Occupational skin disease in New South Wales.
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Dermatitis, Occupational↗
Biomedical subjects
S Freeman
Publications and source records attributed to S Freeman.
Effects of 1,1-dichloroethene and of some of its metabolites on the functional viability of mouse hepatocytes.
1,1-Dichloroethene (DCE) is hepatotoxic in rodents, and the expression of its toxicity involves probably its metabolism. In this study the role of DCE metabolites in the generation of the hepatotoxic lesion was investigated. Hepatocytes from male BALB/c mice in suspension were used as the experimental model. Cells were incubated with DCE for up to 5 hr and cellular viability was assessed by measurement of the release of lactate dehydrogenase into the medium and by alterations in the reduction of the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. After incubation for 3 hr DCE at 0.5 mM caused maximal toxicity, whereas at 0.1 mM DCE was only marginally toxic. Cytotoxicity was exacerbated by pretreatment of mice with buthionine sulfoximine (1.6 g/kg), an inhibitor of glutathione biosynthesis, given 4 hr prior to hepatocyte isolation. Inclusion of N-acetylcysteine (10 mM) into the incubate protected cells against DCE-induced cytotoxicity. Coincubation with octylamine (0.5 mM), an inhibitor of cytochrome P450, abolished the cytotoxic potential of 0.5 mM DCE during incubation for 3 hr. DCE toxicity was increased in hepatocytes from mice which had received ethanol or acetone in their drinking water, both of which induce levels of the hepatic cytochrome P450 isozyme P450 2E1. Incubation of cells with the P450 2E1 inhibitors N,N-dimethylformamide (10 mM) or diethyldithiocarbamate (100 microM) protected liver cells against the detrimental effect of DCE. Pretreatment of animals with phenobarbital, which induces the P450 2B subfamily, or 3-methylcholanthrene, which induces P450 1A1, did not affect the degree of hepatocytotoxicity elicited DCE.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Thyroid hormone induces earlier onset of auditory function in neonatal rats.
The effect of thyroid hormone injection on the development of auditory function in neonatal rats was evaluated using auditory nerve-brainstem evoked responses (ABR). The hormone induced earlier onset of auditory function. In order to differentiate between conductive and sensorineural factors, both air-conducted (AC) and bone-conducted (BC) ABR responses were recorded. Neonatal rats were injected with thyroxine (T4), or with saline (control animals), from day of birth (post-natal day-PND-0), daily, until PND 9. AC- and BC-ABRs were recorded from PND 6 up to PND 20. It was found that both AC- and BC-ABR thresholds were lower in the T4-injected rats up to PND 15, after which no difference was found between the two groups. This indicated earlier maturity of both conductive (external and middle ears) and sensorineural (inner ear) factors and is probably due to the earlier appearance in the blood of higher T4 levels, following injection, than that occurring naturally during the neonatal period in these animals.
Animals↗
Development of hearing in neonatal rats: air and bone conducted ABR thresholds.
While the human full-term neonate can hear at birth, in the rat the onset of auditory function as monitored by recording auditory nerve-brainstem evoked responses (ABR) has been reported to begin on post-natal day (PND) 12-14 and reaches adult thresholds at about 22 days. In order to determine the factors involved in this late onset and then rapid threshold improvement in rats, the ABR to both air conducted (AC) and bone-conducted (BC) auditory stimulation was determined in neonatal rats. ABR to maximal intensity BC stimuli (55 dB above adult rat ABR threshold--55 dB HL*) could be recorded from PND 7-8 while AC responses to 80 dB HL* stimuli, only from PND 11. The air-bone gap (a measure of conductive immaturities only) disappeared on PND 15. This shows that there are both conductive (external and middle ear--Air-bone gap) and sensori-neural (inner ear--BC threshold) immaturities in the neonatal rat; the conductive factors are resolved by PND 15 while the sensori-neural continue after that. With respect to conductive factors, it seems that the state of the ear canal is not important while the chief conductive factors involved probably include mesenchyme resorption and/or ossicular ossification. The chief sensori-neural factor may be the development of the endocochlear potential. It is likely that the human fetus in-utero undergoes similar stages of development.
