Biomedical subjects
Publications and source records attributed to J R Little.
A continuous suture technique for the microsurgical end-to-side anastomosis of extracranial to intracranial arteries is described. This method combines the speed and even tension of a continuous suture line with improved visualization of the arteries to be anastomosed.
A simple implanted device was used to occlude the left middle cerebral artery (MCA) of 50 conscious cats. In the acute experiments, 10 cats were given mannitol (1.2 gm/kg intravenously) and 10 cats were untreated. The neurological status of the treated cats improved. Perfusion with a mixture of colloidal carbon and buffered paraformaldehyde was carried out from 30 minutes to 12 hours following MCA occlusion. Results of the morphological examination of the brains demonstrated that mannitol delayed the development of neuronal alterations and edema. Measurement of capillary luminal diameters in the ischemic cortex of the untreated cats revealed progressive narrowing with microcirculatory obstruction occurring at 6 hours. Capillary narrowing was absent or minimal in the treated cats during the initial 6 hours. Breakdown of the blood-brain barrier also was delayed by treatment. In the 30 subacute experiments, 10 cats were untreated, 10 cats received mannitol (1.2 gm/kg intravenously), and 10 cats were given a combination of mannitol and high-dose dexamethasone. Although early transient clinical improvement occurred in the treated animals, morphological findings in the brains of the treated and untreated cats following 48 hours of ischemia were not significantly different. Despite the finding that the beneficial effects of mannitol were relatively short-lived (6 to 12 hours), the delay in the development of irreversible changes probably is important as it would allow a longer period of time for the institution of a more definitive form of therapy.
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1. The objective of this study was to determine the separate contributions of exogenous substrate and of kidney tissue to the support of function and metabolism in the isolated perfused rat kidney. The effects of the addition of L(+) [U-14C]lactate or D[U-14C]glucose either to a specially prepared substrate-free albumin (SFA) or to Fr. V bovine serum albumin (Fr. V-BSA) were compared. The Fr. V-BSA has significant quantities of lactate, citrate and free fatty acids associated with it. 2. Perfusion of the rat kidney with the Krebs-Ringer bicarbonate solution containing SFA, without addition of exogenous substrate, resulted in a lower % Na+ reabsorption (approximately 43%) than when the perfusions contained Fr. V-BSA (approximately 80%). Thus, kidney tissue can support at most 45% of Na+ reabsorption, while the substrates associated with the Fr. V-BSA can support approximately 30% of Na+ reabsorption. When the initial concentration of L(+)lactate in the perfusate containing SFA was progressively raised from 0 to 10 mM, % Na+ reabsorption increased to between 85 and 90%. 3. The apparent Km (0-59 mM) and the Vmax (0-67 micronmole g-1. min-1) for lactate oxidation in the presence of SFA were both significantly lower than when Fr. V-BSA was present (Km = 2-0 mM; Vmax = 1-1 micronmole g-1. min-1). The lower Km is interpreted as being due to the removal of substances from the Fr. V-BSA which competitively inhibit either the uptake or oxidation of lactate; the lower Vmax is considered to be related to the lower rate of Na+ reabsorption when SFA is present. 4. Addition of glucose enhanced gomerular filtration rate in the presence of both types of albumin. The resulting increase in the filtered load of Na+ in the presence of glucose was associated with either no change (Fr. V-BSA) or an increase (SFA) in fractional Na+ reabsorption. Although absolute Na+ reabsorptive rate was greater in the presence of glucose than in the presence of lactate, the oxidation rate of glucose, on a carbon-atom basis, was less than 50% of the oxidation rate of lactate. 5. The metabolism of glucose may regulate the permeability characteristics of the glomerulus and the tubular epithelium: by contrast, the high oxidation rate of lactate suggests it can provide direct support for a major fraction of the Na+ actively absorbed.
The Sips equation is frequently used in immunochemistry to describe the relationship between antibody-binding site concentration (n0[Ab]), antigen concentration, intrinsic affinity constant (K), and the heterogeneity index (a) of the affinity constant. Usually n0[Ab] is determined before calculating the remaining parameters (K and a). A new method is proposed which does not require knowledge of n0[Ab] nor an extensive calculation to determine K and a. The method can also be used to determine the antibody-binding site concentration without purified antibody or ligand saturation of the binding sites. This method can be applied to any antibody which binds a monovalent ligand and which can be obtained at a concentration greater than 1/K. Since the Sips equation can be applied to any ordinary chemical reaction by setting a=1, the proposed method can be used generally to determine the affinity constant and the initial concentration of one of the reactants.
A series of 54 adult patients with intraventricular hemorrhage diagnosed by computed tomography (CT scan) is described. Hypertension, arterial aneurysm, and arteriovenous malformation (AVM) accounted for 83% of the cases. Three categories of clinical presentation are defined. CT scan reliably demonstrated the presence and distribution of blood within the ventricular system, including the third and fourth ventricles. The increased density caused by intraventricular blood was seen to disappear in 12 days. An intracerebral hematoma was identified in 78% of cases. Surgical treatment was beneficial in only a small number of cases.
A method is described for radiolabeling polyanionic macromolecules by the formation of an electrostatic complex with a radioiodinated tyramine conjugated DEAE-dextran. Data is presented on the use of this technique for the detection and quantitation of immunospecific binding of polynitrophenylated proteins, deoxyribonucleic acids, and cell surface antigens.
