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Biomedical subjects

L Katz

Publications and source records attributed to L Katz.

At least 73 records · Page 4Linked to original sources
PubMed1994

Engineered biosynthesis of a complete macrolactone in a heterologous host.

Macrocyclic polyketides have been subjects of great interest in synthetic and biosynthetic chemistry because of their structural complexity and medicinal activities. With expression of the entire 6-deoxyerythronolide B synthase (DEBS) (10,283 amino acids) in a heterologous host, substantial quantities of 6-deoxyerythronolide B (6dEB), the aglycone of the macrolide antibiotic erythromycin, and 8,8a-deoxyoleandolide, a 14-membered lactone ring identical to 6dEB except for a methyl group side chain in place of an ethyl unit, were synthesized in Streptomyces coelicolor. The biosynthetic strategy utilizes a genetic approach that facilitates rapid structural manipulation of DEBS or other modular polyketide synthases (PKSs), including those found in actinomycetes with poorly developed genetic methods. From a technological viewpoint, this approach should allow the rational design of biosynthetic products and may eventually lead to the generation of diverse polyketide libraries by means of combinatorial cloning of naturally occurring and mutant PKS modules.

Acyl Coenzyme A↗
PubMed1994

Brain morphology in normal and dyslexic children: the influence of sex and age.

Morphometric magnetic resonance imaging techniques were used to compare the convolutional surface area of the planum temporale, temporal lobe volume and superior surface area, and an estimate of overall brain volume in a homogeneous sample of 17 dyslexic children (7 girls) and 14 nonimpaired children (7 girls). Substantial sex differences were apparent for all measured regions, with all the measurements in boys being significantly larger. Age, even within the narrow range employed here (7.5-9.7 years), was positively correlated with the size of each brain region. While initial analyses suggested smaller left hemisphere structures in dyslexics compared to control subjects, subsequent analyses controlling for age and overall brain size revealed no significant differences between dyslexics and nonimpaired children on a variety of measures, in particular surface area and symmetry of the planum temporale. We suggest that differences in subject characteristics (i.e., sex, age, handedness, and definition of dyslexia) as well as procedural variations in the methods used to acquire images and to define and measure anatomical regions of interest such as the planum temporale all may play an important role in explaining apparent discrepant results in the neuroimaging literature on dyslexia.

Age Factors↗
PubMed1994

Case study of the effects of prolonged and severe anorexia nervosa on bone mineral density.

Among the most severe sequelae of anorexia nervosa (AN) are its skeletal complications. Young women who have AN during adolescence may not attain their expected peak skeletal mass, and may enter adulthood with reduced bone mineral density (BMD) and an increased risk of fracture. This case history describes a young woman with severe AN that included prolonged exposure to both low body weight and amenorrhea. BMD measurement during the acute stage of her illness revealed severe osteopenia. Six years after recovery from AN, follow-up studies demonstrated only modest gains in BMD, with measurements for the hip and lumbar spine that are greater than 2 SDs below the age-matched mean.

Adult↗
PubMed1994

Characterization of the genes and attachment sites for site-specific integration of plasmid pSE101 in Saccharopolyspora erythraea and Streptomyces lividans.

The 11.3 kb plasmid pSE101 integrates into the chromosome of Saccharopolyspora erythraea at a specific attB site and into the chromosome of Streptomyces lividans at many sites. Multisite integration in S. lividans was also observed when a 1.9 kb segment of pSE101 containing attP and adjacent plasmid sequence was used to transform a pSE101- S. lividans host. Nucleotide sequencing of this segment revealed the presence of a complete open reading frame (ORF) designated int, encoding a putative polypeptide of 448 amino acids that shows similarities to site-specific recombinases of the integrase family. Sequencing of the 1.3 kb segment upstream of int revealed the presence of three additional ORFs: the one most distal to int encodes a putative 76 amino acid basic polypeptide analogous to the Xis proteins of a number of bacteriophages. Nucleotide sequencing of attP, and the attB, attL and attR sites from Sac. erythraea revealed a 46 bp sequence common to all sites with no duplications of chromosomal sequences in the integrated state. A putative structural gene for a tRNA(Thr) was found to overlap the 46 bp common sequence at attB. Sequencing of four pSE101 integration sites (attB') and corresponding attL' and attR' sites in S. lividans showed that the 46 bp sequence was present at each attR' site, whereas only the first three bases, CTT, were retained at each attL' and attB' site. A feature common to the four attB' sites and to attB is a highly conserved 21 bp segment with inverted repeats flanking the CTT sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Evidence of flexible coding in visual word recognition.