Acoustic Stimulation↗
Prognosis of occupational contact dermatitis in New South Wales, Australia.
570 patients with occupational contact dermatitis (OCD) were seen between 1984 and 1990 at the Skin and Cancer Foundation in Sydney. 336 (59%) were followed up 1 to 5 years later. Roughly 1/3 were healed, 1/3 were improved without complete healing, 1/4 had no change and 1/12 of the patients had deteriorated. The overall improvement rate was in excess of 70%. Data derived from these patients demonstrated that changing the work duties of patients with OCD improved their outcome (p < 0.01), whilst leaving the industry altogether resulted in a greater overall healing rate (p < 0.01). No difference existed between the outcome of irritant contact dermatitis compared with allergic contact dermatitis. Atopics as expected had a worse prognosis. The outcome in the construction industry was significantly poorer than other industries. Patients suffering from allergic contact dermatitis from chromate also had a dismal prognosis.
Dermatitis, Contact↗
Metabolism in the globus pallidus after fetal implants in rats with nigral lesions.
The effect of fetal mesencephalic implants on glucose utilization in selected brain structures and on apomorphine-induced rotational behavior was measured in rats with a unilateral lesion of the substantia nigra. Ipsilateral, but not contralateral, implants decreased the rotational behavior induced by apomorphine. In addition, the nigral lesion decreased glucose utilization in the dorso- and ventrolateral quadrants of the striatum and in the entopeduncular nucleus but increased glucose utilization in the ipsilateral globus pallidus and lateral habenula. The increased metabolism in the globus pallidus was attenuated by ipsilateral, but not contralateral, mesencephalic implants which also decreased glucose utilization in the dorsomedial caudate nucleus. These results indicate that the ability of an ipsilateral mesencephalic graft to ameliorate the motor behavior in rats with nigral lesions is associated with changes in the functional activity of the ipsilateral globus pallidus.
Analysis of Variance↗
Antifection: a new method for targeted gene transfection.
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Animals↗
Cloning, overexpression and mechanistic studies of carboxyphosphonoenolpyruvate mutase from Streptomyces hygroscopicus.
The enzyme carboxyphosphonoenolpyruvate mutase catalyses the formation of one of the two C-P bonds in bialaphos, a potent herbicide isolated from Streptomyces hygroscopicus. The gene encoding the enzyme has been cloned from a subgenomic library from S. hygroscopicus by colony hybridisation using an exact nucleotide probe. An open reading frame has been identified that encodes a protein of molecular mass 32700 Da, in good agreement with the subunit molecular mass of the carboxyphosphonoenolpyruvate mutase recently isolated from this source [Hidaka, T., Imai, S., Hara, O., Anzai, H., Murakami, T., Nagaoka, K. & Seto, H. (1990) J. Bacteriol. 172, 3066-3072]. The gene shares significant sequence similarity with that of phosphoenolpyruvate mutase, an enzyme that catalyses the related interconversion of phosphoenolpyruvate and phosphonopyruvate. When the carboxyphosphonoenolpyruvate-mutase gene was subcloned into the vector pET11a, the mutase was expressed as about 20% of the total soluble cellular protein in Escherichia coli. The mutase has been purified to homogeneity in three steps in 40% yield. With malate dehydrogenase/NADH, (hydroxyphosphinyl)pyruvate gives (hydroxyphosphinyl)lactate (kcat 164 s-1 and Km 680 microM) and this spectrophotometric assay for the product of the mutase reaction has been employed in the mechanistic studies. The kinetics for the mutase reaction have been evaluated for the substrate, carboxyphosphonoenolpyruvate, and for the putative reaction intermediate carboxyphosphinopyruvate, both of which have been prepared by chemical synthesis. Carboxyphosphonoenolpyruvate is converted to (hydroxyphosphinyl)pyruvate with a kcat of 0.020 s-1 and a Km of 270 microM, and carboxyphosphinopyruvate is converted to (hydroxyphosphinyl)pyruvate with a kcat of 7.6 x 10(-4) s-1 and a Km of 2.2 microM. Although the exogenously added intermediate is not kinetically competent, these results suggest that the mechanism for the mutase reaction involves an initial rearrangement to the intermediate carboxyphosphinopyruvate, followed by decarboxylation to yield the product (hydroxyphosphinyl)pyruvate.
