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R Brenner

Publications and source records attributed to R Brenner.

At least 55 records · Page 3Linked to original sources
PubMed1997

Calcium-activated potassium channel gene expression in the midgut of Drosophila.

The slowpoke gene of Drosophila encodes a pore-forming subunit of a BK-type Ca(2+)-activated K+ channel. The gene is expressed in neurons, muscles, tracheal cells and in the midgut. The P1 transgene gene contains the entire slowpoke transcriptional control region and drives the expression of a reporter protein comprised of slowpoke amino terminal sequences fused to beta-galactosidase. Here we show that midgut expression is limited to the copper cell and iron cell regions. The copper cell region is composed of two cell types, the copper cells and the interstitial cells. The P1 transgene is expressed in the interstitial cells but not the copper cells. Furthermore, we show that the reporter protein is apically localized in the interstitial cells. In these cells, the slowpoke Ca(2+)-activated K+ channel is thought to participate in the transport of ions between the hemolymph and the lumen of the gut. Subcellularly localized BK channels may be involved in the secretion of acid into the gut lumen. An analogous role for basolaterally localized BK channels has been proposed in the acid-secreting intercalating cells of the human kidney.

Animals↗
PubMed1997

Increased turnover of small proteoglycans synthesized by human osteoblasts during cultivation with ascorbate and beta-glycerophosphate.

The small proteoglycan decorin had been localized previously at the d-band in the gap zone of collagen fibrils in nonmineralizing tissues. In bone matrix this zone is proteoglycan free and is at least in some species the place where mineralization along collagen fibrils starts. To study the metabolism of the small proteoglycans decorin and biglycan under mineralizing conditions, osteoblasts from human nasal bone were cultured for several weeks in the presence or absence of beta-glycerophosphate and ascorbate. An immediate consequence of the treatment was a reduced expression of decorin, as judged by immune precipitation, whereas the biosynthesis of biglycan was not affected. Pulse-chase experiments were performed with osteoblasts embedded in floating type I collagen gels. In the presence of beta-glycerophosphate and ascorbate, a more rapid turnover of both proteoglycans was noted; the one of biglycan reached statistical significance. Indirect evidence for an enhanced rate of proteoglycan endocytosis was obtained. This effect was not seen in cultured skin fibroblasts. Thus, osteoblasts respond rapidly to mineralizing conditions with alterations of small proteoglycan biosynthesis and turnover.

Adolescent↗
PubMed1996

Developmental- and eye-specific transcriptional control elements in an intronic region of a Ca(2+)-activated K+ channel gene.

The range of electrical properties that a neuron or muscle cell can manifest is determined by which ion channel genes it expresses and in what amounts. The Drosophila slowpoke Ca(2+)-activated K+ channel gene has four distinct promoters. Here we assess the role that a downstream intronic region, called the C2/C3 region, plays in modulating Promoter C1 and Promoter C2 activity. Promoter C1 and Promoter C2 appear to be responsible for all neuronal and muscle expression, respectively. Transgenic flies were used to determine the expression pattern from each promoter in the presence and absence of the C2/C3 region. Deletion of this region silences Promoter C1 in adult but not larval CNS and causes a substantial reduction in Promoter C2 activity in adult but not larval muscle. The C2/C3 region also activates Promoter C1 in the animal's eye. By placing the C2/C3 region adjacent to a basal HSP70 promoter we have demonstrated that it contains elements that can specifically activate a heterologous promoter in the eye and in adult but not larval muscle. These results demonstrate that the C2/C3 region has a important role in regulating slowpoke developmental expression in the CNS and musculature and in regulating eye expression.

Animals↗
PubMed1996

Tissue-specific expression of a Ca(2+)-activated K+ channel is controlled by multiple upstream regulatory elements.

The electrical properties of a cell are produced by the complement of ion channels that it expresses. To understand how ion-channel gene expression is regulated, we are studying the tissue-specific regulation of the slowpoke (slo) Ca(2+)-activated K+ channel gene. This gene is expressed in the central and peripheral nervous system, in midgut and tracheal cells, and in the musculature of Drosophila melanogaster. The entire transcriptional control region has been cloned previously and shown to reproduce the tissue and developmental expression pattern of the endogenous gene. Here we demonstrate that s/o has at least four promoters distributed over approximately 4.5 kb of DNA. Promoter C1 and C1c display a TATA box-like sequence at the appropriate distance from the transcription start site. Promoters C1b and C2, however, are TATA-less promoters. C1, C1b, and C1c transcripts differ in their leader sequence but share a common translation start site. C2 transcripts incorporate a new translation start site that appends 17 amino acids to the N terminus of the encoded protein. Deletion analysis was used to identify sequences important for tissue-specific expression. We used a transgenic in vivo expression system in which all tissues and developmental stages can be assayed easily. Six nested deletions were transformed into Drosophila, and the expression pattern was determined using a lacZ reporter in both dissected tissues and sectioned animals. We have identified different sequences required for expression in the CNS, midgut, tracheal cells, and muscle.

