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Biomedical subjects

M Bard

Publications and source records attributed to M Bard.

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

Utility of untimed urinary albumin measurements in assessing albuminuria in black NIDDM subjects.

OBJECTIVE: To determine the usefulness of an untimed morning urine specimen in screening a black NIDDM population attending an urban diabetes clinic for microalbuminuria. RESEARCH DESIGN AND METHODS: Untimed morning specimens were provided by 218 black NIDDM subjects. Of the 218 subjects, 123 also provided 24-h urine specimens. The 24-h specimens were assayed for albumin excretion rate (AER) in milligrams per 24 h, and the albumin-to-creatinine ratio (A-to-C) in micrograms per milligram was determined on the untimed morning urine specimen. RESULTS: Correlation between the A-to-C ratio and the 24-h AER was 0.96 (P = 0.0001). In the range of clinical proteinuria, r was 0.92 (P = 0.003, n = 7). In the range of microalbuminuria, r was 0.55 (P = 0.005, n = 26), and in the normal range, r was 0.59 (P < or = 0.0001, n = 90). Analysis of the untimed urine specimens from 218 black NIDDM subjects showed that 171 had A-to-C < 30 micrograms/mg, 38 had A-to-C 30-300 micrograms/mg, and 9 had A-to-C > 300 micrograms/mg. Data were grouped according to duration of NIDDM and the presence or absence of hypertension. None of the newly diagnosed NIDDM patients (< 1 year) (n = 40) had microalbuminuria. The frequency of microalbuminuria and clinical proteinuria increased with 1) duration of NIDDM 5-10 years (odds ratio [OR], 3.39; 95% CI 1.17-9.82),2) duration of NIDDM > 10 years (OR, 11.03; 95% CI 4.16-29.25), and 3) presence of hypertension (OR, 2.59; 95% CI I.20-5.61). CONCLUSIONS: The A-to-C ratio obtained from an untimed morning urine specimen correlates with the AER from a 24-h collection. In black subjects with newly diagnosed NIDDM, microalbuminuria is not present to a significant degree. Duration of NIDDM > 5 years is associated with increased prevalence of microalbuminuria, and hypertension is associated with microalbuminuria and clinical proteinuria in this population.

Adult↗
PubMed1996

Positive and negative regulation of a sterol biosynthetic gene (ERG3) in the post-squalene portion of the yeast ergosterol pathway.

Regulation of sterol biosynthesis in the terminal portion of the pathway represents an efficient mechanism by which the cell can control the production of sterol without disturbing the production of other essential mevalonate pathway products. We demonstrate that mutations affecting early and late steps in sterol homeostasis modulate the expression of the ERG3 gene: a late step in sterol biosynthesis in yeast. Expression of ERG3 is increased in response to a mutation in the major isoform of HMG CoA reductase which catalyzes the rate-limiting step of sterol biosynthesis. Likewise, mutations in non-auxotrophic ergosterol biosynthetic genes downstream of squalene production (erg2, erg3, erg4, erg5, and erg6) result in an up-regulation of ERG3 expression. Deletion analysis of the ERG3 promoter identified two upstream activation sequences: UAS1 which when deleted reduces ERG3 gene expression 3-4-fold but maintains sterol regulation and UAS2, which when deleted further reduces ERG3 expression and abolishes sterol regulation. The recent isolation of two yeast genes responsible for the esterification of intracellular sterol (ARE1 and ARE2) has enabled us to directly analyze the relationship between sterol esterification and de novo biosynthesis. Our results demonstrate that the absence of sterol esterification leads to a decrease in total intracellular sterol and ERG3 is a target of this negative regulation.

Acyltransferases↗
PubMed1996

Sterol esterification in yeast: a two-gene process.

Unesterified sterol modulates the function of eukaryotic membranes. In human cells, sterol is esterified to a storage form by acyl-coenzyme A (CoA): cholesterol acyl transferase (ACAT). Here, two genes are identified, ARE1 and ARE2, that encode ACAT-related enzymes in yeast. The yeast enzymes are 49 percent identical to each other and exhibit 23 percent identity to human ACAT. Deletion of ARE2 reduced sterol ester levels to approximately 25 percent of normal levels, whereas disruption of ARE1 did not affect sterol ester biosynthesis. Deletion of both genes resulted in a viable cell with undetectable esterified sterol. Measurements of [14C]acetate incorporation into saponified lipids indicated down-regulation of sterol biosynthesis in the are1 are2 mutant cells. With the use of a consensus sequence to the yeast and human genes, an additional number of the ACAT gene family was identified in humans.

