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Biomedical subjects

L R Williams

Publications and source records attributed to L R Williams.

At least 19 recordsLinked to original sources

Sensitivity of Fischer 344 x brown Norway hybrid rats to exogenous NGF: weight loss correlates with stimulation of striatal choline acetyltransferase.

Nerve growth factor (NGF) infusion into normal Fischer 344 x Brown Norway (F344/BN) hybrid male rats for 2 weeks resulted in a dose-dependent stimulation of choline acetyltransferase (ChAT) enzyme activity to 70% above control values in both the basal forebrain and striatum, and a statistically significant 10% loss in animal weight. There was a significant correlation between weight gain and stimulation of striatal ChAT activity, but not with stimulation of basal forebrain ChAT. Thus, unlike some other rat strains, the normal F344/BN rat is sensitive to exogenous NGF, and can be used to study the efficacy of NGF on normal central cholinergic neurons. The NGF effect on weight gain may be mediated by cholinergic stimulation of the nucleus accumbens.

Animals

Induction of cobalt accumulation by excitatory amino acids within neurons of the hippocampal slice.

Computer-assisted image analysis was used to establish the dose response of excitatory amino acid (EAA) analogs on the induction of cobalt accumulation within pyramidal and granule cell neurons in 400 microns slices of gerbil hippocampus. Slices were incubated 20 min at 22 degrees C in a solution containing 5 mM CoCl2 and 0-1,000 microM EAA analog. The cobalt was visualized by development in (NH4)2S, and the slices were digitized for quantitative densitometry. Kainic acid (KA) had the largest effect and induced cobalt accumulation in the dentate gyrus and CA1, 180% and 150% above control, respectively, with an ED50 = 30 microM. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) induced accumulations of cobalt in CA1 and hilar neurons 130% above control with an ED50 = 30 microM, but had little effect on dentate granule cells. The accumulations induced by KA and AMPA were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but not by DL-2-amino-5-phosphonovaleric acid (AP5) or voltage-dependent calcium channel blockers. N-Methyl-D-aspartate (NMDA) induced accumulation in the dentate and CA1 150% above control in a pattern similar to KA, but with an ED50 of 100 microM. The accumulation was blocked by both AP5 and CNQX. These data indicate that cobalt-permeable, receptor-activated divalent cation channels are differentially distributed within the gerbil hippocampus, and have differential sensitivities to non-NMDA agonists. The localization of KA-activated, cobalt-permeable channels appears to be coincident with the flop form of the AMPA-selective calcium-permeable glutamate receptor-activated channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Maffucci's syndrome (hemangiomatosis osteolytica): a report of four cases.

Maffucci's syndrome is a congenital nonfamilial syndrome combining dyschondroplasia, (enchondromatosis) and hemangiomatosis. It is a rare disease; only 200 cases have been reported throughout the world in the past 140 years. Over the past 20 years, four patients have been admitted with signs and symptoms consistent with Maffucci's syndrome. Three were children ages 3, 7, and 9 years. The fourth was 23 years old. Two were male and two female. All had hemangiomas at birth, and all had skeletal deformities and enchondromas. All complained of pain and heaviness of the involved extremity. Three patients had the arterial inflow evaluated with arteriograms, and one had magnetic resonance imaging. Two also had venograms. Two patients had excision of their hemangiomas, and one had sclerotherapy and compression therapy. All had bone biopsies performed. None of the enchondromas or the soft tissue lesions had undergone sarcomatous transformation.

Adult

Hemolytic activity of Borrelia burgdorferi.

Zones of beta-hemolysis occurred around colonies of Borrelia burgdorferi grown on Barbour-Stoenner-Kelly medium containing agarose and horse blood. Blood plates were inoculated with either the infective strain Sh-2-82 or noninfective strain B-31 in an overlay and incubated in a candle jar. Both strains of B. burgdorferi displayed beta-hemolysis after 1 to 2 weeks of incubation. The hemolytic activity diffused out from the borrelial colonies, eventually resulting in lysis of the entire blood plate. Hemolysis was most pronounced with horse blood and was less intense with bovine, sheep, and rabbit blood. Hemolysis was enhanced by hot-cold incubation, which is typical of phospholipase-like activities in other bacteria. Further characterization of the borrelial hemolysin by using a spectrophotometric assay revealed its presence in the supernatant fluids of stationary-phase cultures. Detection of the borrelial hemolytic activity was dependent on activation of the hemolysin by the reducing agent cysteine. This study provides the first evidence of hemolytic activity associated with B. burgdorferi.

Animals

Prediction of cerebral ischemia by ophthalmoscopy after carotid occlusion in gerbils.

