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Biomedical subjects

J Wade

Publications and source records attributed to J Wade.

At least 37 records · Page 2Linked to original sources
PubMed2000

Lateralization and effects of adult androgen in a sexually dimorphic neuromuscular system controlling song in zebra finches.

Unlike many other sexually dimorphic systems, gonadal secretions do not explain sex differences in the morphology of the telencephalic song control nuclei of zebra finches. It is important to understand whether a novel mechanism for controlling structure is restricted to the forebrain regions specialized for song, and whether other areas respond more typically to gonadal steroids. Therefore, the effects of sex and adult androgen manipulation on the neuromuscular end of the song control system (tracheosyringeal portion of the hypoglossal nucleus, nXIIts, and the syrinx, or vocal organ) were investigated. Because lesion and axotomy experiments indicate a right-side bias in the functional control of song, asymmetry in the motor nucleus and in the ventralis and dorsalis syrinx muscles was also tested. Male-biased dimorphisms existed in the volume of nXIIts, and in syrinx mass and size of muscle fibers, but not in motoneuron number or size. Asymmetries favoring the right side were detected in nXIIts volume and motoneuron number in males, as well as in ventralis and dorsalis fiber size in both sexes. Hormone manipulations had no effect on nXIIts size, neuron size, or number. Testosterone treatment of adult females increased all of the syringeal measures, but the only effect of flutamide in males was to decrease syrinx weight. Thus, male-biased sexual dimorphisms and right side dominance in both nXIIts and the syrinx may facilitate singing behavior. Adult androgen exposure can induce partial masculinization of the syrinx, but other factors must be important in mediating the sex differences in both that structure and the volume of nXIIts.

Age Factors↗
PubMed2000

Energy metabolism in uncoupling protein 3 gene knockout mice.

Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important roles in regulating energy expenditure, body weight, and thermoregulation. Other postulated roles for UCP3 include regulation of fatty acid metabolism, adaptive responses to acute exercise and starvation, and prevention of reactive oxygen species (ROS) formation. To address these questions, we have generated mice lacking UCP3 (UCP3 knockout (KO) mice). Here, we provide evidence that skeletal muscle mitochondria lacking UCP3 are more coupled (i.e. increased state 3/state 4 ratio), indicating that UCP3 has uncoupling activity. In addition, production of ROS is increased in mitochondria lacking UCP3. This study demonstrates that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS. Despite these effects on mitochondrial function, UCP3 does not seem to be required for body weight regulation, exercise tolerance, fatty acid oxidation, or cold-induced thermogenesis. The absence of such phenotypes in UCP3 KO mice could not be attributed to up-regulation of other UCP mRNAs. However, alternative compensatory mechanisms cannot be excluded. The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined.

Animals↗
PubMed2000

Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection.

Certain human leukocyte antigens, by presenting conserved immunogenic epitopes for T cell recognition, may, in part, account for the observed differences in human immunodeficiency virus type 1 (HIV-1) susceptibility. To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.27-0.72; P=.0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P=.0003), which suggests that anti-HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge. These data provide further evidence that resistance to HIV-1 infection in this cohort of sex workers is immunologically mediated.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Arborization of dewlap motoneurons in the green anole lizard (Anolis carolinensis) is not sexually dimorphic.

Male anoles extend a bright red throat fan, called a dewlap, during both courtship and aggressive encounters. Female anoles perform this behavior less often than males and only in aggression towards both sexes. The cartilage, muscle fibers, and motoneuron somata controlling the display are larger in males than females. In the present study, we used the Golgi technique in an effort to characterize more completely the morphology of these dewlap motoneurons, and to investigate whether the dendritic arborization is different between the sexes. In addition to describing the morphology, we report that the length of processes, and numbers of primary processes and branch points are comparable in males and females. This similarity in arborization represents an intriguing contrast to other sexually dimorphic neuromuscular systems.

Animals↗
PubMed2000

TrkB-like immunoreactivity in the song system of developing zebra finches.

