PubMed Health⌕ Search

Biomedical subjects

J J McGrath

Publications and source records attributed to J J McGrath.

At least 19 recordsLinked to original sources
PubMed1999

Season of birth and schizophrenia: a systematic review and meta-analysis of data from the Southern Hemisphere.

AIMS: Data from the Northern Hemisphere support an excess of winter-spring births of individuals who later develop schizophrenia when compared with the general population. The data from the Southern Hemisphere have been less consistent. This paper will present a systematic review and meta-analysis of relevant data from the Southern Hemisphere. METHODS: To identify relevant studies we searched electronic databases, reviewed citations from target publications and wrote letters to published authors in the field. The counts for observed and expected births were assessed in four planned comparisons. In the absence of significant heterogeneity, the data were combined using Mantel-Haenzel odds ratio in a fixed effect model. RESULTS: Twelve studies were identified. Published and unpublished data from eight of these were able to be included in the analyses. For the two seasonal comparisons (n = 20,017), small but non-significant excesses were found in the first comparison (winter versus other seasons; OR = 1.04, 0.99-1.08) and for the second comparison (winter and spring versus other seasons; OR = 1.03, 0.99-1.07). For the two quarterly comparisons (n = 14,799), there was a small but non-significant excess found in the third comparison (third quarter versus other quarters; OR = 1.03, 0.98-1.09), and a small but non-significant deficit in the fourth comparison (third and fourth quarter versus other quarters OR = 0.99, 0.95-1.04). CONCLUSIONS: Assuming that season of birth acts as a proxy marker for fluctuating non-genetic risk-modifying factors for schizophrenia, this review suggests that in the Southern Hemisphere these factors may be weaker, less prevalent, less regular, and/or may be modified by other confounding or modifying variables.

Australia↗
PubMed1999

Continually measured fungal profiles in sick building syndrome.

Buildings with indoor air quality (IAQ) complaints frequently have high airborne concentrations of Penicillium species, while buildings with few IAQ complaints have an indoor air (IDA) fungal ecology similar to outdoor air (ODA), where Cladosporium species is usually the dominant microorganism. These studies compared fungal air profiles, measured continually over 6 h in a documented sick building, in IDA in a room experiencing IAQ problems with fungal profiles measured concurrently in ODA. The dominant species collected at both sites were Penicillium species, Cladosporium species, and Alternaria species. In the IDA, Penicillium species were always the dominant organisms, ranging from 150 to 567 cfu/m3 (89.8-100% of the total fungi). In the ODA, Cladosporium species were dominant in four samples (40.0-70.6%), while Penicillium species were dominant (52.7-79.6%) in two. These data demonstrate that, even though ODA fungal profiles are changing continuously, IDA fungal profiles in "sick" buildings tend to remain unchanged.

Air Microbiology↗
PubMed1998

New techniques for biopsy and culture of human olfactory epithelial neurons.

OBJECTIVE: To improve the success of culturing olfactory neurons from human nasal mucosa by investigating the intranasal distribution of the olfactory epithelium and devising new techniques for growing human olfactory epithelium in vitro. DESIGN: Ninety-seven biopsy specimens were obtained from 33 individuals, aged 21 to 74 years, collected from 6 regions of the nasal cavity. Each biopsy specimen was bisected, and 1 piece was processed for immunohistochemistry or electron microscopy while the other piece was dissected further for explant culture. Four culture techniques were performed, including whole explants and explanted biopsy slices. Five days after plating, neuronal differentiation was induced by means of a medium that contained basic fibroblast growth factor. After another 5 days, cultures were processed for immunocytochemical analysis. RESULTS: The probability of finding olfactory epithelium in a biopsy specimen ranged from 30% to 76%, depending on its location. The dorsoposterior regions of the nasal septum and the superior turbinate provided the highest probability, but, surprisingly, olfactory epithelium was also found anteriorly and ventrally on both septum and turbinates. A new method of culturing the olfactory epithelium was devised. This slice culture technique improved the success rate for generating olfactory neurons from 10% to 90%. CONCLUSIONS: This study explains and overcomes most of the variability in the success in observing neurogenesis in cultures of adult human olfactory epithelium. The techniques presented here make the human olfactory epithelium a useful model for clinical research into certain olfactory dysfunctions and a model for the causes of neurodevelopmental and neurodegenerative diseases.

Adult↗
PubMed1998

Membrane permeability characteristics of metaphase II mouse oocytes at various temperatures in the presence of Me2SO.

