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Biomedical subjects
J Wade
Publications and source records attributed to J Wade.
Low oxygen exposure does not cause pulmonary injury in the newborn rat.
BACKGROUND: Two recent studies have suggested that low levels of supplemental inspired oxygen may cause lung injury in preterm infants. AIMS: To assess lung injury of newborn rats exposed to 14 days of low-level variation of oxygen. STUDY DESIGN: Four groups were compared with 12 animals per group and 4 lung sections per animal. These were, a control group raised in room air and three groups raised in levels of inspired oxygen fluctuating around the following mean values: group Lo (mean FiO(2) 0.179), group N (mean FiO(2) 0.213), and group Hi (mean FiO(2) 0.247). The degree of oxygen variability was identical for each group. Lungs were inflated at 20 cm H(2)O, fixed and stained with H and E and Millers Elastin. SUBJECTS: Sprague Dawley albino newborn rats. OUTCOME MEASURES: Random alveolar areas were studied and analysed using imaging software to assess total amount of tissue and elastin, number of secondary septa, and mean linear intercept. RESULTS: There were no significant differences between the three experimental oxygen groups and the control group in terms of lung/body weight ratio and the measured markers of lung development. CONCLUSION: We conclude that low-level oxygen supplementation during early lung development does not affect alveolar development in the newborn rat.
Animals↗
Testosterone regulates androgen receptor immunoreactivity in the copulatory, but not courtship, neuromuscular system in adult male green anoles.
Androgens regulate the expression of male reproductive behaviour in diverse vertebrate species, often acting on androgen receptors (AR) to induce structural or functional changes in the nervous system and periphery. Male green anoles possess two sexually dimorphic neuromuscular systems, one controlling throat fan (dewlap) extension, which occurs during courtship, and the other mediating copulatory organ function. Although androgens are required for behavioural activation in both systems, testosterone has differential effects on the neuromuscular morphology. It increases the size of copulatory muscle fibres during the breeding season, but significant effects on dewlap muscle fibre size and motoneurone soma size in either system have not been detected. Corresponding to the lack of testosterone-induced morphological effects in the courtship system, relatively low levels of AR are expressed in the associated motoneurones. The present experiment had two goals, aiming to determine whether: (i) the other courtship and copulatory neuromuscular tissues express AR and (ii) testosterone and/or seasonal environmental changes regulate AR expression. The percentage of AR+ nuclei was evaluated in both the breeding and nonbreeding seasons in gonadally intact adult males (Experiment 1) and in castrated males treated with either testosterone or vehicle (Experiment 2). AR was extensively expressed in the dewlap and copulatory muscles, and in a high percentage of the copulatory motoneurones, but immunoreactivity did not vary across season. Testosterone increased the percentage of AR+ nuclei in the copulatory muscles of both breeding and nonbreeding males but not in the dewlap muscle or copulatory motoneurones. Finally, the target structures for both systems (cartilages and hemipenes) expressed AR in all animals. Therefore, the effects of testosterone on AR immunoreactivity suggest that up-regulation of the receptors may be important for morphological change. However, because all structures investigated in the present experiment expressed AR, the data also indicate that the receptors are involved with other functions.
Animals↗
Fiber type composition of the muscle responsible for throat fan extension in green anole lizards.
Throat fan (dewlap) extension is sexually dimorphic in green anole lizards (Anolis carolinensis). Males have larger dewlaps which they display more frequently than females. Correlated with the behavior, sexual dimorphisms occur in the skeletal, muscular and neural structures responsible for dewlap extension in green anoles. We used histochemical techniques to stain for myosin ATPase and succinate dehydrogenase (SDH) to determine whether sex differences also exist in fiber type composition of the ceratohyoideus, the muscle that extends the dewlap. Based on the staining pattern for the two enzymes, four fiber types were identified: fast-oxidative-glycolytic (FOG), fast-glycolytic (FG), slow-oxidative (SO), and tonic. In the ceratohyoideus of both sexes, the predominate fiber types were FOG (approximately 43%) and FG (approximately 34%). Also in both males and females, the FOG and FG fibers had approximately twice the cross-sectional area of the SO and tonic fibers. No sex differences occurred in the percentages of FOG and FG fibers. However, males had a greater percentage of tonic fibers than females, whereas females had a greater percentage of SO fibers than males. The high proportion of FOG fibers in the anole ceratohyoideus makes it similar to other relatively fatigue-resistant muscles used in movements of moderate speed and duration. Although the precise role of tonic fibers in dewlap extension is not known, the greater percentage of these fibers in the male ceratohyoideus might be required to stabilize or maintain extension of the large dewlap apparatus in males.
