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Biomedical subjects

I Schwartz

Publications and source records attributed to I Schwartz.

At least 19 recordsLinked to original sources

Structure-function analysis of Escherichia coli translation initiation factor IF3: tyrosine 107 and lysine 110 are required for ribosome binding.

Translation initiation factor IF3 is required for peptide chain initiation in Escherichia coli. IF3 binds directly to 30S ribosomal subunits ensuring a constant supply of free 30S subunits for initiation complex formation, participates in the kinetic selection of the correct initiator region of mRNA, and destabilizes initiation complexes containing noninitiator tRNAs. The roles that tyrosine 107 and lysine 110 play in IF3 function were examined by site-directed mutagenesis. Tyrosine 107 was changed to either phenylalanine (Y107F) or leucine (Y107L), and lysine 110 was converted to either arginine (K110R) or leucine (K110L). These single amino acid changes resulted in a reduced affinity of IF3 for 30S subunits. Association equilibrium constants (M-1) for 30S subunit binding were as follows: wild-type, 7.8 x 10(7); Y107F, 4.1 x 10(7); Y107L, 1 x 10(7); K110R, 5.1 x 10(6); K110L, < 1 x 10(2). The mutant IF3s were similarly impaired in their abilities to specifically select initiation complexes containing tRNA(fMet). Toeprint analysis indicated that 5-fold more Y107L or K110R protein was required for proper initiator tRNA selection. K110L protein was unable to mediate this selection even at concentrations up to 10-fold higher than wild type. The results indicate that tyrosine 107 and lysine 110 are critical components of the ribosome binding domain of IF3 and, furthermore, that dissociation of complexes containing noninitiator tRNAs requires prior binding of IF3 to the ribosomes.

Amino Acid Sequence

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

Doctor-patient communication in a cancer ward.

This study explored doctor-patient interaction by focusing on a specific type of encounter in an oncology ward, designed to enable discussion of the case by the doctors and informing the patient. In line with the cognitive orientation theory of Kreitler and Kreitler, the encounter's effects were examined in regard to three aspects--disease, treatment, and general state--on four levels: the information the patients have, their feelings, the information they desire, and the information they consider desirable. The patients were 52 men and women with different cancer diagnoses. Comparable questionnaires were administered to the patients before and after the meeting, and to the doctors only after it. The patients responded before and after also to Spielberger's scales of state anxiety and state anger. The results showed that patients claimed they had gained hardly any new information concerning the disease and their overall state. There were no decreases in the desired and desirable information. Their feelings were affected negatively to a slight extent, especially concerning treatment. In a quarter of the subjects, anxiety decreased and was replaced by anger. In regard to all levels and aspects there was a large gap between the evaluations of doctors and patients. The major conclusions were that patients and doctors differ in the meaning they assign to information, and that patients are conflicted in regard to asking for the personally relevant information they want.

Anger

rRNA gene organization in the Lyme disease spirochete, Borrelia burgdorferi.

Lyme disease is the most common vector-borne disease in the United States. The causative agent is the spirochete Borrelia burgdorferi. The copy number and organization of the genes encoding the rRNAs of this organism were determined. There is a single gene for 16S rRNA and two copies each of the 23S rRNA and 5S rRNA genes. All of the genes are located within a chromosomal fragment of approximately 9.5 to 10.0 kb. The 23S and 5S rRNA genes are tandemly duplicated in the order 23S-5S-23S-5S and are apparently not linked to the 16S rRNA gene, which is situated over 2 kb upstream from the 23S-5S duplication. The individual copies of the 23S-5S duplication are separated by a 182-bp spacer. Within each 23S-5S unit, an identical 22-bp spacer separates the 23S and 5S rRNA sequences from each other. The genome organization of the 23S-5S gene cluster in a number of different B. burgdorferi isolates obtained at a number of different geographical locations, as well as in several other species of Borrelia, was investigated. All isolates of B. burgdorferi tested displayed the tandem duplication, whereas the closely related species B. hermsii, B. anserina, and B. turicatae all contained a single copy of each of the genes. In addition, different geographical isolates of B. burgdorferi can be differentiated on the basis of a restriction fragment length polymorphism associated with the 23S-5S gene cluster. This polymorphism can be a useful tool for the determination of genetic relatedness between different isolates of B. burgdorferi.

Base Sequence

Diagnosis of early Lyme disease by polymerase chain reaction amplification and culture of skin biopsies from erythema migrans lesions.

