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Biomedical subjects

S Fish

Publications and source records attributed to S Fish.

At least 19 recordsLinked to original sources
PubMed2001

The tylosin-biosynthetic genes of Streptomyces fradiae.

The tylosin-biosynthetic (tyl) gene cluster occupies about 1% of the genome of Streptomycesfradiae and includes at least 43 open reading frames. In addition to structural genes required for tylosin production, the tyl cluster contains three resistance determinants and several regulatory genes. Tylosin production is evidently controlled by pathway-specific and pleiotropic regulators with the likely involvement of y-butyrolactone signalling factors. Accumulation of the polyketide aglycone is controlled by glycosylated macrolides and optimal performance of the complex polyketide synthase enzyme requires the activity of an editing thioesterase.

Anti-Bacterial Agents↗
PubMed2001

Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice.

The experimental work characterizing the anabolic effect of parathyroid hormone (PTH) in bone has been performed in nonmurine ovariectomized (OVX) animals, mainly rats. A major drawback of these animal models is their inaccessibility to genetic manipulations such as gene knockout and overexpression. Therefore, this study on PTH anabolic activity was carried out in OVX mice that can be manipulated genetically in future studies. Adult Swiss-Webster mice were OVX, and after the fifth postoperative week were treated intermittently with human PTH(1-34) [hPTH(1-34)] or vehicle for 4 weeks. Femoral bones were evaluated by microcomputed tomography (microCT) followed by histomorphometry. A tight correlation was observed between trabecular density (BV/TV) determinations made by both methods. The BV/TV showed >60% loss in the distal metaphysis in 5-week and 9-week post-OVX, non-PTH-treated animals. PTH induced a approximately 35% recovery of this loss and a approximately 40% reversal of the associated decreases in trabecular number (Tb.N) and connectivity. PTH also caused a shift from single to double calcein-labeled trabecular surfaces, a significant enhancement in the mineralizing perimeter and a respective 2- and 3-fold stimulation of the mineral appositional rate (MAR) and bone formation rate (BFR). Diaphyseal endosteal cortical MAR and thickness also were increased with a high correlation between these parameters. These data show that OVX osteoporotic mice respond to PTH by increased osteoblast activity and the consequent restoration of trabecular network. The Swiss-Webster mouse model will be useful in future studies investigating molecular mechanisms involved in the pathogenesis and treatment of osteoporosis, including the mechanisms of action of known and future bone antiresorptive and anabolic agents.

Animals↗
PubMed2000

Outcome of treatment for limb and limb girdle sarcomas at the Royal Marsden Hospital.

AIMS: In this study we aimed to determine local recurrence, mortality an d amputation rates in patients presenting with limb and limb girdle soft tissue sarcomas. METHOD: A review of all 439 patients presenting with p rimary or recurrent soft tissue sarcomas of limb and limb girdle to the Royal Marsden Hospital between 1989 and 1995 was carried out. RESULTS: The local recurrence rate was 15.5% and the mortality rate was 30%, with a median follow up of 3.2 years and an overall amputation rate of 4.8%. CONCLUSION: The outcome of limb and limb girdle sarcomas in this study i s comparable to those reported elsewhere.

Amputation, Surgical↗
PubMed1999

Cocaine absorption after application of a viscous cocaine-containing TAC solution.

STUDY OBJECTIVES: We sought to measure plasma cocaine and benzoylecgonine levels in children after application of a solution of a topical anesthetic containing tetracaine 0.5%, epinephrine 1:2, 000, and viscous cocaine 5.9% (TAC) to lacerations requiring suture repair. Previous reports demonstrating cocaine absorption used aqueous cocaine. The purpose of this study is to determine whether systemic absorption occurs with viscous cocaine. METHODS: We used a convenience sample of children in a pediatric emergency department during the summer months of 1994 and 1995. Participants were pediatric patients less than 15 years of age with simple lacerations requiring suturing. RESULTS: Twenty-five patients were enrolled in the study. The mean age of the patients was 8.5 years (range, 3 to 13 years). Lacerations tended to be small, with a mean length of 2.2 cm (range, 1 to 8 cm). Plasma cocaine and benzoylecgonine levels were measured by means of high-performance liquid chromatography. The mean time for obtaining the plasma sample for cocaine analysis was 67.2+/-23.9 minutes (range, 28 to 130 minutes) after application of the viscous cocaine-containing TAC solution. Qualitative assay results, which were accurate to 50 ng/mL, were negative in all 25 patients for both plasma cocaine and benzoylecgonine. No child demonstrated any signs or symptoms suggestive of cocaine toxicity. CONCLUSION: In our study, application of viscous cocaine-containing TAC solutions to small lacerations did not produce clinically important cocaine absorption.

