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Biomedical subjects

D Flint

Publications and source records attributed to D Flint.

15 recordsLinked to original sources
PubMed2000

Cervical lymphadenitis due to non-tuberculous mycobacteria: surgical treatment and review.

A retrospective study was carried out on 57 children, presenting with non-tuberculous mycobacterial (NTM) lymphadenitis of the head and neck, over a 12 year period. Cultures recovered 56 Mycobacterium avium-intracellulare (MAI), and one Mycobacterium kansasaii. Anti-mycobacterial agents were used in seven patients only. On the basis of the initial operation there were two groups. Group 1 (11 patients) had an excision, and Group 2 (46 patients) had incision and drainage (30 patients), incision and curettage (13 patients), or aspiration (three patients). There was no significant difference in the makeup of these two groups. However, Group 1 had significantly lower number of re-operations than Group 2, P<0.01, and achieved a significantly greater healing rate than Group 2, P<0.001. In Group 2 those who had an excision following failure of the first operation were significantly more likely to heal than those who did not, P<0. 005. Operative excision gives a lower rate of re-operation, and a higher rate of healing than other procedures. The treatment, natural history, clinical presentation, pathogenesis, and diagnosis of NTM cervical lymphadenitis are discussed.

Adult↗
PubMed2000

The role of Stat3 in apoptosis and mammary gland involution. Conditional deletion of Stat3.

STATs (signal transducer and activator of transcription) are a family of latent transcription factors which are activated in response to a variety of cytokines and growth factors. This family of signalling molecules have been implicated in growth, differentiation, survival and apoptosis. In this article, we will review work which highlights the role of individual STAT factors in mammary gland and demonstrate the value of genetically modified mice in defining the function of STAT3. Involution of the mouse mammary gland is characterised by extensive apoptosis of the epithelial cells and the activation of STAT3. STATs 3 and 5 have reciprocal patterns of activation throughout a mammary developmental cycle suggesting that STAT5 may be a survival factor and STAT3 a death factor for differentiated mammary epithelium. To clarify the role of STAT3 in mammary epithelial apoptosis, we have generated a conditional knockout using the lox/Cre recombination system. Mammary glands from crosses of transgenic mice expressing Cre recombinase under the control of the beta-lactoglobulin milk protein gene promoter with mice harbouring one floxed STAT3 allele and one null STAT3 allele, showed a decrease in epithelial apoptosis and a dramatic delay of the involution process upon forced weaning. This was accompanied by precocious activation of STAT1 and increases in p53 and p21 levels--these may act as a compensatory mechanism for initiating the eventual involution which occurs in STAT3 null mammary glands. This demonstrates for the first time the importance of STAT factors in signalling the initiation of physiological apoptosis in vivo and highlights the utility of the lox/Cre system for addressing the function of genes, which have an embryonic lethal phenotype, specifically in mammary gland.

Animals↗
PubMed1998

Predicting return to work. A long-term follow-up study of railroad workers after low back injuries.

STUDY DESIGN: Evaluation of the long-term outcomes of 178 railroad employees with low back injury who had completed a multidisciplinary rehabilitation program. OBJECTIVES: To study two major areas: 1) outcomes of the rehabilitation program in terms of the patient's improvement in function and rate of return to work and 2) factors that predict long-term retention at work, both at the railroad and elsewhere. SUMMARY OF BACKGROUND DATA: Several studies have been published examining rehabilitation outcomes of individuals covered under workers' compensation law, but few exist that have examined railroad workers covered by the Federal Employers Liability Act, and few studies exist with follow-up periods longer than 3 years. METHODS: Physical/medical, self-reported, and employment/financial data were collected on each patient from medical and employment records. Follow-up data regarding employment status were obtained either from the employer or from the patient by telephone interview. RESULTS: On average, the patients improved in all objective and subjective measures after rehabilitation. Improvements in these measures were not predictive of return to work. At follow-up examination, 89% of the contacted patients were employed--61% still at the rail-road. The employment factors of lost work days and length of employment and the financial factor of wage rate were the most predictive of long-term work status. CONCLUSIONS: The multidisciplinary program in the current study was found to improve patient physical functioning and reduce pain. However, success in these measures was not predictive of long-term work status, suggesting that other factors have an impact on work status. Clinicians must be aware that employment and financial factors may have a strong influence on return-to-work outcomes.

Accidents, Occupational↗
PubMed1995

Does an IGF-binding protein (IGFBP) present in involuting rat mammary gland regulate apoptosis?

We examined the effects of GH and prolactin deficiency upon milk production, apoptosis and IGFBP production by the mammary gland. GH deficiency produced a 15% reduction in milk yield, prolactin a 50% reduction and combined prolactin- and GH-deficiency an 85% reduction in milk production. Litter removal led to complete inhibition of milk synthesis within 24 h owing in large part to milk accumulation. GH- and prolactin-deficiency also led to significant loss of mammary cells within 48 h and this was owing at least in part to apoptosis as judged by the appearance of characteristic DNA ladders. Prolactin replacement therapy could prevent all of these changes whilst GH was partially effective. The effects of GH are believed to be mediated via IGF-I, however, we were unable to mimic the effects of GH with IGF-I, IGF-II or a combination of IGF-I, IGF-II and IGFBP-3. We hypothesized that the cell-survival effects of exogenous IGFs might be blocked by an inhibitory IGFBP produced by the gland. Indeed the involuting mammary gland produces large concentrations of an IGFBP which Northern blotting identified as IGFBP-5. There was also a small increase in IGFBP-4 mRNA expression. Both appear to be produced by the secretory epithelial cells as judged by in situ hybridization. Preliminary studies using mouse "mammosphere" cultures suggest that they will be useful for investigating a potential causal relationship between IGFBP-5 synthesis and apoptosis.

