Search PubMed⌕ Search

Biomedical subjects

J Simpson

Publications and source records attributed to J Simpson.

At least 109 records · Page 6Linked to original sources
PubMed1987

Trichothecene mycotoxins in aerosolized conidia of Stachybotrys atra.

Stachybotrys atra is the etiologic agent of stachybotryotoxicosis, and this fungus and its trichothecene mycotoxins were recently implicated in an outbreak of unexplained illness in homes. S. atra was grown on sterile rice, autoclaved, dried, and then aerosolized by acoustic vibration. The distribution of particles (mass and number) was monitored on an aerodynamic particle sizer interfaced with a computer. Dust was collected on preweighed glass-fiber filters and extracted with 90% aqueous methanol. Extracts were tested for the ability to inhibit protein synthesis in rat alveolar macrophages, the ability to inhibit the proliferation of mouse thymocytes, and the presence of specific trichothecene mycotoxins. Virtually all of the particles were less than 15 micron in aerodynamic diameter, and the mass median diameter was 5 micron. Thus, most of the particles were respirable. Microscopic analysis of the generated dust revealed that ca. 85% of the dust particles were conidia of S. atra, another 6% were hyphal fragments, and the remainder of the particles were unidentifiable. Thus, greater than 90% of the particles were of fungal origin. The extracts strongly inhibited protein synthesis and thymocyte proliferation. Purified satratoxin H was also highly toxic in the same systems. Each of the individual filters contained satratoxin H (average, 9.5 ng/mg of dust). Satratoxin G and trichoverrols A and B were found in lesser amounts in some, but not all, of the filters. The limit of analysis is ca. 50 ng. These results establish that the conidia of S. atra contain trichothecene mycotoxins. In view of the potent toxicity of the trichothecenes, the inhalation of aerosols containing high concentrations of these conidia could be a potential hazard to health.

Aerosols↗
PubMed1986

Two apparent Philadelphia chromosomes arising from translocations with different chromosomes in a patient with CML: 46,XY,t(7;22)(p22;q11),t(9;22)(q34;q11).

Chromosome studies on bone marrow cells and unstimulated peripheral lymphocytes from a patient with chronic myelogenous leukemia revealed the presence in all cells of two apparent Philadelphia chromosomes: one resulting from the classical translocation with a chromosome #9, and the other arising from a translocation between chromosomes #22 and #7. There was no normal chromosome #22. Some of the cells also had an i(17q), indicative of blast crisis. Repeated chromosome studies at different times during the course of the disease revealed the evolution of additional karyotypic changes. All cells from later samples had an extra #8; some of these cells had a third Philadelphia chromosome, whereas, others had a second Y chromosome. Although a few normal cells were seen in PHA-stimulated lymphocyte cultures, indicating that the patient has a normal constitutional karyotype, most of the cells had a karyotype identical to that found in unstimulated cultures. This unusual karyotype, 46,XY,t(7;22)(p22;q11),t(9;22)(q34;q11), represents the first case in which two apparent Philadelphia chromosomes are present in the leukemic cells from a patient in the absence of a normal #22 chromosome.

Chromosome Banding↗
PubMed1986

Regional brain 5-hydroxytryptamine levels are reduced in senile Down's syndrome as in Alzheimer's disease.

5-Hydroxytryptamine (5-HT) and choline acetyltransferase (ChAT) were assayed in amygdala, cingulate cortex and caudate nucleus of post-mortem brains from 7 cases of Down's syndrome (6 with the neuropathological features of Alzheimer's disease and one with no such features), 9 cases of Alzheimer's disease and 12 controls. 5-HT was markedly reduced in all 3 areas of the pathologically affected Down brains, unaltered in the Down brain with no Alzheimer pathology and reduced in the amygdala and cingulate cortex of the Alzheimer brains. ChAT showed a similar pattern of reduction. These results supply biochemical evidence that 5-hydroxytryptaminergic, as well as cholinergic, neurons are reduced in Down's syndrome with Alzheimer pathology.

Adult↗
PubMed1986

Multiple forms of somatostatin-like immunoreactivity are not influenced by cholinergic denervation of rat hippocampus.

Hippocampal choline acetyltransferase was reduced by 89% in rats two weeks after electrolytic lesion of the septum. The hippocampal concentrations of somatostatin (SOM)-14, SOM-28 and high-molecular-weight SOM were unaltered, suggesting that the activity of hippocampal SOM neurones is not influenced by cholinergic afferents. The relevance of this finding to Alzheimer-type dementia and Down's syndrome is discussed.

Alzheimer Disease↗
PubMed1986

High-molecular-weight forms of somatostatin are reduced in Alzheimer's disease and Down's syndrome.

