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M Golomb

Publications and source records attributed to M Golomb.

At least 19 recordsLinked to original sources
PubMed2001

Evolution of an autotransporter: domain shuffling and lateral transfer from pathogenic Haemophilus to Neisseria.

The genomes of pathogenic Haemophilus influenzae strains are larger than that of Rd KW20 (Rd), the nonpathogenic laboratory strain whose genome has been sequenced. To identify potential virulence genes, we examined genes possessed by Int1, an invasive nonencapsulated isolate from a meningitis patient, but absent from Rd. Int1 was found to have a novel gene termed lav, predicted to encode a member of the AIDA-I/VirG/PerT family of virulence-associated autotransporters (ATs). Associated with lav are multiple repeats of the tetranucleotide GCAA, implicated in translational phase variation of surface molecules. Laterally acquired by H. influenzae, lav is restricted in distribution to a few pathogenic strains, including H. influenzae biotype aegyptius and Brazilian purpuric fever isolates. The DNA sequence of lav is surprisingly similar to that of a gene previously described for Neisseria meningitidis. Sequence comparisons suggest that lav was transferred relatively recently from Haemophilus to Neisseria, shortly before the divergence of N. meningitidis and Neisseria gonorrhoeae. Segments of lav predicted to encode passenger and beta-domains differ sharply in G+C base content, supporting the idea that AT genes have evolved by fusing domains which originated in different genomes. Homology and base sequence comparisons suggest that a novel biotype aegyptius AT arose by swapping an unrelated sequence for the passenger domain of lav. The unusually mobile lav locus joins a growing list of genes transferred from H. influenzae to Neisseria. Frequent gene exchange suggests a common pool of hypervariable contingency genes and may help to explain the origin of invasiveness in certain respiratory pathogens.

Amino Acid Sequence↗
PubMed1998

The tryptophanase gene cluster of Haemophilus influenzae type b: evidence for horizontal gene transfer.

Among strains of Haemophilus influenzae, the ability to catabolize tryptophan (as detected by indole production) varies and is correlated with pathogenicity. Tryptophan catabolism is widespread (70 to 75%) among harmless respiratory isolates but is nearly universal (94 to 100%) among strains causing serious disease, including meningitis. As a first step in investigating the relationship between tryptophan catabolism and virulence, we have identified genes in pathogenic H. influenzae which are homologous to the tryptophanase (tna) operon of Escherichia coli. The tna genes are located on a 3.1-kb fragment between nlpD and mutS in the H. influenzae type b (Eagan) genome, are flanked by 43-bp direct repeats of an uptake signal sequence downstream from nlpD, and appear to have been inserted as a mobile unit within this sequence. The organization of this insertion is reminiscent of pathogenicity islands. The tna cluster is found at the same map location in all indole-positive strains of H. influenzae surveyed and is absent from reference type d and e genomes. In contrast to H. influenzae, most other Haemophilus species lack tna genes. Phylogenetic comparisons suggest that the tna cluster was acquired by intergeneric lateral transfer, either by H. influenzae or a recent ancestor, and that E. coli may have acquired its tnaA gene from a related source. Genomes of virulent H. influenzae resemble those of pathogenic enterics in having an island of laterally transferred DNA next to mutS.

Amino Acid Sequence↗
PubMed1998

Evolution of the major pilus gene cluster of Haemophilus influenzae.

Haemophilus influenzae is a ubiquitous colonizer of the human respiratory tract and causes diseases ranging from otitis media to meningitis. Many H. influenzae isolates express pili (fimbriae), which mediate adherence to epithelial cells and facilitate colonization. The pilus gene (hif) cluster of H. influenzae type b maps between purE and pepN and resembles a pathogenicity island: it is present in invasive strains, absent from the nonpathogenic Rd strain, and flanked by direct repeats of sequence at the insertion site. To investigate the evolution and role in pathogenesis of the hif cluster, we compared the purE-pepN regions of various H. influenzae laboratory strains and clinical isolates. Unlike Rd, most strains had an insert at this site, which usually was the only chromosomal locus of hif DNA. The inserts are diverse in length and organization: among 20 strains, nine different arrangements were found. Several nontypeable isolates lack hif genes but have two conserved open reading frames (hicA and hicB) upstream of purE; their inferred products are small proteins with no data bank homologs. Other isolates have hif genes but lack hic DNA or have combinations of hif and hic genes. By comparing these arrangements, we have reconstructed a hypothetical ancestral genotype, the extended hif cluster. The hif region of INT1, an invasive nontypeable isolate, resembles the hypothetical ancestor. We propose that a progenitor strain acquired the extended cluster by horizontal transfer and that other variants arose as deletions. The structure of the hif cluster may correlate with colonization site or pathogenicity.

