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Biomedical subjects

J E Griffith

Publications and source records attributed to J E Griffith.

15 recordsLinked to original sources
PubMed2000

Helminth communities of pademelons, Thylogale stigmatica and T. thetis from eastern Australia and Papua New Guinea.

Gastrointestinal helminths were collected from pademelons of the genus Thylogale (Marsupialia: Macropodidae) in eastern Australia and Papua New Guinea. Examined were 12 Thylogale stigmatica stigmatica and 13 T. s. wilcoxi, the latter subdivided into eight specimens from the northern limit of their distribution and five from southern areas, all from eastern Queensland, Australia, one T. s. oriomo from Papua New Guinea and ten T. thetis from southeastern Queensland and northern New South Wales, Australia. Six species of cestodes and 40 species of nematodes were found. The helminth community of T. s. stigmatica was similar to that found in northern specimens of T. s. wilcoxi, while differences from the helminth community present in southern T. s. wilcoxi could be accounted for by parasites acquired from sympatric T. thetis. Thylogale thetis harboured a community of helminths distinct from but related to that in T. stigmatica. The evidence suggests that all subspecies of T. stigmatica examined share a common helminth community, but that in areas of sympatry, T. stigmatica and T. thetis share some of their parasites.

Animals↗
PubMed1993

Severe COPD and acute respiratory failure. Correlates for survival at the time of tracheal intubation.

The recognition of a reversible cause for acute respiratory failure (ARF) is frequently difficult in patients with severe chronic obstructive pulmonary disease (COPD). We sought to identify clinical findings present at the time of tracheal intubation that were associated with successful weaning and short-term survival among a population of male veterans with severe COPD. Over a 5-year period (1987 to 1991), 39 episodes of ARF requiring mechanical ventilation (MV) were identified in 33 men with severe COPD. All the patients had a baseline FEV1 < 1 L. Univariate analysis suggested a higher serum albumin level and absence of pulmonary infiltrates on chest radiography distinguished survivors (weaned from MV for 72 h) from nonsurvivors (died while undergoing MV or within 72 h of weaning). Multivariate analysis revealed the absence of pulmonary infiltrates on initial chest radiography was the strongest correlate for survival. To examine the significance of these correlates in ARF complicating milder COPD, 19 patients with lesser degrees of chronic airways obstruction and ARF were also studied. Unlike patients with severe COPD, the presence or absence of pulmonary infiltrates on chest radiography was not correlated with survival in patients with milder chronic airways obstruction. Analyzing all COPD patients with ARF, the mortality risk associated with the presence of pulmonary infiltrates on chest radiography increased dramatically with declining baseline lung function. Mortality risk ratio analysis revealed the greatest likelihood for survival was predicted by a higher baseline FEV1 and the absence of pulmonary infiltrates on chest radiography. The extent of baseline airways obstruction alone was not correlated with short-term survival in either group. These observations suggest that in the subset of patients with severe COPD and ARF, the presence of pulmonary infiltrates on chest radiography at the time of tracheal intubation may be associated with less likelihood for survival. An exacerbation of COPD may infrequently be the terminal illness in these patients.

Acute Disease↗
PubMed1990

Characterization of two azurphil granule proteases with active-site homology to neutrophil elastase.

Much of the tissue damage associated with emphysema and other inflammatory diseases has been attributed to the proteolytic activity of neutrophil elastase, a major component of the azurophil granule. Recently, two additional azurophil granule proteins with NH2-terminal sequence homology to elastase were isolated (Gabay, J. E., Scott, R. W., Campanelli, D., Griffith, J., Wilde, C., Marra, M. N., Seeger, M., and Nathan, C. F. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 5610-5614) and designated azurophil granule protein 7 (AGP7) and azurocidin. Azurocidin and AGP7 represent significant protein components of the azurophil granule, together comprising approximately 15% of the acid-extractable protein as judged by reverse-phase high performance liquid chromatography analysis. AGP7 migrates on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as four distinct glycoforms of molecular mass 28-34 kDa, whereas azurocidin exhibits three predominant bands with molecular mass of 28-30 kDa. Treatment of intact azurophil granules with [3H]diisopropyl fluorophosphate resulted in labeling of elastase, cathepsin G, and AGP7, whereas azurocidin was not labeled. Tryptic mapping of 3H-labeled AGP7 allowed us to identify and sequence the active-site polypeptide that has 70% identity to elastase over 20 residues. The active site peptide of azurocidin was also identified by sequence analysis of tryptic fragments and showed 65% identity to the active site of elastase. Surprisingly, the catalytic serine of azurocidin is replaced by glycine, explaining its inability to label with [3H]diisopropyl fluorophosphate. Thus, we have identified two azurophil proteins closely related to neutrophil elastase, one of which has apparently lost its proteolytic activity due to mutation of the catalytic serine.

