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Biomedical subjects

R M Lawrence

Publications and source records attributed to R M Lawrence.

At least 37 records · Page 2Linked to original sources

Expression of the cloned gene for enterotoxin STb of Escherichia coli.

This study involved the construction of hybrid plasmids to produce heat-stable enterotoxin type II of Escherichia coli (STb). The translation of the open reading frame for the STb gene estA was demonstrated in several ways. Studies using in vivo labeling with [35S]cysteine demonstrated a radiolabeled protein band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the expected molecular weight of 5,000 for toxin STb. Insertion of translational or transcriptional termination signals into the BglII site of the estA gene blocked the expression of estA. The estA gene was cloned into high-expression vector pKC30 downstream from the strong pL promoter. Northern (RNA) blotting assays revealed a 10- to 20-fold increase in mRNA produced by strain C600F(pKC30STb) over other STb-producing strains, compared with little or no increase in enterotoxin activity demonstrated by bioassay. The estA gene, with its own promoter and Shine-Delgarno region and a portion of the sequence for the signal peptide deleted, was also inserted under the control of the tac promoter. Even after induction of the tac promoter by addition of isopropyl-beta-D-thiogalactopyranoside, no biologic enterotoxin activity could be identified. Neutralizing antibodies to STb were produced in rabbits by using either a purified OmpF-STb-beta-galactosidase fusion protein or a 19-amino-acid synthetic STb peptide coupled to keyhole limpet hemocyanin.

Animals↗

Stereocontrolled synthesis of peptide bond isosteres.

Absolute stereochemical control is employed in the synthesis of isosteres for dipeptide subunits (1; see Fig. 1) in which the amide linkage has been replaced by a trans carbon-carbon double bond. The synthesis affords access to the four stereoisomers of 1 in which R and R' = CH3, including the isostere for D-alanine-D-alanine (D-Ala-D-Ala), 2.

Amino Acid Sequence↗

Diagnostic flexible bronchoscopy in human immunodeficiency virus (HIV)-positive children.

Twelve children with laboratory evidence of human immunodeficiency virus (HIV) infection underwent diagnostic flexible bronchoscopy with washings or bronchoalveolar lavage at Bellevue Hospital Center from October 1987 to April 1989. The patients included 7 boys and 5 girls ranging from age 3.5 months to 10 years 5 months. Indications for bronchoscopy included respiratory distress with or without focal changes on chest radiograph in 11 patients, and persistent but asymptomatic right middle lobe collapse in one child. The etiology of pneumonia was diagnosed in 7 children and included Pneumocystis carinii, (PCP) (17%), Streptococcus viridans (17%), mechanical obstruction (17%) and cytomegalovirus (CMV) (8%). Bronchoscopy was non-diagnostic in 5 cases. Techniques for maximal yield of information using flexible bronchoscopy in HIV-positive children are discussed.

Bronchoalveolar Lavage Fluid↗

Treatment of fungal infections with semisynthetic derivatives of amphotericin B alpha.

AME appeared to be as effective as AmB in the treatment of mycoses in humans. AME was much less nephrotoxic than AmB, and was better tolerated in terms of rapid onset and reversible adverse reactions. AME may be more ototoxic than AmB. AME, even as AmB and OAME, may cause neurotoxicity and leukoencephalopathy, particularly when high doses are given for long periods.

Adult↗

Systemic zygomycosis caused by Apophysomyces elegans.

A case of systemic zygomycosis caused by Apophysomyces elegans in a 56-year-old man is described. The left kidney and the bladder showed presence of broad, nonseptate-to-infrequently septate hyphae in both the bladder lesion and in the septic kidney. Surgical debridement and treatment with amphotericin B cured the infection. No underlying immune defect was ever demonstrated, and the patient was not hyperglycemic or acidotic at any time. This zygomycetous fungus closely resembles Absidia corymbifera, but is distinguished by its distinctive morphological features.

Humans↗

Apparent extracellular glycoprotein turnover product from Candida albicans.

Low molecular weight material was isolated from the culture medium of three strains of Candida albicans. This material was produced from exponentially growing cultures and it appeared from chemical analysis to represent the carbohydrate portion of cell surface glycoproteins. The material contained a few residual amino acids which were interpreted to represent the attachment points of carbohydrate to protein and the remanents protease cleavage sites. Some of this material could be generated artificially by treating intact cells with papain.

Amino Acids↗

Treatment of open fractures: a prospective study.

A double-blind prospective study was done to assess the benefit of delaying closure of the wounds associated with open fractures. An additional double-blind study compared the effectiveness of clindamycin versus cefazolin for prophylactic antibiotic coverage. Quantitative cultures of the wounds were accomplished at the time of debridement and again at the time of closure if the wound was not closed initially. Almost half of the wounds were contaminated (46%) at the time of debridement, although the incidence of wound infection was low (6.5%). Gram-negative organisms resistant to the prophylactic antibiotic were recovered initially only eight times, but four of these (50%) became infected. The contaminating organisms in each case were present in high concentration (greater than 10(5) CFU/gm of tissue) at initial culture. The time of wound closure, cefazolin versus clindamycin, and internal fixation of the fracture were not followed by significant differences in the development of clinical infection in this series.

Adult↗

Treatment of coccidioidomycosis with miconazole.

Miconazole was injected intravenously in six patients with coccidioidomycosis. Two patients received 101 and 185 g, respectively, without clinical response and with persistence of positive cultures for Coccidioides immitis. In one patient, symptoms were suppressed when amphotericin B was given with miconazole, but new lesions developed with miconazole alone (total dose, 963 g). Three patients received smaller doses: 30.6 g before death from an unrelated complication; 17 and 22.3 g before development of severe allergic reactions. Because of the high rate of initial failures and relapses, miconazole is not recommended as primary therapy for coccidioidomycosis.

Adult↗

Phantom pain: a new hypothesis.

This paper deals with a new concept as to the possible nerve circuitry involved in phantom limb paid as well as in other similar disorders associated with an autonomic nervous system dysfunction. The paper deals with a new therapy promulgated by Melzack and Loeser originally presented in the journal "Pain". A discussion of the paper was also given in the Journal of the American Medical Association (editorial section) by R. De Jong. It is our contention that there may be a direct connection between the sympathetic nervous system fibers, carried on the blood vessels, and the central nervous system particularly through the hypothalamic-thalamic axis. This may explain why despite a complete transection of the spinal cord at higher levels (such as in the upper dorsal area) and even with an interruption of the sympathetic chain, pain impulses still reach the higher central nervous system.

Autonomic Nervous System↗