Amino Acid Sequence↗
PubMed1996

Evaluating new vaccines for developing countries. Efficacy or effectiveness?

Despite the profusion of promising new vaccines against illnesses prevalent in developing countries, uncertainties about the balance between costs and benefits of new vaccines have retarded their use in public health practice. Conventional prelicensure trials of vaccine protection exacerbate these uncertainties by focusing on measurement of vaccine efficacy--the performance of a vaccine under idealized conditions. Vaccine effectiveness trials provide a more pragmatic perspective by addressing the performance of a vaccine under the ordinary conditions of a public health program, by capturing direct as well as indirect effects of vaccination, and by comprehensively addressing outcomes of public health concern. The use of effectiveness trials should enable more rational triaging of new vaccines for developing countries and may accelerate the introduction of new vaccines into public health practice by resolving speculative debates about practical costs and benefits.

Case-Control Studies↗
PubMed1995

Agonadism in two sisters with XY gonosomal constitution, mental retardation, short stature, severely retarded bone age, and multiple extragenital malformations: a new autosomal recessive syndrome.

We report on 12- and 14-year old sisters with a 46, XY chromosome constitution, normal female external genitalia, and absence of gonadal tissue. Except for omphalocele, right renal agenesis and malrotation of the colon in the elder sister, the internal organs were normal. Both were mentally retarded, of short stature, and had extremely retarded bone age. In addition, they had an almost identical pattern of minor anomalies: peculiar face, hypodontia, short neck, inverted nipples, thoracolumbar scoliosis, "dysplastic" hips, partial clino-/syndactyly of toes. The occurrence of a basically similar set of malformations in two sisters and the first cousin consanguinity of the parents suggests autosomal recessive inheritance. The conserved region of the SRY gene ([high mobility group] HMG box) was sequenced in the elder sib and was normal. No consistent malformations are observed at present in agonadal patients. This supports the idea that several autosomal genes have the potential of influencing the sequence of events of sex determination.

Abnormalities, Multiple↗
PubMed1995

Efficacy of risperidone treatment for psychoses associated with schizophrenia, schizoaffective disorder, bipolar disorder, or senile dementia in 11 geriatric patients: a case series.

BACKGROUND: Clinical trials of risperidone, a recently approved novel antipsychotic, included elderly healthy patients, but more data are needed on the effects of risperidone in this population, especially those with comorbid medical illnesses. METHOD: Risperidone was used to treat 11 elderly hospitalized patients between 61 and 79 years of age who manifested signs of psychoses related to schizophrenia, schizoaffective disorder, bipolar disorder, or senile dementia. All patients had been treated previously with classic antipsychotics. Response was assessed by clinical observation of the patients' behavior. RESULTS: Eight patients responded to treatment, 1 did not respond, and 2 had treatment discontinued because of hypotension or dizziness. Positive and negative symptoms decreased markedly in 7 of the responding patients. Four patients had preexisting extrapyramidal symptoms (EPS) and symptoms of tardive dyskinesia that also decreased in response to risperidone treatment. In addition, 4 patients were able to discontinue anti-parkinsonian medications, and 2 were able to discontinue antihypertensive medications. Side effects related to blockade of dopamine, histamine, and serotonin were negligible. No adverse consequences occurred when electroconvulsive therapy, carbamazepine, or lithium was given concurrently. CONCLUSION: The reduction of both positive and negative symptoms of schizophrenia and the lack of significant EPS, tardive dyskinesia, sedation, and anticholinergic side effects indicate that risperidone is a safe and effective medication for the elderly.

Aged↗
PubMed1995

Tissue-specific expression of a Drosophila calcium-activated potassium channel.

The Drosophila slowpoke (slo) gene encodes a subunit of a CAK channel homologous to the vertebrate BK channel. We have examined slo expression throughout development. It is expressed in muscle cells, neurons of the CNS and PNS, mushroom bodies, a limited number of cells in embryonic and larval midgut and in epithelial-derived tracheal cells. The promoter has been cloned and shown to direct expression in the same pattern as the endogenous gene in both neural and epithelial-derived cells. During pupariation and embryogenesis, slo is expressed in muscles many hours prior to the appearance of functional channels.

Animals↗
PubMed1993

Osteogenesis imperfecta and hyperplastic callus formation: light- and electron-microscopic findings.

