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Biomedical subjects

J Crosby

Publications and source records attributed to J Crosby.

51 records · Page 3Linked to original sources
PubMed1995

Polyketide synthase acyl carrier proteins from Streptomyces: expression in Escherichia coli, purification and partial characterisation.

Acyl carrier proteins (ACPs) of the type II polyketide synthases for the aromatic antibiotics actinorhodin, granaticin, frenolicin and oxytetracycline were expressed in Escherichia coli downstream of an inducible phage T7 promoter. For the act and otc genes, several of the first eight codons were changed to synonymous codons used in highly expressed E. coli genes. Correlated with these changes, the amounts of the act and otc ACPs purified from the recombinant E. coli cultures were an order of magnitude greater than for the gra and fren ACPs expressed from the unmodified genes. Electrospray mass spectrometry (ESMS) of the purified proteins confirmed their calculated M(r) based on the DNA sequences while also revealing that, in the act and gra ACP samples, some 2% and 30% of the holo-form of the protein was present (i.e., carrying the 4'-phosphopantetheine prosthetic group), with the remainder (and 100% of the otc and fren samples) being in the apo-form. Increasing incubation time post heat induction led to an increase in act holo-ACP. The recombinant act and gra ACPs could function in vitro as substrates for an S. coelicolor malonyl CoA:ACP acyl transferase, as measured by the coupling of a labelled malonyl unit to the ACP; their quantitative abilities to do so correlated with the proportions of deduced holo form in the two samples.

Acyl Carrier Protein↗
PubMed1995

Urocanic acid isomers in human skin: analysis of site variation.

Urocanic acid (UCA) is found in the stratum corneum as the trans-isomer and, on ultraviolet (UV) irradiation, photoisomerization into cis-UCA takes place. Cis-UCA has been suggested to play a part in UV-induced immunosuppression. In the present study, the concentration of UCA and the percentage as cis-UCA at 10 different body sites of 20 normal volunteers were analysed. A large interindividual variation in total UCA concentration was found, but the mean UCA concentration in each site was similar, other than at the sole of the foot. There was little variation in the UCA content between sites normally exposed, and not exposed, to light, but the percentage of UCA in the cis form was clearly higher at exposed areas.

Adult↗
PubMed1994

Ambulatory blood pressure and left ventricular hypertrophy in subjects with untreated obstructive sleep apnoea and snoring, compared with matched control subjects, and their response to treatment.

1. Obstructive sleep apnoea and snoring are associated with daytime hypertension. It is uncertain whether this association is directly due to the disturbed sleeping respiration or the result of confounding variables, particularly obesity, smoking and alcohol intake. 2. Ambulatory blood pressure and echocardiographic left ventricular muscle mass were measured in 19 patients with obstructive sleep apnoea, 19 men who snore without apnoea and 38 control subjects matched for age, sex, body mass index, smoking and alcohol intake. Ambulatory blood pressure was also measured before and after treatment in 11 patients with obstructive sleep apnoea and their matched control subjects. 3. Compared with matched control subjects, untreated obstructive sleep apnoea and snoring were not associated with an increase in daytime blood pressure. A daytime elevation of either systolic or diastolic blood pressure of > 3.8 mmHg due to obstructive sleep apnoea or snoring was excluded with 95% confidence in each of the study groups. Daytime blood pressure was also unchanged when obstructive sleep apnoea was treated with nasal continuous positive airway pressure. Night-time blood pressure was not significantly different in the patients with obstructive sleep apnoea or the snorers when compared with their matched control subjects. However, a fall in night-time systolic blood pressure was seen in the patients with obstructive sleep apnoea after treatment [fall in systolic blood pressure -6.3 (SD 8.2) mmHg, P < 0.02]. 4. Left ventricular diameter, wall thickness and calculated mass were similar in each of the study groups and their matched control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure Determination↗
PubMed1994

Plasma insulin and lipid levels in untreated obstructive sleep apnoea and snoring; their comparison with matched controls and response to treatment.

