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Biomedical subjects

J J Collins

Publications and source records attributed to J J Collins.

At least 37 records · Page 2Linked to original sources
PubMed2001

A review and meta-analysis of formaldehyde exposure and pancreatic cancer.

BACKGROUND: Most reviews on the carcinogenicity of formaldehyde have focused on cancers of the respiratory tract. Two recent studies have suggested that exposure to formaldehyde may increase the risk for pancreatic cancer. METHODS: We examine 14 epidemiology studies of workers exposed to formaldehyde where pancreatic cancer rates were reported and use meta-analytic techniques to summarize the findings. We also rank formaldehyde exposures for the industries in these studies. RESULTS: We found a small increase of pancreatic cancer risk in the studies overall (meta Relative Risk [mRR] 1.1, 95%CI 1.0-1.3); however, this increased risk was limited to embalmers (mRR 1.3, 95%CI 1.0-1.6) and pathologists and anatomists (mRR 1.3, 95%CI 1.0-1.7). There was no increased risk among industrial workers (mRR 0.9, 95%CI 0.8-1.1) who on average had the highest formaldehyde exposures. CONCLUSIONS: A small increased risk of pancreatic cancer from formaldehyde exposure cannot be ruled out from the studies examined. However, the null findings among industrial workers and the lack of biological plausibility would argue against formaldehyde as a cause. The increased risk of pancreatic cancer among embalmers, pathologists, and anatomists may be due to a diagnostic bias or to occupational exposures other than formaldehyde in these professions.

Formaldehyde↗
PubMed2001

A review of adverse pregnancy outcomes and formaldehyde exposure in human and animal studies.

We examine the potential for reproductive and developmental effects from formaldehyde exposure. Formaldehyde is unlikely to reach the reproductive system in humans in concentrations sufficient to cause damage since it is rapidly metabolized and detoxified upon contact with the respiratory tract. While there are effects seen in in vitro studies or after injection, there is little evidence of reproductive or developmental toxicity in animal studies under exposure levels and routes relevant to humans. Most of the epidemiology studies examined spontaneous abortion and showed some evidence of increased risk (meta-relative risk=1.4, 95% CI 0.9-2.1). We found evidence of reporting biases and publication biases among the epidemiology studies and when these biases were taken into account, we found no evidence of increased risk of spontaneous abortion among workers exposed to formaldehyde (meta-relative risk=0.7, 95% CI 0.5-1.0). The small number of studies on birth defects, low birth weight, and infertility among formaldehyde workers; the limitations in the design of these studies; and the inconsistent findings across these studies make it difficult to draw conclusions from the epidemiology data alone. However, information from experimental studies and studies of metabolism indicate reproductive impacts are unlikely at formaldehyde exposures levels observed in the epidemiology studies.

Abnormalities, Drug-Induced↗
PubMed2001

Enhancing human balance control with galvanic vestibular stimulation.

With galvanic vestibular stimulation (GVS), electrical current is delivered transcutaneously to the vestibular afferents through electrodes placed over the mastoid bones. This serves to modulate the continuous firing levels of the vestibular afferents, and causes a standing subject to lean in different directions depending on the polarity of the current. Our objective in this study was to test the hypothesis that the sway response elicited by GVS can be used to reduce the postural sway resulting from a mechanical perturbation. Nine subjects were tested for their postural responses to both galvanic stimuli and support-surface translations. Transfer-function models were fit to these responses and used to calculate a galvanic stimulus that would act to counteract sway induced by a support-surface translation. The subjects' responses to support-surface translations, without and with the stabilizing galvanic stimulus, were then measured. With the stabilizing galvanic stimulus, all subjects showed significant reductions in both sway amplitude and sway latency. Thus, with GVS, subjects maintained a more erect stance and followed the support-surface displacement more closely. These findings suggest that GVS could possibly form the basis for a vestibular prosthesis by providing a means through which an individual's posture can be systematically controlled.