Amino Acid Sequence↗
PubMed1995

Gender differences in personality disorders.

OBJECTIVE: The aim of this study was to assess gender differences in personality disorders. Since heterogeneity of axis I diagnoses could introduce variability in the assessment of axis II diagnoses, the authors studied a group of patients with a primary diagnosis of major depression. METHOD: A total of 316 patients were evaluated with the Personality Diagnostic Questionnaire--Revised, a self-rating measure, or the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II), a clinician-rated instrument, or both. Axis II disorders were assessed with the Personality Diagnostic Questionnaire--Revised for 288 patients with major depression. The SCID-II was administered to 117 subjects, with an additional 95 subjects receiving the SCID-II for cluster B diagnoses only. RESULTS: The mean 17-item Hamilton Depression Rating Scale scores for 108 men (mean age = 39.28 years) and 208 women (mean age = 39.11) were 19.0 (SD = 3.8) and 19.6 (SD = 6.9), respectively. Men were significantly more likely than women to meet criteria for narcissistic, antisocial, and obsessive-compulsive personality disorders as measured by the Personality Diagnostic Questionnaire--Revised and for narcissistic and obsessive-compulsive personality disorders as measured by the SCID-II. CONCLUSIONS: These findings are consistent with those of previous studies showing a greater prevalence of antisocial and narcissistic personality disorders in men. In contrast with other investigations, however, neither the Personality Diagnostic Questionnaire--Revised nor the SCID-II revealed a higher prevalence of any personality disorder in women.

Adult↗
PubMed1993

Post-transcriptional regulation of RNA polymerase II levels in Caenorhabditis elegans.

To investigate the regulation of RNA polymerase II levels in Caenorhabditis elegans, we have constructed nematode strains having one, two, or three copies of ama-1, the gene for the largest subunit of RNA polymerase II. Steady-state levels of RNA polymerase II polypeptides and solubilized enzyme activity are invariant with gene dosage, indicating regulatory compensation. However, steady-state levels of ama-1 mRNA are directly proportional to gene dosage. These results imply that RNA polymerase II levels in C. elegans are regulated post-transcriptionally.

Animals↗
PubMed1992

Gene expression in the Caenorhabditis elegans dauer larva: developmental regulation of Hsp90 and other genes.

Under conditions unfavorable to growth, the nematode Caenorhabditis elegans enters a developmentally arrested stage, the dauer larva. We have examined gene expression in the dauer larva and during recovery from the dauer stage. Run-on transcription assays with isolated nuclei reveal a depression of general RNA polymerase II transcription to 11-17% of that in other stages. Transcription of individual gene families (including actin, collagen, hsp70, and histone) is similarly depressed relative to actively growing stages. Dauer larvae are, however, capable of being induced for heat shock messages, indicating that they are competent to initiate and elongate transcripts. For most genes surveyed, reduced transcription in dauer larvae correlates with a decrease in message abundance. Hsp70 mRNA, however, is transcribed at lower rates but accumulates at levels comparable to those in other stages. Interestingly, dauer larvae are 15-fold enriched in a mRNA for a C. elegans hsp90 gene. Hsp90 mRNA accumulation is regulated at least in part by differential stability. Dauer larvae thus appear to have a unique pattern of gene expression. Upon placement in food, dauer larvae reenter the developmental pathway as late-stage larvae. Dauer recovery is accompanied by a temporally regulated sequence of gene expression. At least four distinct patterns of gene expression can be distinguished during exit from the dauer stage. Steady-state levels of hsp70 and polyubiquitin mRNA rise sharply within 75 min of recovery before declining by the fourth hour. Actin and histone mRNAs increase steadily following 2-4 hr of recovery, whereas myosin mRNA increases after 10 hr. In contrast, hsp90 mRNA declines sharply within the first 75 min of recovery. Changes in mRNA populations during dauer formation and exit may be physiologically relevant.