Amino Acid Sequence↗
Vicariance biogeography in the Pleistocene and speciation in North American wood warblers: a test of Mengel's model.
It is widely believed that habitat fragmentation during the Pleistocene initiated speciation events in many songbird genera. One such vicariance model for avian speciation in the Pleistocene was developed by R. M. Mengel for North American birds. This model suggests that the first Pleistocene glacial advance reduced the area of an extensive, eastern North American deciduous forest, forcing adaptation by some species to boreal forest. This, in turn, facilitated the development of transcontinental range expansions during interglacials. Subsequent glacial advances repeatedly fragmented the ranges of these species into eastern and western populations; western isolates speciated to form the multispecies groups observed among various North American birds. We used mtDNA restriction site data to reconstruct the phylogeny of the black-throated green warbler complex-the group that Mengel considered the best fit to his model. Contrary to Mengel's model, the phylogeny indicates that not all western endemics were derived from an eastern ancestor. Instead, our results imply a mix, wherein some western endemics were budded off an eastern source, as Mengel posits, while others probably resulted from intermontane isolations in the west.
Journal Article↗
Is metabolism an important arbiter of anticancer activity of ether lipids? Metabolism of SRI 62-834 and hexadecylphosphocholine by [31P]-NMR spectroscopy and comparison of their cytotoxicities with those of their metabolites.
Antineoplastic ether lipids have entered phase I clinical trial and, although their mechanism of action remains unclear, it is widely believed that the plasma membrane is the primary cellular drug target. In the present study the hypothesis was tested that metabolism of ether lipids acts as a detoxification process. [31P]-nuclear magnetic resonance (NMR) spectroscopy was used to study the metabolism of the ether lipid SRI 62-834 (SRI) and the phosphate ester hexadecylphosphocholine (HPC) in the presence of both isolated phospholipases C and D and post-mitochondrial rat liver homogenate. Both SRI and HPC were slowly metabolised by phospholipase D to their alkyl phosphates and choline, and the alkyl phosphates were subsequently metabolised by phosphatase to yield the alcohols and inorganic phosphate. These studies failed to detect any metabolism of either SRI or HPC by phospholipase C, and the metabolism of platelet-activating factor (PAF) by this enzyme was not inhibited by the addition of either compound. The cytotoxicity of SRI, the related compound HPC and their metabolites was determined in vitro using three cell lines. Cytotoxicity was measured by analysis of cell growth kinetics, MTT assay and lactate dehydrogenase release. Closely similar results were obtained in the JB1 rat hepatoma cell line, in the non-transformed BL8 rat hepatocyte cell line, and in A549 human lung adenocarcinoma cells. SRI was the most toxic of the compounds analysed, the concentration required to produce 50% toxicity or growth inhibition (IC50) being 6-9 microM. The putative metabolite of SRI, 2,2'-bis(hydroxymethyl)tetrahydrofuran, and the known metabolites [2'-(octadecyloxymethyl)tetrahydrofuran-2'-yl]methyl phosphate and 2-hydroxymethyl-2-octadecyloxymethyltetrahydrofuran exhibited IC50 values of > 200, > 100 and 40-70 microM, respectively, consistent with metabolic detoxification. HPC was more cytotoxic (IC50, 37 microM) than its phosphate metabolite (IC50, 140 microM), but its toxicity was similar to that of its metabolite hexadecanol (IC50, 28 microM), suggesting that only the former metabolic route leads to detoxification.