Adolescent↗
PubMed2001

Estrogen receptor-alpha and beta- immunoreactivity and mRNA in neurons of sensory and autonomic ganglia and spinal cord.

Estrogen receptor-alpha immunoreactivity and mRNAs are present in neurons in locales that innervate genital organs, e.g., parasympathetic pelvic autonomic ganglia, sensory dorsal root and nodose ganglia, and autonomic areas of the lumbosacral spinal cord. With the availability of probes for the beta-isoform of the estrogen receptor, we studied this receptor in autonomic, sensory, and spinal cord neurons and compared it with the distribution of the alpha-receptor. Estrogen receptor-alpha and -beta immunoreactivity were located in the nuclei of neurons, were in subpopulations of parasympathetic neurons in pelvic ganglia, and sensory neurons of dorsal root and nodose ganglia. Both receptor subtypes were present in the lumbosacral spinal cord: in neurons of the outer laminae of the dorsal horn, lateral collateral and medial collateral pathways, sacral parasympathetic nucleus, dorsal intermediate gray, and lamina X. Similar numbers of spinal cord neurons were immunoreactive for estrogen receptor-beta and estrogen receptor-alpha. However, estrogen receptor-beta-immunoreactive neurons appeared less numerous in the outer dorsal horn, but more numerous in the deeper layers of the spinal cord than estrogen receptor-alpha neurons. Retrograde tracing from the uterus revealed "uterine-related" neurons in dorsal root and pelvic ganglia that contained estrogen receptor-alpha and -beta. In situ hybridization revealed both estrogen receptor-alpha and -beta mRNA transcripts in sensory neurons of the dorsal root and nodose ganglia, parasympathetic neurons of pelvic ganglia, and spinal cord neurons in the dorsal horn, sacral parasympathetic nucleus, and dorsal intermediate gray of L6-S1 segments. These studies show that both estrogen receptor-alpha and -beta are synthesized by autonomic and sensory neurons in parts of the nervous system that have connections with the female reproductive system. Such neurons contain neurotransmitters that have important functions in the female reproductive organs; thus, it is likely that estrogen can influence the activity of such neurons and consequently, through them, the activities of the reproductive organs.

Animals↗
PubMed2001

Computational studies of gene regulatory networks: in numero molecular biology.

Remarkable progress in genomic research is leading to a complete map of the building blocks of biology. Knowledge of this map is, in turn, setting the stage for a fundamental description of cellular function at the DNA level. Such a description will entail an understanding of gene regulation, in which proteins often regulate their own production or that of other proteins in a complex web of interactions. The implications of the underlying logic of genetic networks are difficult to deduce through experimental techniques alone, and successful approaches will probably involve the union of new experiments and computational modelling techniques.

Animals↗
PubMed2001

Reduced hip extension during walking: healthy elderly and fallers versus young adults.

OBJECTIVES: To test the hypothesis that reduced hip extension range during walking, representing a limiting impairment of hip tightness, is a consistent dynamic finding that (1) occurs with increased age and (2) is exaggerated in elderly people who fall. DESIGN: Using a 3-dimensional optoelectronic motion analysis system, we compared full sagittal plane kinematic (lower extremity joint motion, pelvic motion) data during walking between elderly and young adults and between elderly fallers and nonfallers. Comparisons were also performed between comfortable and fast walking speeds within each elderly group. SETTING: A gait laboratory. PARTICIPANTS: Twenty-three healthy elderly subjects, 16 elderly fallers (otherwise healthy elderly subjects with a history of recurrent falls), and 30 healthy young adult subjects. MAIN OUTCOME MEASURES: All major peak joint angle and pelvic position values. RESULTS: Peak hip extension was the only leg joint parameter measured during walking that was both significantly lower in elderly nonfallers and fallers than in young adult subjects and was even lower in elderly fallers compared with nonfallers (all p <.05). Peak hip extension +/- standard deviation during comfortable walking speed averaged 20.4 degrees +/- 4.0 degrees for young adults, 14.3 degrees +/- 4.4 degrees for elderly nonfallers, and 11.1 degrees +/- 4.8 degrees for elderly fallers. Peak hip extension did not significantly improve when elderly subjects walked fast. CONCLUSION: An isolated and consistent reduction in hip extension during walking in the elderly, which is exaggerated in fallers, implies the presence of functionally significant hip tightness, which may limit walking performance. Overcoming hip tightness with specific stretching exercises is worthy of investigation as a simple intervention to improve walking performance and to prevent falls in the elderly.

