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Biomedical subjects

J R Little

Publications and source records attributed to J R Little.

At least 127 records · Page 7Linked to original sources

Structural changes following hypothermic preservation of human cadaveric kidneys.

Three kidneys preserved as though for transplantation became available for study. The clinical details relating to the donors and methods of preservation by simple hypothermia and pulsatile perfusion are presented. Light microscopic and ultrastructural features observed following perfusion fixation of the kidneys are described. All three kidneys showed some reversible ischemic cell damage, but only one showed evidence of ischemic cell damage that was considered to be irreversible. The latter was seen focally in the pars recta of the proximal convoluted tubules and in the ascending thick limb of the loop of Henle. The irreversible changes were present in the kidney that had undergone the longest period of simple hypothermic storage prior to transfer to pulsatile perfusion preservation. The similarity of the findings to those seen in vivo in the rat after one hour of total renal ischemia, followed by 24 hours' reflow, is discussed; a hypothesis is suggested to explain the site of the irreversible injury seen in the kidneys under study.

Adolescent↗

Pseudo-tandem stenosis of the internal carotid artery.

Two cases of pseudo-tandem stenosis of the internal carotid artery are presented. Proximal stenosis was produced by a large, focal atherosclerotic plaque. The severe intracranial "stenosis" was thought to be an angiographic artifact. Repeat cerebral angiography after carotid endarterectomy revealed normal intracranial arteries. The recognition of this entity is important because a decision to operate is based largely upon angiographic findings.

Aged↗

Morphological changes in acute focal ischemia: response to osmotherapy.

The sequential morphological changes following acute MCA occlusion in conscious cats were studied. The artery was occluded with a simple implanted device that resulted in immediate contralateral hemiparesis. The ischemic changes in the MCA territory developed in a diphasic fashion. Astrocytic swelling and capillary narrowing preceded the development of ischemic neuronal alterations during the primary phase. Capillary obstruction developed during the secondary phase when tissue injury was advanced. Increased vascular permeability to fluorescein was seen with 90 min of MCA occlusion and was initially confined to ischemic gray matter. Leakage of fluorescein consistently occurred with occlusion periods of 90 min and longer, whereas increased permeability to Evans blue was transient. A single, standard dose of mannitol (1.0 to 1.2 g/kg i.v.) was shown to improve the neurological deficit and delay the onset of ischemic injury. Considerable preservation of cerebral tissue was demonstrated with ischemic periods up to 6 hr. The administration of small (0.5 g/kg i.v.), repeated doses of mannitol was found to prolong the beneficial effects.

Acute Disease↗

Immune response deficiency of BSVS mice. II. Generalized deficiency to thymus-dependent antigens.

BSVS mice gave abnormally low IgG responses to 5 thymus-dependent antigens as well as a weak delayed-type hypersensitivity (DTH) response to sheep red blood cells. In contrast to IgG, the IgM antibody responses of these mice were normal to three T-independent antigens as well as to all five T-dependent antigens. The low immune responsiveness of BSVS mice was also reflected in the low levels of IgG(2)a, IgG(2)b and IgG(3) in their normal serum. The low T-dependent immune responses may result from BSVS mice having been selectively bred for susceptibility to infection with St. Louis encephalitis virus and Salmonella. C57BL/6J mice, which are also highly susceptible to Salmonella, gave low immune responses similar to, but genetically distinct from, those of BSVS mice. The levels of Ig-positive and theta-positive cells were normal in BSVS and C57BL/6J mice.

Animals↗

Bronchogenic carcinoma with a brain metastasis: a continuing challenge.

Twenty-three patients with carcinoma of the lung and a brain metastasis had both the primary and secondary tumors surgically removed (combined operation). Results revealed that 52% of the patients were unimproved and died during the first 6 months. Operation improved short-term survival in 26%. Five patients (22%) lived longer than 2 years, and 3 of them (13%) are alive and well 10 or more years following operation.

Adult↗

Treatment of acute focal cerebral ischemia with intermittent, low dose mannitol.

