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J Jones

Publications and source records attributed to J Jones.

At least 505 records · Page 28Linked to original sources

Immunocytochemical and biochemical characterization of guanine nucleotide-binding regulatory proteins in mammalian spermatozoa.

Polyclonal antisera directed against conserved and subtype-specific peptide sequences of the alpha-subunits of guanine nucleotide-binding regulatory proteins (G proteins) were used to characterize the nature of mammalian sperm G proteins and to determine whether their localization was consistent with their proposed roles in mediating ZP3-induced acrosomal exocytosis. Mouse and guinea pig sperm exhibit positive immunofluorescence in the acrosomal region using an antiserum directed against a peptide region common to all alpha-subunits of G proteins (G alpha). The immunofluorescence disappears after sperm have undergone the acrosome reaction, suggesting that the immunoreactive material is associated with the plasma membrane/outer acrosomal membrane region overlying the acrosome. The presence of G proteins in this region is confirmed by the presence of a Mr 41,000 substrate for pertussis toxin (PT)-catalyzed [32P]ADP-ribosylation in purified plasma membrane/outer acrosomal membrane hybrid vesicles obtained from acrosome-reacted guinea pig sperm. Immunoprecipitation and polyacrylamide gel electrophoresis of PT-catalyzed [32P]ADP-ribosylated protein(s) using anti-peptide antisera generated against sequences unique to Gi alpha 1, Gi alpha 2, and Gi alpha 3 confirm the existence of all three Gi subtypes in mouse sperm extracts. Indirect immunofluorescence using an antiserum directed against a peptide region present in Gz alpha, a PT-insensitive G protein, demonstrates positive immunoreactivity in the postacrosomal/lateral face region of the mouse sperm head. This immunoreactivity is retained during acrosomal exocytosis in response to solubilized ZP and then disappears subsequent to this exocytotic event. These data demonstrate that Gi protein alpha-subunits are present in the acrosomal region of mammalian sperm, consistent with their postulated role in regulating ZP3-mediated acrosomal exocytosis, and that PT-insensitive Gz alpha is found in a region of the sperm head distinct from that of the Gi alpha subunits.

Acrosome↗

Light microscopic diagnosis of human microsporidiosis and variable response to octreotide.

Microsporida are protozoan parasites that have recently been identified as a cause of human disease in immunocompromised patients. Because of their small size, they have been recognized primarily by electron microscopy. This has limited the study of their prevalence, incidence, and association with large-volume diarrhea. The present report describes two cases of Enterocytozoon bieneusi infection of the small intestine in patients with intractable diarrhea in whom the diagnosis was made by light microscopy and confirmed by electron microscopy. Both patients were treated with octreotide, and one had a good response.

Acquired Immunodeficiency Syndrome↗

Measuring personal exposure to airborne mutagens and nicotine in environmental tobacco smoke.

The exposure of individuals to environmental tobacco smoke (ETS) is of increasing public health concern because epidemiological studies have associated passive smoking with increased risk of a variety of adverse health effects among non-smokers including lung cancer. As a way to measure individual exposure to the mutagenic compounds in the complex mixture of ETS, we used a sensitive Salmonella/microsome micro pre-incubation (microsuspension) assay to detect mutagenicity of particulate matter collected on filters from low volume (1.7 1/min flow rate) personal sampling pumps. Airborne nicotine was collected concurrently as a marker for ETS exposure. In pilot-field studies, individual exposure to ETS was measured in two separate indoor environments in which smokers were present: a gambling casino and a bingo parlor. Total suspended particulate matter (TSP) was collected on filters worn near the breathing zone of non-smoking individuals. Sampling times ranged from 40 min to 6 h. All extracts of filters had detectable levels of mutagenic activity (TA98, +S9) resulting in airborne mutagenic activity concentrations of 500-5000 rev/m3. The mutagenic activity of the filters from the casino and bingo parlors was significantly correlated with total particulate matter per filters (n = 12; Rho = 0.85, p less than 0.01) and with airborne nicotine per filter (n = 12; Rho = 0.95, p less than 0.01). The microsuspension assay was sufficiently sensitive to detect the mutagens associated with extracts of particulate matter from low volume samples (0.2-0.6 m3) in these indoor environments over a relatively short sampling time, and could be useful in studies of personal exposure to the mutagens in environmental tobacco smoke. Further, airborne nicotine concentrations were highly correlated with airborne mutagenicity and the mutagenic activity associated with ETS could therefore be estimated by the concentrations of nicotine.

Air Pollution↗

Reproducibility of 24-hour serum growth hormone profiles in man.