Accidental Falls↗
PubMed2001

Cancer pain management in children.

The World Health Organization document Cancer Pain Relief and Palliative Care in Children (WHO, 1998) advocates the global application of the principles of pain management and palliative care for children with cancer. The principles of pain management include the application of the WHO analgesic ladder, appropriate opioid dose escalation, the use of adjuvant analgesics, and the use of non-pharmacological methods of pain control. These principles of pain management should be incorporated into the treatment protocols of all children with cancer, acknowledging that treatment options may be limited for some children.

Analgesics, Opioid↗
PubMed2001

Potential pulmonary effects of man-made organic fiber (MMOF) dusts.

In the first half of the twentieth century epidemiologic evidence linked elevated incidences of pulmonary fibrosis and cancer with inhalation of chrysotile and crocidolite asbestos, a family of naturally occurring inorganic fibrous materials. As the serpentine and amphibole forms of asbestos were phased out, synthetic vitreous fibers (SVFs; fiber glass, mineral wool, and refractory fiber) became increasingly utilized, and concerns were raised that they too might cause adverse health effects. Extensive toxicological research on SVFs has demonstrated that their pulmonary effects are directly related to fiber dose in the lung over time. This is the result of deposition (thin fibers deposit in the lower lung more efficiently than thick fibers) and lung-persistence ("biopersistence" is directly related to fiber length and inversely related to dissolution and fragmentation rates). In rat inhalation studies, asbestos was determined to be 7- to 10-fold more biopersistent in the lung than SVFs. Other than its effect on biopersistence, fiber composition did not appear to play a direct role in the biological activity of SVFs. Recently, the utilization of man-made organic fibers (MMOFs) (also referred to by some as synthetic organic fibers) has increased rapidly for a variety of applications. In contrast to SVFs, research on the potential pulmonary effects of MMOFs is relatively limited, because traditionally MMOFs were manufactured in diameters too thick to be respirable (inhalable into the lower lung). However, new developments in the MMOF industry have resulted in the production of increasingly fine-diameter fibers for special applications, and certain post-manufacturing processes (e.g., chopping) generate respirable-sized MMOF dust. Until the mid-1990s, there was no consistent evidence of human health affects attributed to occupational exposure to MMOFs. Very recently, however, a unique form of interstitial lung disease has been reported in nylon flock workers in three different plants, and respirable-sized nylon shreds (including fibers) were identified in workplace air samples. Whether nylon dust or other occupational exposures are responsible for the development of lung disease in these workers remains to be determined. It is also unknown whether the biological mechanisms that determine the respirability and toxicity of SVFs apply to MMOFs. Thus, it is appropriate and timely to review the current data regarding MMOF workplace exposure and pulmonary health effects, including the database on epidemiological, exposure assessment, and toxicology studies.

Administration, Inhalation↗
PubMed2001

Predicting cerebral blood flow response to orthostatic stress from resting dynamics: effects of healthy aging.

