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Biomedical subjects

H Horowitz

Publications and source records attributed to H Horowitz.

At least 37 records · Page 2Linked to original sources

Use of a novel technique of cutaneous lavage for diagnosis of Lyme disease associated with erythema migrans.

OBJECTIVE: Determining the microbial cause of cellulitis is often difficult. In this study, a novel two-needle lavage technique was used to culture Borrelia burgdorferi from the skin of suspected erythema migrans lesions. DESIGN: The yield of lavage cultures for B burgdorferi was compared with that of a 2-mm skin biopsy sample. SETTING: A Lyme disease diagnostic center located in an area in which Lyme disease is epidemic. PATIENTS: Forty-five patients with suspected erythema migrans who had not been treated with antimicrobial agents. INTERVENTION: Cutaneous lavage of the advancing edge of a suspected primary erythema migrans lesion was done for all 45 participants, 33 of whom also had a skin biopsy of the same lesion at an identical (14) or an adjacent (19) site. MAIN OUTCOME MEASURES: Growth of B burgdorferi in in vitro culture. RESULTS: Lavage fluid cultures grew B burgdorferi in 13 (29%) of the 45 cases (95% confidence interval [CI], 16% to 44%). Among the 33 cases in which both lavage and skin biopsy cultures were done, the yield of lavage culture was less than that of biopsy culture (P less than .09, 12/33 vs 20/33). If contaminated cultures are excluded, this difference is significant (P less than .05, 12/30 vs 20/27). CONCLUSION: Cutaneous lavage is a new diagnostic technique for recovery of B burgdorferi from erythema migrans lesions that has potential applicability to other types of cutaneous infections.

Biopsy↗

Bimodality of plasma apolipoprotein B levels in familial combined hyperlipidemia.

To investigate possible genetic influences on plasma apolipoprotein (apo) B levels in familial combined hyperlipidemia (FCHL), commingling analysis was performed on data from seven large kindreds, including 183 individuals. The overall frequency distribution of apo B was skewed and was compatible with the presence of two normally distributed subdistributions (mean values, 117 and 172 mg/dl). The analysis was repeated after stratification of individuals by low density lipoprotein (LDL) subclass phenotype. Among subjects with phenotype A (predominance of large, buoyant LDL), a single apo B distribution was found (mean, 115 mg/dl). Among subjects with phenotype B (predominance of small, dense LDL), the distribution was bimodal, with mean values, 116 and 167 mg/dl, similar to the unstratified data set. Thus the skewing of the overall apo B distribution in FCHL family members may be due to a distinct subset of individuals with phenotype B who are genetically susceptible to even higher elevations of apo B. The higher apo B/phenotype B subjects also showed significantly higher levels of triglyceride and LDL-cholesterol than the lower apo B/phenotype B subjects. The lower apo B/phenotype B subjects had higher triglyceride and lower LDL-cholesterol than the phenotype A subjects. The enhanced information regarding apo B and lipid levels in the three subgroups of individuals identified here may facilitate a better understanding of genetic susceptibility to coronary heart disease.

Adolescent↗

Endocarditis associated with Comamonas acidovorans.

A case of endocarditis caused by Comamonas acidovorans (Pseudomonas acidovorans) in a 42-year-old intravenous-drug abuser is described. This article appears to be the first detailed report of the isolation of this organism from a systemic clinical infection and its identification as a pathogen.

Adult↗

Staphylococcal scalded skin syndrome mimicking acute graft-vs-host disease in a bone marrow transplant recipient.

A 33-year-old man with mild acute graft-vs-host disease after an allogeneic bone marrow transplant for chronic myelogenous leukemia developed a necrolytic rash 90 days after transplant. A diagnosis of staphylococcal scalded skin syndrome was made when a skin biopsy specimen revealed a split in the granular layer and phage group 2, type 71 Staphylococcus aureus was cultured from the blood.

Acute Disease↗

The yeast ADR6 gene encodes homopolymeric amino acid sequences and a potential metal-binding domain.