Acetates↗
PubMed1996

Transformation of Saccharomyces cerevisiae with a cDNA encoding a sterol C-methyltransferase from Arabidopsis thaliana results in the synthesis of 24-ethyl sterols.

Using an EST-cDNA probe, a full-length cDNA (411) sequence of 1411 bp was isolated from A. thaliana. This sequence contained features typical of methyltransferases in general and in particular showed 38% identity with ERG6, a S. cerevisiae gene which encodes the zymosterol-C-24-methyltransferase. A yeast vector containing this ORF (4118-pYeDP60) was used to transform a wild type S. cerevisiae which accumulates predominantly ergosterol, a 24-methyl sterol as well as a mutant erg6 null mutant accumulating principally zymosterol, a sterol non-alkylated at C-24. In both cases, several 24-ethyl- and 24-ethylidene sterols were synthetized indicating that the 4118 cDNA encodes a plant sterol C-methyltransferase able to perform two sequential methylations of the sterol side chain.

Amino Acid Sequence↗
PubMed1996

Cloning and characterization of the Saccharomyces cerevisiae C-22 sterol desaturase gene, encoding a second cytochrome P-450 involved in ergosterol biosynthesis.

The ERG5 gene from Saccharomyces cerevisiae was cloned by complementation of an erg5-1 mutation using a negative selection protocol involving screening for nystatin-sensitive transformants. ERG5 is the putative gene encoding the C-22 sterol desaturase required in ergosterol biosynthesis. The functional gene was localized to a 2.15-kb SacI-EcoRI DNA fragment containing an open reading frame of 538 amino acids (aa). ERG5 contains a 10-aa motif consistent with its role as a cytochrome P-450 (CyP450) enzyme and is similar to a number of mammalian CyP450 enzymes. Gene disruption demonstrates that ERG5 is not essential for cell viability.

Amino Acid Sequence↗
PubMed1996

Cloning and characterization of ERG25, the Saccharomyces cerevisiae gene encoding C-4 sterol methyl oxidase.

We have cloned the Saccharomyces cerevisiae C-4 sterol methyl oxidase ERG25 gene. The sterol methyl oxidase performs the first of three enzymic steps required to remove the two C-4 methyl groups leading to cholesterol (animal), ergosterol (fungal), and stigmasterol (plant) biosynthesis. An ergosterol auxotroph, erg25, which fails to demethylate and concomitantly accumulates 4,4-dimethylzy-mosterol, was isolated after mutagenesis. A complementing clone consisting of a 1.35-kb Dra I fragment encoded a 309-amino acid polypeptide (calculated molecular mass, 36.48 kDa). The amino acid sequence shows a C-terminal endoplasmic reticulum retrieval signal KKXX and three histidine-rich clusters found in eukaryotic membrane desaturases and in a bacterial alkane hydroxylase and xylene monooxygenase. The sterol profile of an ERG25 disruptant was consistent with the erg25 allele obtained by mutagenesis.

Amino Acid Sequence↗
PubMed1996

Isolation and characterization of an Arabidopsis thaliana cDNA encoding a delta 7-sterol-C-5-desaturase by functional complementation of a defective yeast mutant.

A yeast null mutant (erg 3) defective in ERG 3, the gene encoding the C-5 sterol desaturase required for ergosterol synthesis was transformed with an Arabidopsis thaliana cDNA library inserted in a yeast vector. Transformants (4 x 10(5)) were screened for cycloheximide (CH) resistance and 400 possible clones were analyzed to determine their sterol profile. Low levels of ergosterol in addition to delta 7- and delta 8-sterols normally present in erg3 were isolated in three yeast transformants. Characterization of one transformant indicated a cDNA of 1141 bp. Transformation of an erg 3 strain with this plasmid led to CH resistance, nystatin sensitivity and an ergosterol profile. After subcloning in a pBluescript vector and subsequent sequencing, an ORF of 843 bp encoding a possible 281 amino acid polypeptide was deduced. Three histidine-rich motifs (HX3H, HX2HH and HX2HH) were found in the A. thaliana ORF which are also present in the yeast ERG 3 gene. These histidine-rich motifs are also characteristic of many membrane-bound fatty acid desaturases from higher plants. These data strongly suggest that the A. thaliana cDNA encodes a delta 7-sterol-C-5-desaturase.