The transfer function relating arterial pressure (AP) to cerebral blood flow velocity (CBFV) during resting conditions has been used to predict the CBFV response to hypotension. We hypothesized that this approach could predict the CBFV response to posture change in elderly individuals if impaired autoregulation allowed changes in AP to be passively transferred to CBFV. AP (Finapres) and CBFV (middle cerebral artery transcranial Doppler) were measured in 10 healthy young (age 24 +/- 1 yr) and 10 healthy elderly (age 72 +/- 3 yr) subjects during 5 min of quiet sitting and 1 min of active standing while breathing was paced at 0.25 Hz. Transfer functions between AP and CBFV changes during sitting were estimated from each full waveform in both low-frequency (LF; 0.05-0.2 Hz) and heartbeat-frequency (HBF; 0.7-1.4 Hz) ranges. The impulse-response function was used to compute changes in CBFV during posture change. The LF transfer function did not predict orthostatic changes in CBFV in either group, suggesting normal cerebral autoregulation. In the HBF range, the prediction was high in elderly (R = 0.65 +/- 0.23) but not young subjects (R = 0.19 +/- 0.35; P < 0.003, young vs. elderly). Thus rapidly acting regulatory mechanisms that reduce the transmission of beat-to-beat changes in AP to CBFV may be engaged during posture change in young but not elderly subjects.

Adult↗
PubMed2001

Wavelets of excitability in sensory neurons.

We have investigated variations in the excitability of mammalian cutaneous mechanoreceptor neurons. We focused on the phase dynamics of an action potential relative to a periodic stimulus, showing that the excitability of these sensory neurons has interesting nonstationary oscillations. Using a wavelet analysis, these oscillations were characterized through the depiction of their period as a function of time. It was determined that the induced oscillations are weakly dependent on the stimulus frequency, and that lower temperatures significantly reduce the frequency of the phase response. Our results reveal novel excitability properties in sensory neurons, and, more generally, could prove significant in the deduction of mechanistic attributes underlying the nonstationary excitability in neuronal systems. Since peripheral neurons feed information to the CNS, variable responses observed in higher regions may be generated in part at the site of sensory detection.

Animals↗
PubMed2001

Reevaluation of lung cancer risk in the acrylonitrile cohort study of the National Cancer Institute and the National Institute for Occupational Safety and Health.

OBJECTIVES: The present study provides additional analyses of data obtained earlier on lung cancer risk among workers with acrylonitrile exposure. METHODS: The original authors provided the data. For total mortality and the cancer sites of a priori interest (lung, stomach, brain, breast, prostate, and the lymphatic and hematopoietic systems), standardized mortality ratios (SMR) and 95% confidence intervals (95% CI) were computed, the total United States and surrounding counties being used as standard populations. Regional rate-based SMR values were also computed between lung cancer and cumulative acrylonitrile exposure. RESULTS: Except for lung cancer, the external comparisons corroborated the earlier internal comparisons (no increased cancer mortality risk). For lung cancer, the external comparisons revealed death deficits for the unexposed workers (SMR 0.68, 95% CI 0.5-0.9) and all categories of acrylonitrile-exposed workers. The SMR obtained using external rates and the most exposed group (SMR 0.92. 95% CI 0.6-1.4) differed from the corresponding relative risk (RR) of the internal rates (RR 1.5, 95% CI 0.9-2.4). CONCLUSIONS: The analysis of the present study provides little evidence that acrylonitrile exposure increases the mortality risk of cancers of a priori interest, including lung cancer. The lung cancer findings of the external comparison differed from the earlier findings of the internal comparisons. Selection bias (as the healthy worker effect) was probably not responsible. Additional follow-up and analyses, especially of the unexposed workers with low lung cancer rates, may help elucidate the internal and external comparison differences. Results from both comparisons should be presented when the relative risks differ markedly, as both have advantages and disadvantages.

Acrylonitrile↗
PubMed2000

Noise-based switches and amplifiers for gene expression.