OBJECTIVE: To study the reproducibility of 24-h serum growth hormone (GH) concentration profiles in adults. DESIGN: 24-h serum GH concentrations were constructed by drawing blood samples at 20-min intervals. Four study occasions over a period of 1 year were chosen to assess the reproducibility. SUBJECTS: Six healthy adult male volunteers of normal height and weight and aged between 20 and 22 years. MEASURES: The resulting GH data arrays were analysed by Fourier transformation. Between and within individual variations were calculated and expressed in terms of coefficients of variation and data plotted to show variations between groups and individuals. RESULTS: The frequency component of GH secretion occurred with a dominant periodicity of between 160 and 240 min. Precise estimates of spectral power (strength of oscillatory activity) and period were obtained for group data, but such estimates cannot be inferred from a single profile. There was no significant difference in 24-h mean serum GH concentration over the year of study: occasion 1 (February) mean 2.0 mU/l (SD 0.5); occasion 2 (March) mean 3.7 mU/l (SD 2.8); occasion 3 (July) mean 2.7 mU/l (SD 1.4); occasion 4 (February) 2.5 mU/l (SD 1.5) (mean within individual coefficient of variation 35%, range 9-58). The concentrations of factors known to influence GH synthesis and secretion, insulin-like growth factor I, thyroxine, testosterone and oestradiol, varied little over the year of study. CONCLUSIONS: These data demonstrate that group data are reproducible in terms of oscillatory activity and the amount of GH secreted and that 24-h GH profiles should be used predominantly for analysing group data. The variability between individual profiles limits their value in the investigation of children with growth failure and suspected GH insufficiency.

Adult↗

Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I.

OBJECTIVE: The aim was to study the relationship between growth hormone (GH) and insulin-like growth factor-I (IGF-I) in critically ill patients. DESIGN: Case-control study of critically ill patients admitted to the intensive care unit was carried out. PATIENTS: Six critically ill patients (51-78 years) who required ventilation and parenteral nutrition and six age, weight, height, and sex-matched healthy adults were studied. MEASUREMENTS: The patients and controls were studied for two 24-hour periods; the patients before and after starting parenteral feeding, and the controls during a 36-hour fast and when taking meals equivalent in calories and protein to the patients' parenteral feed. Serum GH was measured at 20-minute intervals and analysed by a pulse detection algorithm (Pulsar) and Fourier transformation. IGF-I was measured at 0, 12, and 24 hours. RESULTS: Patients had low serum IGF-I levels compared with controls, whether fasted or fed, despite having mean GH levels similar to fasted controls. For fasted patients vs fasted controls the mean (+/- 1 SD) GH levels were 4.5 +/- 2.0 vs 4.0 +/- 2.4 mU/l respectively, and IGF-I levels at the end of the fast were 0.17 +/- 0.11 vs 0.78 +/- 0.29 U/ml (P = 0.003). Patients showed elevated baseline GH levels compared with controls when fasted and during parenteral feeding (patients vs controls fasted 3.1 +/- 1.9 vs 0.8 +/- 0.5 mU/l, P = 0.01; patients vs controls fed 4.2 +/- 4.5 vs 0.5 +/- 0.04 mU/l, P = 0.028). Fourier transformation confirmed oscillatory GH levels in the controls, fasted or fed, but this activity was attenuated in the patients. Parenteral feeding had no effect on the GH profiles or IGF-I levels of patients, but controls showed greater mean GH levels during their fast than when fed. CONCLUSIONS: We have demonstrated that critically ill patients have low IGF-I levels associated with augmented baseline GH levels which show reduced oscillatory activity. The results would be compatible with the hypothesis that there is an adaptive change in critically ill patients away from the indirect effects of GH (stimulation of IGF-I production and anabolism) and toward the direct effects (lipolysis and insulin antagonism) which increase the availability of energy substrates. The pattern of GH levels seen in our patients may be important in this adaptation.

Abdomen↗

Pattern of secretion of bioactive and immunoreactive gonadotrophins in normal pubertal children.

