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Biomedical subjects

K Franklin

Publications and source records attributed to K Franklin.

At least 19 recordsLinked to original sources
PubMed2005

Hormone replacement therapy, body mass index and asthma in perimenopausal women: a cross sectional survey.

BACKGROUND: Hormone replacement therapy (HRT) and obesity both appear to increase the risk of asthma. A study was undertaken to investigate the association of HRT with asthma and hay fever in a population of perimenopausal women, focusing on a possible interaction with body mass index (BMI). METHODS: A postal questionnaire was sent to population based samples in Denmark, Estonia, Iceland, Norway, and Sweden in 1999-2001, and 8588 women aged 25-54 years responded (77%). Pregnant women, women using oral contraceptives, and women <46 years were excluded. Analyses included 2206 women aged 46-54 years of which 884 were menopausal and 540 used HRT. Stratified analyses by BMI in tertiles were performed. RESULTS: HRT was associated with an increased risk for asthma (OR 1.57 (95% CI 1.07 to 2.30)), wheeze (OR 1.60 (95% CI 1.22 to 2.10)), and hay fever (OR 1.48 (95% CI 1.15 to 1.90)). The associations with asthma and wheeze were significantly stronger among women with BMI in the lower tertile (asthma OR 2.41 (95% CI 1.21 to 4.77); wheeze OR 2.04 (95% CI 1.23 to 3.36)) than in heavier women (asthma: p(interaction) = 0.030; wheeze: p(interaction) = 0.042). Increasing BMI was associated with more asthma (OR 1.08 (95% CI 1.05 to 1.12) per kg/m2). This effect was only found in women not taking HRT (OR 1.10 (95% CI 1.05 to 1.14) per kg/m2); no such association was detected in HRT users (OR 1.00 (95% CI 0.92 to 1.08) per kg/m2) (p(interaction) = 0.046). Menopause was not significantly associated with asthma, wheeze, or hay fever. CONCLUSIONS: In perimenopausal women there is an interaction between HRT and BMI in the effects on asthma. Lean women who were HRT users had as high a risk for asthma as overweight women not taking HRT. It is suggested that HRT and overweight increase the risk of asthma through partly common pathways.

Adult↗
PubMed2004

Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms.

Several studies have identified obesity as a risk factor for asthma in both children and adults. An increased prevalence of asthma in subjects with gastro-oesophageal reflux (GOR) and obstructive sleep apnoea syndrome has also been reported. The aim of this investigation was to study obesity, nocturnal GOR and snoring as independent risk factors for onset of asthma and respiratory symptoms in a Nordic population. In a 5-10 yr follow-up study of the European Community Respiratory Health Survey in Iceland, Norway, Denmark, Sweden and Estonia, a postal questionnaire was sent to previous respondents. A total of 16,191 participants responded to the questionnaire. Reported onset of asthma, wheeze and night-time symptoms as well as nocturnal GOR and habitual snoring increased in prevalence along with the increase in body mass index (BMI). After adjusting for nocturnal GOR, habitual snoring and other confounders, obesity (BMI >30) remained significantly related to the onset of asthma, wheeze and night-time symptoms. Nocturnal GOR was independently related to the onset of asthma and in addition, both nocturnal GOR and habitual snoring were independently related to onset of wheeze and night-time symptoms. This study adds evidence to an independent relationship between obesity, nocturnal gastro-oesophageal reflux and habitual snoring and the onset of asthma and respiratory symptoms in adults.

Adult↗
PubMed2001

Isolated sternal fracture--a swing-related injury in two children.

Isolated fracture of the sternum is an uncommon injury in a child. We report two cases of sternal fracture following falls from swings, which illustrate the mechanisms of injury in sternal fracture. One fracture resulted from a flexion compression injury of the thoracic spine, which has very rarely been reported in children. Sternal fracture should be considered in the differential diagnosis of acute chest pain in a child where there has been an activity involving hyperflexion force.

Accidental Falls↗
PubMed2001

Bladder diverticulum simulating a pelvic metastasis on a Tc-99m HDP bone scan.