The regulation of cellular function is often controlled at the level of gene transcription. Such genetic regulation usually consists of interacting networks, whereby gene products from a single network can act to control their own expression or the production of protein in another network. Engineered control of cellular function through the design and manipulation of such networks lies within the constraints of current technology. Here we develop a model describing the regulation of gene expression and elucidate the effects of noise on the formulation. We consider a single network derived from bacteriophage lambda and construct a two-parameter deterministic model describing the temporal evolution of the concentration of lambda repressor protein. Bistability in the steady-state protein concentration arises naturally, and we show how the bistable regime is enhanced with the addition of the first operator site in the promotor region. We then show how additive and multiplicative external noise can be used to regulate expression. In the additive case, we demonstrate the utility of such control through the construction of a protein switch, whereby protein production is turned "on" and "off" by using short noise pulses. In the multiplicative case, we show that small deviations in the transcription rate can lead to large fluctuations in the production of protein, and we describe how these fluctuations can be used to amplify protein production significantly. These results suggest that an external noise source could be used as a switch and/or amplifier for gene expression. Such a development could have important implications for gene therapy.

DNA-Binding Proteins↗
PubMed2000

Construction of a genetic toggle switch in Escherichia coli.

It has been proposed' that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage lambda switch and the Cyanobacteria circadian oscillator. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic toggle switch-a synthetic, bistable gene-regulatory network-in Escherichia coli and provide a simple theory that predicts the conditions necessary for bistability. The toggle is constructed from any two repressible promoters arranged in a mutually inhibitory network. It is flipped between stable states using transient chemical or thermal induction and exhibits a nearly ideal switching threshold. As a practical device, the toggle switch forms a synthetic, addressable cellular memory unit and has implications for biotechnology, biocomputing and gene therapy.

Bacterial Proteins↗
PubMed2000

Kinetic alterations independent of walking speed in elderly fallers.

OBJECTIVES: To determine if joint kinetic gait alterations in fallers persist when they attempt to walk at a faster speed that is more comparable with nonfallers' comfortable walking speed. DESIGN: Retrospective, case-control study. Stereophotogrammetric and force platform data were collected. SETTING: A gait laboratory. PARTICIPANTS: Sixteen elderly subjects who had at least 2 falls in the last 6 months from an unclear cause and 23 elderly subjects with no history of repeated falls. MAIN OUTCOME MEASURES: Differences in all major peak joint kinetic (moment and power) values during the gait cycle between elderly nonfallers walking at comfortable speed and elderly fallers walking at (1) comfortable and (2) fast speed. RESULTS: Statistically significant differences present at both comfortable and fast walking speeds were present in 4 sagittal plane parameters. There was an increase in peak external hip flexion moment in stance, a reduction in peak hip extension moment, a reduction in knee flexion moment in preswing, and a reduction in knee power absorption in preswing. CONCLUSION: The presence and persistence of 4 specific alterations in sagittal plane joint kinetics at both comfortable and fast walking speeds imply specific intrinsic pattern differences and allow for new insights into the mechanics of gait in elderly people who fall. The presence of these alterations also suggests they may serve as potential identifiable markers to detect those who may be at risk for falls.

Accidental Falls↗
PubMed2000

Distribution and origin of secretoneurin-immunoreactive nerves in the female rat uterus.

Secretoneurin is a 33-amino acid peptide derived from secretogranin II. Secretoneurin immunoreactivity has been localized in the peripheral nervous system where it exerts potent chemotactic activity for monocytes and may play a role in inflammation. Secretoneurin could play a role in this process, although the presence and distribution of secretoneurin-immunoreactive neurons in the female reproductive system has not been documented. Thus, this study was undertaken to examine secretoneurin immunoreactivity in nerves of the rat uterus and uterine cervix. A moderate plexus of secretoneurin-immunoreactive nerve fibers was present in the myometrium and endometrium of the uterus as well as in the smooth muscle and endocervix of the cervix. Many of these fibers were associated with the vasculature as well as the myometrium. Secretoneurin immunoreactivity was present in small- to medium-sized neurons of dorsal root and nodose ganglia. Retrograde tracing with FluoroGold indicated that some of these sensory neurons project axons to the cervix and uterine horns. Secretoneurin-immunoreactive terminal-like structures were associated with neurons in the sacral parasympathetic nucleus of the lumbosacral spinal cord. In addition, some secretoneurin terminals were apposed to pelvic parasympathetic neurons in the paracervical ganglia that projected axons to the uterus and cervix. Double-immunostaining indicated co-existence of calcitonin gene-related peptide or substance P with secretoneurin in some sensory neurons, in some terminals of the pelvic ganglia, as well as nerve fibers in the uterine horn and cervix. Finally, fibers in the uterus and cervix were depleted of secretoneurin by capsaicin treatment. This study indicates that secretoneurin is present in the uterus in C-afferent nerve fibers whose cell bodies are located in sensory ganglia. Some of these fibers contain both secretoneurin and calcitonin gene-related peptide or substance P. These substances have functions in inflammatory reactions. Further, secretoneurin could influence postganglionic parasympathetic "uterine-related" neurons in the pelvic ganglia and preganglionic parasympathetic neurons in the lumbosacral spinal cord.