BACKGROUND AND PURPOSE: The Mongolian gerbil provides a unique model of unilateral focal cerebral ischemia because of the lack of posterior communicating arteries in all gerbils as well as an absence of an anterior communicating artery in approximately 20% of the gerbil population. It is unclear how to identify unequivocably the subpopulation of animals that would suffer a severe focal cerebral ischemia after unilateral carotid occlusion. METHODS: Ninety-three male gerbils were exposed to unilateral occlusion of the right common carotid artery. The severity of neuronal loss was evaluated histologically in gerbils selected as having significant focal ischemia based on either behavioral criteria (i.e., the demonstration of stereotypical behavior within 1 hour after occlusion) or ophthalmoscopic criteria (i.e., interruption of the retinal arterial perfusion within 10 minutes of carotid ligation as assessed with an ophthalmoscope). After 3 hours of unilateral carotid occlusion, cerebral blood flow was reinstated for 24 hours before fixation for histological analysis. The viability of the CA1 region of the hippocampus, lateral cortex, and medial cortex was scored on a scale of 0-4 based on the percentage of apparent neuronal loss (e.g., 0, no damage; 4, > 75% damage (the Viability Index). RESULTS: Twenty-eight percent of the gerbils met the behavioral selection criteria, and 17% met the ophthalmoscopic criteria. In the specimens selected by behavioral criteria (n = 7), 30% demonstrated no evidence of postischemic neuronal loss; the mean +/- SEM Viability Index scores for CA1, lateral cortex, and medial cortex were 1.6 +/- 0.6, 1.0 +/- 0.3, and 0.3 +/- 0.2, respectively. Of the animals selected by ophthalmoscopic criteria (n = 12), 100% had severe ischemic tissue damage to the ipsilateral hemisphere; the Viability Index scores for CA1, lateral cortex, and medial cortex were 3.5 +/- 0.1, 3.1 +/- 0.2, and 1.2 +/- 0.2, respectively; all scores were significantly larger than those observed in the behaviorally selected group. CONCLUSIONS: Selection of animals by ophthalmoscopic criteria provides a reliable, consistent method to predict animals with severe focal cerebral ischemia.

Animals

The business of preventing African-American infant mortality.

African-American women are twice as likely as women from other ethnic groups to have babies with low birth weights and to experience the loss of infant death. The problem is so endemic in black communities in Alameda County, California, that numerous programs have been developed over the past decade to reduce maternal risk factors and eliminate barriers to prenatal care. Despite these efforts, African-American ethnicity continues to be a major risk factor for infant mortality for reasons that are poorly understood. We take a critical look at 3 types of studies characteristic of infant mortality research: epidemiologic, studies that advocate prenatal care, and ethnomedical (cultural). We argue that the assumptions informing this research restrict the thinking about infant mortality and the political issues involved in how prevention programs are developed and structured. The persistent focus on maternal behavioral characteristics limits more in-depth analysis of the micropolitics of perinatal bureaucracies established in response to this ongoing crisis.

Black or African American

Nerve cables formed in silicone chambers reconstitute a perineurial but not a vascular endoneurial permeability barrier.

The passage of molecules into the endoneurial environment of the axons of normal peripheral nerve is regulated by two permeability barriers, the perineurial-nerve barrier and the endoneurial blood-nerve barrier. These barriers exist because of the presence of tight junctions between adjacent perineurial cells and adjacent endothelial cells. In the present study we investigated whether permeability barriers form in nerve cables, which develop inside silicone chambers. The sciatic nerves of adult rats were cut, and the proximal and distal ends sutured into opposite ends of silicone chambers that were filled with dialyzed plasma. The presence of barriers was determined with the tracer horseradish peroxidase (HRP), which was injected intravenously and detected histochemically in tissues by light and electron microscopy. At four weeks, a regenerated nerve cable extended across the 10 mm length of each chamber. However, no permeability barriers were present since the reaction product for HRP was visible throughout the cable. At twenty-six weeks, all the axons in cables were gathered into minifascicles. Each minifascicle of axons was surrounded by perineurial cells. Blood vessels were excluded from the minifascicles by the perineurial cells and the vessels were permeable to HRP, thus indicating that their endothelial cells had not formed tight junctions. Despite the leakage of HRP from the excluded vessels, the tracer did not reach the axons because the perineurial cells encircling the minifascicles developed tight junctions. In some animals, the chambers were removed at four weeks to determine whether the chamber influenced barrier development. This manipulation had no effect since cables, with or without chambers, exhibited similar findings at twenty-six weeks. Our results indicate that nerve cables regenerate a perineurial but not an endoneurial permeability barrier. We conclude that axons in long-term cables are protected by only a perineurial permeability barrier.

Animals

Hypophagia is induced by intracerebroventricular administration of nerve growth factor.