Animals↗
Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation.
The incidence, etiology, outcome, and risk factors for developing pneumonia late after hematopoietic stem cell transplantation (SCT) were investigated in 1359 patients transplanted in Seattle. A total of 341 patients (25% of the cohort) developed at least one pneumonic episode. No microbial or tissue diagnosis (ie clinical pneumonia) was established in 197 patients (58% of first pneumonia cases). Among the remaining 144 patients, established etiologies included 33 viral (10%), 31 bacterial (9%), 25 idiopathic pneumonia syndrome (IPS, 7%), 20 multiple organisms (6%), 19 fungal (6%), and 16 Pneumocystis carinii pneumonia (PCP) (5%). The overall cumulative incidence of first pneumonia at 4 years after discharge home was 31%. The cumulative incidences of pneumonia according to donor type at 1 and 4 years after discharge home were 13 and 18% (autologous/syngeneic), 22 and 34% (HLA-matched related), and 26 and 39% (mismatched related/unrelated), respectively. Multivariate analysis of factors associated with development of late pneumonia after allografting were increasing patient age (RR 0.5 for <20 years, 1.2 for >40 years, P=0.009), donor HLA-mismatch (RR 1.6 for unrelated/mismatched related, P=0.01), and chronic graft-versus-host disease (GVHD; RR 1.5, P=0.007). Our data suggest that extension of PCP prophylaxis may be beneficial in high-risk autograft recipients. Further study of long-term anti-infective prophylaxis based on patient risk factors after SCT appear warranted.
Adult↗
Timing and aetiology of bacterial infections in a liver intensive care unit.
We undertook a prospective study of 887 consecutive adult patients admitted over an 11 year period to a liver intensive care unit. One or more bacterial infections occurred in 335 (37.8%) patients. Gram-positive cocci predominated. In relation to the date of admission these infections occurred in a statistically significant sequence. Streptococci infections were earliest (median time to infection two days), followed by Staphylococcus aureus (three days), coagulase-negative staphylococci (six days) and enterococci (eight days). Escherichia coli infections occurred earlier than those due to klebsiella-enterobacter (two vs seven days; P = 0.0001) and, overall, Enterobacteriaceae earlier than non-fermentative Gram-negatives (four vs. eight days; P = 0.0081). This study contributes to the management of high-dependency patients by confirming statistically the timing and sequence of infecting bacteria in patients with acute liver failure.
Adult↗
Distribution of androgen receptor mRNA expression and immunoreactivity in the brain of the green anole lizard.
Male courtship and copulation are androgen dependent in the green anole lizard, and female receptivity can be facilitated by testosterone. However, only a few, and relatively large, regions in the brain have been implicated in the control of these behaviours. In situ hybridization and immunohistochemistry were therefore used to determine in detail where androgens are likely to act in the brains of breeding males and females. A 697-bp fragment of the anole androgen receptor (AR) was cloned from total RNA isolated from the kidney, which contains the highly androgen-sensitive renal sex segment. The cloned fragment spanned part of the C, the entire D, and part of the E domains, and shared a high degree of similarity with the AR of various species. 35S-labelled antisense and sense probes were generated from the 697-bp fragment for use in in situ hybridization, and the AR antibody PG-21 was used for immunohistochemistry. Both sexes consistently had AR mRNA expression and immunoreactivity in areas associated with vertebrate reproductive behaviours and in motor areas of the brainstem. Interestingly, the PG-21 antibody produced labelling in both the nucleus and cytoplasm, including neuronal processes. The distribution of mRNA and immunoreactivity were comparable in males and females, and the amount of labelling was generally similar, although slightly greater in females. The expression pattern of AR in this species supports the idea that distribution is highly conserved among vertebrates, but that it probably does not dictate behavioural differences between the sexes in anoles.
Amino Acid Sequence↗
Voice recognition and aphasia: can computers understand aphasic speech?
PURPOSE: This preliminary investigation of the use of voice recognition software by people with aphasia presents a new method of training the software, which allows the aphasic user to by-pass the linguistically demanding standard training. It examines how accurately voice recognition software performed with aphasic speech and language as compared to that of control subjects. METHOD: Five non-impaired controls and six participants with aphasia used a vocabulary of 50 words and 24 phrases to train the software over a maximum of five sessions. For the people with aphasia baseline assessments provided a profile of speech and language impairment. Measures of software accuracy were taken for all subjects at baseline and after four subsequent training sessions, for both single word and phrase level dictation. RESULTS: Word level production resulted in similar accuracy levels for both groups. Phrase level production showed greater accuracy levels than single word level production for both aphasics and controls, but participants with greater speech difficulties had lower software accuracy scores. CONCLUSIONS: Training the software on a specific vocabulary allows people to access it whose speech and language difficulties would otherwise have prevented them. Findings are discussed in relation to use of the software as a dictation tool and as an input device to therapy software.