Obstructive sleep apnoea (OSA), and snoring are associated with coronary heart disease. To assess whether OSA or snoring may contribute to this by raising fasting lipid or insulin levels, venous fasting total cholesterol, triglyceride, very-low-density lipoprotein, low-density lipoprotein, high-density lipoprotein, and insulin were measured in 15 untreated OSA patients and 18 snorers. Each of these subjects was individually matched to a control of the same sex, age +/- 10%, body index +/- 15%, smoking and drinking habits. This produced study groups which did not differ significantly by any of these criteria. Fasting venous blood samples were collected at 06.30 hours following polysomnography, and analysed blind of the subjects respiratory status. The OSA patients were then treated with nasal continuous positive airway pressure. In 10 of these subjects lipid and insulin levels were repeated after more than three months treatment. Lipid and insulin levels were also remeasured in the controls matched to these 10 subjects. The end points were compared with paired t-tests. There was no difference in any of the end points when the untreated OSA patients and the snorers were compared to their matched controls (P > 0.25 for all comparisons), and none of the indices changed when OSA was corrected with nasal continuous positive airway pressure (P > 0.25 for all comparisons). Patients with obstructive sleep apnoea or snoring do not have significant fasting hyperlipidaemia or hyperinsulinaemia when compared to carefully matched controls. These factors are therefore unlikely to be the cause of the excess cardiovascular mortality experienced by this patient group.

Journal Article↗
PubMed1994

Non-invasive beat to beat arterial blood pressure during non-REM sleep in obstructive sleep apnoea and snoring.

BACKGROUND: Obstructive sleep apnoea, and possibly snoring, are associated with a poorly understood increase in cardiovascular mortality which may be explained by their effects on systemic blood pressure during sleep. This study compares changes in mean blood pressure during obstructive sleep apnoea and snoring without apnoeas with those in matched control subjects during non-REM sleep. METHODS: Eighteen men with obstructive sleep apnoea, 16 men who snored without apnoeas, and 34 control subjects matched for age, sex, obesity, smoking, and alcohol intake were studied. During polysomnography non-invasive mean blood pressure (Finapres) was recorded from each cardiac cycle during non-REM sleep and averaged over a 10 minute period. This was compared with the blood pressure during 10 minutes before sleep onset. The changes in the patients' sleeping blood pressure were compared with those in their individually matched control subjects. RESULTS: Compared with the control subjects the change in mean (SD) arterial blood pressure between being awake and asleep was higher during obstructive sleep apnoea (+6.5 (9) mm Hg v-2 (6.5), difference 8.5 (11)), and the rise from wakefulness to sleep in the obstructive sleep apnoea group was itself significant. The average mean arterial pressure was not raised in those who snored without apnoeas compared with either the control subjects or during wakefulness. CONCLUSIONS: Average mean arterial pressure is higher during obstructive sleep apnoea than it is during wakefulness, while normal subjects show a fall in blood pressure at sleep onset. This sleep related rise in blood pressure may contribute to the excess cardiovascular morbidity and mortality experienced by patients with this condition.

Blood Pressure↗
PubMed1993

Action spectra for the trans to cis photoisomerisation of urocanic acid in vitro and in mouse skin.

Urocanic acid (UCA) is a major UV chromophore in the upper layers of the skin where it is found predominantly as the trans isomer. UV irradiation induces photoisomerisation of trans-UCA to cis-UCA which has been shown to mimic some of the immunosuppressive properties of UV exposure. We examined the wavelength dependence for trans-UCA to cis-UCA photoisomerisation in vitro and in mouse skin in vivo over the spectral range 270-340 nm. The resulting action spectra were very similar with maximal effectiveness at 300-315 nm and equal activity at 270 nm and 325-330 nm, demonstrating that UVA-II radiation (320-340 nm) is efficient at UCA photoisomerisation. These action spectra differed markedly from the trans-UCA absorption spectrum in vitro and also the reported action spectrum for UV suppression of contact hypersensitivity in mice. These findings suggest that the relationship between cis-UCA formation in skin and UV-induced immunosuppression may be complex.

Animals↗
PubMed1992

Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos.