The ADR6 gene of Saccharomyces cerevisiae has an open reading frame which could encode a polypeptide of 1314 amino acids. The predicted mRNA encodes a protein with homopolymeric stretches of asparagine and threonine, particularly near its amino terminus and contains additional sequences consisting of polyglutamine repeats. The predicted protein also contains a potential metal binding (Cys)4-type finger near its carboxy-terminus. An ADR6/beta-galactosidase fusion protein was predominantly nuclear in location, consistent with its role as an activator of ADH2 transcription.

Alcohol Dehydrogenase↗

Calcium and osteoporosis.

The loss of bone which starts at the menopause is self-limiting (exponential) and possibly mainly trabecular. It merges into an age-related linear loss of bone which is probably mainly cortical. The menopause is associated with a rise in obligatory urinary calcium loss resulting from an increase in the filtered load of calcium which may be due to the complexed fraction. The dependence of the urinary hydroxyproline on the urinary calcium and sodium suggests that the bone resorption is a response to calcium losses rather than a primary event. In osteoporotic women, there is a further increase in filtered load of calcium and obligatory calcium loss, frequently coupled with malabsorption of calcium. Urinary hydroxyproline can be suppressed by calcium administration in those with normal absorption and by calcitriol in those with calcium malabsorption. It is known that calcium deficiency causes osteoporosis in experimental animals, but there is controversy about the role of calcium deficiency in the pathogenesis of human osteoporosis. Calcium supplementation inhibits cortical bone loss in postmenopausal women but there is some doubt as to whether it can inhibit trabecular bone loss in women close to the menopause. This may be partly a matter of dose, formulation and time of administration.

Bone Resorption↗

Identification of autonomously replicating circular subtelomeric Y' elements in Saccharomyces cerevisiae.

We marked a large number of yeast telomeres within their Y' regions by transforming strains with a fragment of Y' DNA into which the URA3 gene had been inserted. A few of the Ura+ transformants obtained were very unstable and were found to contain autonomously replicating URA3-marked circular Y' elements in high copy number. These marked extrachromosomal circles were capable of reintegrating into the chromosome at other telomeric locations. In contrast, most of the Ura+ transformants obtained were quite stable mitotically and were marked at bona fide chromosomal ends. These stable transformants gave rise to mitotically unstable URA3-marked circular Y' elements at a low frequency (up to 2.5%). The likelihood that such excisions and integrations represent a natural process in Saccharomyces cerevisiae is supported by our identification of putative Y' circles in untransformed strains. The transfer of Y' information among telomeres via a circular intermediate may be important for homogenizing the sequences at the ends of yeast chromosomes and for generating the frequent telomeric rearrangements that have been observed in S. cerevisiae.

Chromosomes↗

Subtelomeric regions of yeast chromosomes contain a 36 base-pair tandemly repeated sequence.

We have determined the nucleotide sequence of a region of DNA derived from the end of one chromosome of the yeast, Saccharomyces cerevisiae. Inspection of the sequence reveals the presence of 12 tandem direct repeats, each 36 nucleotides long and having nearly identical sequence. Each 36 base-pair repeat can be further subdivided into three tandem sub-repeats of a similar 12 base-pair sequence. Analysis of total genomic yeast DNA from several strains by Southern hybridization suggests that the number of tandem 36 base-pair repeat units may vary from approximately 8 to 25 among different telomeric regions. Differences in the number of repeats may have arisen by unequal crossing over between them. Furthermore, the finding that the pattern of bases at multiple variable positions within the repeat unit is not random suggests that these regions may undergo gene conversion events that render them homogeneous.

Base Composition↗

Rearrangements of highly polymorphic regions near telomeres of Saccharomyces cerevisiae.

