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Biomedical subjects

D Schreiber

Publications and source records attributed to D Schreiber.

At least 19 recordsLinked to original sources
PubMed2002

Reproductive characteristics of cloned heifers derived from adult somatic cells.

This study examined the onset of puberty, follicular dynamics, reproductive hormone profiles, and ability to maintain pregnancy in cloned heifers produced by somatic cell nuclear transfer. Four adult somatic cell-cloned heifers, derived from a 13-yr-old Holstein cow, were compared to 4 individual age- and weight-matched heifers produced by artificial insemination (AI). From 7 to 9 mo of age, jugular venous blood samples were collected twice weekly, and from 10 to 11 or 12 mo of age, blood sampling was carried out every other day. After the heifers reached puberty (defined as the first of 3 consecutive blood samples with peripheral plasma progesterone concentrations of >1 ng/ml), ultrasound examination of ovaries and jugular plasma sample collection were carried out daily for 1 estrous cycle. Cloned heifers reached puberty later than controls (mean +/- SEM, 314.7 +/- 9.6 vs. 272 +/- 4.4 days and 336.7 +/- 13 vs. 302.8 +/- 4.5 kg for clones and controls, respectively; P < 0.05). However, cloned and control heifers were not different in estrous cycle length, ovulatory follicle diameter, number of follicular waves, or profiles of hormonal changes (LH, FSH, estradiol, and progesterone). Three of the 4 clones and all 4 control heifers became pregnant after AI. These results demonstrate that clones from an aged adult have normal reproductive development.

Aging↗
PubMed2000

Synthesis and biophysical analysis of transmembrane domains of a Saccharomyces cerevisiae G protein-coupled receptor.

The Ste2p receptor for alpha-factor, a tridecapeptide mating pheromone of the yeast Saccharomyces cerevisiae, belongs to the G protein-coupled family of receptors. In this paper we report on the synthesis of peptides corresponding to five of the seven transmembrane domains (M1-M5) and two homologues of the sixth transmembrane domain corresponding to the wild-type sequence and a mutant sequence found in a constitutively active receptor. The secondary structures of all new transmembrane peptides and previously synthesized peptides corresponding to domains 6 and 7 were assessed using a detailed CD analysis in trifluoroethanol, trifluoroethanol-water mixtures, sodium dodecyl sulfate micelles, and dimyristoyl phosphatidyl choline bilayers. Tryptophan fluorescence quenching experiments were used to assess the penetration of the membrane peptides into lipid bilayers. All peptides were predominantly (40-80%) helical in trifluoroethanol and most trifluoroethanol-water mixtures. In contrast, two of the peptides M3-35 (KKKNIIQVLLVASIETSLVFQIKVIFTGDNFKKKG) and M6-31 (KQFDSFHILLINleSAQSLLVPSIIFILAYSLK) formed stable beta-sheet structures in both sodium dodecyl sulfate micelles and DMPC bilayers. Polyacrylamide gel electrophoresis showed that these two peptides formed high molecular aggregates in the presence of SDS whereas all other peptides moved as monomeric species. The peptide (KKKFDSFHILLIMSAQSLLVLSIIFILAYSLKKKS) corresponding to the sequence in the constitutive mutant was predominantly helical under a variety of conditions, whereas the homologous wild-type sequence (KKKFDSFHILLIMSAQSLLVPSIIFILAYSLKKKS) retained a tendency to form beta-structures. These results demonstrate a connection between a conformational shift in secondary structure, as detected by biophysical techniques, and receptor function. The aggregation of particular transmembrane domains may also reflect a tendency for intermolecular interactions that occur in the membrane environment facilitating formation of receptor dimers or multimers.

Amino Acid Sequence↗
PubMed2000

[Monstrous benign schwannoma of the mandible. Clinical aspects, morphology and therapy].

BACKGROUND: Schwannomas are rare benign neurogenic tumors that arise from Schwann cells of the peripheral nervous system. The most frequent localisation is the head and neck area. Extracranial schwannomas are most often located in the deep soft tissues. Intraosseous tumor types are rare; the mandible is the most common site. CASE REPORT: We present the case of a 63-year-old woman with a schwannoma which originated from the mandible nerve and describe the therapy of this neoplasm. A rare malignant transformation cannot be excluded. Therefore, the treatment of choice is radical local resection.

