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Biomedical subjects

J McKerrow

Publications and source records attributed to J McKerrow.

13 recordsLinked to original sources
PubMed2000

A simple HPLC method for analysing diaminopimelic acid diastereomers in cell walls of Gram-positive bacteria.

A simple and sensitive method for separating and detecting the LL, DD and meso diastereomers of the dibasic amino acid diaminopimelic acid (DAP) in the peptidoglycan of Gram-positive bacteria is described. This method is based on reverse phase HPLC separation of chiral derivatives of DAP followed by fluorescence detection of the o-phthaldehyde derivatives. Its application to the analyses of cell walls of several Gram-positive bacteria is described, where 10 mg or less of dry cells is required.

Cell Wall↗
PubMed1996

Monoclonal antibodies: innovations in diagnosis and therapy.

OBJECTIVE: To provide a review of the use of monoclonal antibodies (MAbs) for diagnosis and therapy, the obstacles affecting their usefulness, and nursing considerations unique to MAb-based treatments. DATA SOURCES: Research studies, review articles, and book chapters pertaining to MAbs in cancer diagnosis and therapy. CONCLUSIONS: Recent clinical trials have shown the potential of MAbs as diagnostic and therapeutic tools in cancer. MAbs may be used alone or conjugated with drugs, radionuclides, and toxins; however numerous obstacles limit their effectiveness. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses caring for patients receiving MAb-based therapies play an important role in the implementation of the patient's regimen. Hypersensitivity reactions, constitutional symptoms, and serum sickness are toxic effects that require monitoring and patient education.

Antibodies, Monoclonal↗
PubMed1994

Naegleria fowleri: characterization of a secreted histolytic cysteine protease.

Naegleria fowleri is the etiologic agent of primary amebic meningoencephalitis, a rare but rapidly fatal disease of humans. It invades the central nervous system via nasal mucosa and cribriform plate. Once in brain tissue, the organism induces an acute hemorrhagic, necrotizing meningoencephalitis. We hypothesize that a protease released by the parasite contributes to tissue destruction and facilitates host invasion. Analysis of conditioned media of N. fowleri cultures revealed a major 30-kDa protease with substrate and inhibitor specificity consistent with cysteine proteases. Amino-terminal amino acid sequence of the purified enzyme showed it to be a thiol protease with homology to cathepsin L. It catalyzed the in vitro degradation of extracellular matrix and had a cytopathic effect on mammalian cells. Both ameba-induced matrix degradation and the cytopathic effect are inhibited by Z-Phe-Ala-fluoromethyl ketone, an irreversible cysteine protease inhibitor. Our results indicate that N. fowleri secretes a cysteine protease with the capacity to destroy host tissue. Naegleria gruberi, a nonpathogenic species, expresses a similar protease but, unlike its pathogenic relative, is not thermotolerant to temperatures above 30 degrees C.

Amino Acid Sequence↗
PubMed1992

Primary pulmonary hypertension and human immunodeficiency virus infection in a non-hemophiliac man.

We describe clinical and postmortem findings in a 44-year-old man with pulmonary hypertension and infection with the human immunodeficiency virus (HIV-1). Plexogenic angiopathy and veno-occlusive lesions were present, in addition to a mild, patchy pulmonary interstitial lymphoid infiltrate. The clinical data for 14 previously reported cases of HIV-associated primary pulmonary hypertension are summarized. We speculate that these vascular changes may be due to damage from a specific immune response to HIV.

Adult↗
PubMed1990

Purification and amino-terminal sequence analysis of the complement-fixing and precipitin antigens from Coccidioides immitis.

Two proteins (21 and 48 kilodaltons) purified from endospore-spherule culture filtrates of Coccidioides immitis are identified as precipitin and complement-fixing antigens, respectively. To allow specific structural comparison to antigens identified by other investigators and as a first step to eventual serodiagnostic antigen production by recombinant DNA technology, amino-terminal amino acid sequences were determined for these antigens.

Amino Acid Sequence↗
PubMed1987

Molecular cloning of Schistosoma mansoni myosin.

A cDNA library representative of adult Schistosoma mansoni mRNA populations was screened with serum from infected rats (refractory hosts), positive plaques being rescreened with serum from infected mice and humans. Based on general reactivity, one clone was selected for further study. As judged by immunofluorescence data, size of corresponding mRNA, and nucleotide sequence analysis, the recombinant expresses approximately 625 amino acids of a schistosome muscle myosin rod. Antibodies evoked by the protein do not cross-react with human cardiac or skeletal muscle, are not invariably stimulated in naturally infected human beings, and rise in titer after chemotherapeutic cure, findings which suggest that the antigen is not a causative agent of Katayama fever, and is probably presented by degenerating worms. The schistosome sarcomeric myosin gene, the most primitive examined to date, appears to be unique inasmuch as it may not be a member of a multigene family and encodes a single mRNA transcript; nonetheless, predicted higher order structure of its translation product is consistent with expected function.

Amino Acid Sequence↗
PubMed1987

Schistosome elastases: biological importance, structure, function and stage-specific expression.

