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Biomedical subjects

J Nelson

Publications and source records attributed to J Nelson.

At least 109 records · Page 6Linked to original sources
PubMed1997

Neurocognitive impairment in human immunodeficiency virus infection is correlated with sexually transmitted disease history.

BACKGROUND AND OBJECTIVES: Neurocognitive impairment is common in human immunodeficiency virus (HIV)-infected subjects. The relationship of sexually transmitted diseases to neurocognitive changes is unknown. GOAL: To establish whether HIV-infected patients with a history of syphilis or gonorrhea have a higher rate of neurocognitive dysfunction. STUDY DESIGN: Neurocognitive function was measured by a battery of quantitative tests in a 453-person HIV-infected cohort and a 219-person HIV-seronegative control group. Neurocognitive function was then correlated with histories of either syphilis or gonorrhea to assess for possible relationships between these sexually transmitted diseases and neurologic impairment. RESULTS: Human immunodeficiency virus-infected subjects with a history of either syphilis or gonorrhea tended to perform worse on neurocognitive testing than their counterparts. This difference could not be explained by educational attainment, age, race or CD4 cell count, and was not noted in the HIV-uninfected control subjects. CONCLUSIONS: Sexually transmitted diseases in HIV-infected subjects are correlated with neurocognitive impairment through an unidentified mechanism.

Adult↗
PubMed1997

Consanguineous marriage and its clinical consequences in migrants to Australia.

Marriage between close biological relatives is strongly favoured in many countries in Asia and Africa. Although substantial numbers of migrants from these regions are now living in Australia, little information is available either on the prevalence of consanguineous unions among migrants or on their clinical outcome. Data are presented on a range of generally rare autosomal recessive genetic disorders diagnosed in the children of parents of Eastern Mediterranean origin who attended Westmead Hospital, Sydney for genetic counselling during the period 1990 to 1994. The effects of parental consanguinity are assessed both in terms of the specific recessive disorders detected, and the perceived role of consanguineous marriage in the communities investigated.

Australia↗
PubMed1997

Effects of the combination of skin cooling and hyperpnea of frigid air in asthmatic and normal subjects.

To investigate whether reducing integumental temperature influences pulmonary mechanics and interacts with inhaling cold air, 10 normal and 10 asthmatic subjects participated in a three-part trial in which cooling the skin of the head and thorax and isocapnic hyperventilation of frigid air were undertaken as isolated challenges and then administered in combination. Integumental cooling for 30 min caused airway obstruction to develop in both populations [change in 1-s forced expiratory volume (delta FEV1) asthmatic subjects = 10% ; normal subjects = 6%)]. Hyperventilation, however, only affected the asthmatic subjects (delta FEV1 asthmatic subjects = 18%; normal subjects = 3%). In contrast to expectations, the combined challenge did not produce a summation effect (delta FEV1 asthmatic subjects = 21%; normal subjects = 7%). These data demonstrate that the skin of the trunk and head is cold sensitive and when stimulated causes similar degrees of bronchial narrowing in both normal subjects and patients with airway disease independent of any ventilatory effect. They also indicate that cooling of the skin does not add to the obstructive consequences of hyperpnea.

Adult↗
PubMed1997

Federal Nursing Service Award. Rhythms of War: activation experiences during the Persian Gulf War.

Reserve military members and families require family support; however, support needs may increase in war. Stress may stem from entering active duty or change in family situations. This ethnographic study illuminates patterns of activation through deactivation of reserve military members, their families, family support personnel, and commanders during the Persian Gulf War. The sample included 59 individuals. Five themes were uncovered: (1) staying connected, (2) living with war, (3) fluctuating emotions, (4) refocus your sense of life, and (5) challenges of living the day-to-day. This study contributes to understanding family support experience from activation through deactivation. Recommendations are offered.

Anthropology, Cultural↗
PubMed1996

Development of hearing and vocalization in a marsupial, the Northern Quoll, Dasyurus hallucatus.