Adenocarcinoma↗
Photodynamic inactivation of retrovirus by benzoporphyrin derivative: a feline leukemia virus model.
The ability of a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), and either broad-spectrum (400-1200 nm) or narrow-band (600-700 nm) red light to kill feline leukemia virus (FeLV) and FeLV-infected cat T cells (cell line 3201) was investigated in culture medium containing fetal calf serum and in blood from infected cats. A molecular clone of FeLV, 61E, is minimally pathogenic and productively infects 3201 cells while causing no change in rate of cell division, viability, or size. Active virus (either free or within infected cells) was quantified by using a limiting dilution assay that involved cocultivation of test samples with naive 3201 cells, after which either the polymerase chain reaction or a reverse transcriptase assay was used to detect the presence of virus. It was shown that 61E-infected T cells in culture were slightly more sensitive to photodynamic killing than were uninfected cells. Infected cells and free virus were eliminated from whole blood taken from infected cats by using 4 micrograms per mL of BPD-MA and 40 J per cm2 of red light. These results correlate well with previous results with BPD-MA and vesicular stomatitis virus in whole human blood and suggest that this photosensitizer is a promising agent for the elimination of retroviruses that are either free or located within infected cells in blood.
Animals↗
Effects of a nursing education intervention on parents' knowledge of hydrocephalus and shunts.
The purpose of this nursing intervention study, which used a pre- and posttest design, was to determine the effect of an education program on parents' knowledge of hydrocephalus and shunt dynamics in a sample of parents of children with hydrocephalus. Study participants were parents of hydrocephalic children treated with an initial shunt or a shunt revision. The convenience sample of 41 subjects was divided into two groups (A or B). Group A participants were parents whose child received an initial shunt. Group B participants were parents whose child was admitted for a shunt revision. The shunt education intervention had three components: a shunt handbook, a preoperative teaching session with the clinical nurse specialist and a subsequent reinforcement teaching session. The pre- and posttest were the same seven multiple choice questions on hydrocephalus and shunts. In both groups, the pretest was given before the shunt education intervention. The posttest was given 2-3 weeks after the patient's surgery. There was a statistically significant change in the scores from the pre- and posttests for Group A (p = 0.0092). The nursing education appeared to have a positive effect upon this group's knowledge of hydrocephalus and shunts.
Adolescent↗
Occupational contact dermatitis in New South Wales.
Five hundred and seventy patients with occupational contact dermatitis (OCD) were seen between 1984 and 1990 at the Skin and Cancer Foundation in Sydney. Data derived from these patients demonstrated that hairdressing, food, construction and the medical industries were the most at risk of OCD. The hairdressing and food industries had a high percentage of apprentices suffering OCD whilst the 35 to 44 year age bracket was most at risk in the construction industry. Allergic contact dermatitis was responsible for 38.2% of cases. The main allergens were chromate, thiuram, epoxy resin, nickel and cobalt. A third (33.9%) of patients were atopic. The average time lost from work was 16 days each year and the calculated yearly cost of OCD in New South Wales was approximately $12 million.
Adolescent↗
Cerebral metabolic responses and vasopressin and oxytocin secretions during progressive water deprivation in rats.