We have isolated two mouse genes, Mox-1 and Mox-2 that, by sequence, genomic structure and expression pattern, define a novel homeobox gene family probably involved in mesodermal regionalization and somitic differentiation. Mox-1 is genetically linked to the keratin and Hox-2 genes of chromosome 11, while Mox-2 maps to chromosome 12. At primitive streak stages (approximately 7.0 days post coitum), Mox-1 is expressed in mesoderm lying posterior of the future primordial head and heart. It is not expressed in neural tissue, ectoderm, or endoderm. Mox-1 expression may therefore define an extensive 'posterior' domain of embryonic mesoderm before, or at the earliest stages of, patterning of the mesoderm and neuroectoderm by the Hox cluster genes. Between 7.5 and 9.5 days post coitum, Mox-1 is expressed in presomitic mesoderm, epithelial and differentiating somites (dermatome, myotome and sclerotome) and in lateral plate mesoderm. In the body of midgestation embryos, Mox-1 signal is restricted to loose undifferentiated mesenchyme. Mox-1 signal is also prominent over the mesenchyme of the heart cushions and truncus arteriosus, which arises from epithelial-mesenchymal transformation and over a limited number of craniofacial foci of neural crest-derived mesenchyme that are associated with muscle attachment sites. The expression profile of Mox-2 is similar to, but different from, that of Mox-1. For example, Mox-2 is apparently not expressed before somites form, is then expressed over the entire epithelial somite, but during somitic differentiation, Mox-2 signal rapidly becomes restricted to sclerotomal derivatives. The expression patterns of these genes suggest regulatory roles for Mox-1 and Mox-2 in the initial anterior-posterior regionalization of vertebrate embryonic mesoderm and, in addition, in somite specification and differentiation.

Amino Acid Sequence↗
PubMed1991

Localization of components involved in protein transport and processing through the yeast Golgi apparatus.

Saccharomyces cerevisiae sec7 mutants exhibit pleiotropic deficiencies in the transit of proteins through the Golgi apparatus, and elaborate an array of Golgi apparatus-like cisternae at a restrictive growth temperature (37 degrees C). The SEC7 gene encodes an essential high-molecular weight protein (227 kD) that is phosphorylated in vivo. In cell lysates, Sec7 protein (Sec7p) is recovered in both sedimentable and soluble fractions. A punctate immunofluorescent pattern of Sec7p-associated structures seen in SEC cells coalesces in sec14 mutant yeast that accumulate exaggerated Golgi cisternae at 37 degrees C. Sec7p may function as a peripheral membrane protein that cycles between a soluble, cytosolic pool and a sedimentable, membrane-associated complex for its essential role in vesicular traffic through the Golgi apparatus. The transmembrane Kex2 protease, which processes precursors of secreted peptides within the yeast secretory pathway, is also localized by indirect immunofluorescence to multiple structures in the yeast cell (Redding, K., and R. Fuller, manuscript submitted for publication). In double-immunofluorescence labeling experiments, significant colocalization of Sec7 and Kex2 proteins was found. Colocalization of the two antigens, one implicated in protein transport through the Golgi apparatus and the other in processing within a late Golgi compartment, supports the conclusion that we have visualized the yeast Golgi apparatus.

Biological Transport↗
PubMedDate not supplied

Indomethacin and oxaprozin lower seminal prostaglandin levels but do not influence sperm motion characteristics and serum hormones of young healthy men in a placebo-controlled double-blind trial.

To evaluate the influence of indomethacin and oxaprozin on reproductive function in healthy young men, 34 volunteers with normal semen parameters were recruited. In a randomized double-blind design, 12 men were treated with placebo, 12 received 600 mg/day of oxaprozin and 10 took indomethacin 25 mg t.i.d. This treatment phase lasted for 14 days after which a follow-up period extended for another 10 weeks. Sperm counts, percentage of motile and normally formed sperm cells, sperm velocity, linearity, lateral head displacement and beat frequency were evaluated by computerized image analysis once before treatment and at weekly intervals during the rest of the study. Prostaglandin levels in seminal plasma were significantly reduced after 2 weeks of treatment and remained suppressed for at least 2 additional weeks. In spite of this long lasting impairment of physiologic prostaglandin concentrations, no changes in any of the measured parameters were detectable when compared with the placebo group. Basal levels of testosterone, estradiol, LH, FSH, TSH and prolactin were unchanged. The response of hypophyseal hormones to a combined GnRH/TRH test before, during and after the treatment also was not affected. Overall, no negative influence of indomethacin or oxaprozin treatment on male reproductive function could be found in healthy volunteers. Since the active treatment phase was only 14 days, one can only speculate about long term effects of the tested drugs on reproductive parameters in men.

Adult↗