The development of hearing was studied in the Northern Quoll, a nocturnal marsupial carnivore whose young are born into a pouch in an immature state after about 21 days in utero. Startle responses to noise bursts of 105 dB sound pressure level first appeared at 60 days after arrival in the pouch, but only to occasional stimuli; forelimb rather than whole body twitches were evoked. The latter were elicited regularly at 67 days onward. Auditory brainstem response (ABR) audiograms were measured during the period when startle responses first appeared. At 68 days responses were elicited between 1 and 16 kHz with thresholds in excess of 55 dB. At 81-88 days responses occurred over the adult range at lower thresholds than observed in the adult. The waveform of the ABR increased in complexity and decreased in latency during development. Pouch-young emitted acoustically well-defined isolation cells when separated from their mothers. Fourier analysis of these calls revealed peak energy at 8-11 kHz irrespective of the sex of the pouch-young. The isolation call first became evident at about 35 days, when the young were deliberately removed from the nipple, and ceased being emitted beyond about 80 days, some 5 or so days after the eyes open, when the young leave the pouch for substantial amounts of time. The spectrum of the call was similar at all ages within this 45 day period, and its peak frequency correlated closely with the best frequency in the adult quoll's ABR audiogram. At approximately 80 days of age the calls developed major low frequency components, similar to those measured in adult vocalizations, and the contributions of frequencies between 8-11 kHz waned in importance. The results indicate that the onset of hearing in quolls occurs at a relatively early time in the course of their development, but prior to this time the pouch-young emit characteristic isolation calls easily detectable by the mother.

Acoustic Stimulation↗
PubMed1996

Features of the structural development of the inferior colliculus in relation to the onset of hearing in a marsupial: the northern quoll, Dasyurus hallucatus.

The time course of synaptogenesis and the arrival and myelination of afferent connections were studied in the developing inferior colliculus (IC) of a marsupial, the Northern Quoll, and related to the onset of hearing and patency of peripheral auditory structures in that species. The quoll is born after 3 weeks of intrauterine growth and completes its development in a pouch for a further 80 days before weaning. Synaptic terminals in the IC at 9 days after arrival in the pouch were extremely rare and were associated with very low vesicle numbers. The number of synapses increased smoothly during pouch life, whereas the number of neurons with nucleoli fell over the same time period. The ratio of synapses to cells steadily increased from day 9 to day 63, then rapidly accelerated to day 73; a similar high ratio was observed in adults. Retrograde labeling from the IC of fibers projected from the medullary auditory nuclei, first observed on day 36, became progressively denser during pouch life. Myelination of lateral lemniscal fibers was absent on day 45, extremely sparse on day 54, and clear on day 63. Myelin sheaths were not observed within the IC electron microscopically until day 73. Examination of the peripheral auditory system revealed that until about day 40 the middle ear was fluid-filled, and middle ear structures were spongy. Between days 51 and 63 the middle ear cleared, the eardrum became shiny, and the ear canal became patent. The structural development of the IC is therefore very mature at the time hearing begins (67 days), and the last major anatomical change preceding hearing appears to be the opening of the external ear canal.

Animals↗
PubMed1996

Murine epidermal growth factor peptide (33-42) binds to a YIGSR-specific laminin receptor on both tumor and endothelial cells.

A laminin-antagonist peptide, comprising amino acids 33-42 of murine epidermal growth factor (mEGF-(33-42)), interacts with a breast cancer- and endothelial cell-associated receptor, which is specific for the laminin B1 chain sequence, CDPGYIGSR-NH2 (Lam.B1-(925-933)), and is immunologically similar to a previously described 67-kDa laminin receptor. In whole cell receptor assays, mEGF-(33-42), Lam. B1-(925-933), and laminin all have IC50 values for displacement of 125I-laminin in the range 1-5 nM. Cell attachment to solid-phase laminin is also blocked by all three ligands, but in contrast to the receptor assays, mEGF-(33-42) or Lam.B1-(925-933), while equipotent with each other, were less effective than laminin. The concentrations of the peptides required to produce half-maximal inhibition of attachment were in the range 230-390 nM, but those for laminin were 1000-fold lower, in the range 0.2-0.3 nM. Like laminin, solid-phase mEGF-(33-42) supports cell attachment, and this ability is blocked by anti-67-kDa receptor antibodies. Modeling studies suggest that both peptides present a tyrosyl and an arginyl residue on the same face of a right-handed helical fold with elliptical cross-section.

Amino Acid Sequence↗
PubMed1996

Tyrosine kinase inhibitors. 9. Synthesis and evaluation of fused tricyclic quinazoline analogues as ATP site inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor.