Progressive water deprivation increased plasma osmolality, plasma Na+ concentration, and hematocrit in proportion to the severity of dehydration. With increases of 2% in plasma osmolality (24 h dehydration), glucose utilization increased in the supraoptic nuclei and tended to increase in the neural lobe. With further dehydration, glucose utilization also increased in the paraventricular nuclei. These increases were paralleled by depletion of vasopressin and oxytocin contents in the neural lobe and by the enhanced secretion of both hormones into plasma, with a predominant increase of vasopressin. These changes were proportional to the degree of dehydration. With progression of dehydration, decreases in intracellular and extracellular volumes accentuate. Reductions in extracellular volume result in increased angiotensin II (ANG II) formation. Accordingly, glucose utilization in the subfornical organ (SFO), a primary site of ANG II action, increased after 48 and 72 h of dehydration. The median preoptic nucleus, which receives direct inputs from the SFO, also increased glucose utilization at these times. Glucose utilization also increased in the organum vasculosum laminae terminalis, probably in response to the converging inputs from osmoreceptors, volume receptors, and ANG II receptors. Decreases in glucose utilization were observed in the caudal and rostral ventrolateral medulla, perhaps as compensatory responses to decreased extracellular volume to prevent fall in arterial blood pressure.
Animals↗
Effects of chemical stimulation of the subfornical organ on metabolic activity of the hypothalamo-neurohypophysial system in rats.
Topical stimulation of the subfornical organ (SFO) with angiotensin II (ANG II) or acetylcholine (ACh) increased blood pressure, water intake, and the activity of the hypothalamo-neurohypophysial system (HNS). The pressor and drinking responses were higher and the metabolic activity of the HNS, measured with the [14C]deoxyglucose (DG) method, was lower with ANG-II than with ACh. Glucose utilization in the neural lobe increased by 165% with ACh as opposed to 65% with ANG II. These results demonstrate the ANG II and ACh mobilize differentially the mechanisms increasing blood pressure, drinking responses, and the activity of the HNS.
Acetylcholine↗
Urticarial contact dermatitis in food handlers.
OBJECTIVE: To show that prick testing (using fresh samples of the food suspected from the patient's history) and not only patch testing is the appropriate investigation in selected cases of hand dermatitis in patients who spend considerable time handling foods (for example, catering workers, cooks). SETTING: The Contact and Occupational Dermatitis Clinic at the Skin and Cancer Foundation, a tertiary referral centre in Sydney. PATIENTS: Fourteen patients with hand dermatitis present for an average of 6.17 years referred by dermatologists and occupational health physicians. INTERVENTIONS: Patch and prick tests were performed for each patient. RESULT: In all patients prick tests identified the food allergens. Seafood was the most common allergen giving positive results in 10 patients. Patch tests did not identify any of the food allergens. Of the 14 patients nine were followed up and seven of these had been forced to change their career direction. CONCLUSION: Prick testing is the appropriate investigation in selected cases for the diagnosis of urticarial contact dermatitis in food handlers.
Adolescent↗
The effect of stimulus repetition rate on the diagnostic efficacy of the auditory nerve-brain-stem evoked response.
This study investigates the hypothesis that an increase in the click presentation rate during diagnostic testing with the auditory nerve-brain-stem response (ABR) will increase the efficiency with which lesions may be detected in the nervous system. Cats were exposed to conditions of hypoxia, hypercapnia and acidemia, and hypoglycemia was induced in rats. ABR was recorded using the standard 10/sec click rate and also a higher (55/sec) rate during both the control state and experimental state. Various parameters of the ABR were compared at the two click rates in the control and experimental states to see if the higher click rate was more effective in detecting pathology in the nervous system. It was found that in only a very few cases was the higher stimulus presentation rate more effective, and that in general ABR recordings at one stimulus rate only is quite sufficient for work in a clinical setting.
Acidosis↗
Contrast sensitivity of optokinetic nystagmus.
To determine the threshold characteristics of optokinetic nystagmus (OKN), contrast thresholds for involuntary OKN were measured for gratings of different spatial frequency to yield an OKN-contrast sensitivity function (OKN-CSF). The OKN-CSF resembled an inverted U-shaped function with temporal-to-nasal and nasal-to-temporal movement yielding similar functions. In addition, when psychophysical CSFs were determined for separate form and movement thresholds, it was discovered that the OKN-CSF approximated the psychophysical-movement CSF rather than the psychophysical-form CSF.
Adult↗