The neural song system in zebra finches develops for approximately the first 2 months after hatching. During that time, male-biased sexual dimorphisms emerge in the volume of song control nuclei as well as in the number and size of neurons within them. Brain derived neurotrophic factor (BDNF) has been documented in song control nuclei at various stages of development. Its high affinity receptor (tyrosine kinase B; trkB) is also in the song system, at least at around I month of age. The present study was designed to more completely describe the timing and potential location of BDNF action by investigating trkB expression during sexual differentiation of the song control nuclei. The pattern of immunoreactivity to a trkB antibody was examined in male and female zebra finches at post-hatching days 3-60. Labeling in somata and neuropil appeared to define the telencephalic components of the motor pathway (high vocal center and robust nucleus of the archistriatum) for song production in males from days 30 to 60, and in females on days 45 and 60 (high vocal center). These results are consistent with the hypothesis that the receptor, and its ligand BDNF, play a role in processes related to song learning in both sexes, including perhaps the motor component exhibited by developing males.

Animals↗
PubMed2000

Granulocyte colony-stimulating factor given to donors before apheresis does not prevent aplasia in patients treated with donor leukocyte infusion for recurrent chronic myeloid leukemia after bone marrow transplantation.

We conducted 2 sequential studies of donor leukocyte infusion (DLI) in 26 patients with chronic myeloid leukemia in hematologic relapse after unmodified allogeneic bone marrow transplantation. In the first study, cells for DLI were collected from 13 donors who were not treated with granulocyte colony-stimulating factor (G-CSF) (group 1). In the second study, cells were collected from 13 donors who received G-CSF before apheresis (group 2) in an attempt to avoid aplasia after DLI. Patients in group 2 received 550-fold more CD34+ cells than those in group 1. We found no significant difference in the incidence (31% versus 22%), onset time (41 vs. 48 days), or duration (15 vs. 14 days) of cytopenia after DLI in the 2 groups. G-CSF given to donors before collection of cells did not prevent aplasia. These findings support the hypothesis that the pathogenesis of aplasia after DLI is not restricted to the destruction of recipient hematopoietic cells but also involves failure of donor hematopoiesis by undefined mechanisms.

Adolescent↗
PubMed2000

The systemic inflammatory response syndrome in acute liver failure.

The systemic inflammatory response syndrome (SIRS) in acute liver failure (ALF), in which infection is common, has not been studied. In this study, SIRS components were recorded on admission and during episodes of infection, in 887 ALF patients admitted to a single center during an 11-year period. Overall, 504 (56.8%) patients manifested a SIRS during their illness, with a maximum of 1, 2, and 3 concurrent SIRS components in 166, 238, and 100 patients, respectively. In 353 (39.8%) patients who did not become infected, a SIRS on admission was associated with a more critical illness, subsequent worsening of encephalopathy, and death. Infected patients more often developed a SIRS and one of greater magnitude. The magnitude of the SIRS in 273 patients with bacterial infection correlated with mortality, being 16.7%, 28.4%, 41.2%, and 64.7% in patients with 0, 1, 2, and 3 maximum concurrent SIRS components, respectively. Similar correlations with mortality were seen for SIRS associated with fungal infection, bacteremia, and bacterial chest infection. Fifty-nine percent of patients with severe sepsis died, as did 98% of those with septic shock. A significant association was found between progressive encephalopathy and infection. Infected patients with progressive encephalopathy manifested more SIRS components than other infected patients. For patients with a SIRS, the proportions of infected and noninfected patients manifesting worsening encephalopathy were similar. In ALF, the SIRS, whether or not precipitated by infection, appears to be implicated in the progression of encephalopathy, reducing the chances of transplantation and conferring a poorer prognosis.

Acetaminophen↗
PubMed2000

Infection control training: evaluation of a computer-assisted learning package.

