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Biomedical subjects

G D Roberts

Publications and source records attributed to G D Roberts.

At least 91 records · Page 5Linked to original sources

Complete primary structure of prostatropin, a prostate epithelial cell growth factor.

Bovine brain prostatropin is a potent and essential mitogen for prostate epithelial cell growth. The major form of prostatropin contains 154 amino acid residues in a single amino terminally blocked chain corresponding to a molecular weight of 17,400. The amino acid sequence of the 150 carboxy-terminal residues of prostatropin was derived by Edman degradation of overlapping peptides primarily generated by cleavage at lysyl and glutamyl residues. Analysis of the amino-terminal tetradecapeptide by fast atom bombardment mass spectrometry identified the blocking group as an acetyl moiety, and tandem mass spectrometry provided the sequence of the first 12 residues. Prostatropin residues 15-154 contain the sequence of bovine brain polypeptides recently described as acidic fibroblast growth factor and class I heparin-binding growth factor. The sequence of the first 25 residues of prostatropin is acetyl-Ala-(Gly, Glu)-Glu-Thr-Thr-Thr-Phe-Thr-Ala-Leu-Thr-Glu-Lys-Phe-Asn-Leu-Pro-Leu-Gly -Asn-Tyr-Lys-Lys-Pro. Reduced and carboxymethylated prostatropin exhibits mitogenic activity, suggesting that disulfide bonds among cysteine residues 30, 61, and 97 are not functionally essential. These results demonstrate by rigorous structural analysis that the brain-derived polypeptide previously described only as a mesenchymal and neuroectodermal cell mitogen is also an epithelial cell growth factor that may be involved in support of prostate hyperplasia and adenocarcinoma.

Amino Acid Sequence↗

Replication of fungi in K-Sol corneal preservation medium at 4 degrees C.

We examined the growth of six fungi during 18 days at 4 degrees C in a corneal preservation medium containing 2.5% chondroitin sulfate (K-Sol). The number of viable organisms decreased with time for all six fungi, the average decrease being 65%. The risk of transplanting fungal organisms with a donor cornea stored for up to 18 days at 4 degrees C in preservation media containing chondroitin sulfate is no greater than that with the same cornea stored for only one day.

Aspergillus↗

Carbohydrate mapping by mass spectrometry: a novel method for identifying attachment sites of Asn-linked sugars in glycoproteins.

A new method is described for locating the specific sites of attachment of Asn-linked carbohydrates in glycoproteins. The molecular weights of peptides released from the glycoprotein with proteases of known specificity are determined by fast atom bombardment mass spectrometry and fitted to the known or DNA-derived sequence. Oligosaccharides attached to Asn are released either before or after proteolysis with a glycosidase, usually peptide: N-glycosidase F, an enzyme that cleaves the beta-aspartylglycosylamine linkage of all known types of Asn-linked sugars and converts the attachment-site Asn to Asp. New peaks appearing in the mass spectra after treatment with glycosidase correspond to formerly glycosylated sites. Conversely, signals which disappear after glycosidase treatment correspond to glycopeptides. The differences in mass between these sets of signals define the composition of the carbohydrate at the given site in terms of deoxyhexose, hexose, N-acetylhexosamine, and sialic acid content. The extent of glycosylation at a given site can be estimated from the ratio of the peak heights corresponding to the Asn- vs Asp-containing peptides which differ by 1 Da in mass. This rapid and sensitive (low nmol) technique is illustrated here for ribonuclease B and for tissue plasminogen activator, a multiply glycosylated glycoprotein.

Asparagine↗

Results of a survey of antifungal susceptibility tests in the United States and interlaboratory comparison of broth dilution testing of flucytosine and amphotericin B.

In a survey of 350 laboratories, 41 of 210 respondents indicated that they performed antifungal susceptibility tests. Two-thirds performed 20 or fewer tests per year, and most used a broth dilution method to test amphotericin B and flucytosine activity against Candida albicans. The broth dilution procedure of S. Shadomy and A. Espinel-Ingroff (p. 647-653, in E.H. Lennette, ed., Manual of Clinical Microbiology, 3rd ed., 1980) was the method most frequently cited, and therefore this method was used to test the susceptibility of five isolates of C. albicans and one of Saccharomyces cerevisiae to amphotericin B and flucytosine in seven research laboratories. Agreement among replicates performed on the same day by each laboratory was excellent for both drugs, all values being within 1 twofold drug dilution. Precision from week to week for each laboratory was also good, with 95 and 92% of values being within 1 drug dilution for amphotericin B and flucytosine, respectively. Interlaboratory precision, however, was poor. For amphotericin B, values varied 8- to 32-fold, and for flucytosine, they varied 32- to greater than 512-fold. We conclude that antifungal susceptibility testing is currently being performed in small volumes by numerous laboratories in the United States and that results from one laboratory may not agree with results from another. Improved standardization of fungal susceptibility tests is necessary before their results can be generally applied to clinical situations.