Amino Acid Sequence↗
PubMed1996

[Modes of administration of beta agonists in asthma].

Short-acting beta 2 agonists have a rapid and potent bronchodilating effect and represent the basis of treatment of acute asthma. Whatever the level of severity, the inhaled route is preferred because of its high efficacy/tolerance ratio. The doses and modes of administration depend on the severity of the airway obstruction, the site of management and the available devices. Long-acting beta 2 agonists are administered as regular treatment in moderately-severe to severe chaonic asthma in association to inhaled corticosteroids, mainly by the inhaled route whereas the oral route may be considered for the administration of prodrugs.

Administration, Inhalation↗
PubMed1995

Cloning of the late genes in the ergosterol biosynthetic pathway of Saccharomyces cerevisiae--a review.

Research on the ergosterol biosynthetic pathway in fungi has focused on the identification of the specific sterol structure required for normal membrane structure and function and for completion of the cell cycle. The pathway and its end product are also the targets for a number of antifungal drugs. Identification of essential steps in ergo-sterol biosynthesis could provide new targets for the development of novel therapeutic agents. Nine of the eleven genes in the portion of the pathway committed exclusively to ergosterol biosynthesis have been cloned, and their essentiality for aerobic growth has been determined. The first three genes, ERG9 (squalene synthase), ERG1 (squalene epoxidase), and ERG7 (lanosterol synthase), have been cloned and found to be essential for aerobic viability since their absence would result in the cell being unable to synthesize a sterol molecule. The remaining eight genes encode enzymes which metabolize the first sterol, lanosterol, to ultimately form ergosterol. The two earliest genes, ERG11 (lanosterol demethylase) and ERG24 (C-14 reductase), have been cloned and found to be essential for aerobic growth but are suppressed by mutations in the C-5 desaturase (ERG3) gene and fen1 and fen2 mutations, respectively. The remaining cloned genes, ERG6 (C-24 methylase), ERG2 (D8AE7 isomerase), ERG3 (C-5 desaturase), and ERG4 (C-24(28) reductase), have been found to be nonessential. The remaining genes not yet cloned are the C-4 demethylase and the C-22 desaturase (ERG5).

Cloning, Molecular↗
PubMed1995

Interaction of hypertension and diabetes on renal function in black NIDDM subjects.

We studied renal function of 194 black subjects with duration of diagnosed NIDDM from 1 month to 36 years to determine the interaction of hypertension and diabetes on nephropathy. Renal function was assessed by isotopic GFR and RPF studies, and serum creatinine. One hundred seventeen of the 194 subjects had 24-hour urinary albumin excretion (AER). AER > 300 mg/24 h correlated with longer duration of NIDDM, decrease in GFR and RPF, and rise in serum Cr, and all subjects were hypertensive. AER 30 to 300 mg/24 h also correlated with a longer duration of NIDDM and 80% had hypertension. When 194 subjects were grouped according to duration of NIDDM and the presence or absence of hypertension, subjects who remained normotensive had normal renal function. In hypertensive subjects a decrease in GFR occurred with duration of NIDDM > 1 year and decrease in RPF with duration of NIDDM > 5 years. In hypertensive subjects with NIDDM > 10 years, 36% had impaired renal function (GFR < 80 ml/min/1.73 m2 or serum creatinine > 1.4 mg/dl) and 75% had microalbuminuria or clinical proteinuria. Within this group, those subjects who developed hypertension after their diagnosis of diabetes were likely to have evidence of nephropathy as compared to those subjects whose hypertension was diagnosed prior to or simultaneous with their diabetes: 17 of 20 (85%) versus 7 of 13 (54%), respectively (P = 0.05). These data provide insight into the relationship between hypertension and diabetes in the development of nephropathy in black NIDDM individuals.