In the intact dog, decreases in both glomerular filtration rate and net renal Na+ reabsorption due to raised ureteral pressure were not associated with a decrease in renal lactate oxidation rate, although total renal CO2 production decreased in proportion to the changes in net renal reabsorption of Na+ and glomerular filtration rate. 2. In order to determine whether, in the absence of other added substrates, the metabolism of lactate supports only the 'basal' renal metabolism or can enhance renal function as well, the rate of lactate utilization and decarboxylation by the isolated perfused rat kidney have been quantified in relation to renal function and one measure of renal basal metabolism, glucose production. 3. The perfusate was Krebs-Ringer bicarbonate (pH 7-35-7-48) with Fraction V bovine serum albumin, 6g/100 ml. L-(+)-lactate was added to raise the lactate concentration from endogenous levels to 2-5, 5-0 or 10 mM. 4. We determined: net lactate utilization rate, lactate decarboxylation rate (14CO2 produced from L-(+)-[U-14C]lactate), net glucose production rate, and net re-absorptive rate of Na+. 5. The apparent Km and Vmax for lactate oxidation were 2-1 mM and 1-29 mumole.g-1.min-1 respectively. There was no apparent maximum for total lactate utilization rate due to continuing increases in glucose production rate as lactate concentration was raised. At ca. 10 mM lactate, glucose production accounted for about half of the total lactate utilized. Therefore the basal energy requirements of the kidney need not be constant since glucose production increases as lactate concentration is raised. 6. Both lactate oxidation rate and lactate utilization rate were significantly correlated with the net reabsorption of Na+ by the renal tubules, with the percentage of filtered Na+ reabsorbed and with the glomerular filtration rate. The major fraction of the net renal reabsorption of Na+ was probably supported by the metabolism of substrates either bound to albumin or derived from renal tissue since the percentage of filtered Na+ reabsorbed increased from ca. 78%, when no lactate was added, to 97% when initial lactate concentration was 10 mM. Therefore, addition of lactate increased both the basal mebabolism and tubular function. However, these observations do not permit us to conclude whether it was the presence of lactate, or its utilization by oxidative or by other pathways which enhanced net renal reabsorption of Na+ and the glomerular filtration rate.
A case of tension pneumocephalus after the insertion of a ventriculoperitoneal shunt for aqueductal stenosis is reported. The possible mechanisms producing this complication are discussed.
An indirect radioimmunoassay has been used to study the antibody-induced changes in expression of TL antigens on mouse thymus and leukemia cells. The results obtained indicate that the incubation of TL+ cells in relatively high concentrations of anti-TL antisera results in a detectable, but not major, loss in the quantity of antigen detected in the plasma membranes. This decrease is not inhibited by azide. Although the antigen loss seems to coincide with the appearance of patching of membrane TL antigens on leukemia cells observed in indirect immunofluorescence microscopy, this is not the case when thymocytes are used as targets. Fab fragments prepared from anti-TL antibodies can also induce a quantitative decrease in antigen expression. The major mechanism involved in membrane antigen loss seems to be endocytosis, although some shedding may also occur. Resistance to immune cytolysis (antigenic modulation) occurs during incubation in anti-TL antibodies before either endocytosis or antigen redistribution has progressed enough to be directly responsible. Since antigenic modulation does not represent a depletion in TL antigens being expressed on the cell surfaces, another mechanism must account for the failure of guinea pig complement to achieve cell lysis.
An indirect radioimmunassay for thymus leukemia (TL)2 antigens has been developed and its specificity documented. The assay makes use of anti-TL antibodies produced in congenic mice (A-Tla(b)) and radioiodinated purified rabbit anti-mouse IgG. Using this assay, differences can be detected in the amounts of antigen expressed on thymocytes of the three known phenotypes (TL.1,2,3;TL.2;TL-) of inbred mouse strains. Significant differences are also detected in comparison of the thymocytes from homozygous TL.1,2,3 mice (A-Tla(a)) and heterozyhotes from Tla(a) and Tla(b) parents. Optimum conditions for the assay have been established. Its ability to detect antigens on glutaraldehyde-fixed cells and the binding of noncytolytic antibodies on both viable and fixed cells are documented. The assay has also been used to quantitate the changes in TL antigen expression on cells incubated in anti-TL antisera under conditions of antigenic modulation.
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The authors review 17 cases of aqueductal stenosis in adults and describe five modes of clinical presentation. The average duration of symptoms was 6 years. Dementia was infrequent. Skull x-ray films frequently demonstrated some degree of cranial enlargement and signs of chronic increased intracranial pressure. Characteristic alterations of the sella included elongation of the anterior wall and flattening, erosion, and anterior displacement of the dorsum. Aqueductal configurations as defined by ventriculography and pneumoencephalography in all cases, and the angiographic findings in seven cases are described. Most of the patients improved substantially after shunt insertion. The clinical findings suggested that aqueductal narrowing and associated hydrocephalus had been present in most of these patients since early life.
The cerbral microcirculation in squirrel monkeys was studied by the carbon perfusion technique after middle cerebral artery occlusion. No filling impairment was detected with 90 minutes of ischemia, and only slight impairment was detected with 3 hours of ischemia. Severe microcirculatory obstruction was found after ischemia longer than 3 hours. The obstruction appeared to be at the capillary level and seemed partly the result of narrowing of cappillary channels by perivascular glial swelling and developing cerebral edema. The relationship between the developing microcirculatory obstruction and the distribution and severity of the neuronal alterations was studied. The results of this investigation using the same experimental model suggest that obstruction of parenchymal vessels does not play a major role in the production of an infarct in areas of acute focal ischemia.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.