Following the discovery of 4-[(3-bromophenyl)amino]-6,7-dimethoxyquinazoline (4; PD 153035) as an extremely potent (IC(50) 0.025 nM) inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), several fused tricyclic quinazoline analogues have been prepared and evaluated for their ability to inhibit the enzyme. The most potent compound was the linear imidazo[4,5-g]quinazoline (8), which exhibited an IC(50) of 0.008 nM for inhibition of phosphorylation of a fragment of phospholipase C-gamma-1 as substrate. While N-methyl analogues of 8 showed similar potency, analogous N-[2-(dimethylamino)ethyl] derivatives were less effective. The next most potent compounds were the linear pyrazoloquinazolines (19 and 20) (IC(50)s 0.34 and 0.44 nM) and pyrroloquinazoline (21) (IC(50) 0.44nM), while several other linear tricyclic ring systems of similar geometry to 8 (triazolo-, thiazolo-, and pyrazinoquinazolines) were less effective. In the imidazo[4,5-g]quinazoline and pyrroloquinazoline series, the corresponding angular isomers were also much less effective than the linear ones. These results are consistent with structure-activity relationship studies previously developed for the 4-[(3-bromophenyl)amino] quinazolines, which suggested that small electron-donating substituents at the 6- and 7-positions were desirable for high potency. Cellular studies of the linear imidazoloquinazoline 8 show that it can enter cells and rapidly and very selectively shut down EGF-stimulated signal transmission by binding competitively at the ATP site of the EGFR.

3T3 Cells↗
PubMed1996

Reactions of nitric oxide and peroxynitrite with organic molecules and ferrihorseradish peroxidase: interference with the determination of hydrogen peroxide.

Endothelial, inflammatory, and other cell types, in addition to forming reactive oxygen species, under proper stimulation release free radicals such as nitric oxide (.NO) and strong oxidants such as peroxynitrite (ONOO-), which is the product of the reaction of nitric oxide with superoxide. Several methods for the detection of H2O2 are based on the ferrihorseradish peroxidase catalyzed oxidation of organic molecules. We investigated the reactions of nitric oxide and peroxynitrite with organic molecules as well as with ferrihorseradish peroxidase and examined the potential interference with the detection of H2O2. Peroxynitrite at low concentrations (0-10 microM) induced a concentration-dependent oxidation of 1,2 phenylenediamine, 3-3' dimethoxybenzidine (o-dianisidine) and para-hydroxyphenylacetic acid (pHPA). With the exception of pHPA, the oxidation of the above compounds by peroxynitrite was not affected by the presence of ferrihorseradish peroxidase. The yield of HPA-dimmer, the oxidation product of pHPA by peroxynitrite, was decreased because ferrihorseradish peroxidase catalyzed the formation of a different product, 3-nitro-HPA. Nitrogen oxides, formed by the reaction of nitric oxide with oxygen, oxidized the aromatic amines o-phenylenediamine and o-dianisidine. A 10-fold excess of nitric oxide over H2O2 decreased the yield of pHPA and dihydrorhodamine 123 (DHR123) by 58 and 72%, respectively, as compared to H2O2 plus ferrihorseradish peroxidase. The inhibition of pHPA oxidation by nitric oxide was in part to the reaction of nitric oxide with compound I and compound II and in part due to the reaction with the phenoxyl radical. These data suggest that the simultaneous generation of nitric oxide and peroxynitrite can interfere with the detection of H2O2. The overestimation or underestimation of the H2O2 detected is dependent upon the organic molecule utilized for detection and by the relative rate of nitric oxide, superoxide, and peroxynitrite generation.

Analysis of Variance↗
PubMed1996

Correlates of the perceived health risks of marijuana use among Australian adults.

A quota sample of 3272 people from the Australian population was surveyed by telephone about the health risks of marijuana use. Three-fifths of the sample (62%) believed that there were health problems caused by marijuana use and one in four (27%) were uncertain. The most commonly cited health effects were: lung cancer, mental problems, memory loss and respiratory disease. The health risks of marijuana use were perceived to increase with increasing frequency of use, and to be greater when the user was a teenager rather than an adult. The perceived health risks of marijuana increased with age, were higher among women than men, decreased with increasing education and frequency and quantity of alcohol and were substantially lower among those who had used marijuana, and those who knew someone who had used marijuana.

Journal Article↗
PubMed1996

Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer.