In previous experiments examining the stimulatory effect of intracerebroventricular (icv) NGF treatment on basal forebrain choline acetyltransferase (ChAT) activity, many of the rats treated with the maximally effective dose of NGF appeared gaunt compared to the vehicle-treated control animals. The present experiments determined that icv infusion of NGF at a dose of 1.2 micrograms/day causes a significant reduction in food consumption during the entire period of treatment compared to untreated and vehicle-treated animals. Male rats infused with NGF lost an average of about 30 g of body wt during the first week after the start of infusion and did not gain appreciable weight during the second week of NGF treatment. The hypophagic effect of NGF is dose-dependent, centrally mediated, and reversible. There is no correlation between the stimulatory effect of NGF on basal forebrain ChAT and the inhibitory effect of NGF on weight gain. A therapeutic dose of NGF for Alzheimer's patients comparable to the rat dose for maximally stimulating central cholinergic neurons would approach 1 mg/day. If such therapy is applied, the potential exits for induction of hypophagia as a side effect of the NGF administration.

Animals

Evaluation of a rapid fluorogenic method for the detection of Escherichia coli in dairy products.

A rapid fluorogenic medium was evaluated for the detection of Escherichia coli in dairy products. The medium was capable of detecting Esch. coli after 7.5 h incubation at 41.5 degrees C. Samples of pasteurized milk (136), raw milk (63), soft cheese (60) and pasteurized cream (39) were examined with media based on 4-methylumbelliferyl-beta-D-glucuronide (MUG-7) and Violet red bile agar and there were no significant differences between the numbers of Esch. coli detected on the two media. MUG-7 medium had a specificity of 98.6% and the small number of organisms giving a false positive reaction were identified as Klebsiella pneumoniae. The incidence of false negative results was approximately 2%. MUG-7 medium was suitable for pour plate, spread plate and membrane filtration methods. Possible applications of the method are discussed.

Animals

Exogenous NGF affects cholinergic transmitter function and Y-maze behavior in aged Fischer 344 male rats.

Chronic ICV administration of NGF stimulates the activity of the cholinergic neuronal markers, HACU and ChAT, as well as the evoked release of both endogenous and newly synthesized acetylcholine in the brain of aging Fischer 344 male rats. However, the pattern of cholinergic phenotype stimulation indicates an age-related differential regulation of ChAT, HACU, and ACh release between specific brain areas, with the largest effects found in the striatum. NGF treatment also increases the effectiveness of neurotransmission between basal forebrain cholinergic neurons and postsynaptic amygdaloid target neurons. The stimulation of central cholinergic transmitter function after NGF treatment affects behavior in a Y-maze brightness discrimination paradigm. NGF treatment does not affect the cognitive measure of brightness discrimination, but reduces the number of avoidance attempts, a measure of motor function.

Acetylcholine

Effects of massage on alpha motoneuron excitability.

The purpose of this study was to investigate the specificity of the effects of massage (petrissage) on spinal motoneuron excitability as measured by changes in the peak-to-peak amplitude of H-reflex recordings. H-reflexes (and M-responses) were recorded from the distal aspects of the right triceps surae muscle of 8 men and 8 women, aged 20 to 37 years, with no neuromuscular impairments of the lower extremities. The H-reflexes were recorded during five control and four experimental conditions (20 trials at each condition). The control conditions (C1-C5) preceded and followed each experimental condition, providing a measure of the stability of the H-reflex. Each experimental condition consisted of a 4-minute period of massage of the ipsilateral and contralateral triceps surae and hamstring muscle groups (ITS, CTS, IHS, and CHS, respectively). The mean peak-to-peak amplitude of the H-reflex was found to be stable (range = 1.91-1.95 mV) across the five control conditions. H-reflex amplitudes recorded during the experimental conditions indicate that massage of the ITS resulted in a reduction of the H-reflex (0.83 mV) in comparison with the pretest control condition (C1) and the remaining experimental conditions (range = 1.77-2.23 mV). This difference was significant, and subsequent Newman-Keuls tests indicated a specificity of the effects of massage on the muscle group being massaged. [Sullivan SJ, Williams LRT, Seaborne DE, Morelli M. Effects of massage on alpha motoneuron excitability.

Adult

Suggested reference values for regional blood volumes in humans.

Estimates of regional blood volumes (BVs) in man are needed for the dosimetry of radionuclides that decay in the circulation to a significant extent. The tabulation of regional BVs in Publication No. 23 of the International Commission on Radiological Protection (ICRP Reference Man document) may be the best available for dosimetric applications but is not consistent with current information for some organs and does not address some important blood pools. The purpose of this paper is to suggest an improved set of reference values for regional BVs in adult humans. The total blood volume (TBV) is viewed as comprising 22 separate pools, including several pools not addressed in the ICRP Reference Man document. Values suggested here for brain, liver, skin, active marrow, inactive marrow, and bone differ by at least a factor of two from those given for ICRP Reference Man.

Adult

Cutaneous malignancies mimicking herpes zoster.

