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Biomedical subjects

L Katz

Publications and source records attributed to L Katz.

At least 19 recordsLinked to original sources

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

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

High-level expression and purification of mature HIV-1 protease in Escherichia coli under control of the araBAD promoter.

A 1.3-kb segment of Escherichia coli DNA containing the regulatory gene, araC, and the promoter of the araBAD operon was amplified by the polymerase chain reaction (PCR) and cloned into pUC18, resulting in plasmid pKB130 that produced the alpha fragment of beta-galactosidase upon addition of L-arabinose (L-ara). A synthetic gene for human immunodeficiency virus (HIV)-1 preprotease was placed downstream of the ara-BAD promoter in pKB130 to create a translational fusion inducible by addition of L-ara. The fusion protein correctly autoprocessed in vivo to yield a mature 99-amino-acid HIV-1 protease, which was found predominantly in inclusion bodies. This material could be refolded to an active form, which was purified to homogeneity. A small fraction of the protease was expressed in vivo as a soluble active form, which allowed the monitoring of expression during fermentation by a rapid and simple whole cell assay employing an HIV-1 protease-specific fluorogenic substrate.

Amino Acid Sequence

Coping ability, stress, productive load, and symptoms.

A study of 450 college students demonstrated (a) the importance of a distinction between self-produced and externally produced stressors, (b) the usefulness of a construct of productive load, and (c) stronger relations of the Constructive Thinking Inventory than of the Hardiness Questionnaire with productive load and with mental and physical symptoms. Because a major path through which coping ability influences symptoms is negative emotions, the widely recommended practice of partialing self-reported negative affect out of relations among coping, stress, and symptoms is often inappropriate. However, as total daily stressors (e.g., hassles) consist largely of self-produced stressors, it is highly confounded with coping ability, and it is therefore important to partial coping ability out of relations between total stressors and other variables.

Adaptation, Psychological

Nursing caries in Head Start children, St. Thomas U.S. Virgin Islands: assessed by examiners with different dental backgrounds.

The purposes of this study were to determine the prevalence of nursing caries in 3- to 5-year-old Head Start (HS) children on St. Thomas, U.S. Virgin Islands and to assess the reliability of examiners with different dental backgrounds. A dentist, hygienist, and nondental HS personnel participated in a 1/2 day training session (lecture and workshop) and then independently conducted visual examinations for caries of the maxillary anterior teeth including nursing caries. Twenty-three HS personnel examined a total of 375 children; the dentist and hygienist examined a random sample of 74 and 73 children, respectively. Seventy-one children received all three independent examinations. Reliability was assessed by percent agreement, sensitivity, specificity, and kappa value. The dentist found 41% of the children had caries of the maxillary incisors, which included nursing caries. The percentage of children with nursing caries was 12%. There was strong-to-good diagnostic agreement between the dentist and hygienist. The HS personnel also found that 12% of the children had nursing caries, but the diagnostic agreement between the dentist and HS personnel was only good-to-fair.

Bottle Feeding

Cancer in Jewish migrants to Israel.

Data on the incidence of 15 cancers in the Jewish population of Israel from the period 1961-1981 have been studied with emphasis on the risk of disease in relation to birthplace, calendar time, and duration of residence in Israel. The results show wide variations in incidence by birthplace, from less than 2-fold for pancreatic cancer to a 40-fold difference for oesophageal cancer in females; the reasons for these are often little understood. The potential importance of environmental agents in aetiology for different migrant groups is discussed in relation to the size and rapidity of changes in risk related to the duration of residence in Israel.

Africa, Northern

Charcot-Marie-Tooth disease and schizophrenia in identical twins.

Charcot-Marie-Tooth disease and schizophrenia occurred in monozygotic twins. Dermatoglyphics and blood grouping determined monozygocity. Charcot-Marie-Tooth disease appeared to be an autosomal dominant trait transmitted from the mother. No definite evidence of inheritance was seen for schizophrenia.

Adult

Cancer patterns in Israel: selected aspects.

Data on cancer incidence in Israel have been collected by the Israel Cancer Registry since 1960. Overall incidence patterns are similar to those observed in other "Westernized" countries. In the total Jewish population, lung cancer accounts for one in seven cancers in males and breast cancer, for one in four cancers in females. The main time trends are: a decrease in stomach cancer, a halt in the increase of male lung cancer and a continuing rise for female lung cancer, female breast cancer, cancer of the colon and rectum, and malignant melanoma. Cancer of the uterine cervix may be on the rise in Israel-born women. The relatively high incidence of cancer of the esophagus in immigrants from Iran and Yemen and of cancer of the nasopharynx in immigrants from North Africa probably reflect incidence patterns in their countries of origin.

Adolescent

Breast cancer in Israel: incidence and mortality, 1960-75.

Between 1960 and 1975, the incidence of breast cancer in Israel rose 20%. A steady rise in incidence was seen for women aged 60 or more years, whereas for women younger than 60 years, the incidence pattern was less regular, showing a definite rise only in the period 1970-75. Mortality from breast cancer also rose among women aged 60 or more years, but much more slowly than incidence. Among women younger than 60 years, breast cancer mortality was essentially unchanged. When mortality rates from a disease rise more slowly than incidence rates, it can be inferred that a greater proportion of new cases are being cured or are experiencing longer survival. It would appear that this is the case with breast cancer in Israel, and this trend, probably the result of earlier diagnosis, is encouraging.

Adult

Computer-based case tracing (COMTRAC).

To assist clinical assessment and decision making, a computer-based system has been developed to organize key data of individual medical records and display these data in a standard graphic format for each disease. A program for multiple myeloma has been completed and 150 case records entered. The data accessed by computer-based case tracing on all cases of a particular disease are available for cumulative and comparative analyses of different therapeutic regimens.

Data Display

Huntington's disease. Cerebrospinal fluid GABA levels in at-risk individuals.

Gamma-aminobutyric acid (GABA) was measured by the ion-exchange fluorometric method in CSF from 22 individuals at risk for Huntington's disease (HD), six individuals with HD, and five neurologically normal controls. The mean (+/- SD) GABA level in the specimens from patients with HD was 142 +/- 27 pmoles/ml, whereas that of the normal control specimens was 297 +/- 87 pmoles/ml. The mean GABA level of the specimens from the individuals at risk for HD was 209 +/- 79 pmoles/ml; however, nine of these were in the normal range with a mean value of 281 +/- 72 pmoles/ml, while the other 13 were below the normal range with a mean value of 159 +/- 27 pmoles/ml. The data indicate that low GABA levels in CSF are evident prior to the onset of symptoms of HD but a predictive value can only be determined by continued observation of the clinical course of these at-risk individuals.

Adolescent

Sensitivity of in vitro diagnostic dipstick tests to urinary protein.

Two commonly used brands of reagent strip (dipsticks) were evlauated for their sensitivity to Bence-Jones and seven other urinary proteins. Both brands showed significant differences in sensitivity to albumin, glycoprotein, ribonuclease and lysozyme; both were most sensitive to albumin and least sensitive to globulin. Furthermore, their comparative sensitivities to these proteins also differed markedly. These differences in sensitivity could lead to underestimation of protein content in urine specimens. Tests on urines from patients with multiple myeloma showed that a negative urinary dipstick test result did not rule out the presence of the disease.

Albuminuria