Adult↗
Zebra finch sexual differentiation: the aromatization hypothesis revisited.
Zebra finches have emerged as an outstanding model system for the investigation of the mechanisms regulating brain and behavior. Their song system has proven especially useful, as the function of discrete anatomical regions have been identified, and striking parallels exist between the morphology of these regions and the level of their function in males and females. That is, the structures are substantially more developed in males, who sing, compared to females, who do not. These parallels extend from higher (telencephalic) centers to the brainstem motor nucleus that innervates the muscles of the vocal organ. Other dimorphic aspects of reproduction in the zebra finch, such as copulatory behaviors and sexual partner preference, however, are not associated with known sex differences in anatomy. In many species, sex differences in neural and peripheral structures and behavior are regulated by secretions from the gonads, which of course are sexually dimorphic themselves. In birds, sex differences at all of these levels (gonad, brain, and behavior) can be mediated by steroid hormones. However, it is not entirely clear that gonadal secretions normally participate at all of the levels. This paper reviews the evidence relating to the role of gonadal steroids in the sexual differentiation of reproductive behaviors and the central and peripheral structures known to regulate them in zebra finches, with a focus on estradiol, which has been most extensively studied in the masculinization of song system morphology and function.
Animals↗
The Earth's 'missing' niobium may be in the core.
As the Earth's metallic core segregated from the silicate mantle, some of the moderately siderophile ('iron-loving') elements such as vanadium and chromium are thought to have entered the metal phase, thus causing the observed depletions of these elements in the silicate part of the Earth. In contrast, refractory 'lithophile' elements such as calcium, scandium and the rare-earth elements are known to be present in the same proportions in the silicate portion of the Earth as in the chondritic meteorites-thought to represent primitive planetary material. Hence these lithophile elements apparently did not enter the core. Niobium has always been considered to be lithophile and refractory yet it has been observed to be depleted relative to other elements of the same type in the crust and upper mantle. This observation has been used to infer the existence of hidden niobium-rich reservoirs in the Earth's deep mantle. Here we show, however, that niobium and vanadium partition in virtually identical fashion between liquid metal and liquid silicate at high pressure. Thus, if a significant fraction of the Earth's vanadium entered the core (as is thought), then so has a similar fraction of its niobium, and no hidden reservoir need be sought in the Earth's deep mantle.
Journal Article↗
Androgen metabolism in the brain of the green anole lizard (Anolis carolinensis): effects of sex and season.
Courtship behavior in male green anoles is partly mediated by the 5alpha-reductase enzyme, which converts testosterone (T) to 5alpha-dihydrotestosterone. This study aimed to determine whether the activity of 5alpha-reductase is enhanced in breeding males compared to females and nonbreeding males who do not normally display masculine behaviors. In some cases, aromatase, which converts T to 17beta-estradiol, also was assessed to determine whether the pattern of its activity in anoles is similar to that in other vertebrates. 5alpha-Reductase is greatest in the brainstem, so its activity was determined separately in homogenates of whole brain and brainstems. The following comparisons were done in different assays: (1) breeding males with breeding females, (2) nonbreeding males with nonbreeding females, and (3) breeding males with nonbreeding males. Aromatase activity was greater in breeding males (mean +/- SE, 0.61 +/- 0.06 fmol/min/mg protein) than in breeding females (0.41 +/- 0.08 fmol/min/mg protein). It was also greater in breeding males (0.84 +/- 0.16 fmol/min/mg protein) than in nonbreeding males (0.33 +/- 0.07 fmol/min/mg protein). In contrast, sex or seasonal differences did not exist in 5alpha-reductase activity. The results are consistent with those of other vertebrate species in which male-biased sex dimorphisms and seasonal differences occur in aromatase, but not in 5alpha-reductase activity. The greater levels of aromatase activity in breeding male anoles suggest that this enzyme might mediate male-specific functions. The equivalently high levels of 5alpha-reductase activity in both sexes suggests that, in addition to facilitating male courtship behavior, the enzyme has a basic function common to both sexes.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Maternal plasma and egg yolk testosterone concentrations during embryonic development in green anoles (Anolis carolinensis).