OBJECTIVE: The aim was to investigate the relationship between the nocturnal pulsatile secretory patterns of immunoreactive and bioactive luteinizing hormone in normal children at various stages of puberty. DESIGN: Blood samples were taken at 15-minute intervals from 2000 hours to 0800 hours. Pubertal stage was assessed by the method of Tanner (1962). PATIENTS: Thirty-four healthy siblings (17 males, 17 females) of diabetic children were recruited (median age 13.1, range 9.1-20.9 years). They were of normal height, non-obese, and covered the range of puberty. MEASUREMENTS: Follicle stimulating and luteinizing hormone levels were measured by radioimmunoassay in all 34 subjects; bioactive LH (B-LH) was assayed in a subgroup of 13 subjects selected to encompass the range of normal puberty. Oestradiol (girls) and testosterone (boys) were also measured at hourly intervals. RESULTS: Immunoreactive luteinizing and follicle stimulating hormone concentrations showed a progressive rise during puberty in both sexes. FSH concentrations were significantly higher in females than in males at all stages of puberty. Overnight mean bioactive luteinizing hormone concentrations were higher than immunoreactive luteinizing hormone levels in all the girls studied (n = 7). Although the number of bioactive luteinizing hormone pulses (31) was greater than immunoreactive pulses (27), the profiles were generally very similar. In the early pubertal girls an increase in the bioactive: immunoreactive ratio was observed during the middle of the night with the onset of pulsatility. Oestrogen was detected in the girls in breast stage 4-5 but not in two of the early pubertal girls, despite pulses of immunoreactive and bioactive luteinizing hormone. The boys had higher mean bioactive than immunoreactive luteinizing hormone levels and overall bioactive and immunoreactive luteinizing hormone and testosterone concentrations increased with puberty stage. Concordance between bioactive and immunoreactive hormone pulses was good although more immunoreactive pulses (16) were seen than bioactive pulses (14). As in the girls, an increase in the bioactive: immunoreactive ratio was observed in the middle of the night with the onset of pulsatility at genital stage 2 but, in contrast to the oestrogen data in the girls, testosterone secretion always followed luteinizing hormone pulsatility overnight. CONCLUSION: We conclude that mean overnight immunoreactive luteinizing and follicle stimulating hormone concentrations increase during puberty in both sexes. Bioactive luteinizing hormone levels are two to three times higher than immunoreactive luteinizing hormone in both sexes, but there is very little discordance between immunoreactive and bioactive luteinizing hormone pulsatility. The bioactive: immunoreactive ratio increases with the occurrence of pulsatility overnight in early pubertal children. The relationship between these changes in bioactive and immunoreactive luteinizing hormone and sex steroids is clearest in boys where the nocturnal testosterone rise always follows pulsatile LH secretion.

Adolescent↗

Respiratory effects of exposure of shipyard workers to epoxy paints.

Epoxy resin systems have been associated with occupational asthma in several case reports, but medical publications contain little on the potential adverse respiratory effects of these chemicals in exposed worker populations. To further evaluate the association of workplace exposure to epoxy paints and respiratory dysfunction, the cross workshift changes in pulmonary function and symptoms of 32 shipyard painters exposed to epoxy paints were compared with 28 shipyard painters not exposed to epoxy paints. The prevalence of lower respiratory tract symptoms was significantly higher among painters exposed to epoxy paints compared with controls. Among exposed painters the mean cross workshift change in forced expiratory volume in one second (FEV1) (-3.4%) was greater than the decrement in the non-exposed group (-1.4%). A significant linear relation was seen between % decrement in FEV1 and hours of exposure to epoxy paints. This study suggests that epoxy resin coatings as used by shipyard painters are associated with increased lower respiratory tract symptoms and acute decrements in FEV1. Adequate respiratory protection and medical surveillance programmes should be established in workplaces where exposure to epoxy resin systems occurs.

Adult↗

Low growth hormone levels are related to increased body mass index and do not reflect impaired growth in luteinizing hormone-releasing hormone agonist-treated children with precocious puberty.

To test the hypothesis that GH deficiency might explain the low growth velocity of some LHRH agonist (LHRHa)-treated children with central precocious puberty, we measured stimulated (n = 81) and spontaneous (n = 32) GH levels during or after LHRHa treatment. GH stimulation tests in the children who were receiving LHRHa treatment were performed after 2 days of ethinyl estradiol administration. Thirty-one of 81 children (38%) who underwent GH stimulation tests had subnormal responses (less than or equal to 7 micrograms/L) to all tests administered (at least 2 stimuli), including 22 of 67 (33%) who had precocious puberty that was idiopathic or associated with hypothalamic hamartoma. Eleven of 32 children (34%) who underwent measurement of the mean nighttime spontaneous GH level had levels below the normal range for prepubertal children (less than 1.2 microgram/L). Despite the high incidence of subnormal GH levels, there appeared to be no relationship between the GH levels of these children and their growth characteristics. The height, growth velocity, bone maturation rate, predicted height, and insulin-like growth factor-I levels were not different between the children with low GH levels and the children with normal GH levels. Conversely, the GH levels were not different between the children with subnormal growth rates and the children with normal growth rates. Thus, variation in the growth rates of these LHRHa-treated children with central precocious puberty could not be explained by variation in the stimulated or spontaneous secretion of GH. In attempting to understand the high incidence of low GH levels in children with precocious puberty, we examined the relationship between GH level and body mass index (BMI). Both the stimulated (r = -0.33; P less than 0.002) and the spontaneous (r = -0.61; P less than 0.0002) GH levels were inversely related to BMI. Moreover, the children with precocious puberty as a group had significantly elevated BMI [1.2 +/- 0.1 (+/- SE) SD units] compared to normal children of the same age (P less than 0.0001). Thus, increased body mass may explain the high incidence of subnormal GH levels in these patients, and normative GH levels adjusted for body mass are needed before it can be concluded that the apparently subnormal GH levels in LHRHa-treated children with precocious puberty are in fact low.