The object of this investigation was to study the effects of intermittent, low dose mannitol therapy on conscious cats after acute left middle cerebral artery (MCA) occlusion. A simple implanted device was applied to the proximal left MCA of 40 adult cats using microsurgical techniques. In the acute experiments, 10 cats were untreated and 10 cats received mannitol (0.5 g/kg intravenously) immediately before occlusion and again 3, 6, and 9 hours later. They subsequently underwent intra-arterial perfusion with colloidal carbon and buffered paraformaldehyde 12 hours after occlusion. The plasma osmolality immediately before perfusion was 316 +/-2 (SD) milliosmoles in untreated cats and 331 +/- 5 milliosmoles in treated cats. Gross swelling, impaired carbon filling, and breakdown of the blood-brain barrier (BBB) to fluorescein were seen in the left MCA territory of 8 untreated cats and 1 treated cat. The mean percentage of gray matter cross sectional area where severe ischemic neuronal alterations predominated was 45 +/- 12% in untreated and 14 +/- 16% in treated cats (p less than 0.01). The mean capillary luminal diameter in the left sylvian cortex was 4.5 +/- 1.0 mu in untreated cats (control, 6.5 +/- 1.0 mu) and 5.5 +/- 1.0 mu in treated cats. In the subacute experiments, 10 cats were not treated and 10 cats received mannitol as in the acute experiments. The cats were killed with a large bolus of sodium pentobarbital 48 hours after left MCA occlusion. Gross swelling and breakdown of the BBB were less severe in treated cats. The mean cross sectional area of infarcted tissue was 55 +/- 12% in untreated cats and 33 +/- 21% in treated cats (p less than 1.0). The findings of this study indicate that intermittent, low dose mannitol therapy delays the onset of ischemic cerebral injury and may reduce the size of the eventual infarct or convert a potential infarct into a so-call "transient ischemic attack." (Neurosurgery, 5: 684--691, 1979).

Acute Disease↗

Superficial temporal artery to middle cerebral artery anastomosis. Intraoperative evaluation by fluorescein angiography and xenon-133 clearance.

Fluorescein angiography and xenon-133 (133Xe) clearance studies were performed during surgery on 15 patients who were undergoing superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis. Fourteen patients had occlusive disease of the internal carotid artery (ICA), and one patient had severe stenosis of the MCA. Before anastomosis, fluorescein angiography showed slow filling of the MCA branches through collateral channels. Focal areas of impaired microcirculatory filling and washout were seen in the territory of severely sclerotic cortical arteries. The findings of preanastomotic 133Xe clearance studies were variable and a uniform pattern of regional cerebral blood flow (rCBF) changes was not defined. In 55% of the patients, rCBF was reduced to 25 ml/100 gm/min or less at one or more detector sites. Fluorescein angiography provided an immediate assessment of anastomotic patency and clearly displayed the distribution of blood entering the epicerebral circulation through the STA. In 67% of patients, multiple MCA cortical branches filled with fluorescein, whereas in 33% filling was restricted to the receptor artery territory. An immediate, substantial (greater than or equal to 15 ml/100 gm/min) increase in rCBF was demonstrated in 73% of patients after anastomosis. The rCBF changes were consistently better in patients with donor and receptor arteries greater than 1 mm in diameter. Redistribution of collateral input acted to increase rCBF in areas distant from the anastomotic site. Some improvement in fluorescein circulation and rCBF also was seen in cortex supplied by sclerotic MCA branches.

Adolescent↗

Computerized tomography findings in arteriovenous malformations of the brain.

Computerized tomography (CT) scans of 54 patients with an arteriovenous malformation (AVM) of the brain were reviewed. The 31 males and 23 females (mean age: 33 years) were classified according to clinical presentation: 1) intracranial hemorrhage (30 patients); 2) seizure disorder (19 patients); and 3) other neurological disturbance (five patients). A brain hematoma was identified in all of the patients in the hemorrhage group have a CT scan within 1 week of the bleed. Extension of hemorrhage into the ventricular system as seen in eight cases was invariably accompanied by severe neurological dysfunction. A high-density lesion without associated mass effect was found in 48% of patients presenting with a seizure disorder. Dilatation of the ipsilateral lateral ventricle, a common finding in this group of patients, was thought to indicate an atrophic process. Evidence of discrete brain infarction was unusual. Intravenous infusion with Hypaque provided additional information in 31 of the 35 patients so studied. Demonstration of prominent or enlarged feeding arteries and/or draining veins occurred in 20% of patients with large malformations. Six cases of angiographically occult AVM's were found. A correlation of the CT scan with clinical, angiographic, and histological findings is presented.

Adolescent↗

Limited trypsin cleavage distinguishes MHC and thymus-leukemia antigens.

A simple technique is presented for the identification of particular cell membrane antigens. The method employs labeled membrane antigens that are isolated immunospecifically and subjected to limited trypsin digestion followed by polyacrylamide gel electrophoresis in detergent. A large "core" peptide is produced by proteolysis of murine thymus-leukemia antigens (TLA) and from antigens of the major histocompatibility complex (MHC). The tryptic cores from H-2K and H-2D are regularly distinguishable from the thymus-leukemia antigens (TLA) by gel electrophoresis in one dimension. This chemical distinction is particularly important in the analysis of antigen mixtures isolated with antisera specific for beta 2 microglobulin. These techniques have been used to identify thymus-restricted beta 2 microglobulin-associated antigens on cell membranes from mouse, man, guinea pig, and monkey. In appropriate inbred mouse strains, these are the TLA and it is proposed that in the three other species examined they may be analogues, although not necessarily homologues, of TLA. The broad species distribution of these thymus-restricted cell membrane antigens suggests that they are involved in the differentiation of thymus-dependent lymphocytes (T cells).