An evaluation of the training module of an interactive infection control computer-assisted learning (CAL) software program was carried out with ward-based nurses, third-year medical students and infection control personnel. All nursing staff, 87% of the medical students and all infection control staff found the programme easy and enjoyable to use. The module was accessed 3101 times on the hospital network in 18 months with usage settling to between 100-150 times per month. There was a higher level of use by night-duty and weekend staff. Medical students gained as much infection control knowledge from using the CAL package (increase in correct responses from 63.5% to 83.4%;P<0.0001) as they did from a formal lecture (increase in correct responses from 62.1% to 79.5%;P<0.0001). We conclude the training module which is accessible on the hospital wards and across the academic network, is a convenient and effective way for staff and students to gain a basic understanding in evidence-based infection control practices, at locations and times suitable for them.

Attitude of Health Personnel↗
PubMed2000

Small, stable shuttle vectors based on the minimal pVS1 replicon for use in gram-negative, plant-associated bacteria.

The minimal replicon of the Pseudomonas plasmid pVS1 was genetically defined and combined with the Escherichia coli p15A replicon, to provide a series of new, oligocopy cloning vectors (5.3 to 8.3 kb). Recombinant plasmids derived from these vectors were stable in growing and nongrowing cells of root-colonizing P. fluorescens strains incubated under different environmental conditions for more than 1 month.

Amino Acid Sequence↗
PubMed2000

Granulocyte colony-stimulating factor improves function of neutrophils from patients with acute liver failure.

OBJECTIVE: To evaluate the in vitro effects of granulocyte colony-stimulating factor (G-CSF) on function of neutrophils in acute liver failure (ALF). METHODS: Neutrophil functions (superoxide and hydrogen peroxide production; phagocytosis and killing; complement receptor expression) were determined simultaneously in 23 patients with ALF due to paracetamol overdose and compared with 23 healthy control subjects. RESULTS: Phagocytosis was reduced in neutrophils from ALF patients compared to controls (P< 0.005) and was significantly increased by incubation with 1,000 or 5,000 IU/ ml G-CSF (P< 0.05). This correlated with increased expression of CD11b (r= 0.93) and CD18 (r= 0.98) after incubation with 5,000 IU/ml G-CSF (P< 0.05). Killing was reduced in ALF neutrophils compared to controls (P< 0.005) and was similarly restored by G-CSF (P< 0.005). An increase in killing correlated with increases in production of superoxide (r = 0.96) and hydrogen peroxide (r= 0.97) by ALF neutrophils after incubation with 1,000 and 5,000 IU/ml of G-CSF when formylmethionylleucylphenylalanine (fMLP) was the stimulant. G-CSF at 5,000 IU/ml increased the production of hydrogen peroxide (P< 0.01) when zymosan was the stimulant. CONCLUSIONS: G-CSF improves the neutrophil dysfunction of ALF.

Adolescent↗
PubMed2000

Administering granulocyte colony-stimulating factor to acute liver failure patients corrects neutrophil defects.

OBJECTIVES: Neutrophil function is defective in acute liver failure (ALF) and the in vitro ability of granulocyte colony-stimulating factor (G-CSF) to reverse these defects has been reported. The effects of administering G-CSF to ALF patients are presented in this study. DESIGN: This was a prospective, phase I/II, open label, study. SETTING: The liver intensive therapy unit at King's College Hospital, London. PARTICIPANTS: Sequential patients admitted with acute liver failure due to acetaminophen overdose. INTERVENTIONS: G-CSF was given to four groups (each n = 6) of ALF patients as a daily infusion at 25, 50, 100 or 150 microg/m2. A control group of eight patients did not receive G-CSF. MAIN OUTCOME MEASURES: Neutrophil phagocytosis and killing of Staphylococcus aureus and superoxide release before G-CSF administration and at 24 and 96 h thereafter. RESULTS: Neutrophils from patients receiving 50, 100 or 150 microg/m2 G-CSF, but not from control patients or those receiving 25 microg/m2, showed significantly increased phagocytosis and killing at 96 h. Doses of 50 or 150 microg/m2 G-CSF resulted in increased superoxide production at 96 h. No patients discontinued treatment as a consequence of side effects related to G-CSF administration. CONCLUSIONS: G-CSF administration is a safe and effective means of reversing the neutrophil defects of ALF, and may have a role in the prevention and treatment of infection in these patients. A dose of 50 microg/m2/day is as effective as higher doses and was associated with fewer side effects.