Amino Acid Sequence↗
PubMed1990

Bactericidal/permeability-increasing protein has endotoxin-neutralizing activity.

Neutrophil granules contain proteins important in host defense against bacterial pathogens. Granule proteins released from activated neutrophils facilitate opsonization, phagocytosis, tissue digestion, and antimicrobial activity. Three similar, if not identical, neutrophil proteins, bactericidal/permeability-increasing protein (BPI), 57,000 m.w. cationic antimicrobial protein, and bactericidal protein have been described that specifically kill gram negative bacteria. Since LPS is a structure common to all gram-negative bacteria, we investigated whether the microbicidal protein BPI affects biologic activity of LPS in vitro. Human neutrophils can be activated both in vitro and in vivo by LPS. Upon stimulation, surface expression of CR1 and CR3 increases markedly. Using flow microfluorimetry, we analyzed surface expression of CR1 and CR3 as a measure of neutrophil stimulation in response to LPS. CR up-regulation on neutrophils was TNF independent, suggesting direct LPS stimulation of neutrophils in this system. Purified BPI completely inhibited CR up-regulation on neutrophils stimulated with both rough and smooth LPS chemotypes at 1.8 to 3.6 nM (100 to 200 ng/ml). By comparison, the polypeptide antibiotic polymyxin B completely inhibited the same dose of LPS at 0.4 nM. The inhibitory activity of BPI appeared to be specific for LPS because neutrophil stimulation by formylated peptide or TNF was unaffected. The specificity of BPI for LPS was further demonstrated by inhibition of LPS activity in the limulus amebocyte lysate assay. Therefore, the role of BPI in infection may not be limited to its microbicidal activity, but it may also regulate the neutrophil response to LPS.

Antimicrobial Cationic Peptides↗
PubMed1989

Purification and characterization of human neutrophil peptide 4, a novel member of the defensin family.

Primary (azurophil) granules of neutrophils contain proteins which play a major role in the killing and digestion of bacteria in the phagolysosome. We have isolated and characterized a novel antimicrobial peptide from the azurophil granule fraction of discontinuous Percoll gradients. We have named this peptide human neutrophil peptide 4 (HNP-4) based on its structural similarity to a group of antimicrobial polypeptides known as defensins (HNP 1-3). Using size exclusion and reverse-phase high performance liquid chromatography, HNP-4 was purified to homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino-terminal sequence analysis. The amino acid sequence determined from isolated HNP-4 and from tryptic fragments of reduced and alkylated peptide is: NH2-Val-Cys-Ser-Cys-Arg-Leu-Val-Phe-Cys-Arg-Arg-Thr-Glu- Leu-Arg-Val-Gly-Asn-Cys-Leu-Ile-Gly-Gly-Val-Ser-Phe-Thr-Tyr-Cys-Cys-Thr- Arg-Val - COOH. Based on this sequence, HNP-4 has a calculated molecular weight of 3715 and a theoretical pI of 8.61. HNP-4 shows structural similarity to the family of three human defensins. HNP-4 and the defensins have identical cysteine backbones and, like the defensins, HNP-4 is rich in arginine (15.2 mol %). However, the amino acids at 22 of the 33 positions differ between HNP-4 and human defensins. Further, HNP-4 is significantly more hydrophobic than the defensins, as determined by its retention time on reverse-phase high performance liquid chromatography. In vitro, purified HNP-4 was shown to kill Escherichia coli, Streptococcus faecalis, and Candida albicans. Compared to a mixture of the other human defensins, HNP-4 was found to be approximately 100 times more potent against E. coli and four times more potent against both S. faecalis and C. albicans.

Amino Acid Sequence↗
PubMed1989

Subacute disseminated mucormycosis in a diabetic male.

Mucormycosis is an opportunistic invasive infection caused by fungi of the order Mucorales. Rhizopus, Absidia, and Mucor are the most commonly encountered genera. Disease is characterized by vascular invasion, thrombosis, and tissue necrosis. Rhinocerebral disease is the most common manifestation but pulmonary, cutaneous, gastrointestinal, and widely disseminated forms have been reported. Pulmonary and disseminated disease are usually seen in neutropenic patients with leukemia or lymphoma. Both present as fever and unexplained pulmonary infiltrates unresponsive to antibacterials and corticosteroids. Disease is usually fulminant and has a high mortality rate. Diagnosis is most commonly made at autopsy. A single case of disseminated disease is reported that is unusual in its subacute course and its occurrence in an otherwise healthy non-neutropenic diabetic male.

