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Biomedical subjects

N Allen

Publications and source records attributed to N Allen.

At least 37 records · Page 2Linked to original sources

Determination of Cu, Mn, Fe, and Ca in six regions of normal human brain, by atomic absorption spectroscopy.

A method is reported for measuring copper, manganese, iron, and calcium in brain tissue. We solubilized 100-mg samples of brain tissue with Soluene-350 and diluted the mixtures with methyl isobutyl ketone. Copper and manganese concentrations were measured by using a carbon rod atomizer, iron and calcium concentrations by using an air/acetylene and nitrous oxide/acetylene flame, respectively. The basal ganglia (caudate, putamen, globus pallidus, and substantia nigra) contained high concentrations of iron (10 to 19 mumol/g dry wt) as compared to concentrations found in the cortex (4 mumol/g) or the hippocampus (2.8 mumol/g). Copper exhibited a similar distribution pattern among the regions studied; 526 to 1140 mumol/g (dry wt) in the basal ganglia vs 496 mumol/g in the cortex and 426 mumol/g in the hippocampus. Manganese and calcium were uniformly distributed in the regions examined.

Brain Chemistry

CSF beta-glucuronidase assay in the diagnosis of neoplastic meningitis.

The clinical value of CSF beta-glucuronidase assay in the differential diagnosis of chronic meningitis had been investigated over the past 20 years. Significant (P < .001), often marked, elevation of the enzyme level was found in the first sample submitted in 29 of 30 cases of neoplastic meningitis, irrespective of treatment (mean, 324 units), and in 12 of 14 untreated cases with meningeal lymphoma (mean, 174 units). On the other hand, untreated patients with chronic meningitis of other etiologies had significantly lower of other etiologies had significantly lower levels of enzyme elevation, eg, leukemic meningitis (mean, 46 units), fungal meningitis (mean, 41 units), and tuberculous meningitis (mean, 79 units). In the few cases of chronic meningitis studied during appropriate therapy, a tendency toward a decrease in enzyme activity was noted, thus offering further diagnostic support. In our opinion, the finding of a marked elevation of beta-glucuronidase activity in a patient with chronic meningitis is presumptive evidence of neoplastic etiology.

Diagnosis, Differential

Factor VII and fibrinolytic response to deamino-8-D-argenine vasopressin in normal subjects and dissociate response in some patients with haemophilia and von Willebrand's disease.

Deamino-8-D-argenine vasopressin (DDAVP) was given by intravenous infusion to normal subjects, haemophiliacs and patients with von Willebrand's disease (vWd) and the factor VIII and plasminogen activator response was studied. In normal subjects and most patients with mild haemophilia and mild (intermediate) von Willebrand's disease there was an increase in plasminogen activator and all factor VIII related activities. In patients with mild vWd the prolonged bleeding time was shortened by DDAVP despite only a modest rise in factor VIII related Ristocetin cofactor activity (VIIIR:RiCoF). Sub-groups of patients have been characterized in whom atypical responses was observed. In two brothers with clinically severe haemophilia, but with 5--6 u/dl procoagulant factor VIII (VIIIC), there was an increase in VIIIC but no rise of the corresponding antigen, suggesting increased release of an antigenically abnormal poorly functioning molecule. A patient with intermediate vWd was studied in whom neither DDAVP, adrenaline infusion, nor venous occlusion resulted in an increase in either plasminogen activator or factor VIII related antigen (VIIRAg), although there was a significant increase in VIIIC. In a further patient with severe vWd, DDAVP failed to elicit any plasminogen activator or VIII response. The results obtained from these two patients suggested that in some individuals the presumed endothelial cell abnormality in vWd may be more extensive than a defect in VIIIRAg synthesis. Sub-groups of patients have been identified for whom treatment with factor VIII concentrates would be more appropriate than DDAVP prior to minor surgery.

Adolescent

An improved rat brain-tumor model.