In this study, the hydraulic conductivity (Lp), Me2SO permeability (PMe2SO), and the reflection coefficients (sigma) and their activation energies were determined for Metaphase II (MII) mouse oocytes by exposing them to 1.5 M Me2SO at temperatures of 30, 20, 10, 3, 0, and -3 degrees C. These data were then used to calculate the intracellular concentration of Me2SO at given temperatures. Individual oocytes were immobilized using a holding pipette in 5 microliters of an isosmotic PBS solution and perfused with precooled or prewarmed 1.5 M Me2SO solutions. Oocyte images were video recorded. The cell volume changes were calculated from the measurement of the diameter of the oocytes, assuming a spherical shape. The initial volume of the oocytes in the isoosmotic solution was considered 100%, and relative changes in the volume of the oocytes after exposure to the Me2SO were plotted against time. Mean (means +/- SEM) Lp values in the presence of Me2SO were (LpMe2SO) at 30, 20, 10, 3, 0 and -3 degrees C were determined to be 1.07 +/- 0.03, 0.40 +/- 0.02, 0.18 +/- 0.01, 7.60 x 10(-2) +/- 0.60 x 10(-2), 5.29 x 10(-2) +/- 0.40 x 10(-2), and 3.69 x 10(-2) +/- 0.30 x 10(-2) microns/min/atm, respectively. The PMe2SO values were 3.69 x 10(-3) +/- 0.3 x 10(-3), 1.07 x 10(-3) +/- 0.1 x 10(-3), 2.75 x 10(-4), +/- 0.15 x 10(-4), 7.83 x 10(-5) +/- 0.50 x 10(-5), 5.24 x 10(-5) +/- 0.50 x 10(-5), and 3.69 x 10(-5) +/- 0.40 x 10(-5) cm/min, respectively. The sigma values were 0.70 +/- 0.03, 0.77 +/- 0.04, 0.81 +/- 0.06, 0.91 +/- 0.05, 0.97 +/- 0.03, and 1 +/- 0.04, respectively. The estimated activation energies (Ea) for LpMe2SO, and PMe2SO, and sigma were 16.39, 23.24, and -1.75 Kcal/mol, respectively. These data may provide the fundamental basis for the development of more optimal cryopreservation protocols for MII mouse oocytes.

Animals↗
PubMed1998

Chirality of reduced haloperidol in humans.

In vitro, cytosolic human ketone reductases catalyse the stereospecific (i.e. >99%) formation of S(-) reduced haloperidol (RHP) from haloperidol (HP). Whether this situation is reflected in patients taking the drug is unknown. In this study in nine patients taking HP, only 73.2+/-18.2% of the RHP excreted in urine was the S(-) enantiomer. Thus, enzymes other than cytosolic ketone reductases must be responsible for the formation of the minor enantiomer.

Adult↗
PubMed1997

The influence of cryopreservation on murine oocyte water permeability and osmotically inactive volume.

Osmotic experiments were performed on unfrozen (N = 18) and cryopreserved (N = 21) ICR murine oocytes in order to determine whether a standard cryopreservation process alters membrane water permeability (hydraulic conductivity, Lp) and/or osmotically inactive volume (Vb). Oocytes, initially in an isotonic (288 mOsm) NaCl solution, were exposed to 900 mOsm NaCl in a microdiffusion chamber. Cell size changes were videotaped and analyzed using a parameter estimation program. Best estimates for a two-parameter model (Lp and Vb) which includes the osmotically inactive volume as a fitting parameter are presented for the first time. The cryopreservation process produced no significant difference between the mean Lp or the mean Vb values for the unfrozen control population (Lp = 0.64 +/- 0.15 micron/min/atm, Vb = 24.7 +/- 2.9%) and the cryopreserved population (Lp = 0.63 +/- 0.12 micron/min/atm, Vb = 28.0 +/- 10.8%). While the cryopreservation process did not cause significant changes in the mean values of Lp, Vb, or the variability of Lp, it did produce more variability of Vb. The cause of the increased variability of Vb produced by cryopreservation is unknown. These results suggest that the osmotic properties of unfrozen control oocytes can be used as a reasonable approximation for frozen-thawed oocytes. They also suggest that multiple parameter models and parameter estimation methods may be useful in developing a more comprehensive understanding of the more subtle alterations in osmotic properties that were detected here. Statistical tests were also used for the first time to confirm the assumption that all of the experimental populations were derived from normal distributions.