Amphotericin B↗

Candida lusitaniae--an opportunistic pathogen.

Candida lusitaniae is a newly recognized opportunistic pathogen amongst immunocompromised patients. The epidemiology and pathology remain largely unknown. This case report describes a 27-year-old female with vasculitis who acquired a fatal C. lusitaniae fungemia.

Adult↗

Clinical significance of Pseudallescheria boydii: a review of 10 years' experience.

Pseudallescheria boydii is a recognized cause of mycetoma, a chronic fungal disease that usually affects the extremities. Isolated case reports have also implicated P. boydii in infections of other sites. We report the first large series (83 isolates) of P. boydii in 46 patients, including the second report of P. boydii brain abscess and disseminated infection in a noncompromised host. Between 1974 and 1984 at our institution, P. boydii was cultured from a variety of sites: respiratory tract, 36; soft tissue, 25; bone, 9; gastric aspirate, 4; maxillary sinus, 2; wound, 2; urine, 2; brain abscess, 1; ear, 1; and toenail, 1. Pulmonary colonization proved to be the most common form of pseudallescheriasis of the lung (34 of 36 cultures in this category); 28 of the 32 patients with pulmonary infections had received immunosuppressive therapy or had an underlying disorder. The importance of isolation of P. boydii from bone and soft tissue is supported in this series because all 9 cultures from bone and 21 of 25 cultures from soft tissue were associated with infection. Of 10 cases of infection, 5 were osteomyelitis and 2 were infected wounds; in addition, maxillary sinusitis, disseminated infection, and a lung abscess occurred in 1 patient each.

Adult↗

Chlorocardicin, a monocyclic beta-lactam from a Streptomyces sp. II. Isolation, physico-chemical properties and structure determination.

Chlorocardicin, a novel monocyclic beta-lactam, was isolated from the fermentation broth of a Streptomyces sp. by the use of non-ionic porous resin and reverse phase chromatography. This chlorine-containing antibiotic is structurally related to nocardicin A. Its physico-chemical characteristics and detailed NMR analysis are described.

Anti-Bacterial Agents↗

Structural characterization of glycopeptide antibiotics related to vancomycin by fast atom bombardment mass spectrometry.

A series of glycopeptide antibiotics related to the vancomycin-ristocetin family have been successfully analyzed by fast atom bombardment mass spectrometry (FABMS). The FAB mass spectra of glycopeptides weighing up to 2,100 daltons exhibit intense molecular ions and fragment ions from which information concerning carbohydrate composition and sequence are readily obtained. Careful adjustment of the FABMS experimental conditions has enabled the accurate masses of the glycopeptides to be determined by high resolution FABMS with an accuracy of better than six ppm. Comparison of the observed molecular ion cluster pattern with calculated isotope distributions reveals the precise number of chlorine atoms in these molecules, which, together with the accurate mass data, can be used to restrict the number of possible elemental compositions to a meaningfully small value. These techniques have been used to characterize several glycopeptides of known structure including ristocetin, actinoidin, avoparcin, vancomycin and A35512B, as well as aridicins A, B and C which are three new, novel members of the vancomycin class.

Anti-Bacterial Agents↗

The histopathologic spectrum in Mycobacterium marinum infection.

Review of nine culture-positive cases of Mycobacterium marinum infection revealed a broad range in the histopathologic features of lesions produced by this organism. Four synovial lesions and five cutaneous infections were observed. A range of inflammatory changes were seen in both synovial and skin lesions, varying from mostly acute inflammation with suppuration to a more chronic process with numerous, well-formed granulomas. Organisms were observed in the biopsy sections of only one of the nine cases. Therefore, culture of the biopsy tissue at 30 degrees C is crucial in establishing the diagnosis. These cases emphasize the importance of considering mycobacterial infection and performing cultures even when granulomatous changes in the synovium or skin are subtle.

Adult↗

Synthesis and characterization of iodinated vasopressin antagonists which retain high affinity for the vasopressin receptor.

The mono- and di-iodinated analogs of lysine and arginine vasopressin have been prepared previously but not well characterized chemically. Their biological activities are greatly reduced with respect to LVP or AVP. In this paper we report a convenient synthesis of iodinated AVP agonists and antagonists, their purification by high performance liquid chromatography, and their characterization by fast atom bombardment mass spectrometry. In contrast to the results obtained with agonists, the mono-iodinated vasopressin antagonist retains virtually the full receptor activity of its non-iodinated parent. This should allow the preparation of labeled vasopressin antagonists of high specific activity for receptor characterization and isolation.

Arginine Vasopressin↗

Trimethoprim/sulfamethoxazole-resistant Nocardia asteroides causing multiple hepatic abscesses. Successful treatment with ampicillin, amikacin, and limited computed tomography-guided needle aspiration.