Four molecular forms of somatostatin-like immunoreactivity (SOM-LI) are present in the human temporal cortex: SOM-14, SOM-28 and high-molecular-weight forms (HMW-SOM) of 7500 and 12,000 daltons. SOM-14 and HMW-SOM are depleted in cortical tissue from cases of pre-senile Alzheimer-type dementia (ATD), but there is a disproportionate reduction in HMW-SOM. In cases of Down's syndrome (DS) with the neuropathological and neurochemical changes of ATD, the total concentration of SOM-LI was similar to that in control cases and the proportions of molecular forms present were comparable. However, there was a significant reduction in the concentration of HMW-SOM. These results show that ATD and DS may share a common abnormality in the biosynthesis and/or post-translational processing of cortical SOM.

Age Factors↗
PubMed1986

Autoantibodies to Alzheimer and normal brain structures from virus-transformed lymphocytes.

B-Lymphocytes from two patients with Alzheimer's disease and one healthy subject were transformed into lymphoblastoid cells by exposure to Epstein-Barr virus. In culture, more than 50% of these cells secreted sufficient IgM or IgG antibody (mainly IgM) to allow immunohistochemical screening against cryostat sections of normal and Alzheimer temporal cortex. More than 30% of the IgM antibodies from each subject recognised brain components, namely: neurons, astrocytes, nuclei, nucleoli, and Alzheimer plaques and neurofibrillary tangles. This methodology represents a major addition to the procedures currently available for the generation of antibodies towards normal and pathological structures in human brain.

Alzheimer Disease↗
PubMed1986

Catheter reperfusion to allow optimal coronary bypass grafting following failed transluminal coronary angioplasty.

At present, intimal dissection, restenosis, or vessel closure occurs in approximately 5 to 10% of patients undergoing percutaneous transluminal coronary angioplasty. Coronary artery bypass grafting is usually required to remedy this complication and prevent substantial myocardial damage. The results of these revascularization procedures, however, are less satisfactory than those of elective coronary bypass grafting. Hemodynamic instability of the patients and the presence of ongoing myocardial ischemia usually necessitate that the operations be performed on an emergent basis. This report describes a series of 9 patients who had either dissected or re-stenosed coronary arteries at the time of angioplasty, as well as acute onset of ischemic symptoms. All underwent emergent coronary bypass grafting, but once it became apparent that angioplasty had failed, a specially designed reperfusion catheter was placed across the coronary lesion to reestablish blood flow to the ischemic area of myocardium. This catheter was removed after aortic cross-clamping and delivery of cardioplegic solution. The presence of the catheter thus reduced the ischemic period to the interval from the onset of dissection until the positioning of the catheter across the lesion. In all patients, the catheter temporarily reestablished coronary blood flow to the region of ischemic myocardium, thereby producing resolution of symptoms, and allowed antegrade delivery of cardioplegic solution infused into the aortic root to this area of myocardium. This, in turn, made it possible to perform the subsequent coronary bypass operation as a controlled, optimal revascularization procedure.

Angioplasty, Balloon↗
PubMed1986

Toxicity of penicillic acid for rat alveolar macrophages in vitro.

Penicillic acid (PA) is a polyketide mycotoxin produced by several species of Aspergillus and Penicillium. This mycotoxin is toxic in experimental animals and has also been reported to be carcinogenic. The cytotoxicity of penicillic acid was studied in rat alveolar macrophages (AM) in vitro. The effects of penicillic acid on membrane integrity were studied by measuring cell volume changes and 51Cr release. There was significant 51Cr release after 2 hr exposure to 1.0 mM penicillic acid, but not after 1 hr exposure. There was a significant decrease in adenosine triphosphate (ATP) in cell cultures exposed to 1.0 mM penicillic acid for 4 hr. Inhibition of the incorporation of [3H]leucine into protein was both dose- and time-dependent and protein synthesis was inhibited significantly after 2 hr exposure to greater than or equal to 0.1 mM penicillic acid. RNA synthesis was inhibited to a lesser extent than protein synthesis. Although there was a significant inhibition of RNA synthesis at 1.0 mM PA after 4 hr, there was no inhibition of RNA synthesis even after 4 hr at any concentration less than 1.0 mM. The ED50 dose after 2 hr exposure was 0.18 and 0.60 mM for protein and RNA synthesis, respectively. There was significant inhibition of phagocytosis after 2 hr exposure at greater than or equal to 0.3 mM penicillic acid and the ED50 for phagocytosis was 0.09 mM. Thus phagocytosis was more sensitive to the toxic effects of penicillic acid than any other cellular process studied. The results reported in this study are similar to those observed for patulin in an earlier study from our laboratory except that patulin was generally more toxic to alveolar macrophages than penicillic acid. The data demonstrate that penicillic acid is toxic to rat alveolar macrophages in vitro and suggest the possibility of a respiratory hazard to agricultural workers exposed to contaminated grain.