Adolescent↗

Adult height in precocious puberty after long-term treatment with deslorelin.

Precocious puberty often leads to short adult height. Since the introduction of luteinizing hormone-releasing hormone (LHRH) agonist treatment for LHRH-dependent precocious hormone (LHRH) agonist treatment for LHRH-dependent precocious puberty in 1979, several reports have shown increased predicted height among LHRH agonist-treated children. To determine whether the LHRH agonist deslorelin can normalize the adult height of children with precocious puberty, we are conducting a long-term pilot study involving 161 children. This report describes the first 44 children to have attained final or proximate adult height. These children were 7.1 +/- 1.2 (mean +/- SD) yr old (bone age 11.8 +/- 1.5 yr) and had been in puberty for 3.1 +/- 0.3 yr at the start of treatment. They were treated with deslorelin (4 micrograms/kg/day sc) for 4.1 +/- 1.3 yr and had been withdrawn from treatment for an average of 2.4 yr at the time of this study (age 13.6 +/- 0.9 yr). Fourteen of the 44 children, who had grown less than 0.5 cm during the previous year, were considered to have attained adult height. The other 30 children had achieved 98.6% of predicted mature height (Bayley-Pinneau method) and were considered to be at proximate adult height. The final or proximate adult height of these 44 children averaged -1.1 SD compared to the adult height of the normal population. This height was significantly greater than the pretreatment height (-1.1 vs. -2.0 SD, P less than 0.01), but significantly less than both the predicted height at the end of treatment (-1.1 vs. -0.5 SD, P less than 0.01) and the target height derived from the mean height of the parents adjusted for the sex of the child (-1.1 vs. 0.1 SD, P less than 0.01). The observation that the Bayley-Pinneau height prediction at the end of treatment overestimated the actual adult height emphasizes the importance of using final height data to assess the ultimate impact of LHRH agonist treatment. It also indicates the need for caution when predicting the adult height of children who are still receiving treatment. We conclude that deslorelin has improved the adult height of these patients but has not fully restored height to the patients' genetic potential. We hypothesize that further improvement will be seen in patients who are treated with less delay and at a younger bone age.

Body Height↗

Luteinizing hormone-releasing hormone (LHRH)-independent precocious puberty unresponsive to LHRH agonist therapy in two girls lacking features of the McCune-Albright syndrome.

Two girls with precocious puberty (chronological age, 1 and 4 yr; bone age, 3 and 6 yr, respectively) were initially given the diagnosis of idiopathic, central precocious puberty and treated with the LHRH agonist deslorelin (D-Trp6-Pro9-NEt-LHRH) for 5 yr. Unlike other girls with central precocious puberty, both had persistently elevated rates of growth and bone maturation, and both menstruated during therapy. One girl had episodic ovarian enlargement and markedly elevated serum estradiol levels due to recurrent unilateral ovarian cysts. Although the bone and skin manifestations of McCune-Albright syndrome were absent, we hypothesize that the underlying defect of McCune-Albright syndrome was expressed in the ovaries, but not in the skin or bones, of these two girls. One of these girls appeared to benefit from the aromatase inhibitor testolactone, which is effective in suppressing precocious puberty in girls with the McCune-Albright syndrome.

Child Development↗

Evidence for temporal coupling of growth hormone, prolactin, LH and FSH pulsatility overnight during normal puberty.