Aged↗
PubMed2000

Developmental competence of juvenile calf oocytes in vitro and in vivo: influence of donor animal variation and repeated gonadotropin stimulation.

Juvenile calf oocytes represent an untapped source of germ plasm for reproduction. Reports on the developmental competence of calf oocytes have been controversial. In this research, oocytes were recovered after gonadotropin stimulation from Holstein calves (N = 10) at 2-3 mo of age (2-mo cycle) and again at 4-5 mo of age (4-mo cycle). The in vitro developmental competence was measured, and prestimulation follicle numbers (for 2-mo cycle) and poststimulation follicle numbers (both cycles) were obtained. The number of antral follicles doubled after stimulation (23.4 +/- 6.1 vs. 55.1 +/- 16.1) for the 2-mo cycle and for the 4-mo cycle (47.4 +/- 12.4). The number of follicles observed prior to stimulation in the 2-mo cycle was found to be highly correlated with the poststimulation oocyte recovery for both collection cycles (r = 0.95, 2-mo cycle; r = 0.81, 4-mo cycle). The majority (90-96%) of recovered oocytes were found to be usable for in vitro maturation and fertilization; of these, 41-42% cleaved and 10-11% developed to morulae or blastocysts. Eighty-four in vitro-produced embryos were transferred to synchronized recipients and resulted in 11 pregnancies, leading to 7 live (4 males, 3 females) and 2 dead (one male, one female) calves at full term. No significant differences were observed between the 2-mo and 4-mo collection cycles; however, 73% of the total pregnancies resulted from the 2-mo cycle. All pregnancies resulted from embryos of high-responding donors. The high correlation between the number of follicles prior to stimulation and the poststimulation response suggests the possibility of screening calves prior to stimulation for routine embryo production.

Aging↗
PubMed1999

Coordinate alterations in the expression of BRCA1, BRCA2, p300, and Rad51 in response to genotoxic and other stresses in human prostate cancer cells.

BACKGROUND: BRCA1 and BRCA2 participate in cell cycle progression, apoptosis, and DNA repair pathways. The latter role may be mediated by interaction with DNA recombinase Rad51. The purpose of this study was to evaluate the effects of genotoxic and other cytotoxic agents on expression of DNA damage-response genes (BRCA1, BRCA2, p300, and Rad51) in human prostate cancer cells. METHODS: Subconfluent proliferating cultures of Tsu-Prl or DU-145 cells were treated with various stressful agents and assayed 24 hr later for alterations in: 1) mRNA expression (by semiquantitative reverse transcription-PCR); 2) cell viability (by trypan blue dye exclusion); and 3) protein expression (by Western blotting). RESULTS: Of 26 agents screened, BRCA1 and BRCA2 mRNA reductions were observed in both cell lines after exposure to adriamycin (ADR), camptothecin (CPT), sodium selenite (SLN), and ultraviolet radiation (UV), while nitrogen mustard (HN2) caused mRNA reduction in DU-145 but not in Tsu-Prl. Inhibition of BRCA1/2 expression by ADR and HN2 was blocked by cycloheximide, suggesting that this requires new protein synthesis, while inhibition by CPT, SLN, and UV did not require protein synthesis. Reduction of p300 and Rad51 mRNA levels occurred in parallel with that of BRCA1/2, suggesting coordinate regulation of these genes. The ability of an agent to inhibit mRNA expression was not directly correlated with cytotoxicity. ADR, CPT, UV, and SLN also caused reduction of protein levels; but the kinetics of decreases in protein vs. mRNA differed. After ADR treatment, high molecular weight (Mr hyperphosphorylated) BRCA1 decreased more rapidly than the low Mr species. BRCA2 showed a more rapid decrease in protein than mRNA, while Rad51 showed the opposite. By 48 and 72 hr post-ADR, all four mRNAs and proteins were reduced to well below control levels, except for Rad51 protein, which was only moderately decreased. CONCLUSIONS: Selected DNA-damaging agents (ADR, CPT, and UV) and a reducing agent (SLN) inhibited BRCA1/2, p300, and Rad51 expression in prostate cancer cells, although decreases in mRNA vs. protein did not coincide. We postulate that temporal changes in relative protein levels affect different phases of the stress response, and that the ultimate downregulation of all four genes promotes prostate cancer survival.