Adolescent↗
PubMed2000

A novel model of retinopathy of prematurity simulating preterm oxygen variability in the rat.

PURPOSE: To examine changes in the retinal vasculature of rat pups after 14 days of minute-by-minute small variations in oxygen. METHODS: Arterial oxygen data from a preterm infant who developed severe retinopathy of prematurity (ROP) was translated to equivalent values for the rat. Newborn rat pups were raised for 14 days in a cage in which a computer controlled the atmosphere to mimic the fluctuating oxygen profile (group V). Positive controls (P) of 12-hour cycles of 80% and 21% were run concurrently, as were room air controls (C). All were killed at day 14. RESULTS: Groups V and P had significantly larger avascular retinal areas than C [median, interquartile range (IQR) 1.7%, 0-7.9%; 10%, 8.1-13%; 0%, 0-0%, respectively; each group n = 30]. Group P had a higher capillary branch count than C (median, IQR: 310/mm(2); 253-311 mm(2); versus 277/mm(2), 272-364/mm(2), respectively), but this was not significant using a multilevel analysis. Group V had significantly reduced capillary counts compared with C (median, 261/mm(2); IQR, 215-290/mm(2); P < 0.05 multilevel analysis). No neovascularization was seen in any group, though abnormal terminal vessels were seen at the avascular/vascular retina interface in 73% of rats in group P and 21% of rats in group V. In situ hybridization on serial sections demonstrated VEGF in the inner nuclear layer of the retina in P and V, whereas C showed trace levels only. CONCLUSIONS: The vaso-obliterative stage of ROP can be induced in rats using clinically relevant oxygen levels.

Animals↗
PubMed1999

Interactions between nerve growth factor binding and estradiol in early development of the zebra finch telencephalon.

The zebra finch telencephalon exhibits rapid and substantial development in the first few weeks after hatching. In parallel, the rate of estradiol synthesis is very high in the zebra finch forebrain, and estradiol can have potent neurotrophic effects in specific telencephalic regions, including those that control the learning and production of song. In an attempt to elucidate mechanisms regulating telencephalic development, potentially including a role for the large capacity for estrogen production, (125)I-nerve growth factor (NGF) binding was measured in homogenates of telencephalon from zebra finches age 3, 15, 30, 60, and 120 days. The highest density of low- and high-affinity (125)I-NGF binding sites was observed in 3-day-old finches. Using an aromatase inhibitor, Fadrozole, to reduce estradiol levels in 1 to 4-day-old zebra finches significantly decreased both high- and low-affinity (125)I-NGF binding sites. Conversely, treating adult or 8 to 14-day-old hatchlings with estradiol increased high-affinity (125)I-NGF binding sites. These results are consistent with the hypothesis that estradiol influences the level of NGF receptors, and suggest one mechanism through which the steroid could affect brain development. The data also indicate that estradiol and NGF activity may be important for very early development of the telencephalon.

Age Factors↗
PubMed1999

Sexual dimorphisms in a neuromuscular system regulating courtship in the green anole lizard: effects of season and androgen treatment.