We have examined the mitotic and meiotic properties of telomeric regions in various laboratory strains of yeast. Using a sequence (Y probe) derived from a cloned yeast telomere (J. Szostak and E. Blackburn, Cell 29:245-255, 1982), we found that various strains of Saccharomyces cerevisiae show extensive polymorphisms of restriction endonuclease fragment length. Some of the variation in the lengths of telomeric fragments appears to be under the control of a small number of genes. When DNA from various strains was digested with endonuclease KpnI, nearly all of the fragments homologous to the Y probe were found to be of different size. The pattern of fragments in different strains was extremely variable, with a greater degree of polymorphism than that observed for fragments containing the mobile TY1 element. Tetrad analysis of haploid meiotic segregants from diploids heterozygous for many different Y-homologous KpnI fragments revealed that most of them exhibited Mendelian (2:0) segregation. However, only a small proportion of these fragments displayed the obligate 2:2 parental segregation expected of simple allelic variants at the same chromosome end. From the segregations of these fragments, we concluded that some yeast telomeres lack a Y-homologous sequence and that the chromosome arms containing a Y-homologous sequence are different among various yeast strains. Regions near yeast telomeres frequently undergo rearrangement. Among eight tetrads from three different diploids, we have found three novel Y-homologous restriction fragments that appear to have arisen during meiosis. In all three cases, the appearance of a new fragment was accompanied by the loss of another band. In one of these cases, the rearrangement leading to a novel fragment arose in an isogenic diploid, in which both homologous chromosomes should have been identical. Among these same tetrads we also found examples of apparent mitotic gene conversions and mitotic recombination involving telemetric regions.

Base Sequence↗

Nucleotide sequence of the trpD and trpC genes of Salmonella typhimurium.

We have completed the nucleotide sequence determination of trpD and trpC, the second and third genes of the trp operon of Salmonella typhimurium. These genes encode two bifunctional proteins thought to have arisen by gene fusions: the trpD polypeptide contains the glutamine amido transferase and the phosphoribosyl anthranilate transferase activities, and the trpC protein possesses the N-(5'-phosphoribosyl)-anthranilic acid isomerase and the indole-3-glycerol phosphate synthetase activities. The trpD gene consists of 1593 nucleotides encoding 531 amino acids, and possesses an internal promoter (p2) located within a region from about 1400 to 1441 of the nucleotide sequence. The trpC gene contains 1356 nucleotides encoding 452 amino acids. In this paper we compare the trpD and trpC genes of S. typhimurium to those of Escherichia coli with respect to codon usage, nucleotide and amino acid conservation, p2 promoter characteristics and intercistronic regions. The sequence of the two genes we present here completes the sequence determination of the trp operon of S. typhimurium and should prove useful in comparisons with the E. coli trp operon and in future studies of operon structure in S. typhimurium.

Amino Acid Sequence↗

Initiation in vivo at the internal trp p2 promoter of Escherichia coli.

We have identified an RNA transcript initiated in vivo at the internal promoter of the Escherichia coli trp operon. The 5' end of this message overlaps the distal portion of the trpD structural gene, and the startpoint of transcription is the same as that previously determined in vitro. The relative abundance of the primary and secondary promoter transcripts in cells grown under varying conditions confirms previous genetic data suggesting that the p2 promoter is expressed at a low level, but constitutively. Comparison of p2 with a number of other recently identified internal promoters suggests that the primary function of these elements may be to provide a differentially regulated source of transcription for a subset of genes within the operon.

Base Sequence↗

Minimal brain dysfunction in adolescent and young adult psychiatric inpatients.

This paper presents data on a study of 100 consecutive young adult psychiatric admissions to Horsham Hospital, to determine the incidence of minimal brain dysfunction in this population, to define the subcategories of common psychiatric presentation, and to compare these data with those from the companion study conducted by our research group of fifty consecutive adolescent psychiatric admissions, reported by Horowitz, 1981.

Adolescent↗

Regulation of transcription from tandem and convergent promoters.

We have examined transcription on templates containing the trp and lac UV5 promoters arranged in tandem or opposing orientations. These studies have revealed that the strengths of the two promoters are comparable, though the lac UV5 promoter is much more sensitive to the level of initiating purine present. Kinetic experiments have shown that a polymerase molecule poised at the lac promoter, or a lac repressor molecule bound to the lac operator, can temporarily block a polymerase molecule initiated from the trp promoter, though transcription eventually continues through. In the convergent construct, transcription from the lac promoter is hindered only when initiation is suboptimal due to low purine concentrations.

Base Sequence↗