In rare cases of osteogenesis imperfecta, an "overshoot" growth of new bone may occur, which, clinically gives the impression of a tumour. This condition is known as hyperplastic callus formation. Morphology showed an excessive mixed desmal-chondral osteoneogenesis. Atypical collagen fibrils in non-callus tissue represent an indicator for this callus formation in individual patients.

Bony Callus↗
PubMed1993

Effects of transforming growth factor beta on cells derived from bone and callus of patients with osteogenesis imperfecta.

We studied the influence of transforming growth factor beta (TGF-beta) on cultured bone cells derived from two patients with osteogenesis imperfecta (OI) and from human controls. Additionally, cells from a hyperplastic callus that had developed spontaneously at the femur of the patient in Case 1 and cells from a normal fracture callus were included in the study. TGF-beta increased the synthesis of total protein and collagen of all cells without changing the pattern of interstitial collagens. Proliferation was stimulated by TGF-beta in the OI bone cells from Case 1, in cells from the central part of the hyperplastic callus, and in cells from the fracture callus. In Case 2, proliferation of bone cells was decreased by low concentrations of TGF-beta. Alkaline phosphatase (AP) activity was enhanced by TGF-beta in normal human bone cells, not affected in bone cells from the patient in Case 2 or in cells from the central part of the hyperplastic callus, and inhibited in bone cells and cells from the peripheral part of the hyperplastic callus of Case 1 and in cells from the fracture callus. We conclude that TGF-beta has common and specific effects on cultured human cells derived from different types of skeletal tissues. Simultaneous stimulation of collagen synthesis and AP activity by TGF-beta was restricted to normal human bone cells and might reflect their mature state of osteoblastic differentiation. Cells derived from bone of both patients with OI, from the hyperplastic callus, and from the fracture callus showed a different response pattern to TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

In vitro translation of RNA from the German cockroach Blattella germanica.

The translation of mRNA within total RNA of German (Blattella germanica) cockroaches was performed using a rabbit reticulocyte lysate system. Analysis of the translation products by SDS-PAGE and combined autoradiography revealed several synthesized proteins with apparent molecular weights ranging from 20 kD to 110 kD. SDS-PAGE/Western blotting of non-radiolabeled translation products and incubation with human serum with IgE to cockroach allergens showed the presence of a 36 kD and 50 kD allergen. The confirmation of the translation of the cockroach allergens from total RNA is an important first step in the cloning of cockroach allergens.

Allergens↗
PubMed1993

Allergenicity of the cat flea (Ctenocephalides felis felis)

Adult fleas, spent and unspent culture media were extracted and the radio-allergosorbent test (RAST) performed with sera of 48 cat flea skin test-positive individuals from the Tampa Bay area of Florida. Sixteen sera (33.6%) had a positive RAST to the cat flea extract prepared in our laboratory [1.7-11.4% of the total counts (TC) added]. Six of the 16 sera (12.5%) also contained specific IgE to allergens in the spent medium (0.8-3.3% TC). The allergen composition and strength were studied by RAST inhibition of two commercial cat flea extracts and compared with our in-house flea extract. The results demonstrated similar allergen compositions and different potencies. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the in-house flea extract showed several Coomassie blue-stained bands (10-85 kD). SDS-PAGE immunoblots revealed five IgE-binding bands at 34, 35, 39, 54 and 60 kD. Flea allergens were quantified in eight house dust samples using RAST inhibition assays and expressed as RAST inhibition units; five of these samples contained detectable levels. Cat flea allergens may contribute to the allergenicity of house dust in areas of heavy flea infestation.

Allergens↗
PubMed1992

Extracellular matrix formation by osteoblasts from patients with osteogenesis imperfecta.

Extracellular matrix proteins synthesized by bone cells isolated from 16 patients with different forms of osteogenesis imperfecta (OI) were analyzed in vitro. Specific components of the extracellular matrix by OI and age-matched cultures were investigated by steady-state radiolabeling followed by quantitation of label into specific proteins and comparison of OI cultures to those of age-matched controls. The in vitro proliferation of OI bone cells was found to be lower than that of control cells. In seven patients, abnormalities of the alpha 1(I) and/or alpha 2(I) chains of type I collagen were detected by gel electrophoresis. In two of these patients, the mutations in the COLIA1 and COLIA2 genes have been previously identified. Although the amount of total protein synthesized by the cells in culture was the same for OI bone cells and age-matched control cells, OI bone cells showed a significantly reduced synthesis of not only collagen but also other bone matrix glycoproteins. The synthesis of osteonectin (SPARC/BM40) and three proteoglycans [a large chondroitin sulfate proteoglycan, biglycan (PGI), and decorin (PGII)] was found to be decreased in OI cells. The reduction was most pronounced at the developmental age at which these macromolecules reach maximal levels during normal development.

Adolescent↗