During the breeding season, male green anoles (Anolis carolinensis) court females by extending a red throat fan called a dewlap. Motoneurons controlling this sexually dimorphic behavior are located in two portions of the brain stem: (a) the vagal portion of nucleus ambiguus (AmbX), and (b) the region containing the glossopharyngeal portion of nucleus ambiguus and the ventral motor nucleus of the facial nerve (AmbIX/VIImv). These motoneurons project to the ceratohyoideus muscle via the ramus pharyngo-laryngeus IX+X. To investigate the effects of season on and androgen regulation of neural and peripheral structures controlling dewlap extension, two experiments were conducted: (a) During the breeding and nonbreeding seasons, motoneuron number, soma size, and nucleus size were investigated in intact males and females and in castrated males treated with a testosterone propionate (TP) or a blank Silastic capsule. (b) Cross-sectional area of the nerve and muscle fiber size, number, and density were investigated in the four treatment groups during the breeding season only. No significant differences were found in motoneuron number. In the breeding season, subtle male-biased sex differences existed in both AmbX and AmbIX/VIImv soma size. Nerve cross-sectional area and muscle fiber size and number were substantially larger in males than females. Muscle fiber density was higher in females. No consistent effects due to season or androgen treatment were detected, although characteristics of motoneurons were in some cases slightly larger in the nonbreeding season. These results suggest that, while parallels to behavior exist between the sexes, morphological changes in adulthood in the dewlap motoneurons and muscle do not normally regulate courtship behavior in the male green anole.

Animals↗
PubMed1999

Sexual differentiation of the zebra finch song system parallels genetic, not gonadal, sex.

Mechanisms regulating sexual differentiation of the zebra finch song system present an intriguing puzzle. Masculine development of brain regions and behavior can be induced in genetic females by posthatching estradiol treatment. That result is consistent with the hypothesis that estradiol, converted within the brain from testicular androgen via the aromatase enzyme, masculinizes neural structure and function. In contrast, treatment during specific stages of development with the aromatase inhibitor Fadrozole has not prevented masculine development, and the presence of testicular tissue in genetic females did not induce masculine organization of neuroanatomy or singing behavior. Fadrozole treatments in those previous studies were limited, however, and most genetic females had both ovarian and testicular tissue. The present experiments were designed to provide increased aromatase inhibition and to reliably produce genetic females with only testicular tissue. Eggs received a single injection at a later age or with higher doses of Fadrozole than had been used previously. Some embryos were exposed to Fadrozole more frequently by either injecting eggs on 2 days of development or dipping them for 10-12 days in Fadrozole. Finally, in some individuals from Fadrozole-treated eggs, the left gonad was removed, leaving each genetic male and female with a single right testis. None of these treatments significantly affected development of the song system compared to appropriate control groups. These results suggest that sexual differentiation of the zebra finch song system is not regulated by embryonic aromatase activity or by gonadal secretions and instead involves events that need not be mediated by steroid hormones.

Animals↗
PubMed1999

Use of decompressive craniectomy after severe head trauma.

Ten percent of head injuries quality as "severe," requiring prompt diagnosis and treatment. This level I trauma center uses an aggressive approach to treatment of severe head injuries and, when indicated, intervenes with decompressive craniectomy. This article explains decompressive craniectomy, including indications, procedures, and protocols. The case studies presented highlight two patients with profound head injuries. Additionally, cranioplasty replacement of autograft flap is explained and discussed.

Adolescent↗
PubMed1999

Sexual dimorphisms in avian and reptilian courtship: two systems that do not play by mammalian rules.

Sexual dimorphisms in the central nervous system exist in numerous vertebrate species, and in many cases these structural differences between males and females parallel differences in the display of reproductive behaviors. Often both the behavioral and anatomical differences are controlled by exposure to gonadal steroid hormones, either during ontogeny or in adulthood. This article reviews some of the evidence supporting the hypothesis that in mammals, testosterone or its metabolites regulate the structure and function of neural and muscle systems involved in the control of masculine sexual behaviors. It then describes data suggesting that the mechanisms regulating sexually dimorphic courtship systems in zebra finches and green anole lizards are not completely parallel to the mammalian systems. Finally, some directions for future study are suggested, with the hope that they will stimulate thought about the nature of comparisons made across vertebrate models when investigators are attempting to determine both which morphological sex differences are important to the control of the reproductive behaviors, and which mechanisms regulating both structure and function are widely employed or are unique.

Animals↗