Animals↗
PubMed2000

The measurement of symptoms in children with cancer.

The purpose of this study was to determine symptom prevalence, characteristics, and distress in children with cancer. The Memorial Symptom Assessment Scale (MSAS) 10-18, a 30-item patient-rated instrument adapted from a previously validated adult version, provided multidimensional information about the symptoms experienced by children with cancer. This instrument was administered to 160 children with cancer aged 10-18 (45 inpatients, 115 outpatients). To confirm the instrument's reliability and validity, additional data about symptoms were collected from both the parents and the medical charts, and retesting was performed on a subgroup of inpatients. Patients could easily complete the scale in a mean of 11 minutes. The analyses supported the reliability and validity of the MSAS 10-18 subscale scores as measures of physical, psychological, and global symptom distress, respectively. Symptom prevalence ranged from 49.7% for lack of energy to 6.3% for problems with urination. The mean (+/- SD) number of symptoms per inpatient was 12.7 +/- 4.9 (range, 4-26), significantly more than the mean 6.5 +/- 5.7 (range, 0-28) symptoms per outpatient. Patients who had recently received chemotherapy had significantly more symptoms than patients who had not received chemotherapy for more than 4 months (11.6 +/- 6.0 vs. 5. 2 +/- 5.1), and those patients with solid tumors had significantly more symptoms than patients with either leukemia, lymphoma, or central nervous system malignancies (9.9 +/- 7.0 vs. 6.8 +/- 5.5 vs. 6.8 +/- 5.0 vs. 8.0 +/- 6.1). The most common symptoms (prevalence > 35%) were lack of energy, pain, drowsiness, nausea, cough, lack of appetite, and psychological symptoms (feeling sad, feeling nervous, worrying, feeling irritable). Of the symptoms with prevalence rates > 35%, those that caused high distress in more than one-third of patients were feeling sad, pain, nausea, lack of appetite, and feeling irritable. Subscale scores demonstrated large variability in symptom distress and could identify subgroups with high distress. The prevalence, characteristics, and distress associated with physical and psychological symptoms could be quantified in older children with cancer. The data confirm a high prevalence of symptoms overall and the existence of subgroups with high distress associated with one or multiple symptoms. Symptom distress is relatively higher among inpatients, children with solid tumors, and children who are undergoing antineoplastic treatment. Systematic symptom assessment may be useful in future epidemiological studies of symptoms and in clinical chemotherapeutic trials. Symptom epidemiology may also provide a focus for future clinical trials related to symptom management in children with cancer.

Adolescent↗
PubMed2000

A framework for addressing health issues in or near a manufacturing facility.

Clustering of health events in or around industrial facilities sometimes leads to worker and community concerns that plant management or local health professionals must address. We provide an eight-step process to deal with these concerns systematically. We emphasize the use of good scientific practices with managerial oversight for effective worker and community communication. This process is directed to plant management and the local health professional and emphasizes the practical aspects of the investigation.

Contract Services↗