Cutaneous metastases occur in 2.5% to 5% of patients with malignant disease. The relative frequency of the primary site roughly parallels the frequency of the various malignancies in each sex. We present two cases of cutaneous malignancy occurring in a dermatomal distribution and masquerading as herpes zoster. The differential diagnosis of zosteriform eruptions is reviewed and the possible pathogenesis of metastatic disease in this cutaneous distribution is discussed. Skin biopsy is recommended in these cases to determine the etiology of the eruption.

Adenocarcinoma

Exogenous nerve growth factor reverses age-related structural changes in neocortical neurons in the aging rat. A quantitative Golgi study.

The role of chronic exogenous intracerebroventricular administration of nerve growth factor (NGF) on the morphology of layer V pyramidal cell dendrites in aging rats was quantified using Golgi impregnations. Both dendritic branching and dendritic spines from the basilar tree of randomly selected pyramidal neurons of the frontal cortex were evaluated in young control (4-month-old) Fischer 344 rats, in old controls (24-month-old), and in 24-month-old rats administered NGF for 4 weeks. Sholl analysis of basilar dendritic trees showed that neuronal branching in older rats was significantly greater than that in young rats (probably due to compensatory dendritic hypertrophy). The extent of dendritic material in aged rats receiving NGF, however, was identical to that in young rats, that is, the dendritic tree had regressed in size. Dendritic spine response to NGF treatment depended on the region of the dendritic tree sampled. Normal aging resulted in spine loss. However, NGF treatment restored dendritic spine densities to those seen in young controls on terminal tip segments ("plastic" regions). Internal branch segments ("nonplastic" regions) showed no response to NGF. As dendritic spines are thought to represent the neuroanatomic basis of learning and memory, results suggest that NGF can influence the morphology of cortical neurons (probably indirectly via the basal forebrain projections) and therefore may play an efficacious role in the treatment of geriatric cognitive dysfunction and even perhaps in Alzheimer's disease.

Aging

The perception of torque pulses.

The reliability of perception of a series of torque pulses and the influence of practice on the perceptual threshold were assessed. Eleven subjects were tested. Analysis showed distinctive cumulative frequency curves with the threshold of perception ranging from 0.016 Nm to 0.049 Nm. The reliability of individual differences over 100 trials was .998 and, when the number of trials was reduced to 25, reliability was .992. There was little evidence of a practice effect. It was clear that individual differences in torque perception could be accurately measured.

Adult

Vascular rehabilitation: benefits of a structured exercise/risk modification program.

A vascular rehabilitation program was designed to increase exercise tolerance and reduce the risk of cardiovascular disease in patients with lower extremity arterial occlusive disease. Sixty-eight patients (32 men, 36 women); ages 55 to 85 years (mean, 68 years) with claudication 30 (44%), or recovering from lower extremity revascularization 36 (53%), or endovascular procedures 2 (3%) entered the vascular rehabilitation program. Each underwent a physical examination, risk factor assessment, noninvasive arterial studies, and cardiac evaluation. A history was taken from each patient also. Six patients (9%) were excluded on recognition of silent myocardial ischemia. Sixty-two patients (91%) were accepted for exercise training in a program designed to offer 24 (1-hour) monitored exercise sessions, 12 (1-hour) personalized education lectures, and development of a home maintenance exercise program. No deaths or major morbidity occurred. Seventeen patients (27%) did not finish the program, eight (13%) because of development of significant cardiac, extremity, or cerebrovascular disease and nine for nonmedical reasons. Of the 45 patients (73%) who completed the program, 38 (88%) had documented increases in walking distances of greater than 100% (122% to 450%). All 45 patients designed home exercise programs, and 88% of the smokers quit. Long-term follow-up was available on 100% of the patients. Thirty-eight patients (84%) have been followed for 2 years or more. Thirty-eight (84%) maintained or improved walking distances recorded on exit from the program. Thirty of the 36 patients (83%) who stopped smoking remained nonsmokers. Significant reductions in cholesterol were seen at 1 year, and significant reductions in triglycerides were seen at 12 weeks and 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver--conditioned medium.

We have identified a novel growth factor, stem cell factor (SCF), for primitive hematopoietic progenitors based on its activity on bone marrow cells derived from mice treated with 5-fluorouracil. The protein was isolated from the medium conditioned by Buffalo rat liver cells. It is heavily glycosylated, with both N-linked and O-linked carbohydrate. Amino acid sequence following removal of N-terminal pyroglutamate is presented. The protein has potent synergistic activities in semisolid bone marrow cultures in conjunction with colony-stimulating factors. It is also a growth factor for mast cells. In two companion papers, we present the sequences of partial SCF cDNAs, identify SCF as a c-kit ligand, and map the SCF gene to the Sl locus of the mouse.

Amino Acid Sequence