Carcinoma of the prostate was diagnosed in a 74-year-old man. A Tc-99m HDP bone scan was performed as part of the initial staging process. The findings on the bone scan were normal except for an area of increased tracer uptake projected over the left sacroiliac joint, which was seen best on the anterior view. When this was investigated further, the findings of a plain radiograph were inconclusive. Computed tomography showed a large diverticulum projecting from the left side of the bladder; the tracer retained within this diverticulum had produced the findings on the bone scan.

Aged↗
PubMed2001

Overexpression and characterization of the chromosomal aminoglycoside 2'-N-acetyltransferase of Providencia stuartii.

The gene coding for aminoglycoside 2'-N-acetyltransferase Ia [AAC(2')-Ia] from Providencia stuartii was amplified by PCR and cloned. The resulting construct, pACKF2, was transferred into Escherichia coli for overexpression of AAC(2')-Ia as a fusion protein with an N-terminal hexa-His tag. The fusion protein was isolated and purified by affinity chromatography on Ni(2+)-nitrilotriacetic acid agarose and gel permeation chromatography on Superdex 75. Comparison of the specific activity of this enzyme with that of its enterokinase-digested derivative lacking the His tag indicated that the presence of the extra N-terminal peptide does not affect activity. The temperature and pH optima for activity of both forms of the 2'-N-acetyltransferase were 20 degrees C and pH 6.0, respectively, while the enzymes were most stable at 15 degrees C and pH 8.1. The Michaelis-Menten kinetic parameters for AAC(2')-Ia at 20 degrees C and pH 6.0 were determined using a series of aminoglycoside antibiotics possessing a 2'-amino group and a concentration of acetyl coenzyme A fixed at 10 times its K(m) value of 8.75 microM. Under these conditions, gentamicin was determined to be the best substrate for the enzyme in terms of both K(m) and k(cat)/K(m) values, whereas neomycin was the poorest. Comparison of the kinetic parameters obtained with the different aminoglycosides indicated that their hexopyranosyl residues provided the most important binding sites for AAC(2')-Ia activity, while the enzyme exhibits greater tolerance further from these sites. No correlation was found between these kinetic parameters and MICs determined for P. stuartii PR50 expressing the 2'-N-acetyltransferase, suggesting that its true in vivo function is not as a resistance factor.

Acetyltransferases↗
PubMed2000

Autonomic cardiovascular regulation in patients with obstructive sleep apnoea: a study based on spectral analysis of heart rate variability.

The aim of this study was to assess the function of the autonomic nervous system in patients with obstructive sleep apnoea syndrome (OSAS). The study was designed as a cross-sectional case-control study. Fifty-one patients were included, and the findings were compared with those in 66 controls. Spectral analysis of heart rate variability (HRV) during supine rest, during controlled breathing and after tilting was performed in each patient and control case. The patients performed overnight sleep recordings the night before the HRV recordings. Individuals with an apnoea-hypopnoea index (AHI) above 20 were regarded as OSAS patients and those with AHI lower than 20 as snorers. Differences in HRV and blood pressure between patients and controls were analysed by multiple linear regression with age, body mass index and sex as independent variables. During free and controlled breathing there was a significant decrease in indices reflecting vagal modulation, indicating parasympathetic dysfunction in OSAS patients compared with controls. The mid-frequency component was also significantly reduced in OSAS patients after tilting but not in the lying position. This may be related to the parasympathetic dysfunction, but could also indicate a decreased sympathetic reserve capacity. We found no significant relation between AHI and indices of vagal modulation in the patient group. Our findings show an autonomic dysfunction in patients with OSAS. The dysfunction involves the parasympathetic system, and may be related to the increased cardiovascular mortality and malignant arrhythmia described in OSAS.

Adult↗
PubMed1999

Chemically synthesized ubiquitin extension proteins detect distinct catalytic capacities of deubiquitinating enzymes.