The patterns of secretion of GH, LH, FSH and prolactin were determined over a single night (20.00-08.00 h; 15-min sampling) in 34 normal subjects (17 male, 17 female, aged 9.1-20.9 years). Plasma GH was measured by an immunoradiometric assay and LH, FSH and prolactin by radioimmunoassay in all samples. Data were analysed by Fourier transformation and cross-correlation after stationarization. The highest mean GH levels were noted in girls at Tanner stage 2/3 and in boys at stages 4/5. Prolactin levels were highest in girls at stage 4/5 and in boys at stage 2/3. LH and FSH showed a progressive rise by puberty stage in both sexes. The dominant pulse periodicities of GH and prolactin were 150-180 min in girls and 180 min in boys. LH and FSH pulse periodicity was around 90 min in early puberty and 180 min in later puberty in both sexes. LH and prolactin pulses showed a phase relationship with GH with a lag of 30-75 min (r = 0.32; P less than 0.001) and 30 min (r = 0.47; P less than 0.0001) respectively. Generally, LH and prolactin pulses were in phase (r = 0.42; P less than 0.0001) and there was a highly significant correlation (r = 0.64; P less than 0.0001) between FSH and LH pulsatility. Whereas mean overnight concentrations and pulse periodicity of the principal pituitary hormones varied between the sexes during early puberty, by the end of puberty a dominant pulse periodicity of around 150-180 min was established and there was remarkable temporal coupling of pulsatility.

Adolescent↗

Development of an efficient transposon tagging system in Arabidopsis thaliana.

We are currently developing a transposon tagging system in Arabidopsis thaliana using the maize transposable elements Ac and Ds. In order to make the system as efficient as possible, four different antibiotic resistance markers have been tested for their usefulness in monitoring excision and reinsertion of transposons in the Arabidopsis genome. Owing to the low transposition frequency of wild-type Ac in Arabidopsis we have also tested a number of modifications to the Ac element. Deletion of the CpG-rich region in the transposase 5' untranslated leader was found to significantly increase the activity of Ac in Arabidopsis. In our first non-targeted tagging experiment, 200 individuals with an inherited transposed Ac element have been collected and their progeny are being screened in families of twelve for segregation of mutant phenotypes. A two-element system, using Ac and Ds, is also being developed and a way of stabilising the Ds-induced mutations by counter selecting plants carrying the transposase source is being investigated. The Agrobacterium T-DNA insertions carrying the different transposons are currently being mapped onto the Arabidopsis RFLP map. Inverse polymerase chain reaction (IPCR) is being used to generate flanking DNA probes, that will be used on the RFLP blots to map the T-DNA relative to the other known markers. Once the first few have been mapped the first targeted tagging experiment will be initiated.

Arabidopsis↗

Imaging Ca2+ changes in individual oligodendrocytes attacked by T-cell perforin.

Cytosolic-free calcium changes in cultured rat oligodendrocytes attacked with murine T-cell perforin were measured using digital image processing of fura-2-loaded cells. Permeability to the membrane impermeant dye, propidium iodide, and the ability to retain fura-2 were also assessed. Oligodendrocyte response to perforin attack was heterogeneous, ranging from small, transient increases in cytosolic calcium to rapid cell death. Changes in cytosolic calcium occurred in all cells and about half of the cells also became permeable to propidium iodide. Only a minority of these cells proceeded to lysis, as evidenced by loss of fura-2. The cytosolic-free calcium rises visualized here in single cells could initiate non-lethal effects, thereby disturbing oligodendrocyte function and synthesis and maintenance of myelin.

Animals↗

Effects of all-trans retinoic acid on neutrophil-mediated endothelial cell injury in vitro and immune complex injury in rats.

All-trans retinoic acid (RA) has beneficial effects when used in a variety of inflammatory skin conditions. In this study, the authors found that RA inhibited superoxide anion production and proteolytic enzyme release by human and rat neutrophils. Concomitantly, the authors found that RA-treated neutrophils were less able than untreated neutrophils to injure endothelial cells in culture even though the adhesion of the RA-treated neutrophils to endothelial cell monolayers was not diminished. Inhibition of cytotoxicity occurred over the same range of concentrations that inhibited oxygen radical formation and protease release. In additional studies, it was observed that pretreatment of endothelial cells with RA-induced resistance to subsequent injury by activated neutrophils. Finally, in vivo studies showed that pretreatment of rats for 3 days with RA (1-10 mg/day, IP) reduced the degree of injury in the lungs and skin sites after treatment with bovine serum albumin and antibodies to bovine serum albumin in the reverse-passive Arthus reaction. Thus, RA can modulate neutrophil-mediated endothelial cell injury by an effect on both the neutrophils and their target cells. Together, these effects may underlie the reduction in immune complex-mediated injury seen in experimental animals. The beneficial effects that retinoids have in a variety of inflammatory skin diseases may likewise be a reflection of their effects on the physiology of both neutrophils and endothelial cells.

Animals↗