Animals↗
PubMed1997

Quantitative measurement of cell membrane transport: technology and applications.

The transport of water and cryoprotective chemicals across cell membranes plays an absolutely fundamental role in the outcome of cryopreservation processing. The diversity of cell types as well as the remarkable range of perturbations that cells are subjected to as part of cryopreservation practices generate many interesting research questions. Simply stated, the extreme conditions typical of cryopreservation protocols extend the limits of membrane transport inquiry well beyond that considered in "normal" cell physiology. This paper provides a brief review of methods which have been used for measuring membrane transport properties, especially those methods developed during the past decade which allow us to measure coupled and uncoupled membrane transport properties of water and cryoprotective agents for individual cells in terms of classical Kedem-Katchalsky membrane transport theory. Representative results obtained from these new technologies will be offered to illustrate their utility and relevance to membrane transport issues arising in cryopreservation practice. Engineers have made significant contributions to this area of research primarily in terms of device development and the application of inverse methods to estimate membrane transport properties.

Biological Transport↗
PubMed1996

Formation of pyridinium species of haloperidol in human liver and brain.

Recent interest in the neurotoxicity of haloperidol is based on its oxidation in rodents to the pyridinium derivative, HPP+, a structural analog of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). Recently, we reported that HPP+ and a newly identified reduced pyridinium, RHPP+, were present in blood and urine of haloperidol-treated schizophrenics and that the concentrations of RHPP+ exceeded those of HPP+. In this study, we examined pathways for formation of RHPP+ in subcellular fractions of human liver (n = 5) and brain (basal ganglia; n = 5). The major pathway was reduction of HPP+ (20 microM) to RHPP+ in cytosol (0.17-0.39 and 0.03-0.07 microM RHPP+/g cytosolic protein per h in liver and brain, respectively). The reactions were inhibited significantly by menadione and in brain also by daunorubicin. The inhibition profile, cytosolic location and strict NADPH dependence suggest that the enzymes involved are ketone reductases. A second pathway was oxidation of reduced haloperidol (50 microM), a major metabolite of haloperidol in blood and brain, to RHPP+. In liver microsomes, 0.17-0.63 mumol RHPP+ was formed /g microsomal protein per h. A potent inhibitor of the pathway was ketoconazole (IC50, 0.8 microM), which suggests that P-450 3A isozymes could be involved. In brain mitochondria but not microsomes, reduced haloperidol (120 microM) was oxidised to RHPP+ at a small but significant rate (0.005-0.020 mumol RHPP+/g mitochondrial protein per h) which was not attenuated by SKF 525A, quinidine, ketoconazole, or monoamine oxidase inhibitors. Further studies are warranted to establish the biological importance of these metabolites in vivo.

Adolescent↗
PubMed1996

Incorporating lag effects in register-based age-of-onset distributions in schizophrenia.

Epidemiological studies often use age-of-first-admission from psychiatric case registers to estimate age-of-onset in schizophrenia. Retrospective, interview-based methods have shown that there is a delay between onset of symptoms and eventual contact with psychiatric services, and that this delay can vary both among individuals and at different ages. This delay or lag can confound the interpretation of first admission data such as age-of-onset. To evaluate the potential impact of this factor, we constructed a flexible mathematical model which integrates age-at-first-admission with estimates of this lag, which were derived from interview-based studies and clinical judgement. We applied this model to age-of-first-admission data for 4218 patients with ICD8/9 schizophrenia drawn from a state-wide psychiatric register. Both the raw age-of-first-admission distribution curve and the transformed data ('estimated age-of-onset') reinforce previous findings that (a) there is a wide range of age-of-onset and (b) the shapes of the curves differ between the sexes. Inspection of the mathematically derived distribution supports the proposition that (a) transformation for a lag effect produces a lower onset age and (b) including a variable length of lag produces a change in shape of the distribution. We propose that the mathematical transformation of age-of-first-admission data may have heuristic value, but requires further empirical data on which to base the assumptions of the model.

Adolescent↗
PubMed1996

Development of a novel microperfusion chamber for determination of cell membrane transport properties.