In 3 visual word recognition experiments, the authors examined Ss' differential dependence on phonological versus orthographic information in accessing the lexicon. The critical manipulation was the presence or absence of pseudohomophones in the nonword context of a lexical decision task. Ss received a list with either no pseudohomophones (NPsH group) or 17%-30% pseudohomophones among the nonwords (PsH group). In the first 2 experiments Ss in the PsH group were faster and no less accurate on word trials than Ss in the NPsH group. Furthermore, performance in the NPsH group was adversely affected by phonological inconsistency in the target's orthographic neighborhood. In the final experiment, a double lexical decision paradigm was used, and performance on orthographically similar but phonologically dissimilar pairs differed in the 2 conditions.

Humans↗
PubMed1994

Neighborhood effects in visual word recognition: effects of letter delay and nonword context difficulty.

The role of a target's orthographic neighborhood in visual word recognition was investigated in 2 lexical decision experiments. In both experiments, some stimuli had 1 letter delayed relative to the presentation of the rest of the stimulus. Experiment 1 showed that delaying a letter position, which yielded a potentially competitive neighbor, was more costly to target recognition than delaying a position that yielded no neighbors. This effect was strongest when one of these neighbors was of higher frequency than the target itself. Additionally, the effect was reduced for words with a high friendly-to-unfriendly-neighbor ratio (friendly neighbors being those words containing the delayed letter). In Experiment 2 the difficulty of the word-nonword discrimination was manipulated by varying the density of the nonwords' neighborhoods. Only when the nonwords had many neighbors at several positions did the word responses show neighborhood competition effects.

Decision Making↗
PubMed1994

A high capacity microbial screen for inhibitors of human rhinovirus protease 3C.

We have developed a high capacity screen for compounds that inhibit the 3C protease of human rhinovirus-1b. The assay uses a recombinant strain of Escherichia coli expressing both the protease and a tetracycline resistance-conferring protein modified to contain the minimal protease cleavage site. Cultures growing in microtiter plates containing tetracycline are treated with potential inhibitors and simultaneously monitored for change in growth over time using an oxygen probe. Most of the cultures, not containing an inhibitor of the 3C protease, show reduced growth due to cleavage of the essential gene product; normal growth is seen only in the infrequent culture that contains an inhibitor. In the present example, we have used the tetA gene of plasmid pACYC184 as the modified gene. The system has been validated using inhibitors of protease 3C, and has been used to identify three new inhibitors of the enzyme, active in the micromolar range.

3C Viral Proteases↗
PubMed1993

An erythromycin analog produced by reprogramming of polyketide synthesis.

The polyketide-derived macrolactone of the antibiotic erythromycin is made through successive condensation and processing of seven three-carbon units. The fourth cycle involves complete processing of the newly formed beta-keto group (beta-keto reduction, dehydration, and enoyl reduction) to yield the methylene that will appear at C-7 of the lactone ring. Synthesis of this molecule in Saccharopolyspora erythraea is determined by the three large eryA genes, organized in six modules, each governing one condensation cycle. Two amino acid substitutions were introduced in the putative NAD(P)H binding motif in the proposed enoyl reductase domain encoded by eryAII. The metabolite produced by the resulting strain was identified as delta 6,7-anhydroerythromycin C resulting from failure of enoyl reduction during the fourth cycle of synthesis of the macrolactone. This result demonstrates the involvement of at least the enoyl reductase from the fourth module in the fourth cycle and indicates that a virtually complete macrolide can be produced through reprogramming of polyketide synthesis.