Diabetes Mellitus, Type 1↗
PubMed1989

American education: the challenge of change.

The American education system is being challenged to raise the academic achievement of students to prepare them for the jobs of the future. Yet many demographic, as well as economic and social factors, are making the task more difficult. Low birth rates, especially among non-Hispanic whites, along with high immigration rates, have increased the share of minority and non-English students in public schools. The rise in single-parent families has increased the number of poor students and migration from the cities to the suburbs has concentrated poor and minority students in inner city schools. These same children will make up a greater share of the future labor force. At the same time, the aging of the general population may lessen the commitment of homeowners- -whose taxes pay between 1/3 and 1/2 of education costs. The aging labor force may bring a shortage of qualified teachers, particularly in specialized subject areas. Poor and minority students generally have below average academic skills and are more likely to drop out of high school than non-minority students. However, the skills of American students rank below those of most other industrialized nations, calling into question the ability of Americans to succeed in an increasingly international economic system. How can schools be improved and minority student achievement be enhanced? Reforms of education finance systems, court-ordered integration, and stiffer requirements for teachers and for graduation from high school are among many attempts to meet the immense challenges faced by American schools.

Achievement↗
PubMed1985

Staging of lung cancer. A cost-effectiveness analysis.

Previous reports found the 67Ga scan highly accurate in staging lung cancer. In the present study the cost-effectiveness of the 67Ga scan was measured and compared with that of routine tests (radionuclide liver and bone scans, brain CT scan) used to stage lung cancer. In 160 patients, the 67Ga scan had a lower sensitivity, specificity, and negative predictive value than the combination of routine tests in detecting metastatic disease. The 67Ga scan was less accurate than the appropriate routine test in establishing the presence of liver, bone, and brain metastases. In the mediastinum the 67Ga scan was not more accurate than the chest radiograph. The average cost to accurately stage a patient by 67Ga scan was $812.12 and by routine tests was $737.60. The cost for metastatic disease was $1,417.70 by 67Ga scan and $1,287.70 by routine tests. It is concluded that at our institution the use of 67Ga scan to stage lung cancer is not cost-effective.

Bone Neoplasms↗
PubMed1979

Acute miliary blastomycosis presenting as fluminating respiratory failure.

A patient with miliary blastomycosis had acute fulminating respiratory failure requiring prolonged external ventilatory support. Treatment consisted of antifungal chemotherapy with two drugs and administration of corticosteroids. Restrictive ventilatory impairment and exercise-induced hypoxemia persist at one year after completion of therapy.

Acute Disease↗
PubMedDate not supplied

Amino acid analysis of feedstuff hydrolysates by cation exchange high performance liquid chromatography.

Corn, peanut meal, and soybean meal samples were either untreated or oxidized with performic acid before hydrolysis; the amino acids were determined by cation exchange high performance liquid chromatography (LC) and conventional cation exchange LC using an amino acid analyzer (AAA). Reproducibility of each procedure was assessed by repeated injections of the same calibration standard solution over a period of several days. LC data were more precise with regard to coefficients of variation for amino acid retention times, but were more variable with regard to peak areas. Although some significant differences between methods were noted, feedstuff amino acid values obtained by LC and AAA compared very well. The only consistent differences observed within each feedstuff were that Phe and Tyr values were significantly lower when analyzed by LC compared with AAA. Results of this study suggest that modular LC instrumentation can be used to accurately and reproducibly analyze amino acids in feedstuff hydrolysates. Advantages of using ninhydrin derivatization for feedstuff analysis, as opposed to using o-phthalaldehyde or dansyl chloride, are discussed.

Amino Acids↗
PubMedDate not supplied

Hydrolysate preparation for analysis of amino acids in sorghum grains: effect of oxidative pretreatment.

Sorghum samples were either untreated or oxidized with performic acid (PA) before hydrolysis, and their amino acid contents were determined by cation exchange chromatography using an amino acid analyzer. HCl was used to destroy excess PA. Oxidative pretreatment of the samples resulted in increased yields of Cys (as cysteic acid), Met (as Met dioxide), and His, destroyed Tyr and Phe, and resulted in the appearance of an extraneous peak which most likely consisted of halogenation by-products (HBP) of Tyr and Phe. The destruction of Tyr and Phe occurred despite the presence of phenol, a halogen scavenger, in both the PA and hydrolysis reagents. The higher His values observed in all oxidized samples most likely resulted from the co-elution of His with Tyr and Phe HBP. It was concluded that the complete (except Trp) amino acid content of a feedstuff cannot be accurately determined from only one oxidized hydrolysate preparation by using this particular procedure.

Amino Acids↗