Animals↗

Shared chemical properties of different murine thymus-leukemia antigens.

Immunochemical studies of murine thymus-leukemia antigens (TLA) have confirmed that the subunit structure consists of a 45,000-dalton heavy chain and a beta 2 microglobulin (beta 2m) light chain. Similar structural features are exhibited by the TLA from thymocytes of Tlaa, Tlac, Tlad, and a leukemia cell derived from C57BL/6, a Tlab strain. In addition to the similar subunit structure from the four haplotypes, each TLA shows a similar pattern of trypsin proteolysis. This procedure yields a major heavy chain cleavage product of approximately 37,000 daltons that remains associated with beta 2m and retains most or all of the antigenic determinants of the intact TLA. Evidence is presented that TLA do not exhibit Fc receptor properties, nor do they adsorb to murine leukemia virus antigens under the conditions of isolation for analysis on polyacrylamide gel electrophoresis (PAGE) in sodium dodecyl sulfate (SDS). Taken together these findings strongly support the hypothesis that TLA comprise a family of chemically similar antigens belonging to a structurally and genetically related group that includes H-2D, H-2K, and Qa-2,3.

Animals↗

Immunopotentiating effects of amphotericin B. I. Enhanced contact sensitivity in mice.

Contact sensitivity responses to dinitrofluorobenzene (DNFB) or oxazolone were enhanced by amphotericin B (AmB) administration. This adjuvant effect of AmB was documented in mice by ear thickness measurements, ear histology, and the 5-iodo-2'-deoxyuridine-125I ear assay. The optimum immunopotentiating effect of AmB required its simultaneous administration at the time of skin sensitization. AmB-induced adjuvant effects were also observed in adoptive transfer experiments in which syngeneic recipients of lymph node cells from animals sensitized with DNFB plus AmB gave stronger contact sensitivity responses than recipients of cells from mice sensitized with DNFB alone. AmB also interfered with tolerance induction by i.v. dinitrobenzene sulfonic acid, suggesting that its adjuvant effects involve inhibition of suppressor cells or their precursors.

Adjuvants, Immunologic↗

Immunopotentiating effects of amphotericin B. II. Enhanced in vitro proliferative responses of murine lymphocytes.

Enhanced in vitro proliferative responses to DNBSO3 were seen in lymph node cells and spleen cells after in vivo sensitization of mice with DNFB plus AmB compared with mice primed with DNFB alone. The T cell proliferation in the nylon column nonadherent fraction for both groups was highly similar, and the enhanced lymph node cell proliferation with AmB was demonstrated to be in the nylon adherent population consisting of both T and B cells. These and earlier studies of immunopotentiation by AmB are consistent with a mechanism that depends on selective interaction of the polyene with a subset of T cells and a resultant impairment of the normally induced suppressor regulation that limits the magnitude and duration of immune responses.

Amphotericin B↗

Surgical treatment of bronchogenic carcinoma with a brain metastasis.

Twenty-three patients with bronchogenic carcinoma and a brain metastasis had their primary and secondary tumors treated surgically. The 10 men and 13 women had an average age of 52 years. Fifteen patients presented with a lesion of the lung and eight patients presented initially with neurological findings of an intracranial mass lesion. The most common histological type of tumor was adenocarcinoma (48%), followed by squamous cell carcinoma, undifferentiated small cell carcinoma, and bronchoalveolar carcinoma. Twelve patients (52%) had a poor result and died during the first six months. Surgery appeared to improve short-term survival in six patients (26%). Five patients (22%) had a good result and lived longer than 2 years without significant neurological deficit. Three patients (13%) are alive 10 or more years following surgery.

Adult↗

Cerebellar hemorrhage in adults. Diagnosis by computerized tomography.

A series of 10 adult patients with cerebellar hemorrhage diagnosed by computerized tomography (CT) is described. Hypertension was the most common etiological factor, accounting for 70% of the cases. The clinical presentation appeared to fall into two basic groups. The first group (60% of the cases) ran a progressive course with early brain-stem compression. The second group had a benign course with findings of focal cerebellar dysfunction. The CT findings reflected the two clinical categories. The scans of Group 1 patients revealed a lorge hematoma (greater to or equal to 3cm) and substantial ventricular dilatation. In contrast, scans of Group 2 patients demonstrated a small hematoma (less than 3 cm) without ventricular dilatation. Use of CT scanning allowed the accurate diffferentiation of cerebellar hemorrhage from primary brain-stem and intraventricular hemorrhage. The findings of the CT investigations proved very helpful in defining appropriate therapy.

Adult↗