A novel microperfusion chamber was developed to measure kinetic cell volume changes under various extracellular conditions and to quantitatively determine cell membrane transport properties. This device eliminates modeling ambiguities and limitations inherent in the use of the microdiffusion chamber and the micropipette perfusion technique, both of which have been previously validated and are closely related optical technologies using light microscopy and image analysis. The resultant simplicity should prove to be especially valuable for study of the coupled transport of water and permeating solutes through cell membranes. Using the microperfusion chamber, water and dimethylsulfoxide (DMSO) permeability coefficients of mouse oocytes as well as the water permeability coefficient of golden hamster pancreatic islet cells were determined. In these experiments, the individual cells were held in the chamber and perfused at 22 degrees C with hyperosmotic media, with or without DMSO (1.5 M). The cell volume change was videotaped and quantified by image analysis. Based on the experimental data and irreversible thermodynamics theory for the coupled mass transfer across the cell membrane, the water permeability coefficient of the oocytes was determined to be 0.47 micron. min-1. atm-1 in the absence of DMSO and 0.65 microns. min-1. atm-1 in the presence of DMSO. The DMSO permeability coefficient of the oocyte membrane and associated membrane reflection coefficient to DMSO were determined to be 0.23 and 0.85 micron/s, respectively. These values are consistent with those determined using the micropipette perfusion and microdiffusion chamber techniques. The water permeability coefficient of the golden hamster pancreatic islet cells was determined to be 0.27 microns. min-1. atm-1, which agrees well with a value previously determined using an electronic sizing (Coulter counter) technique. The use of the microperfusion chamber has the following major advantages: 1) This method allows the extracellular condition(s) to be readily changed by perfusing a single cell or group of cells with a prepared medium (cells can be reperfused with a different medium to study the response of the same cell to different osmotic conditions). 2) The short mixing time of cells and perfusion medium allows for accurate control of the extracellular osmolality and ensures accuracy of the corresponding mathematical formulation (modeling). 3) This technique has wide applicability in studying the cell osmotic response and in determining cell membrane transport properties.

Animals↗
PubMed1996

Heat stress lipids and schizophrenia.

The neurodevelopmental hypothesis of schizophrenia implicates abnormal or disrupted neural growth during embryogenesis. It is postulated here that stress-inducing agents acting upon a compromised cellular system resulting from abnormal plasma membrane lipids could effect the neuronal abnormalities observed in schizophrenia. The heat stress response is induced by exposure to hyperthermia as well as a variety of other agents. The response to these agents includes the cessation of most transcriptional and translational activities, accompanied by the induction of a highly specific set of proteins. A concomitant reduction in metabolic activity including cell cycle delays is also observed. Much of the enormous literature on the heat stress response concentrates on protein and DNA interactions, especially with regard to transcriptional control. However, a variety of lipids are intrinsically involved in the heat stress response. This paper will provide a brief introduction to the heat shock proteins and will explore the roles that lipids play in the heat shock response.

Heat-Shock Proteins↗
PubMed1996

Pathological laughing and crying.

OBJECTIVE: To review the clinical features, neurobiological correlates and treatment of pathological laughing and crying. METHOD: Selective literature review. RESULTS: Attacks of involuntary, irresistible laughing or crying have long been recognised as sequelae of brain damage. There is controversy about the clinical features of these attacks, the stimuli that provoke them and their relation to affective disorder. The pathophysiology of pathological laughing and crying is still unclear. It can occur in the presence of focal as well as diffuse brain disease. Treatment with antidepressant medications has been found to be of benefit in patients with cerebrovascular disease and multiple sclerosis. CONCLUSIONS: Clinicians should remain vigilant for these symptoms, and offer effective treatments, such as antidepressants, where indicated. Further research is needed to delineate the underlying neurobiological correlates of pathological laughing and crying. The efficacy of both pharmacological and non-pharmacological interventions requires critical evaluation.

Brain↗
PubMed1995

Minor physical anomalies in psychoses: associations with clinical and putative aetiological variables.

This study of patients with functional psychoses set out to examine associations between minor physical anomalies (MPAs) and demographic, clinical, CT scan measures, and putative aetiological variables. 157 psychotic patients had minor physical anomalies assessed using a modified Waldrop scale. RDC diagnoses for these patients were: schizophrenia (n = 79), schizoaffective disorder (n = 31), mania (n = 24), major depression (n = 13), unspecified functional psychosis (n = 8), other organic psychosis (n = 2). 63 healthy white controls were also assessed with the modified Waldrop scale. Minor physical anomalies were not associated with any particular diagnosis. For white subjects, patients had significantly more MPAs than well controls. Anomalies of the palate were the most frequent item reported in patients and controls. For males, there was a weak association between the presence of MPAs and positive family history of a major psychiatric disorder. Those with MPAs required more frequent and longer psychiatric admissions, and showed impaired ability on a test sensitive to left parietal system function. Within the patient group, there were no associations between MPAs and gender, age at onset, negative symptoms, premorbid level of functioning, estimated premorbid intelligence, pregnancy and birth complications, and selected CT variables. Minor physical anomalies are found in a range of functional psychoses. There may be overlap between the various genes that predispose to psychiatric illness (especially in males) and those genes that predispose to developmental instability.