The widely used intracerebral tumor implantation method by freehand injection into parietal or hippocampal areas of the rat brain has proven inadequate for reliable experimental therapeutic studies. Problems include poor intracerebral growth yields and significant rates of spread to extracranial tissues, lungs, and spinal cord. Major variables have been examined experimentally on a model using nitrosourea-induced nervous system tumor cell lines in sygeneic rats. A rapid stereotaxic method greatly improved the consistency of tumor placement. The optimal site was found to be the caudate nucleus. The production of a spheroid intracerebral growth was further facilitated by the use of 1% agar in the cell suspension medium and by an injection volume of 10 mu1 containing at least 10(4) cells. Further improvements involved injection technique and flushing of the operative field. These modifications have resulted in a 99% to 100% yield of intracerebral growth, with a marked reduction in the number and size of extracranial extensions and with distant metastasis rates of 0% to 5%. These results have continually improved with further experience. The method is satisfactory for radiation and chemotherapeutic trials in which survival time as an index of tumor size may be used an an end point.

Animals

The effect of dimethyl sulfoxide on gray matter injury in experimental spinal cord trauma.

The possible effect of dimethyl sulfoxide upon the development of lesions in the gray matter after experimental spinal cord trauma has been investigated with the use of cytochrome oxidase assay and quantitative histologic measurement of total liquefaction necrosis. Observations were made in 17 unconditioned dogs receiving an impact trauma of 400 gm cm force. Experimental animals were given 2.5 gm/kg of dimethyl sulfoxide in 40% solution intravenously one hour prior to trauma, and control animals received a similar volume of saline. No reduction could be found in the degree of loss of cytochrome oxidase at one hour after trauma, nor in the extent of acute necrosis. A slight but non-significant increase in the amount of hemorrhage was noted in gray matter at the trauma site following treatment with dimethyl sulfoxide. The agent resulted in an increase in cytochrome oxidase activities in nontraumatized control gray matter.

Animals

Activities of enzymes of the hexose monophosphate pathway in nervous system tumors induced by ethylnitrosourea.

The activities of three enzymes of the hexose monophosphate pathway (HMP) were measured in frozen samples of rat cerebral cortex and ethylnitrosourea-induced tumors of the rat nervous system. Results show that in most tumors, adequate amounts of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and transketolase (TK) were present so as not to be rate-limiting for utilization of the HMP. When enzyme activites were expressed on the basis of fresh weight, TK was increased in most tumors as compared with cerebral cortex; G6PDH and 6PGDH were more variable, showing either higher or lower activities in tumors as compared to control. Tumors in general had a lower protein content than cerebral cortex. When activities were expressed in terms of this protein content, mean values for the dehydrogenases in all groups of tumors were higher than the average value in cortex, indicating that G6PDH and 6PGDH were spared in tumors relative to other proteins. TK activities in tumors, expressed in terms of cytosol protein were lower than or in the same range as cortex. Increased activities of HMP enzymes in some tumors indicated that the potential activity of the HMP in some (but not all) tumors of the nervous system is greater than that of cerebral cortex.

Animals

Inhibition of Na+-K+-activated ATPase activity following experimental spinal cord trauma.

The specific activity of the membrane-bound enzyme, Na+-K+-activated adenosine triphosphatase (ATPase), has been shown to be decreased following experimental impact injury (400 gm-cm) to the spinal cord in dogs. The prompt and significant (p less than 0.01) fall in activity was evident as early as 5 minutes after injury, and remained at 56% to 67% of control for the 1-hour period studied. This decrease was most prominent in the central core of the traumatized segments of spinal cord. Central core samples, excised immediately adjacent to the trauma site, gave values for the Na+-K+-activated enzyme intermediate to those of the trauma and control sites. For these same samples, the activity of the Mg+2-dependent ATPase did not change appreciably. No alterations were observed in the tissue surrounding the zone of maximum injury at these early time periods. The relationship of membrane-bound enzyme alterations to blood flow, clotting mechanisms, and abnormal free radical reactions are briefly discussed.

Adenosine Triphosphatases