Adenosine Triphosphate↗
PubMed1985

Biochemical studies on rabbits with aluminium induced neurofilament accumulations.

The activities of acid phosphatase, hexosaminidase, beta-galactosidase, Mg2+-stimulated Na+K+ATPase, fumarase and ATP:citrate lyase were measured in grey matter of rabbit spinal cord 7-8 days after intra-ventricular or intra-cisternal injection of aluminium. RNA, DNA, and water content were measured in whole spinal cords. Choline acetyltransferase (CAT) and acetylcholinesterase were assayed in dorsal grey matter of the cord, which contained no aluminium-induced neurofilament accumulations (NFAs), and ventral grey matter, which had large numbers of such NFAs. CAT was also assayed in the hypoglossal nerve. None of these measures were consistently altered in the aluminium treated rabbits, although the activity of beta-galactosidase was increased in the NFA-free caudate nucleus of rabbits given aluminium intra-ventricularly, possibly due to the presence of phagocytes on the ventricular surface of the caudate. It is concluded that neither aluminium nor its induced NFAs has a gross effect on neuronal metabolism within 7-8 days.

ATP Citrate (pro-S)-Lyase↗
PubMed1985

Toxicity of the mycotoxin patulin for rat alveolar macrophages.

Agricultural workers are exposed to a variety of organic dusts containing fungi and their secondary metabolites. Patulin, a polyketide lactone mycotoxin produced by several common species of Aspergillus and Penicillium, is found in corn silage. Patulin is toxic in experimental animals and has been reported to be mutagenic, teratogenic, and carcinogenic. The cytotoxicity of patulin was studied in rat alveolar macrophages in vitro. The effects of patulin on membrane integrity were studied by measuring cell volume changes and release of 51Cr. There was a significant release of 51Cr after 1 hr exposure to submillimolar concentrations of patulin. Similarly, there was a significant decrease in ATP in cell cultures exposed to 0.5 mM patulin for 15 min and in cultures exposed to 0.05 mM patulin for 2 hr. There was a significant increase in mean cell volume after 2 hr exposure to 1.0 mM patulin but not after a 1 hr exposure. The effects of patulin on protein and RNA synthesis were studied by monitoring the incorporation of [3H]leucine and [3H]uridine, respectively. Inhibitions of protein and of RNA synthesis were both dose and time dependent. Protein synthesis was the most sensitive cellular parameter studied, with 50% inhibition after 1 hr at ca. 0.002 mM patulin. The data demonstrate that patulin is cytotoxic for rat alveolar macrophages in vitro.

Adenosine Triphosphate↗
PubMed1985

Neurotensin immunoreactivity in post-mortem brain is increased in Down's syndrome but not in Alzheimer-type dementia.

Neurotensin immunoreactivity and choline acetyltransferase (ChAT) activity were measured in post-mortem brain from 10 cases of Down's syndrome (7 aged 53-63 years, one aged 27 years, one aged 16 months and one aged 10 months), 6 cases of Alzheimer-type dementia (ATD) and 19 control subjects (13 aged 40-88 years and 6 aged 9-18 months). Neurotensin concentrations in anterior and basal hypothalamus, amygdala, septal area, caudate nucleus and temporal cortex were unaltered in ATD. The concentrations of neurotensin were significantly increased in the caudate nucleus, temporal cortex and frontal cortex in the cases of Down's syndrome aged 53-63 years with the neuropathological features of ATD, and were also increased in the cerebral cortex of the 27-year-old, which did not have the neuropathological features of ATD, and in two infant Down's cases. ChAT activity was reduced in the ATD and the 53-63-year-old cases of Down's syndrome, but not in the 27-year or 10-month-old Down's cases. The increased neurotensin concentrations appear to be a feature of Down's syndrome not related to the presence of plaques and neurofibrillary tangles or to a deficit in ChAT activity.

Adult↗
PubMed1985

Skin test, RAST and clinical reactions to peanut allergens in children.

One-hundred-and-four children were skin-tested with four peanut-allergen preparations, a commercial extract, extracts of raw and roast peanuts prepared by NH4HCO3 extraction, and a wheatgerm lectin-reactive glycoprotein obtained by affinity chromatography. The presence of symptoms after ingestion of peanut or peanut products was also recorded. The roast allergen extract provided the greatest specificity with eight symptomatic children having a positive skin test and only one positive skin-test reaction in an asymptomatic child in the group of 104 children tested. Despite differences in the incidence of skin-test reactions there was a strong correlation between raw, roast and commercial RAST suggesting common allergens were being identified by circulating IgE. Clinical sensitivity was observed particularly in younger children with 75% of the children being under 4 years of age. A positive roast skin test or a RAST test adds confirmation to the clinical history of allergic reactions to peanuts.

Adolescent↗