Amino Acid Sequence↗
PubMed1993

[Endoscopic ultrasound in the demonstration and staging of non-Hodgkin's lymphomas of the stomach].

Nine patients (five women, four men, mean age 64.2 [49-77] years) with histologically confirmed gastric non-Hodgkin lymphoma (NHL) were investigated before starting therapy and during follow up, using endoscopic ultrasound, computer-assisted tomography and conventional ultrasound. Of ten gastric NHL infiltrations, nine were demonstrable using endoscopic ultrasound, three by computed tomography and two with conventional ultrasound. Accurate assessment of the primary tumour stage was possible in six out of eight cases using endoscopic ultrasound, but in none using tomography or conventional ultrasound. Three of these patients had inflammatory changes in enlarged paragastric lymph nodes and five malignant lymphomatous involvement. The latter was demonstrable by endoscopic ultrasound in all cases, by computed tomography in three cases and by conventional ultrasound in two cases. False positive results were obtained in two cases using endoscopic ultrasound and computed tomography. Regression of the tumour and of paragastric lymph nodes on radio-chemotherapy was demonstrable in two cases, and progression in one using endoscopic ultrasound; the other techniques showed progression of extragastric lymphoma involvement in only one case. Endoscopic ultrasound is an efficient method for demonstration and local staging of gastric non-Hodgkin lymphomas.

Aged↗
PubMed1993

Identification of a Saccharopolyspora erythraea gene required for the final hydroxylation step in erythromycin biosynthesis.

In analyzing the region of the Saccharopolyspora erythraea chromosome responsible for the biosynthesis of the macrolide antibiotic erythromycin, we identified a gene, designated eryK, located about 50 kb downstream of the erythromycin resistance gene, ermE. eryK encodes a 44-kDa protein which, on the basis of comparative analysis, belongs to the P450 monooxygenase family. An S. erythraea strain disrupted in eryK no longer produced erythromycin A but accumulated the B and D forms of the antibiotic, indicating that eryK is responsible for the C-12 hydroxylation of the macrolactone ring, one of the last steps in erythromycin biosynthesis.

Amino Acid Sequence↗
PubMed1993

Polyketide synthesis: prospects for hybrid antibiotics.

Polyketides fall into two structural classes: aromatic and complex. The former are built mainly from acetate units through a reiterative process wherein the beta-carbonyl groups formed after each condensation cycle are left largely unreduced. Complex polyketides are composed of acetates, propionates, or butyrates, and the extent of beta-carbonyl reduction varies from one cycle to the next. Two themes for polyketide synthases are emerging. Aromatic PKSs are determined by four to six genes encoding mono- or bifunctional enzymes; one PKS complex is used for all synthesis steps. Complex PKSs are composed of several multifunctional polypeptides that contain enzymatic domains for the condensation and reduction steps; each domain is used at a unique step in the pathways, and the extent of beta-carbonyl processing depends on the functional domains operating at that cycle. Mutations rendering certain domains nonfunctional have been introduced into genes for complex polyketides, resulting in the production of novel molecules.

Amino Acid Sequence↗
PubMed1993

A neuropsychological approach to the Bannatyne recategorization of the Wechsler Intelligence Scales in adults with learning disabilities.

An investigation was conducted of the diagnostic ability of the Bannatyne recategorization of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) into spatial, verbal-conceptual, and sequential components for adults with learning disabilities. A comparison among neuropsychological, intelligence, and achievement test data was made to evaluate the applicability of this recategorization. The Luria-Nebraska Neuropsychological Battery (LNNB), the WAIS-R, and the Wide Range Achievement Test-Revised (WRAT-R) were administered to 103 adult subjects with learning disabilities. The LNNB scales were cluster analyzed, and cluster membership was cross-tabulated against WAIS-R, WRAT-R, and demographic data. The major findings were that (a) the mean scores fit the Bannatyne pattern in two of the four clusters; and (b) the Bannatyne pattern was found in only about 20% of the total sample. It was concluded that identification of the Bannatyne pattern is of diagnostic utility, but its absence is inconclusive.