Current laboratory diagnosis of Lyme disease relies on tests for the detection of antibodies to Borrelia burgdorferi, the etiologic agent of the disease. These tests are often unreliable because of a lack of sensitivity and specificity and test-to-test variability. The purpose of this study was to evaluate the sensitivity and specificity of polymerase chain reaction (PCR) amplification for detection of B. burgdorferi in skin biopsy specimens. Forty-six 2-mm skin biopsy samples were obtained from 44 patients with a clinical diagnosis of erythema migrans, 9 of whom were receiving antibiotic therapy at the time of biopsy. Specimens were ground in BSK medium with separate aliquots taken for culture and PCR. Of the specimens from the untreated group, 57% (21 of 37) were positive by culture and 22% (8 of 37) were culture negative; 22% (8 of 37) of the cultures were uninformative because of contamination. By comparison, 22 (59%) of 37 specimens were positive by PCR amplification. Of 21 culture-positive samples, 13 (62%) were also positive by PCR analysis. Thus, the sensitivity of the PCR was 59 to 62%, based on either a clinical or cultural diagnosis of untreated Lyme disease. None of the nine specimens from antibiotic-treated patients grew in culture, whereas two of the nine were positive by PCR analysis. Given the complexity and time required for culture, PCR is a promising technique for the diagnosis of early Lyme disease.

Base Sequence

Vesicular erythema migrans.

BACKGROUND: Lyme disease is the most common vector-borne disease in the United States. The characteristic rash, erythema migrans, is an early sign of the disease. Clinical criteria remain the "gold standard" for diagnosis at this stage of illness. OBSERVATIONS: Five (8%) of 65 patients with erythema migrans seen in a Lyme disease diagnostic center in Westchester County, New York, had a lesion with vesicles. Borrelia burgdorferi was cultured from two of five. In one case the positive culture came from a swab of the blister fluid. CONCLUSIONS: Recognition of erythema migrans and its variants is important, since early treatment of Lyme disease may prevent late complications. Vesicular erythema migrans should be added to the differential diagnosis of inflammatory vesicular rashes in the appropriate clinical setting.

Adolescent

Growth rate regulation of translation initiation factor IF3 biosynthesis in Escherichia coli.

infC, the gene encoding translation initiation factor IF3 in Escherichia coli, can be transcribed from three promoters. Two of these promoters, PI1 and PI2, are located in the upstream thrS sequence which codes for threonyl-tRNA synthetase. Previous studies had shown that PI2 was the major promoter for infC. In the present study, the extent of transcription from PI1 and/or PI2 at a variety of steady-state growth rates was analyzed by promoter fusion studies. PI2 was the more active promoter (two- to threefold stronger than PI1) at all growth rates tested. A fusion plasmid containing both PI1 and PI2 exhibited a transcription level approximately equal to the sum of those observed with the fusion plasmids containing the individual promoters. The transcriptional activities of PI1 and PI2 did not change as the growth rate was varied from 0.3 to 1.7 doublings per h. In contrast, a fusion plasmid carrying the rrnB P1 promoter displayed the expected growth rate response. The steady-state concentrations of infC mRNA in cells grown at different rates were measured and found not to vary. These results indicate that the previously reported growth rate regulation of IF3 biosynthesis neither is accomplished by transcriptional control nor is a result of differential mRNA stability. In view of these results, the steady-state levels of IF3 in cells grown at a number of different growth rates were determined by quantitative immunoblotting. IF3 levels were found to vary with growth rate in a manner essentially identical to that observed for ribosomes. A model accounting for these results and describing a mechanism for coordinate growth rate-regulated expression of ribosomes and IF3 is presented.

Bacterial Proteins

Nonpalpable ductal carcinoma in situ versus infiltrating carcinoma of the breast--can they be differentiated by mammography?

The radiologic patterns of 193 consecutive women with nonpalpable breast carcinoma were evaluated. The results were correlated with patient age and with the histopathologic diagnosis. Of the 193 women in the study, 135 (70%) were older than 50 years; 102 women had ductal carcinoma in situ, and 67 (62%) of them were over age 50; the remaining 91 women had infiltrating carcinoma, and 73 (80%) of these patients were older than 50 years. Of the 58% of women who presented with microcalcifications, 75% had ductal carcinoma in situ and 25% infiltrating carcinoma. Of the 36% of patients who presented with a mass, 87% had infiltrating carcinoma and 90% were over age 50. Six percent presented with a mass with microcalcifications; 75% of these masses were found to be infiltrating carcinoma. Most of the masses were infiltrating carcinoma, and of these 90% were high-density masses. The small number of masses representing ductal carcinoma in situ were proportionately of low density.

Adult

Base changes at position 792 of Escherichia coli 16S rRNA affect assembly of 70S ribosomes.