Adolescent↗
PubMed1999

Assessment of the "scholarly project" requirement for emergency medicine residents: report of the SAEM Research Directors' workshop. SAEM Research Directors' Interest Group.

OBJECTIVES: Differences in interpretation of the residency review committee (RRC) directive concerning resident scholarly activity have resulted in inconsistencies in the practical fulfillment of this responsibility among the various training programs in emergency medicine. During a workshop organized by the SAEM Research Directors' Interest Group (RDIG), a consensus statement was developed regarding the scope, definition, and purpose of the scholarly project requirement. METHODS: During the workshop, the NIH model of consensus building was used to develop statements pertaining to specific questions of the goals, definition, and endpoints of the scholarly project. The program consisted of an overview of the history and issues related to the scholarly project and presentations of varying viewpoints from interested parties. A final consensus of answers to the defined questions was then developed by the workshop participants during roundtable discussions and further refined through interactive debate using the RDIG e-mail list server. RESULTS: By consensus it was agreed that the primary role of the scholarly project is to instruct residents in the process of scientific inquiry, to teach problem-solving skills, and to expose the resident to the mechanics of research. To realize these goals, the project should include the general elements of hypothesis formulation, data collection, analytic thinking, and interpretation of results. It was also thought that these elements should be documented in some written form with a literature review. CONCLUSIONS: While each residency program must implement the RRC residency requirements in a manner that best suits the needs and culture of its individual environment, a concurrence of definition and approach to satisfying the scholarly project requirement would provide better consistency in resident training. Guidelines developed by consensus during the SAEM RDIG workshop may serve as a general recipe that can be used to fulfill the goals of the scholarly project and the spirit of the RRC directive.

Decision Making↗
PubMed1996

The macrolide-lincosamide-streptogramin B resistance phenotypes characterized by using a specifically deleted, antibiotic-sensitive strain of Streptomyces lividans.

Genes conferring resistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics via ribosomal modification are widespread in bacteria, including clinical isolates and MLS-producing actinomycetes. Such erm-type genes encode enzymes that mono- or dimethylate residue A-2058 of 23S rRNA. The different phenotypes resulting from monomethylation (MLS-I phenotype, conferred by erm type I genes) or dimethylation (MLS-II phenotype due to erm type II genes) have been characterized by introducing tlrD or ermE, respectively, into an MLS-sensitive derivative of Streptomyces lividans TK21. This strain (designated OS456) was generated by specific replacement of the endogenous resistance genes lrm and mgt. The MLS-I phenotype is characterized by high-level resistance to lincomycin with only marginal resistance to macrolides such as chalcomycin or tylosin, whereas the MLS-II phenotype involves high-level resistance to all MLS drugs. Mono- and dimethylated ribosomes were introduced into a cell-free protein-synthesizing system prepared from S. lividans and compared with unmodified particles in their response to antibiotics. There was no simple correlation between the relative potencies of MLS drugs at the level of the target site (i.e., the ribosome) and their antibacterial activities expressed as MICs.

Anti-Bacterial Agents↗
PubMed1995

Malignant epithelial parotid tumours: a rational treatment policy.

Formal parotidectomy was undertaken in 271 patients by one surgeon over 11 years. Forty patients were treated for malignant salivary tumours (nine were recurrent). Low-grade tumours (45 per cent) were treated by surgery alone, untreated high-grade tumours (55 per cent) by surgery and radiotherapy, before or after operation, depending on clinical findings. The aims of surgery were to obtain tumour clearance, to preserve the facial nerve if possible, and to perform radical neck dissection for palpable malignant lymphadenopathy proven cytologically and for high-grade tumours when intraoperative jugulodigastric lymph node biopsy confirmed metastasis. Four patients sustained facial weakness as a result of surgery. At a median of 46 months follow-up two patients had developed local recurrence. Eleven patients with high-grade but none with low-grade tumours died from metastases. Patients with high-grade lesions with facial weakness from malignant infiltration and those with lymphatic metastasis have a significantly worse prognosis than those without. Locoregional control of parotid cancers can be achieved by formal parotidectomy and selective irradiation without routine sacrifice of the facial nerve.