Animals↗
PubMed1991

Psychotherapy of an Arab patient by a Jewish therapist in Israel during the Intifada.

Fragments of a psychotherapy of an Arab patient by a Jewish psychotherapist in Israel, during an exacerbation of a historical political conflict, are presented. In addition to the delineated characteristic difficulties embedded in a cross-cultural/ethnic/national psychotherapy, an Arab-Jewish dyad evokes a complicated interaction between external political reality and the therapeutic space, confusing and obscuring the discourse, the transference, and the countertransference. We believe that the complex and intricate relationship between external reality and inner psychic reality, as it appeared in the therapeutic space, endangered the psychotherapeutic process by blurring the boundaries and creating a fertile ground for projective identification. Both the use of political reality as a defense, or its denial may preclude the possibility for a real dialogue. Implications for emphasizing the differences between patient's and therapist's ethnic affiliations, guarding sensitively the authenticity of interaction, and strengthening both participants' identity in all the relevant levels are pointed out to facilitate the dialectic process of the psychotherapy.

Adult↗
PubMed1990

Mutant Caenorhabditis elegans RNA polymerase II with a 20,000-fold reduced sensitivity to alpha-amanitin.

A doubly mutant ama-1(m118m526) gene results in an RNA polymerase (Rpo) II that is unusually resistant to alpha-amanitin. Rpo II activity in isolated Caenorhabditis elegans cell nuclei is inhibited 50% by alpha-amanitin at a concentration of 150 micrograms/ml, making this enzyme 150 times more resistant to the toxin than Rpo II from the singly mutant allele, ama-1(m118), 20,000 times more resistant than the wild-type Rpo II, and about six times more resistant to amanitin than is Rpo III. It was determined that the SL1 spliced leader precursor is transcribed by Rpo II, and this transcript was used to measure Rpo II activity. The Rpo II activity is unstable in vitro, and the mutant strain has a temperature-sensitive sterile phenotype. The highly resistant double mutant was selected among four million progeny of the mutagenized ama-1(m118) parent by its ability to grow and reproduce in 200 micrograms/ml amanitin in the presence of a permeabilizing agent, Triton X-100.

Amanitins↗
PubMed1989

Psychiatric features of adult GM2 gangliosidosis.

The report describes three unrelated Ashkenazi Jewish women with adult GM2 gangliosidosis in whom mental symptoms were prominent, mimicking different psychiatric disorders, and thus delaying accurate diagnosis.

Adult↗
PubMed1988

Transcription elongation factor SII interacts with a domain of the large subunit of human RNA polymerase II.

Genomic sequences for the large subunit of human RNA polymerase II corresponding to a part of the fifth exon were inserted into an expression vector at the carboxy-terminal end of the beta-galactosidase gene. The in-frame construct produced a 125-kilodalton fusion protein, containing approximately 10 kilodaltons of the large subunit of RNA polymerase II and 116 kilodaltons of beta-galactosidase. The purified bacterially produced fusion protein inhibited specific transcription from the adenovirus type 2 major late promoter, while beta-galactosidase had no effect. This effect of the fusion protein was during RNA elongation, not at the level of initiation, resembling the faithfully initiated but incomplete transcripts produced with purified factors in the absence of SII. Similarly, monoclonal antibody 2-7B, which reacts with the RNA polymerase II region represented in the fusion protein, inhibited specific transcription at the level of elongation in a whole-cell extract. Both monoclonal antibody 2-7B and the fusion protein, although unable to inhibit purified RNA polymerase II in a nonspecific transcription assay, selectively blocked the stimulation elicited by transcription elongation factor SII on the activity of the purified enzyme in vitro. This suggests that the fusion protein traps the SII in nonstimulatory interactions and that antibody 2-7B inhibits SII binding to RNA polymerase II. Thus, this suggests that an SII-binding contact required for specific RNA elongation resides within the fifth exon region of the largest RNA polymerase II subunit.