We have used solid-phase chemistry to synthesize proteins equivalent to a human ubiquitin precursor (ubiquitin-52-amino-acid ribosomal protein fusion; UBICEP52) and representative of isopeptide-linked ubiquitin-protein conjugates [ubiquitin-(epsilonN)-lysine]; these proteins were precisely cleaved by a purified recombinant Drosophila deubiquitinating enzyme (DUB), UCH-D. Along with the previously synthesized ubiquitin-(alphaN)-valine, these synthetic proteins were used as substrates to assess the catalytic capacities of a number of diverse DUBs expressed in Escherichia coli: human HAUSP; mouse Unp; and yeast Ubps 1p, 2p, 3p, 6p, 11p, and 15p and Yuh1p. Distinct specificities of these enzymes were detected; notably, in addition to UCH-D, isopeptidase activity [ubiquitin-(epsilonN)-lysine cleavage] was only associated with Yuh1p, Unp, Ubp1p, and Ubp2p. Additionally, human placental 26S proteasomes were only able to cleave UBICEP52 and ubiquitin-(epsilonN)-lysine, suggesting that 26S proteasome-associated DUBs are class II-like. This work demonstrates that the synthetic approach offers an alternative to recombinant methods for the production of small proteins in vitro.

Animals↗
PubMed1999

Site-directed mutagenesis and molecular modeling identify a crucial amino acid in specifying the heparin affinity of FGF-1.

Heparin potentiates the mitogenic activity of FGF-1 by increasing the affinity for its receptor and by extending its biological half-life. During the course of labeling human FGF-1 with Na(125)I and chloramine T, it was observed that the protein lost its ability to bind to heparin. In contrast, bovine FGF-1 retained its heparin affinity even after iodination. To localize the region responsible for the lost heparin affinity, chimeric FGF-1 proteins were constructed from human and bovine FGF-1 expression constructs and tested for their heparin affinity after iodination. The results showed that the C-terminal region of human FGF-1 was responsible for the loss of heparin affinity. This region harbors a single tyrosine residue in human FGF-1 in contrast to a phenylalanine at this position in bovine FGF-1. Mutating this tyrosine residue in the human FGF-1 sequence to phenylalanine did not restore the heparin affinity of the iodinated protein. Likewise, changing the phenylalanine to tyrosine in the bovine FGF-1 did not reduce the ability of the iodinated protein to bind to heparin. In contrast, a mutant human FGF-1 that has cysteine-131 replaced with serine (C131S) was able to bind to heparin even after iodination while bovine FGF-1 (S131C) lost its binding affinity to heparin upon iodination. In addition, the human FGF-1 C131S mutant showed a decrease in homodimer formation when exposed to CuCl(2). Molecular modeling showed that the heparin-binding domain of FGF-1 includes cysteine-131 and that cysteine-131, upon oxidation to cysteic acid during the iodination procedures, would interact with lysine-126 and lysine-132. This interaction alters the conformation of the basic residues such that they no longer bind to heparin.

Amino Acid Sequence↗
PubMed1998

The ultrasound diagnosis of posterior shoulder dislocation associated with Erb's palsy.

A case is presented of an infant with Erb's palsy whose posterior dislocation of the humeral head was identified using high-resolution ultrasound following non-diagnostic plain radiographs. Posterior dislocation is associated with Erb's palsy but the diagnosis can be delayed. We suggest the early use of ultrasound in patients with Erb's palsy, as this technique is a safe, quick and reliable method of excluding posterior dislocation.

Birth Injuries↗
PubMed1998

Knowing what to remember and forget: a developmental study of cue memory in intentional forgetting.

These experiments are the first to investigate children's encoding and use of information about a memory cue in Bjork's (1972) intentional forgetting task. In Experiment 1, children in Grades 2, 4, and 6 and college students were given cues to either remember or forget after the presentation of each picture. Recall and recognition tests of pictures and cues followed. The procedure in Experiment 2 was identical to that in Experiment 1 except that the list of presentation pictures was altered for some children (Grades 3 and 4) and adolescents (Grades 8 and 9) so that remember and forget cues were associated with particular taxonomic categories. In Experiment 3, the testing component was modified so that children (Grades 2, 3, and 4) and college students were asked to recall only the cue associated with each picture. The results indicated that (1) children as young as second graders encode the cue associated with each picture, although to a lesser extent than do college students, (2) much improvement in intentional forgetting is still occurring during adolescence, (3) only adults adequately cluster their recall by cue, (4) associating remember and forget cues with items from different categories does not increase the differentiation between cues, and (5) eliminating picture recall and recognition has minimal effects on the magnitude of cue judgments. These results suggest that children's difficulties on intentional forgetting tasks stem, at least in part, from their poorer encoding of information about whether an item should be remembered or forgotten.