Adolescent↗
PubMed1994

Superficial parotidectomy in the treatment of cutaneous melanoma of the head and neck.

The preauricular lymph nodes are frequently the first site of metastatic disease from primary malignant melanoma of the upper two-thirds of the face or the anterior scalp. For these patients, or those with adjacent metastatic nodal disease, the prognosis is poor. The median survival of 13 such patients presented was 2 years, with two long-term survivors at 4 and 6 years. Palliative surgery can, however, prevent uncontrolled locoregional disease. Patients with palpable preauricular and cervical node disease should be treated by facial nerve-preserving parotidectomy and radical neck dissection. When no cervical nodes are palpable in patients with preauricular node metastasis, peroperative jugulodigastric node biopsy and frozen-section histopathological examination are useful to select patients for radical neck dissection.

Adolescent↗
PubMed1994

Management of soft tissue sarcoma.

A total of 485 patients with a proven or suspected diagnosis of soft tissue sarcoma were referred over a 3-year period. Of these, 61 were referred for opinion only and 424 for definitive treatment. Overall there were 223 patients with primary soft tissue sarcoma and 84 with recurrent sarcoma, 84 with benign soft tissue tumours and 22 with non-soft tissue sarcoma malignancy; 11 patients were referred with known metastatic disease. The commonest benign tumours mimicking soft tissue sarcoma were fibromatosis and benign intermuscular or intramuscular lipoma. The malignant tumours suspected clinically of being soft tissue sarcoma were bone tumours, lymphoma and metastatic carcinoma. Of the 172 patients with primary soft tissue sarcoma referred with a proven diagnosis this had been established by excision biopsy in 94 and open incision biopsy in 48. By contrast, of those undiagnosed at referral, 44 of 51 patients with soft tissue sarcoma had the diagnosis made by Tru-cut core biopsy. Amputation was performed in four of 165 patients with primary extremity soft tissue sarcoma and in five of 54 with recurrent extremity sarcoma, giving an overall amputation rate of 4 per cent. It is proposed that the amputation rate for extremity soft tissue sarcoma can be reduced by the use of reconstructive procedures, particularly myocutaneous flaps to the proximal limbs and limb girdles, and free vascularized flaps to sites distal to the midthigh and midarm.

Adolescent↗
PubMed1993

Purification and characterization of an enzyme involved in oxidative carbon-carbon bond cleavage reactions in the methionine salvage pathway of Klebsiella pneumoniae.

The 5-methylthio-D-ribose moiety of 5'-(methylthio)-adenosine is converted to methionine in a wide variety of organisms. 2,3-Diketo-5-methylthio-1-phosphopentane is an advanced intermediate in the methionine recycling pathway present in the Gram-negative bacterium Klebsiella pneumoniae. This unusual metabolite is oxidatively cleaved to yield formate (from C-1), 2-keto-4-methylthiobutyrate (the transamination product of methionine), and 3-methylthiopropionate. To further characterize this oxidative conversion, the desthio analog of the naturally occurring diketone, namely 2,3-diketo-1-phosphohexane I, was synthesized. If the metabolism of I is analogous to that of 2,3-diketo-5-methylthio-1-phosphopentane it should be converted to formate, 2-ketopentanoate, and butyrate. An enzyme (E-1), which mediates the oxidative conversion of I to formate and 2-ketopentanoate, was isolated from extracts of K. pneumoniae. E-1 was purified 100-fold to homogeneity in 10% yield. The native enzyme is a monomeric protein of M(r) 27,000. The activity of E-1 requires magnesium ion as a cofactor. No other prosthetic groups were detected. Incubation of the enzyme with I, under anaerobic conditions, led to the discovery of two intermediates. These species have been identified by 1H and 13C NMR, UV-visible spectroscopy, and model chemistry studies as 2-hydroxy-3-keto-1-phospho-1-hexene II, generated by enolization of I; and 1,2-dihydroxy-3-keto-1-hexene III, generated by enzymatic dephosphorylation of II. Intermediates II and III are released from the active site of the enzyme; III accumulates under anaerobic conditions. Under aerobic conditions, III is non-enzymically oxidized to 2-ketopentanoate, formate, and other products. Compound II was also generated by heating I at pH 7.5 for 7 min. Action of alkaline phosphatase on II produces III.

Amino Acid Sequence↗