BRCA2 Protein↗
PubMed1999

Evolutionary, mechanistic, and predictive analyses of the hydroxymethyldihydropterin pyrophosphokinase family of proteins.

A prediction has been prepared ab initio for the secondary structure of the hydroxymethyldihydropterin pyrophosphokinase (HPPK) family of proteins starting from a set of aligned homologous protein sequences. Attempts to identify a fold by threading failed, judging by the inability to find a threading "hit" that had a secondary structure that was plausibly congruent to the predicted secondary structure for the HPPK family. Therefore, a set of tertiary structure models was assembled ab initio, where alternative models were built and used to select between alternative secondary structure models. This prediction report illustrates the importance of non-computational approaches to structure prediction at its present frontier, which is to obtain medium resolution models of tertiary structure.

Amino Acid Sequence↗
PubMed1999

[Severe course of a mutilating pansclerotic circumscribed scleroderma in childhood. Clinical aspects and therapy].

Disabling pansclerotic morphea of childhood is the most severe variant of localized scleroderma. It is characterized by rapid progression of deep cutaneous fibrosis expanding over large areas of body surface. The prognosis in terms of normal life activity is poor and the disease may even take a fatal course. Presented is a case with extremely severe and rapidly progressive lesions resulting in cutaneous ulcerations joint contractures, and multilaing deformities of the extremities. Histopathological analysis revealed extensive intravascular calcinosis of the small vessels, which may be an important factor in the pathogenesis of this poorly understood disease. UVA1-phototherapy was performed and induced a softening of sclerosis and a distinct decrease of skin thickness. Based on these observations UVA1-phototherapy may be promising in the treatment of extensive sclerotic disease of this kind, and possibly other diseases accompanied by excessive sclerosis.

Adolescent↗
PubMed1999

Acute asthma among pregnant women presenting to the emergency department.

Asthma complicates up to 4% of pregnancies. Our objective was to compare emergency department (ED) visits for acute asthma among pregnant versus nonpregnant women. We performed a prospective cohort study, as part of the Multicenter Asthma Research Collaboration. ED patients who presented with acute asthma underwent a structured interview in the ED, and another by telephone 2 wk later. The study was performed at 36 EDs in 18 states. A total of 51 pregnant women and 500 nonpregnant women, age 18 to 39, were available for analysis. Pregnant women did not differ from nonpregnant women by duration of asthma symptoms (median: 0.75 versus 0.75 d, p = 0.57) or initial peak expiratory flow rate (PEFR) (51% versus 53% of predicted, p = 0.52). Despite this similarity, only 44% of pregnant women were treated with corticosteroids in the ED compared with 66% of nonpregnant women (p = 0.002). Pregnant women were equally likely to be admitted (24% versus 21%, p = 0.61) but less likely to be prescribed corticosteroids if sent home (38% versus 64%, p = 0.002). At 2-wk follow-up, pregnant women were 2.9 times more likely to report an ongoing exacerbation (95% CI, 1.2 to 6.8). Among women presenting to the ED with acute asthma, pregnant asthmatics are less likely to receive appropriate treatment with corticosteroids.

Acute Disease↗
PubMed1999

May 1999--16 year old male with an unexpected MRI finding.

Four years after resection of a supratentorial pilocytic astrocytoma this 16-year-old boy displayed widespread leptomeningeal seeding. Although the primary tumor lacked contrast enhancement, the multiple metastatic nodules were markedly contrast enhancing. Both the initial and disseminated tumor were consistent with a pilocytic astrocytoma. He was treated with vincristin and carboplatinum and the tumor was stable up to Dec. 1998. Dissemination of low-grade intracranial astrocytoma in children occurs in only 4%. It is not a sign of malignancy. The present case is similar to previously published cases. The prognosis of these patients might be quite favorable when treated with radiotherapy and/or chemotherapy.