Adolescent↗
PubMed1997

Capillary electrophoresis assay for ubiquitin carboxyl-terminal hydrolases with chemically synthesized ubiquitin-valine as substrate.

Ubiquitin is expressed in eukaryotic cells as precursors, fused via its carboxyl terminus either to other ubiquitin sequences in linear polyubiquitin arrays or to specific ribosomal proteins. In some of the polyubiquitin fusions a single amino acid (e.g., valine in humans) is attached to the carboxyl terminus. These gene products are rapidly (probably cotranslationally) cleaved by ubiquitin carboxyl-terminal hydrolase (UCH) enzymes; therefore, although ubiquitin precursors are suitable substrates for assays of UCH activity, they are difficult to isolate from nucleated cells. While the recombinant approach allows the production of ubiquitin precursors in prokaryotic cells (which do not contain the ubiquitin system), proteins produced in this manner require purification and may also be susceptible to modification by bacterial enzymes, e.g., adventitious proteolysis. As an alternative we have chemically synthesized human ubiquitin-valine. In the assay described here the cleavage of ubiquitin-valine to ubiquitin (77 and 76 residue proteins, respectively) by a purified recombinant Drosophila UCH was monitored by capillary electrophoresis. Mass spectrometry verified the precise cleavage of ubiquitin-valine, confirming that this synthetic protein is a UCH substrate. Synthetic ubiquitin-valine may serve as a generic substrate for UCHs allowing the purification and identification of new members of this enzyme family.

Animals↗
PubMed1994

Case report: ultrasound diagnosis of unsuspected necrotizing enterocolitis.

We report a case of portal and systemic venous gas detected in a neonate without clinical or radiographic evidence of necrotizing enterocolitis who then subsequently developed unequivocal clinical and radiographic signs of this condition. These findings are discussed in relation to previous reports in the literature.

Enterocolitis, Pseudomembranous↗
PubMed1992

99Tcm-mercapto acetyl triglycine in paediatric renal tract disease.

The use of 99Tcm-mercapto acetyl triglycine (99Tcm-MAG3), a new hippuran substitute, has been reported widely in adults but not in children. Our experience of its use in 100 infants and children for renography and indirect micturating cystography (IMC) is reported. The average age was 5.6 years. 65 patients completed IMC studies and nine patients had 99Tcm-dimercaptosuccinic acid (99Tcm-DMSA) scans performed on the same day. The majority of patients were referred for the investigation of urinary tract infection. 32 kidneys were found to be scarred on 99Tcm-MAG3 scans, 17 kidneys and ureters refluxed on IMC and 14 kidneys were obstructed. The results of 99Tcm-MAG3 scans were compared with those of other urinary tract investigations including ultrasound, micturating cystography (MCUG), intravenous urography (IVU) and 99Tcm-DMSA scintigraphy. No kidney which was scarred had a normal 99Tcm-MAG3 scan. All significant degrees of dilatation or obstruction on IVU or ultrasound were also detected by 99Tcm-MAG3. 99Tcm-MAG3 gave more information than any other single imaging modality and we believe it represents an ideal initial screening test in the investigation of urinary tract infection in older toilet-trained children.

Adolescent↗
PubMed1992

Patterns of accreditation performance in army family practice residencies.

Army leadership emphasizes training in all segments of its population, including family medicine. Standards for medical professional training, however, are provided by a civilian agency, the Accreditation Council for Graduate Medical Education (ACGME). In order to search for performance patterns, the authors reviewed the last two accreditation documents of each Army Family Practice residency. After independently scoring the documents against the written standards, the scores were compared with the actual written findings from the ACGME Residency Review Committee. The authors discuss patterns and trends resulting from this analysis, and recommend areas for future growth in the military training of family physicians.

Accreditation↗