Adult↗
PubMed1993

Alpha interferon and hepatitis B and C. An integrated approach using practice guidelines.

Utilizing the techniques of total quality management, a team designed a clinical guideline for the use of alpha interferon as a treatment for patients with chronic hepatitis. The team included TEMINEX staff, a primary care physician, the plan's internal gastroenterologist, and its university-based consultant gastroenterologists. A synopsis of the available published research data and clinical opinion (a draft TEMINEX report) was used to focus discussions. The final TEMINEX report represented consensus on patient selection criteria and treatment regimens. All members of the team agreed to a review and approval process. Although quantitative data concerning the effects of guideline implementation are not yet available, it appears that the concerns of all members of the team have been satisfied. Patient selection criteria supported by the results of well-designed research are in place. Appropriate candidates for alpha-interferon therapy receive expedited treatment and the plan's internal monitoring processes are more efficient. Primary care physicians and consultant gastroenterologists feel that they made positive contributions both to the quality of care and to the consensus development process.

Health Maintenance Organizations↗
PubMed1993

Relationships among academic, neuropsychological, and intellectual status in subtypes of adults with learning disability.

A study was conducted of 102 adults with learning disability for the purposes of (1) contrasting a rule-based with an empirical method of classification into subtypes based on academic achievement levels in reading and arithmetic; and (2) examining cognitive profiles obtained with the Luria-Nebraska Neuropsychological Battery and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) associated with each of the rule and empirically based subtypes. Both similarities and differences were found between classification methods. Both methods indicated that specific reading disability was associated with the most impaired cognitive profiles of the three subtypes identified. However, they did not agree concerning cognitive profiles of subtypes, characterised by a specific arithmetic deficit or a global deficit. It was found that both the Lurid-Nebraska and WAIS-R profiles distinguished among subtypes more by pattern than by level of performance.

Journal Article↗
PubMed1992

Biosynthesis of the erythromycin macrolactone and a rational approach for producing hybrid macrolides.

The three eryA genes involved in the formation of the polyketide portion of the macrolide antibiotic erythromycin in Saccharopolyspora erythraea, appear to be organized in a single transcriptional unit on the basis of the results of gene disruption experiments. An insertion sequence-like element of lower G + C content separates eryAI from eryAII. The organization of the enzymatic domains present in the eryA-encoded multifunctional polypeptides, determined by computer-assisted analysis, is presented. This has enabled the determination of a putative dehydratase domain. A rational approach for producing novel macrolides by introducing selected changes in polyketide synthase genes is outlined. The isolation of a lactone intermediate resulting from an early synthesis step in macrolactone formation is also presented.

Amino Acid Sequence↗
PubMed1992

Organization of the enzymatic domains in the multifunctional polyketide synthase involved in erythromycin formation in Saccharopolyspora erythraea.

Localization of the enzymatic domains in the three multifunctional polypeptides from Saccharopolyspora erythraea involved in the formation of the polyketide portion of the macrolide antibiotic erythromycin was determined by computer-assisted analysis. Comparison of the six synthase units (SU) from the eryA genes with each other and with mono- and multifunctional fatty acid and polyketide synthases established the extent of each beta-ketoacyl acyl-carrier protein (ACP) synthase, acyltransferase, beta-ketoreductase, ACP, and thioesterase domain. The extent of the enoyl reductase (ER) domain was established by detecting similarity to other sequences in the database. A segment containing the putative dehydratase (DH) domain in EryAII, with a potential active-site histidine residue, was also found. The finding of conservation of a portion of the DH-ER interdomain region in the other five SU, which lack these two functions, suggests a possible evolutionary path for the generation of the six SU.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