Larval schistosomes (Digenea: Trematoda) invade their definitive host by directly penetrating the skin. During the process they secrete a number of macromolecules, ostensibly to facilitate their entry. Among these we have identified and characterized a dominant proteolytic species: a serine protease capable of fragmenting keratin, types IV and VIII collagen, proteoglycan, fibronectin, laminin, and elastin. The enzyme exhibits the specificity characteristic of elastases, has a molecular mass of 30,000 Da and pI of 7.8, and is potently immunogenic in its native form. Specificity of the active site has been analysed, tetrapeptides having large hydrophobic or aromatic amino acids at size P1 serving as best substrates. The amino terminal 20 amino acids of the mature enzyme have been sequenced and the information derived has been used to construct an oligonucleotide (22-mer) complement of its corresponding mRNA. The latter has been used to establish, by Northern analysis, that expression of the enzyme is stage specific (differing in this respect from most schistosome immunogens), and under transcriptional control. Transcripts are encoded by a multigene family. Several cDNAs hybridizing to the oligonucleotide have been isolated, subcloned into bacteriophage M-13, and sequenced by the di-deoxy method. It is our expectation that this line of investigation will lead towards: (i) an anti-infection vaccine; (ii) a means for chemically preventing infection (using enzyme inhibitors), and/or (iii) a rapid diagnostic assay of prepatent infection.

Amino Acid Sequence↗
PubMed1986

Schistosoma mansoni: purification and characterization of the major acidic proteinase from adult worms.

We report purification of the major digestive proteinase from adult worms of Schistosoma mansoni. This enzyme is a thiol proteinase with a pH optimum of 5 and is activated by thiol reagents. It was purified 300-fold using a combination of gel chromatography and chromatofocusing. It readily hydrolyzed hemoglobin with an apparent Km of 0.29 microM and a specific activity of 27 micrograms degraded/min/mg enzyme at 37 C. Peptides with positively charged amino acids were preferentially cleaved. The enzyme degraded Boc-Arg-Arg-7-amino-4-methyl coumarin with a kcat/Km of 9083 M-1 sec-1. Lengthening the peptide chain to 3 amino acids or substituting glycine for the amino terminal arginine resulted in decreased activity. The enzyme was inhibited by chloromethylketone-derivatized peptides of similar sequence and by leupeptin. The purified proteinase exhibits microheterogeneity in different preparations with forms ranging in molecular weight from 30,000 to 35,000, and pI 5.7-6.0.

Animals↗
PubMed1984

Hepatic cirrhosis: magnetic resonance imaging.

The effect of periportal collagen deposition on magnetic resonance images and T1 and T2 relaxation times was studied in the rat. Hepatic cirrhosis was induced in 29 rats by chronic intraperitoneal thioacetamide injections. Another 14 rats in which liver abnormalities did not develop were used as controls. The rats were imaged using a small-bore resistive magnet. Histologic correlations and hydroxyproline measurements were performed to document the changes in periportal collagen deposition. The T1 and T2 relaxation times, determined both in vivo and in vitro with spectroscopy, were compared between the normal group and the group with moderate to severe histologic evidence of cirrhosis. The deposition of two to four times the normal amount of collagen in the liver did not affect the T1 or T2 relaxation time. Relatively pure periportal collagen fibrosis does not appear to affect the magnetic resonance image or T1 or T2 relaxation times of the rat liver.

Animals↗
PubMed1983

The epidermal barrier to Schistosoma mansoni infection.

The stratified epithelium serves as protection for underlying tissues and organs, and the structural fitness of the epidermal cells has been extensively reported. We studied the possible roles played by the epidermis as a barrier against the migration of Schistosoma mansoni larvae. Freshly shed cercariae were collected and placed on the back skin of 2-day-old rats. Electron microscopy of biopsies taken at various intervals showed the larvae and their secretory granules in keratinocytes in which the cytoplasm had become homogeneous in appearance. SDS gel electrophoresis showed the digestion of purified epidermal keratin (60K protein) by a proteinase secreted from cercariae, but this activity was inhibited by an inhibitor purified from epidermal cells. These findings suggest that epidermal cells function both structurally and chemically as a barrier against cercariae invasion.

Animals↗
PubMed1981

Murine embryonal carcinoma hybrids: decreased ability to spontaneously differentiate as a dominant trait.

The F9 murine embryonal carcinoma (ec) cell line does not differentiate spontaneously at high frequency either in vitro or in vivo. A derivative of this variant ec cell line resistant to ouabain and thioguanine was fused with the PSA1 ec cell line, which retains the ability to differentiate to a variety of cell types, either in vitro or in vivo. Hybrids were selected in media containing ouabain, hypoxanthine, aminopterin, and thymidine at a frequency of approximately 10(-3). Authentic hybrids were chosen by screening for the expected hybrid DNA content by flow microfluorometry and the lack of parental cell contamination in appropriate selective media. After injection into strain 129 mice, five or eight independently isolated hybrids formed tumors composed exclusively of embryonal carcinoma cells. The remaining three hybrids of this cross caused tumors composed of greater than 95% embryonal carcinoma cells but with small foci of differentiated tissues as well. Like the F9-derived parental line, less than 10 percent of the clones, formed by the hybrids after six days of growth, contained cells that secreted plasminogen activator. Since control hybrids derived from the fusion of either two F9 derivatives or two pluripotent cell lines resembled their parental cell lines with regard to the types of tumors formed and their differentiation in vitro, it appears that the F9 phenotype is dominant to the pluripotent phenotype in early passage embryonal carcinoma hybrids.

Animals↗
PubMedDate not supplied

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