Adolescent↗
PubMed1995

Contraction, relaxation, and economy of force generation in isolated human diaphragm muscle.

Contraction, relaxation, and energetics of normal human diaphragm strips (n = 10) were investigated over the whole load continuum in both twitch and tetanus modes. For a given level of isotonic total force and over a large part of the contraction phase, instantaneous velocity was shown to be a unique function of instantaneous length, regardless of time and initial length. In afterloaded tetanic contractions and over a wide range of loads, the peak lengthening velocity (VL) linearly decreased when maximum extent of muscle shortening (delta L) decreased. Stimulation mode modulated the VL versus delta L relationship, the slope of this linear regression being greater in tetanus than in twitch. Conversely, over a wide range of load, an increase in load linearly accelerated the peak rate of force decay, regardless of the stimulation mode. The energetics of human diaphragm muscle was evaluated in terms of both mechanical activity and economy of force generation. Maximum mechanical work (Wmax) differed significantly according to the stimulation mode, and the relative force at which Wmax occurred was higher in tetanus than in twitch (p < 0.05). The G curvature of the P-V hyperbola and maximum mechanical efficiency were significantly higher in tetanus than in twitch. This strongly suggests that the economy of force generation is higher in tetanus contractions than in twitch.

Adult↗
PubMed1994

The identification of a gene family in the Saccharomyces cerevisiae ergosterol biosynthesis pathway.

The Saccharomyces cerevisiae ERG24 gene, encoding sterol delta 14 reductase (Erg24p), was cloned by selecting strains carrying sequences on a 2 mu-based vector for resistance to the morpholine fungicide, fenpropimorph (Fp). Four distinct plasmid inserts which conferred Fp resistance (FpR) were recovered (plasmids pML99, pML100, pML101 and pM103). Although Fp is reported to inhibit activity of Erg24p and sterol delta 8-delta 7 isomerase (Erg2p; encoded by ERG2), none of the inserts had restriction maps resembling ERG2. In addition, a 2 mu plasmid overexpression of the ERG2 sequence did not produce FpR. Characterization studies were focused on plasmid pML100, because it was the only plasmid to confer FpR consistently when tested in a number of different genetic backgrounds. Tests with a panel of fungicides indicated that pML100 conferred significant resistance only to compounds (Fp, tridemorph, fenpropidin and azasterol) which have a shared site of action, Erg24p. An insertional disruption of pML100 resulted in an obligate anaerobic phenotype, indicating a lesion in sterol biosynthesis. Sterol analysis of the disrupted mutant demonstrated the accumulation of ignosterol, indicating a loss of Erg24p activity. A SphI-XbaI fragment of pML100 was sequenced, revealing the presence of an ORF encoding a 438-amino-acid protein, which is highly similar to those encoded by two previously reported yeast drug sensitivity genes, sts1+ (Schizosaccharomyces pombe) and YGL022 (S. cerevisiae). Analyses of these genes demonstrated that strains carrying disruptions of sts1+ or YGL022 have ergosterol biosynthesis defects in the enzyme, sterol C-24(28) reductase (Erg4p; encoded by ERG4).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Identification of a gene encoding a new Ypt/Rab-like monomeric G-protein in Saccharomyces cerevisiae.

A Saccharomyces cerevisiae sequence cloned by serendipity was found to encode a protein that is a new member of the Ypt/Rab monomeric G-protein family. This sequence shows high homology to the yeast genes SEC4 and YPT1 and, like SEC4 and YPT1, is essential for viability. The sequence was localized to chromosome V based upon hybridization to pulse-field gel-separated yeast chromosomes. The sequence has been deposited in the GenBank data library under Accession Number L17070.

Amino Acid Sequence↗
PubMed1994

Isolation of the ERG2 gene, encoding sterol delta 8-->delta 7 isomerase, from the rice blast fungus Magnaporthe grisea and its expression in the maize smut pathogen Ustilago maydis.