Adult↗
PubMed1994

Schizophrenia and the influenza epidemics of 1954, 1957 and 1959: a southern hemisphere study.

The dates of birth of patients who were admitted with schizophrenia to public hospitals in Queensland between the years 1972 and 1988 were examined for associations between risk of schizophrenia and influenza epidemics. The hypothesis that infants born between four and six months after an influenza epidemic onset have increased risk of schizophrenia was examined for the 1954, 1957 and 1959 epidemics. After the 1954 epidemic there was a significant excess of male schizophrenia births four months after the onset of the epidemic. In 1957, there was a significant excess of female schizophrenia births in the fifth month after the onset of the epidemic. The 1959 epidemic was not associated with any significant excess.

Adult↗
PubMed1994

Quantitative analysis of two pyridinium metabolites of haloperidol in patients with schizophrenia.

OBJECTIVE: A pyridinium metabolite (HPP+) of the neuroleptic drug haloperidol has been identified in rats and in the urine of patients. The purpose of this study was to measure the steady-state blood and plasma concentrations and daily urinary excretion of HPP+ in patients treated with haloperidol. METHODS: HPP+ was measured by HPLC with fluorescence detection. The chromatograms also revealed the presence of a previously unknown pyridinium species, which was identified in urine by liquid chromatography/mass spectrometry/mass spectrometry as 4-(4-chlorophenyl)-1-4-(4-fluorophenyl)-4-hydroxybutylpyridinium (RHPP+). Concentrations of RHPP+ were then measured by HPLC. RESULTS: The steady-state concentrations of HPP+ or RHPP+ in blood and plasma from 34 patients were virtually identical. The plasma concentrations of each metabolite were related to the daily dose of haloperidol and to its plasma concentrations. Nonlinearity in the elimination of RHPP+ was suggested by the increase in the ratio between RHPP+ and HPP+ plasma concentrations with dose or steady-state concentrations of haloperidol. The concentrations of RHPP+ in plasma and urine generally exceeded those of HPP+; the ratio between them in plasma ranged from 0.9 to 14.1. The daily urinary excretion of HPP+ and RHPP+ accounted for 0.40% +/- 0.18% and 2.3% +/- 1.4% of the haloperidol dose, respectively. The renal clearance of each species was 4.5 +/- 2.5 and 11.3 +/- 5.3 L/hr, respectively. CONCLUSIONS: The presence of these pyridinium species in humans raises the concern that they may be neurotoxic in a manner similar to the dopaminergic pro-neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Adult↗
PubMed1994

Membrane transport properties of mammalian oocytes: a micropipette perfusion technique.

A perfusion technique using micropipette methodology was developed to determine quantitatively the membrane transport properties of mammalian oocytes. This method eliminates modelling ambiguities inherent in microdiffusion, a closely related technology, and should prove to be especially valuable for study of the coupled transport of water and cryoprotectant through mammalian oocytes and embryos. The method is described and evidence given for validity of the method for the simple case of uncoupled flow of water through the mouse oocyte membrane. The zona pellucida of a mouse oocyte was held by a micropipette with an 8-10 microns diameter tip opening and perfused by hyperosmotic media. The kinetic volume change of the cell was videotaped and quantified by image analysis. Experimental data and mathematical modelling were used to determine the hydraulic conductivity of the oocyte membrane (Lp) found to be 1.05, 0.45 and 0.26 microns min-1 atm-1 at 30 degrees C, 22 degrees C and 12 degrees C, respectively. The corresponding activation energy, Ea, for Lp was calculated to be 13.0 kcal mol-1. These values are in agreement with data obtained by other techniques. One of the major advantages of this technique is that the extracellular osmotic condition can be changed readily by perfusing a single cell with a prepared medium. To study the response of the same cell to different osmotic conditions, the old perfusion medium can be removed easily and the cell reperfused with a different medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