To investigate the function of base 792 of 16S rRNA in 30S ribosomes of Escherichia coli, the wild-type (adenine) residue was changed to guanine, cytosine, or uracil by oligonucleotide-directed mutagenesis. Each base change conferred a unique phenotype on the cells. Cells containing plasmid pKK3535 with G792 or T792 showed no difference in generation time in LB broth containing ampicillin, whereas cells with C792 exhibited a 20% increase in generation time in this medium. To study the effect on cell growth of a homogeneous population of mutant ribosomes, the mutations were cloned into the 16S rRNA gene on pKK3535 carrying a spectinomycin-resistance marker (thymine at position 1192), and the cells were grown with spectinomycin. Cells containing G792 or C792 showed 16% and 56% increases in generation time, respectively, and a concomitant decrease in 35S assimilation into proteins. Cells with T792 did not grow in spectinomycin-containing medium. Maxicell analyses indicated decreasing ability to form 70S ribosomes from 30S subunits containing guanine, cytosine, or uracil at position 792 in 16S rRNA. It appeared that C792-containing 30S ribosomes had lost the ability to bind initiation factor 3.

Base Sequence

Function of kidney grafts from brain-dead donor pigs. The influence of dopamine and triiodothyronine.

There are conflicting reports about the effects of administration of dopamine to brain-dead donors upon posttransplant organ function. This study compared the survival and serum creatinine levels in pigs that received renal grafts from untreated controls, from controls in which either the donor or donor and recipient received dopamine or from animals rendered brain dead for 16 hr by acute elevation of intracranial pressure, and given standard supportive treatment. In two additional groups, brain-dead donors were given dopamine or dopamine with triiodothyronine. Recipients of grafts from control animals or from brain-dead donors survived the 7-day period of study and showed minimal changes in serum creatinine. Recipients of grafts from brain-dead donors given dopamine however showed reduced survival and progressive increase in serum creatinine. This did not occur in the group given triiodothyronine concurrently with dopamine. It is suggested that if administration of dopamine is essential to treat donor hypotension, concurrent use of triiodothyronine may preserve posttransplant renal function.

Animals

Cholecystostomy as a definitive operation.

Cholecystostomy for decompression and drainage of the biliary tree is indicated when the elderly, poor risk patient with destructive inflammatory process in the gallbladder is unable to tolerate a more extensive operation. Cholecystostomy is often criticized as an inferior operation, because it provides some palliation but leaves the patient with most problems unattended. To re-evaluate the role of cholecystostomy in the management of acute disease of the gallbladder, we reviewed our experience with it. During the years 1974 to 1987, 37 patients underwent a cholecystostomy. Patients ranged in age from 58 to 90 years, with an average age of 69 years. Twenty-eight patients had acute destructive cholecystitis, usually complicated by perforation, peritonitis or ascending cholangitis. Five had severe pancreatitis; three, cholelithiasis, and one patient, carcinoma of the bladder. Twenty-seven of the 37 patients had severe systemic disease and were critically ill. At the operation, calculi were extracted and the gallbladder and abscess were drained. Two patients died, yielding a mortality rate of 5.4 per cent. Tube cholangiography was done in 33 patients. Although residual stones were demonstrated in seven patients, the stones were removed electively at a later date under much more favorable conditions. None of the 35 survivors had symptoms of disease of the gallbladder during the follow-up period, which ranged from one to 12 years. Cholecystostomy is a curative operation indicated in critically ill and elderly patients for whom extensive operation is a prohibitive risk.

Acute Disease

Perforated adenocarcinoma of the colon during pregnancy.

Performated carcinoma of the colon in pregnant women is a rare event. Only six cases have been reported in the literature, all except one in the recto-sigmoid. We present a case of perforated adenocarcinoma of the colon located above the peritoneal reflection and discuss the problem of diagnosis and management.

Adenocarcinoma

Mexico, maquiladoras, and occupational medicine training.

Industrialization and its concomitant social and environmental effects in developing countries are considered in this paper. Mexico offers one example of economic progress achieved through the promotion of industrial growth. Recognising the need for trained experts with global experience in occupational health, the University of Arizona (UA) has begun a programme to train occupational and preventive medicine residents in international aspects of occupational health in the nearby industrialized border regions of Mexico. By using the maquiladora (assembly plant) industries and the resources of the Instituto Mexicano del Seguro Social with the State of Sonora, residents observe existing problems in occupational safety and health in addition to adding to their understanding of the need for worldwide cooperation for research and reform in this field.

Arizona

Shigellosis in adults: epidemiologic, clinical, and laboratory features.

One hundred and sixteen cases of adult patients hospitalized for shigellosis have been reviewed. The most common presentation included diarrhea (most frequently watery), fever, and abdominal pain, while dysentery has been less frequent. S. flexneri infection, as compared to S. sonnei, was more common in elderly patients and in males, and was characterized by a more prolonged clinical course. Abnormalities of serum electrolytes and hepatic enzymes were the most common laboratory complications, most often seen in elderly patients. Most isolates exhibited susceptibility to the common antimicrobial agents used in shigellosis therapy.

Anti-Bacterial Agents