Sex steroids of presumably maternal origin have been found in avian, crocodilian, and chelonian egg yolks, and they can affect offspring morphology and behavior. The present study reports testosterone (T) levels to which embryos are potentially exposed in the green anole (Anolis carolinensis), a lizard with genotypic sex determination. We documented plasma and yolk T concentrations in adult females, in their developing follicles and eggs, and in freshly oviposited and incubating eggs. Plasma T was higher in reproductively active than in reproductively inactive females. Within reproductively active females, those with a single, large yolking follicle had higher plasma T than those that had one or more shelling, oviductal eggs. Individual females contributed different amounts of T to their yolks, but within females, more mature follicles or eggs consistently had higher yolk T concentrations than did less mature follicles or eggs. Similar to previous research, yolk T concentrations at oviposition were higher in male eggs than in female eggs. However, T levels during incubation did not differ by embryo sex, but rather increased in both male and female eggs. These results suggest that T plays a role in the reproductive physiology of females and potentially in the phenotypic development of their offspring. Furthermore, whereas the yolk T increase observed during follicular maturation is clearly a maternal influence, it remains unclear whether that observed during egg development (i.e., postfertilization) results from a lack of T uptake by the embryo as yolk is absorbed, from embryonic production of T that diffuses into the yolk, or from some combination of these processes. Because lizard embryos are comparatively well developed at oviposition, the assumption that yolk steroids are strictly of maternal origin may require modification, and the possibility that embryos are modulating their own steroid environment needs to be explored.
Animals↗
Masculinized sexual partner preference in female zebra finches with sex-reversed gonads.
Previous research in the zebra finch, a socially monogamous pair-bonding species, suggests that the preference for opposite-sex partners may arise in part through the organizing actions of sex steroids. To further investigate this process, zebra finch eggs were injected with 20 microg fadrozole, a potent estrogen synthesis inhibitor, or with the saline vehicle on embryonic day 5. As adults they were given two-choice sexual partner preference tests followed by group aviary tests. Fadrozole females had masculinized beak color and had testes or ovotestes instead of ovaries. Males were not affected by fadrozole; they did not differ from controls on any measure. In contrast, sexual partner preference was substantially masculinized in fadrozole females in the group aviary tests. Untreated males given a choice between fadrozole and untreated females preferred the untreated females, but this was equally the case when they were given a choice between saline-treated and untreated females. These results suggest that males do not specifically avoid females with testes and that male avoidance is unlikely to explain why fadrozole-treated females pair with other females. The present data add to the evidence that actions of gonadal steroids during development contribute to adult sex differences in partner preference in this pair-bonding species. Furthermore, because fadrozole-treated females do not produce audible song, the mechanisms regulating partner preference and song system development are dissociated.
Animals↗
Randomized phase 2 trial of ketoconazole and ketoconazole/doxorubicin in androgen independent prostate cancer.
Eighty-nine patients with progressive prostate cancer despite suppression of testosterone and withdrawal of anti-androgens were studied. This was a relatively advanced population, with 63 of 89 having either osseous metastases (mets) beyond the axial skeleton or visceral mets. Patients were randomly assigned to receive either ketoconazole alone, or ketoconazole with weekly doxorubicin. All patients received replacement hydrocortisone. The primary endpoints were response and survival. Based on PSA reduction criteria (>/= 80% maintained for at least 8 weeks), 14 of 45 patients (31%) in the single-agent ketoconazole arm responded. Sixteen of 44 patients (36%) in the combination ketoconazole/doxorubicin arm responded. There were no important differences between the two treatments in any outcome measure. The median overall survival for all patients was 12.5 months; median time to progression was 3.3 months. Toxicity was significant with both regimens, and more severe in the doxorubicin arm. Fully 20% of patients in each arm discontinued therapy due to intolerable side effects.Each of these regimens is toxic, and produced responses in fewer than half of treated patients. Although the observed median survival does compare favorably with reports from similar cohorts treated in the community, the potential benefit is only modest. In our view, neither of these regimens is sufficiently promising to justify phase 3 evaluation.
Journal Article↗
Phase II studies of bryostatin-1 in patients with advanced sarcoma and advanced head and neck cancer.