Amino Acid Sequence↗
PubMed1987

Peripheral benzodiazepine binding sites on platelet membranes are increased during diazepam treatment of anxious patients.

Reduced (24%) [3H]PK 11195 binding capacity to platelet membranes was observed in anxious patients in comparison to age- and sex-matched normal controls. Four weeks of diazepam treatment induced elevation (69%) in the maximal number of binding sites, and 1 week of drug withdrawal resulted in a slight decrease (16%) in 'peripheral' benzodiazepine binding sites as compared to their level during treatment.

Adult↗
PubMed1985

Purification and immunological analysis of RNA polymerase II from Caenorhabditis elegans.

We describe a rapid procedure for obtaining highly purified RNA polymerase II from the nematode Caenorhabditis elegans. The structure of the enzyme was examined by denaturing gel electrophoresis and found to consist of three large polypeptides (molecular weights 200,000, 175,000, and 135,000) and eight smaller polypeptides (molecular weights 29,500, 20,000, 16,000, 15,000, 13,000, 11,500, 10,500, and 9,500). As observed for the analogous enzyme from other organisms, the 175,000 polypeptide (II175) appeared to be a degraded form of the 200,000 polypeptide (II200). The structure of nematode RNA polymerase II closely resembles that of the corresponding enzyme from other animals. Four of its larger subunits shared antigenicity with Drosophila RNA polymerase II. Antibody raised against purified RNA polymerase II reacted with several enzyme subunits in "Western" blots of purified polymerase and impure enzyme fractions. Immunofluorescence staining was used to visualize RNA polymerase II in the nuclei of a nematode squash preparation and the nucleoplasm of cultured mammalian cells.

Animals↗
PubMed1983

RNA polymerase II from wild type and alpha-amanitin-resistant strains of Caenorhabditis elegans.

DNA-dependent RNA polymerases I, II, and III have been isolated from the soil nematode, Caenorhabditis elegans, and RNA polymerase II has been partially purified. The sensitivities of these enzymes to alpha-amanitin resemble those of the cognate enzymes from vertebrates. RNA polymerase II from C. elegans is 50% inhibited by 7 ng/ml of the amatoxin and RNA polymerase III by 80 micrograms/ml, whereas RNA polymerase I is insensitive to 500 micrograms/ml. We have obtained mutants of C. elegans which can grow and reproduce in concentrations of alpha-amanitin which arrest development of wild type animals. One of these mutants (DR432) has an altered RNA polymerase II which in partially purified extracts is 150 times less sensitive to the drug than the wild type enzyme. The mutation, ama-1(m130), in DR432 is dominant and maps near dpy-13 on linkage group IV. RNA polymerase II isolated from ama-1/+ heterozygotes contains equal proportions of two components, corresponding in alpha-amanitin sensitivity to the enzymes from DR432 and wild type. Thus, ama-1 appears to affect a subunit of RNA polymerase II.

Amanitins↗
PubMed1981

Virus-coded DNA endonuclease from avian retrovirus.

Reverse transcriptase from avian retrovirus has a physically associated DNA endonuclease with novel substrate and cofactor requirements. A similar endonuclease activity copurifies with pp32, a protein from viral cores that has been identified with the non-alpha region of the beta subunit of reverse transcriptase. Several temperature-sensitive mutants of avian retrovirus with thermolabile DNA polymerase were tested for thermal sensitivity of their DNA endonuclease activity. Two pol mutants of Rous sarcoma virus, ts335 and ts337, had thermolabile DNA endonuclease; a temperature-resistant revertant of ts335 had a heat-stable DNA endonuclease. DNA endonuclease is therefore a product of the pol gene and an integral part of the reverse transcriptase. A second class of pol mutants, typified by ts568 and ts553, had thermolabile DNA polymerase, but heat-stable DNA endonuclease.

Avian Leukosis Virus↗