The Magnaporthe grisea ERG2 gene, encoding delta 8-->delta 7 sterol isomerase, was isolated from a genomic library by heterologous hybridization to a fragment of the Ustilago maydis ERG2 gene. The isolated gene contained a reading frame of 745 bp which encoded a protein of 221 amino acids. The coding region was interrupted by a single putative 79-bp-long intron. The deduced amino-acid sequence exhibited similarity to the ERG2 gene products of U. maydis and of Saccharomyces cerevisiae, particularly in the central region of the proteins. The NH2-terminal of all three proteins contained a long stretch of amino acids that were strongly hydrophobic, suggesting that they may function by anchoring the protein to a membrane surface. The M. grisea ERG2 gene complemented a U. maydis deletion mutant in which the ERG2 gene had been removed using a one-step gene replacement procedure. The delta 8-->delta 7 sterol isomerase produced by the M. grisea ERG2 gene exhibited a level of sensitivity to the sterol biosynthesis inhibitor, tridemorph, similar to that of the enzyme derived from the U. maydis ERG2 gene.

Amino Acid Sequence↗
PubMed1994

Magnetic resonance imaging findings in shoulders of hemodialyzed patients.

Twenty two patients (24 shoulders) who had undergone hemodialysis for a mean of 13.4 years, and who had reported chronic shoulder pain for > 6 months, were examined by magnetic resonance imaging (MRI), including T1 and T2 echo gradient images in the frontal plane and T1 images after gadolinium. An increase in thickness of the rotator cuff as well as synovitis and bursitis were documented. Twenty shoulders demonstrated a mean thickness of 8.05 mm. Most often, the signal intensity of T2 and T1 weighted images was intermediate, and T1 images failed to show an uptake of gadolinium. Of the 24 shoulders, 20 had subacromial subdeltoid bursitis and 21 had glenohumeral synovitis. These results indicate that MRI is of help in the early diagnosis of arthropathy in long term hemodialyzed patients. Magnetic resonance imaging findings are more precise than those of ultrasound, particularly for thickness measurements. Moreover, MRI films are easier to read and permit the detection of synovial involvements. The therapeutic value of MRI lies in the fact that it can isolate the two principal causes of shoulder pain in hemodialyzed patients. The increase in cuff thickness leading to impingement syndrome can be treated by surgical decompression; the synovitis can be treated by radioisotope synovectomy.

Adult↗
PubMed1993

Sterol synthesis and viability of erg11 (cytochrome P450 lanosterol demethylase) mutations in Saccharomyces cerevisiae and Candida albicans.

The identification of the precise structural features of yeast sterol molecules required for the essential "sparking" function has been a controversial area of research. Recent cloning and gene disruption studies in Saccharomyces cerevisiae have shown that C-24 methylation (ERG6), C-5 desaturation (ERG3) and delta 8-delta 7 isomerization (ERG2) are not required, while C-14 demethylation (ERG11) and C-14 reduction (ERG24) are each required for aerobic viability. Earlier observations had indicated that C-14 demethylase deficient strains could be restored to aerobic growth by suppressor mutations that caused a deficiency in C-5 desaturase. These strains were reported to synthesize some ergosterol, indicating that they contained leaky mutations in both ERG11 and ERG3, thereby making it impossible to determine whether the removal of the C-14 methyl group was required for aerobic viability. The availability of the ERG11 and ERG3 genes has been used in this study to construct strains that contain null mutants in both ERG11 and ERG3. Results show that these double disruption strains are viable and that spontaneously arising suppressors of the ERG11 disruption are erg3 mutants. The erg11 mutants of S. cerevisiae are compared to similar mutants of Candida albicans that are viable in the absence of the erg3 lesion.

Aerobiosis↗
PubMed1992

The need for multidisciplinary training in counseling the medically ill. Report of the training committee of the Linda Pollin Foundation.

Training for medical counselors requires that medicine and psychiatry give up the position that counseling is only a negligible offshoot that almost any professional can readily do. Instead, counseling can be considered a generic concept that covers a wide variety of interventions designed to help patients cope with the complications and consequences of their chronic illness. This report outlines the principles and scope of training for consideration in the area of counseling the medically ill and reviews the current status of training programs in the fields of psychiatry, psychology, social work, and nursing. Recommendations are made for future directions, including role clarification for disciplines, building a credible research base, provision of guidelines and possible accreditation, and incorporating medical counseling into training fellowships.

Chronic Disease↗