BACKGROUND: Bryostatin 1 is a marine derived macrolactone with antineoplastic activity modulated through protein kinase C, and with good activity in in vitro and in vivo models. There are few drugs that offer palliation for metastatic soft-tissue sarcoma and head and neck cancer, and drugs with new mechanisms of action warrant detailed disease specific study. PATIENTS AND METHODS: Two phase II studies for patients with incurable soft tissue sarcoma (12), or head and neck cancer (12) were conducted. Patients were treated with bryostatin, 120 mg/m2/72 hours every 2 weeks for 3 cycles prior to re-evaluation. Most patients had received prior chemotherapy. RESULTS: No patients had objective responses to therapy. Six patients had brief periods of disease stabilization. Toxicity was generally mild, with myalgia being prominent (n=8). Hyponatremia, not previously described, occurred in 5 patients. The mechanism of this toxicity was unclear. CONCLUSIONS: Bryosytatin 1 given as a single agent for advanced adult soft tissue sarcoma and head and neck cancer is inactive. Myalgia and hyponatremia were the predominant toxicities.
Adult↗
Glycopeptide-resistant Enterococcus faecium infections in paediatric liver transplant recipients: safety and clinical efficacy of quinupristin/dalfopristin.
We describe our experience of quinupristin/dalfopristin for glycopeptide-resistant Enterococcus faecium (GREF) infections in 19 paediatric liver transplant recipients. The median patient age was 2 years and all were receiving immunosuppressive regimens. Quinupristin/dalfopristin was well tolerated and complete resolution of infection was seen in 74% of patients. Side-effects included reversible elevation of serum alkaline phosphatase, skin rash, itching, diarrhoea and vomiting, but therapy was not withdrawn from any patient. Quinupristin/dalfopristin appears safe and efficacious in critically ill immunocompromised children with renal or hepatic impairment.
Adolescent↗
Development of a sexually dimorphic neuromuscular system involved in green anole courtship behavior.
During courtship and aggression, adult male green anoles (Anolis carolinensis) extend a large red throat fan called a dewlap. Adult females have a very small dewlap; they rarely use it during agonistic encounters and never during courtship. The motoneurons, nerve, muscle fibers, neuromuscular junctions, and cartilage pieces responsible for dewlap extension are all larger in adult males than females, parallel to the behavioral dimorphisms. However, the general developmental pattern of these structures, and when they become sexually dimorphic, was largely unknown. In the present study, we examined the length of the 2nd ceratobranchial cartilages (which unfold the dewlap), muscle fiber size, nerve cross-sectional area, and motoneuron soma size, as well as measures of body size (snout-vent length and body weight) at post-hatching days 1, 30, 60, 75, and 90. All measures other than motoneuron soma size increased over time. However, only cartilage length and muscle fiber size became sexually dimorphic in the first three months after hatching. The cartilage was greater in males than females by d60, and muscle fiber size differentiated by d75. The results indicate that peripheral structures involved in dewlap extension differentiate prior to those in the brain and thus, because males and females in this age range are identical in size, dewlap (cartilage) size could be a relatively specific factor contributing to the sexual differentiation of the rest of the neuromuscular system.
Animals↗
Expression of human alpha 2-adrenergic receptors in adipose tissue of beta 3-adrenergic receptor-deficient mice promotes diet-induced obesity.
Catecholamines play an important role in controlling white adipose tissue function and development. beta- and alpha 2-adrenergic receptors (ARs) couple positively and negatively, respectively, to adenylyl cyclase and are co-expressed in human adipocytes. Previous studies have demonstrated increased adipocyte alpha 2/beta-AR balance in obesity, and it has been proposed that increased alpha 2-ARs in adipose tissue with or without decreased beta-ARs may contribute mechanistically to the development of increased fat mass. To critically test this hypothesis, adipocyte alpha 2/beta-AR balance was genetically manipulated in mice. Human alpha 2A-ARs were transgenically expressed in the adipose tissue of mice that were either homozygous (-/-) or heterozygous (+/-) for a disrupted beta 3-AR allele. Mice expressing alpha 2-ARs in fat, in the absence of beta 3-ARs (beta 3-AR -/- background), developed high fat diet-induced obesity. Strikingly, this effect was due entirely to adipocyte hyperplasia and required the presence of alpha2-ARs, the absence of beta 3-ARs, and a high fat diet. Of note, obese alpha 2-transgenic beta 3 -/- mice failed to develop insulin resistance, which may reflect the fact that expanded fat mass was due to adipocyte hyperplasia and not adipocyte hypertrophy. In summary, we have demonstrated that increased alpha 2/beta-AR balance in adipocytes promotes obesity by stimulating adipocyte hyperplasia. This study also demonstrates one way in which two genes (alpha 2 and beta 3-AR) and diet interact to influence fat mass.
Adipose Tissue↗