosomal mosaics is still considered to be difficult in clinical diagnosis if aberrant metaphases are only present at low frequencies. Classical cytogenetic findings cannot significantly exclude low mosaic levels, obviously, because of the relatively low number of analyzed metaphases. To study this problem, the number of gonosomes in lymphocyte interphase nuclei was determined by FISH (fluorescence in situ hybridization) application of two satellite DNA probes. DXZI and DYZI. The results obtained with this method from lymphocytes of clinically and cytogenetically inconspicuous persons showed a high degree of reliability. The DNA probe yielded correct signals in more than 95% of the analyzed nuclei. Additionally, patients were examined who showed cytogenetically confirmed numerical gonosome aberrations. These results were compared with those obtained from the control group of inconspicuous patients and discussed with respect to the evaluation of gonosomal mosaics.

Adolescent↗

Effects of two breath-holding maneuvers on oropharyngeal swallow.

This study quantified the effects of the supraglottic maneuver (SGM) and super supraglottic maneuver (SSGM) on laryngeal and pharyngeal movements before and during swallow. Simultaneous videofluoroscopic and videoendoscopic examinations of oropharyngeal swallowing were performed in eight healthy volunteers with and without maneuvers. Data analysis compared 1) temporal relationships of oropharyngeal events, 2) airway conditions at the time of selected oropharyngeal events, and 3) biomechanical computer analysis of swallowing events. Using these maneuvers, normal subjects produced earlier cricopharyngeal opening, prolonged pharyngeal swallow, some degree of laryngeal valving before swallow, and change in extent of vertical laryngeal position before swallow. These changes are more successful and maintained longer with the SSGM than the SGM. We concluded that breath-holding maneuvers alter not only airway conditions before swallow but also both the temporal relationships and biomechanical events during oropharyngeal swallow.

Adult↗

[Duration of treatment and case cost in different inpatient psychiatric facilities in Berlin].

In this study length of stay and costs per case were examined in three different types of psychiatric hospitals: Psychiatric departments in general hospitals and psychiatric hospitals each liable to provide in-patient care for a defined catchment area, and psychiatric departments in general hospitals without such liability. Data basis were all hospital treated cases in Berlin West that are covered by general insurance. Length of stay and costs differed significantly depending on the type of psychiatric hospital as well as on diagnoses, way of referral and age of patients. Psychiatric departments with catchment area have the shortest length of stay and lowest costs per case. This is independent of age, gender, way of referral and diagnosis of the patients. Influence of each factor is quantified.

Adolescent↗

[Refractive errors and strabismus in premature infants].

AIM: We aimed to investigate the incidence of refractive errors and strabismus in premature infants relative to their individual birth weight. METHODS: We investigated 107 premature infants with birth weight < 1250 g (group A, n = 54) and > 1250 g (group B, n = 53). All children were evaluated at the ages of 6 and 24 months for their spherical equivalent and the presence of high myopia (< or = 6.0 D) and strabismus. RESULTS: At 6 months the spherical equivalent was -0.93 +/- 4.2 D in group A and 1.09 +/- 1.9 D in group B, at 24 months -0.75 +/- 5.0 D vs 1.44 +/- 1.9 D (P < 0.01). At 6 months the incidence of high myopia was 10% in group A and 0% in group B, at 2 years 12% vs 2% (P < 0.01). Low birth weight and a long period of artificial ventilation correlated with the development of high myopia. At 6 months 21% of group A and 8.5% of group B showed strabismus, at 2 years 25% vs. 8.5% (P < 0.01). CONCLUSION: Because of the increased incidence of high myopia and strabismus we recommend routine retinoscopy and orthoptic evaluation at the age of 6 months in every child weighing less than 1250 g at birth.

Birth Weight↗

Characterization of functionally independent domains in the human ubiquitin conjugating enzyme UbcH2.

UbcH2 encodes a human ubiquitin conjugating enzyme (E2) able to conjugate ubiquitin to histone H2A in an E3 independent manner in vitro, which indicates that UbcH2 directly interacts with its substrates. To identify parts of the enzyme that are capable of binding H2A, we expressed several deletion mutants of UbcH2 in E. coli and tested the ability of the affinity purified mutant proteins to ubiquitinate H2A in the presence of bacterial expressed E1 and ubiquitin. With this in vitro assay we identified a C-terminal part of UbcH2 to be important for the interaction with H2A. Transfer of this C-terminal domain to another human E2, which is unable to catalyze ubiquitination of histones, leads to a fully active hybrid human ubiquitin conjugating enzyme capable of H2A ubiquitination. These results demonstrate that UbcH2 consists of two functionally independent domains. A N-terminal core domain with ubiquitin conjugating activity, and a C-terminal domain which interacts with substrate proteins.

Base Sequence↗

Sibutramine: a novel new agent for obesity treatment.

Sibutramine is a novel new pharmacologic agent which is a specific reuptake inhibitor for norepinephrine and serotonin. Preclinical data show that sibutramine and its two metabolites reduce food intake of animals eating either high or low carbohydrate diets and of obese Zucker rats. An 8-week clinical trial showed a dose-dependent decrease on body weight. Sibutramine, 5 and 20 mg/day, produced a dose-related weight loss in obese subjects compared to placebo in an 8-week trial. In doses varying from 1 to 30 mg, sibutramine also produced a dose-dependent decrease in weight in the healthy obese population when used in 6-,8-,12-24- and 52-week trials. Although the majority of the weight loss occurred during the first 12 weeks of treatment, weight loss had not plateaued in by 24 weeks in the higher doses. Side effects were mild. This drug shows promise as an antiobesity drug.

Adolescent↗