Hepatic abscesses are rarely encountered in disseminated Nocardia infections. Sulfonamides alone or trimethoprim/sulfamethoxazole is often efficacious in treating infections caused by Nocardia asteroides. In vitro resistance of N. asteroides to trimethoprim/sulfamethoxazole is occasionally present. The patient described in this report had disseminated nocardiosis initially manifesting as multiple subcapsular hepatic abscesses. In vitro susceptibility studies demonstrated resistance to trimethoprim/sulfamethoxazole. Subsequent treatment with ampicillin and amikacin in conjunction with computed tomography-guided needle aspiration of several of the hepatic abscesses, surgical drainage of a right pleural empyema, and eventual discontinuation of use of corticosteroids resulted in cure of the infection.

Amikacin↗

Disseminated sporotrichosis with Sporothrix schenckii fungemia.

The laboratory diagnosis and therapeutic management of disseminated sporotrichosis can present many problems to the clinical laboratory and the clinician. Culturing of clinical specimens is necessary because the direct microscopic examination of specimens for Sporothrix schenckii often is not useful. Although this organism has been recovered from many specimen sites, recovery from blood has been rare. This report summarizes data concerning recovery of S. schenckii from clinical specimens and the use of serologic and fungal antimicrobial susceptibility data. It appears to be the first antemortem recovery of S. schenckii from blood reported since 1909.

Amphotericin B↗

Fungal sinusitis in healthy and immunocompromised individuals.

Clinical and microbiologic aspects of fungal sinusitis occurring in six patients are presented. Three of the six patients were immunosuppressed. Fatal disseminated fungal disease developed in two of those immunosuppressed. The three patients with normal immune function had fungal infections confined to the nasal sinuses. Aspergillus fumigatus and Aspergillus flavus were recovered from the immunosuppressed patients and Sporothrix schenckii, Alternaria species, and Pseudallescheria boydii were recovered from the immunocompetent patients. Surgical debridement was performed on all patients; however, anti-fungal therapy only was prescribed in patients who were at risk of progressive fungal disease. The microbiology laboratory aids in the diagnosis of fungal sinusitis by examining surgical biopsy material for fungal organisms and by culturing the material for recovery of the fungal pathogen.

Adult↗

In vitro activities of norfloxacin and ciprofloxacin against Mycobacterium tuberculosis, M. avium complex, M. chelonei, M. fortuitum, and M. kansasii.

The activities of ciprofloxacin and norfloxacin against 100 mycobacteria isolates were studied in vitro by the 1% standard proportion method. Ciprofloxacin was more active against M. tuberculosis and M. fortuitum with MICs of 1.0 and 0.25 microgram/ml, respectively, against 90% of isolates; norfloxacin had MICs of 8.0 and 2.0 micrograms/ml, respectively, against 90% of isolates.

Anti-Bacterial Agents↗

Clinical evaluation of the lysis-centrifugation blood culture system for the detection of fungemia and comparison with a conventional biphasic broth blood culture system.

In a comparative fungal blood culture study, a lysis-centrifugation system (Isolator; Du Pont Co., Wilmington, Del.) detected 89% of all episodes of fungemia; the lysis-centrifugation system detected fungemia exclusively or significantly earlier than did a biphasic brain heart infusion bottle system 83% of the time. The lysis-centrifugation system was particularly useful in the early detection of fungemia caused by Candida tropicalis and Candida glabrata. In 53% of the clinically significant episodes, the earlier detection was directly helpful in the management of patients with fungemia. High-magnitude candidemia (greater than 5 CFU/ml of blood) was significantly associated with the presence of an infected intravascular catheter and with Candida species other than Candida albicans. The lysis-centrifugation system was sensitive in the detection of fungemia during the monitoring of patients receiving antifungal agents or after removal of an infected intravascular catheter.

Candidiasis↗

Effect of storage of the du Pont lysis-centrifugation system on recovery of bacteria and fungi in a prospective clinical trial.

A commercially available lysis-centrifugation system was compared with a conventional biphasic brain heart infusion medium in a prospective clinical study of 5,125 fungal blood cultures. Recovery rates were compared between two time periods to assess the effect of 25 degrees C storage before processing by the lysis-centrifugation system. The lysis-centrifugation tubes processed within 9 h showed a significantly higher yield (3.4 versus 1.49%) for yeasts (Candida glabrata), filamentous fungi (Histoplasma capsulatum), and bacteria (8.84 versus 7.34%) (Klebsiella pneumoniae and Serratia marcescens) than did those processed after 9 h.

Bacteria↗

Candida pseudotropicalis fungemia and invasive disease in an immunocompromised patient.

A case of Candida pseudotropicalis fungemia and invasive disease in an immunocompromised patient is reported. Multiple blood cultures taken over a 2-week period were positive, and histopathological slides of postmortem spleen and kidney tissue showed tissue invasion by the organism. The source of the yeast infection was determined to be the urinary tract. This is the first report of C. pseudotropicalis fungemia documented by culture.

Candida↗