Animals↗
PubMed1994

Crystal structure of an ATP-dependent carboxylase, dethiobiotin synthetase, at 1.65 A resolution.

BACKGROUND: In Escherichia coli, the enzymes of the biotin biosynthesis pathway are encoded by the bio operon. One of these enzymes, ATP-dependent dethiobiotin synthetase, catalyzes the carboxylation of 7,8-diaminopelargonic acid leading to the formation of the ureido ring of biotin. The enzyme belongs to the class of ATP-dependent carboxylases and we present here the first crystal structure determined for this class of enzyme. RESULTS: We have determined the crystal structure of homodimeric dethiobiotin synthetase to 1.65 A resolution. The subunit consists of a seven-stranded parallel beta-sheet, surrounded by alpha-helices. The sheet contains the classical mononucleotide-binding motif with a fingerprint peptide Gly-X-X-X-X-X-Gly-Lys-Thr. The mononucleotide binding part of the structure is very similar to the GTP-binding protein H-ras-p21 and thus all GTP-binding proteins. A comparison reveals that some of the residues, which in H-ras-p21 interact with the nucleotide and the metal ion, are conserved in the synthetase. CONCLUSIONS: The three-dimensional structure of dethiobiotin synthetase has revealed that ATP-dependent carboxylases contain the classical mononucleotide-binding fold. Considerable similarities to the structure of the GTP-binding protein H-ras-p21 were found, indicating that both proteins might have evolved from a common ancestral mononucleotide-binding fold.

Adenosine Triphosphate↗
PubMed1993

Decreased fat content and increased lean in pigs treated with antibodies to adipocyte plasma membranes.

Antibodies were prepared in sheep against purified plasma membranes from pig adipocytes. Western (immuno) blotting revealed reactions of the antisera with a large number of proteins in adipocyte plasma membranes but remarkably few in plasma membranes from muscle, kidney, liver, lung, brain, spleen, and erythrocytes. This illustrated the high degree of specificity the serum had for adipose tissue. When injected into localized subcutaneous sites such antisera were able to cause considerable adipocyte destruction, which resulted in complete loss of adipose tissue from the site for > or = 14 wk. This cell destruction was probably mediated in part by lymphocytic infiltration. Subcutaneous injections were of limited use because of the localized nature of the effects, but, when treatment was administered intraperitoneally, systemic effects were produced that resulted in a 30% reduction in backfat thickness in the region of the last rib and a 25% reduction in fat content of fore- and hind-loin joints that resulted in a significant increase in the percentage of lean tissue. Total feed intake, live weight gain, hot carcass weights, and dressing percentage were unaffected. These results demonstrate the potential for producing long-term reductions in body fat in pigs by an immunization technique that may also provide the unexpected, potential benefit of increased lean deposition. This suggests that fat deposition per se exerts a restrictive influence on lean carcass development.

Adipose Tissue↗
PubMed1990

Increased growth and protein deposition in rats treated with antibodies to adipocytes.

Young growing rats treated with an antiserum to adipocytes showed marked reductions in several adipose tissue depots but surprisingly demonstrated increased body weight gain. During the first 3 wk after treatment body weight gain increased by 17% with no effect on food intake, whereas during weeks 3-7 body weight gain increased by 40-50% and was accompanied by a 15% increase in food intake. These animals thus exhibited increased food conversion efficiencies (intake/gain) of approximately 15-20% for almost 2 mo. Subsequently, food intake and body weight gain returned to normal (although body weight remained elevated) up to 6 mo. By this time several fat depots were still reduced in size, although total (chemical) fat was identical in treated and control groups. These results suggest that 1) reduction of body fat depots can be achieved using antibodies to adipocytes, 2) compensatory increases in lean body mass can occur, and 3) total fat mass may be regulated.

Adipose Tissue↗
PubMed1975

Synthesis of Endosperm Proteins in Wheat Seed during Maturation.

The time of synthesis, the molecular weight, and the relative glutamine-glutamate and proline to leucine ratios of the endosperm proteins of wheat (Triticum aestivum L. cv. Logan) were determined using a sodium dodecyl sulfate-polyacrylamide gel technique. In general, synthesis of most proteins occurred through much of the maturation of the seed, but past 20 days the rate of synthesis of the high molecular weight proteins declined more rapidly than those of lower molecular weight. The synthesis of at least one protein occurred only late in seed maturation. Several of the high molecular weight proteins had glutamate-glutamine to leucine ratios higher than the remainder of the proteins. No evidence for proteins of a polyglutamine-glutamate and/or proline nature was found.

Journal Article↗