PURPOSE: To evaluate irinotecan (CPT-11; Yakult Honsha, Tokyo, Japan) in patients with metastatic colorectal carcinoma that had recurred or progressed following fluorouracil (5-FU)-based therapy. PATIENTS AND METHODS: Patients were treated with irinotecan 125 to 150 mg/m2 intravenously (IV) every week for 4 weeks, followed by a 2-week rest. Forty-eight patients were entered onto the study and all were assessable for toxicity. Forty-three patients completed one full course of therapy and were assessable for response. RESULTS: One complete and nine partial responses were observed (response rate, 23%; 95% confidence interval [CI], 10% to 36%). The median response duration was 6 months (range, 2 to 13). The median survival time was 10.4 months and the 1-year survival rate was 46% (95% CI, 39% to 53%). Grade 4 diarrhea occurred in four of the first nine patients (44%) treated on this study at the 150-mg/m2 dose level. The study was amended to reduce the starting dose of irinotecan to 125 mg/m2. At this dose, nine of 39 patients (23%) developed grade 4 diarrhea. Aggressive administration of loperamide also reduced the incidence of grade 4 diarrhea. Grade 4 neutropenia occurred in eight of 48 patients (17%), but was associated with bacteremia and sepsis in only case. CONCLUSION: Irinotecan has significant single-agent activity against colorectal cancer that has progressed during or shortly after treatment with 5-FU-based chemotherapy. The incidence of severe diarrhea is reduced by using a starting dose of irinotecan 125 mg/m2 and by initiating loperamide at the earliest signs of diarrhea. These results warrant further clinical evaluation to define the role of irinotecan in the treatment of individuals with colorectal cancer.

Adenocarcinoma↗
PubMed1996

Depression and multiple sclerosis.

The objective of the present study were (1) to ascertain the lifetime risk of a depression in a representative group of multiple sclerosis (MS) patients, (2) to assess the morbidity risks for depression among first-degree relatives of these MS patients, and (3) to compare these familial risks for first-degree relatives of MS patients with those for first-degree relatives of a primary depression population, i.e., depression but no MS. We psychiatrically evaluated 221 MS patients (index cases) using a structured clinical interview for the DSM-III-R and calculated the rate and lifetime risk of depression for these index cases using the product limit estimate of survival function. We obtained psychiatric histories for all first-degree relatives of index cases, and we calculated morbidity risks for depression for these relatives using the maximum likelihood approach and compared the risks using the likelihood ratio tests. Index cases had a 50.3% lifetime risk of depression. Morbidity risks for depression among first-degree relatives of index cases were decidedly lower when compared with morbidity risks among first-degree relatives of the reference population. Although there appears to be a very high rate of depression among MS patients, the data for their first-degree relatives do not support a clear genetic basis for this depression, or at least the same genetic basis that probably operates within families when depression occurs in the absence of MS.

Adolescent↗
PubMed1996

The effects of salinity change on the exercise performance of two Atlantic cod (Gadus morhua) populations inhabiting different environments

The objective of this study was to determine whether differences in exercise physiology between Atlantic cod (Gadus morhua) populations from different salinity environments could be changed by acclimating individuals of each population to the natural salinity of the comparison population. The exercise-associated blood chemistry of cod from the brackish Bras d'Or lakes, which had previously been shown to be quite different from that of 'open-ocean' cod, changed to resemble the blood chemistry of their oceanic relatives after only 2 months of acclimation to full-strength salinity. In contrast, the blood chemistry of cod from the Scotian Shelf of the Northwest Atlantic Ocean showed little change after 2 months of acclimation to brackish water. These results demonstrate that the degree of osmoconformity to changes in environmental salinity is a population-specific not a species-specific trait. The blood chemistry differences between populations and salinities did not translate into differences in exercise performance: i.e. critical swimming speeds were statistically uniform across all combinations of population and salinity, although performance was more varied in fish swimming in 'non-native' waters. Other 'whole-animal' physiological characteristics, such as metabolic rate and the aerobic cost of transport, were dependent upon both population origin and the environmental salinity. Vigorous swimming was more energetically expensive at full-strength salinity than at 20 salinity, yet estimates of standard (i.e. resting) metabolic rate were lower for full-strength salinity. Environmental salinity also influenced the relative appearance of lactate and metabolic acid in the extracellular fluid compartment, with full-strength salinity favouring the relative appearance of lactate in the blood. Multivariate statistical analyses of this data set showed that, in contrast to other fish species and studies, differences in blood oxygen transport appear to account for some of the swimming performance differences seen in Atlantic cod at 2 °C. The two experimental populations were cleanly separated by a principal components analysis, regardless of the salinity to which they were acclimated, confirming our earlier contention that these cod populations are physiologically distinct. A key feature of that distinctness is the greater phenotypic plasticity exhibited by the population from the more euryhaline, more eurythermal environment.

Journal Article↗