Adolescent↗
PubMed1998

Apolipoprotein E4 promotes incipient Alzheimer pathology in the elderly.

To evaluate the influence of the apolipoprotein E (ApoE) epsilon4 allele on the age at which Alzheimer-like lesions appear in the brain, we analyzed the degree of cerebral beta-amyloidosis and neurofibrillary tangle formation in the hippocampal formation and adjacent cortical areas 28, 27, and 36 of persons who had died between the ages of 50 and 93 years and who had shown no signs of clinical dementia. The occurrence of the three common polymorphisms of the ApoE gene in this sample of 147 routine autopsy cases from eastern Germany was comparable to previously reported values in European and North American populations: ApoEepsilon2/2, 0.7%; ApoEepsilon2/3, 14.3%; ApoEepsilon2/4, 4.1%; ApoEepsilon3/3, 56.5%; ApoEepsilon3/4, 22.4%; and ApoEepsilon4/4, 2.0%. Nondemented persons carrying the ApoEepsilon4 allele were significantly more likely to have senile plaques, diffuse amyloid deposits, cerebrovascular amyloid, and neurofibrillary tangles than were those lacking E4. Comparing the two largest ApoE subgroups, ApoEepsilon3/3 and ApoEepsilon3/4, the relative increase in the occurrence of beta-amyloid in the epsilon3/4 group was evident by the mid-60s, with the relative increase in neurofibrillary tangles in this group emerging slightly earlier. The ApoEepsilon2 allele appears to delay the appearance of the lesions somewhat. We conclude that ApoEepsilon4 promotes the early appearance of beta-amyloid and neurofibrillary tangles in the elderly and that the increased frequency of these lesions is related to the higher risk of Alzheimer disease in persons bearing the ApoEepsilon4 allele.

Aged↗
PubMed1997

[Keratosis palmoplantaris maculosa seu papulosa (Davies-Colley) simulating multiple cornua cutanea].

Patient with extensive keratosis palmoplantaris maculosa seu papulosa (Davies-Colley) presented with multiple cutaneous horns. The clinical picture, the histology, the electro microscopic examination, the negative tumor screening and the viral classification in the tissue allowed the differentiation from other palmoplantar keratoses. The patient was treated successfully using a combination of acitretin with physical and chemical measures.

Callosities↗
PubMed1995

The intracellular signal transduction mechanism of interleukin 5 in eosinophils: the involvement of lyn tyrosine kinase and the Ras-Raf-1-MEK-microtubule-associated protein kinase pathway.

Interleukin 5 (IL-5) regulates the growth and function of eosinophils. The objective of this study was to investigate the intracellular signal transduction mechanism of IL-5 in eosinophils. Purified eosinophils were stimulated with IL-5, and the involvement of various kinases was investigated by immunoblotting, immune complex kinase assay, and in situ denatured/renatured kinase assay. We found that IL-5 induced tyrosine phosphorylation and activation of a number of kinases. Two species of lyn kinases (53 and 56 kD) were present in eosinophils. Both forms were Tyr-phosphorylated and activated rapidly within 1 min. Further, lyn kinase was physically associated with the IL-5 beta receptor in eosinophils. Ras was studied by immunoprecipitation followed by thin-layer chromatography. Ras bound higher quantities of [alpha-32P]guanosine 5'triphosphate upon stimulation with IL-5. Raf-1 kinase showed increased Tyr phosphorylation on immunoblotting and increased activity in the immune complex kinase assay. Two species of MEK (MAP or Erk kinase) (41 and 45 kD) were identified in eosinophils, which underwent autophosphorylation upon stimulation. Microtubule-associated protein (MAP) kinase (p44) was Tyr-phosphorylated on immunoblotting and had increased activity in the immune-complex kinase assay. MAP kinases were also studied after metabolic radiolabeling of the cells with [32P]orthophosphates. IL-5 stimulated phosphorylation of MAP kinases in situ. Thus, we have delineated major components of an important signaling pathway in eosinophils. We believe that one of the signals generated by IL-5 receptor activation is propagated through the lyn-Ras-Raf-1-MEK-MAP kinase pathway.

Calcium-Calmodulin-Dependent Protein Kinases↗