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Biomedical subjects

L R Williams

Publications and source records attributed to L R Williams.

At least 73 records · Page 4Linked to original sources
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

MK-801 impedes the acquisition of a spatial memory task in rats.

Several studies have reported that MK-801 impairs the acquisition of various learning and memory tasks, while others suggest that MK-801 may interfere with performance rather than having a specific effect on memory. To characterize further the effects of MK-801 on learning and memory, MK-801 (0.05 mg/kg, SC) was administered prior to or immediately after learning trials in a trial-independent water maze task. Since MK-801 may affect nonassociative variables that may influence learning and memory, motor activity and general reactivity measures were also determined for 0.0125, 0.025, or 0.05 mg/kg of MK-801 administered SC. Since MK-801 may also be used to treat children with epilepsy, we investigated the possible persistent cognitive effects on neonates. MK-801 (0.02 mg/kg, SC) was administered at postnatal days 9-15 and tested in the same task as above starting at day 36 of age. There were no persistent effects of neonatal treatment. However, in adult rats, MK-801 impaired the acquisition of the water maze task but did not affect performance during a recall task in the same apparatus. At doses affecting learning, there were no effects on motor activity or general reactivity in adult rats. These results are consistent with the conclusion that MK-801 interferes with acquisition of spatial learning in the rat.

Aging↗
PubMed1990

Exogenous nerve growth factor increases the activity of high-affinity choline uptake and choline acetyltransferase in brain of Fisher 344 male rats.

The objective of this study was to determine the effect of age and chronic intracerebral administration of nerve growth factor (NGF) on the activity of the presynaptic cholinergic neuronal markers hemicholinium-sensitive high-affinity choline uptake (HACU) and choline acetyltransferase (ChAT) in the brain of Fisher 344 male rats. In 24-month-old rats, a substantial decrease in ChAT activity (30%) was measured in striatum, and decreases in HACU were found in frontal cortex (28%) and hippocampus (23%) compared with 4-month-old controls. Cholinergic neurons in brain of both young adult and aged rats responded to administration of exogenous NGF by increased expression of both phenotypes. In 4-month-old animals, NGF treatment at 1.2 micron/day resulted in increased activities of both ChAT and HACU in striatum (175 and 170%, respectively), frontal cortex (133 and 125%), and hippocampus (137 and 125%) compared with untreated and vehicle-treated 4-month-old animals; vehicle treatment had no effect on the activity of either marker. In 24-month-old animals treated with NGF for 2 weeks, ChAT activity was increased in striatum (179%), frontal cortex (134%), and hippocampus (119%) compared with 24-month-old control animals. Synaptosomal HACU in 24-month-old rats was increased in striatum (151%) and frontal cortex (128%) after 2 weeks of NGF treatment, but hippocampal HACU was not significantly different from control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Effects of chronic haloperidol on vitamin E levels and monoamine metabolism in rats fed normal and vitamin E deficient diets.

Experiments were conducted to study the effects of chronic haloperidol treatment on brain catechols and indoles in rats fed vitamin E deficient diets. Rats were fed basal diet or vitamin E deficient diet and injected with saline or haloperidol (1 mg/kg/day x 28 days i.p.). Tissue levels of catechols, indoles and vitamin E were measured using HPLC-EC techniques. Chronic haloperidol reduced striatal vitamin E levels. Activity in the striatal dopaminergic systems was also reduced, as, shown by reduced 3,4-dihydrophenylanine (DOPA), homovanillic acid (HVA), 3-methoxytyramine (3-MT), and dopamine (DA) levels. In addition, serotonergic activity was reduced, as indicated by lowered 5-hydroxytryptophan (5-HTP), 5-hydroxyindoleacetic acid (5-HIAA), and 5-hydroxytryptamine (5-HT) levels. In the substantia nigra, only 5-HIAA levels were reduced by treatment with haloperidol. These effects of haloperidol on monoamine metabolism were noted in both the vitamin E deficient and basal diet treated rats. However, vitamin E deficiency alone resulted in reduced DOPA and dopamine in the striatum. The vitamin E deficient diets resulted in markedly lowered vitamin E levels in the striatum and substantia nigra. All of these effects were more profound in rats that had been maintained on a vitamin E deficient diet for 7 weeks than those that were so treated for 5 weeks. These results suggest that alterations in dopamine metabolism and endogenous antioxidant systems may interact. Neuroleptics such as haloperidol that acutely accelerate dopamine synthesis and metabolism may cause peroxidative stress as indicated by depletions of vitamin E. Such depletions are capable of reducing dopamine levels and synthesis. The possibility that this and the effect of chronic haloperidol are mediated by peroxidative damage to dopamine neurons must be considered.

Animals↗
PubMed1989

Axotomy-dependent stimulation of choline acetyltransferase activity by exogenous mouse nerve growth factor in adult rat basal forebrain.

Transection of the adult rat dorsal fornix and fimbria (F-F) induced a sensitivity of the cholinergic neurons in the medial septum and diagonal band (MS/DB) to exogenous mouse nerve growth factor (mNGF). Continuous infusion of mNGF for two weeks after complete unilateral F-F aspiration resulted in a stimulation of choline acetyltransferase (ChAT)-specific activity in precise micro-dissections of the MS/DB ipsilateral to the transection to a level that was 200% higher than that measured in normal adult animals. This supranormal stimulation of ChAT activity reached plateau levels after 10 days of NGF infusion and was dose-dependent with an E.D.50 equal to 120 ng/day. Administration of mNGF had no effect on the ChAT activity in the MS/DB of normal animals or animals with a unilateral transection of only the supracallosal dorsal septo-hippocampal pathway. Partial transection experiments indicated that a predominent pathway for cholinergic neurons potentially sensitive to exogenous mNGF runs in the paramedian F-F. Administration of mNGF also induced a stimulation of ChAT activity in dissections of the caudate-putamen both ipsi- and contralateral to the infusion cannula. This indicates that unlike the cholinergic projection neurons of the MS/DB, adult cholinergic striatal interneurons are sensitive to exogenous NGF without prior axotomy.

Animals↗
PubMed1989

Reference values for resting blood flow to organs of man.

The lack of a reliable quantitative description of blood flow in man has hampered the development of accurate biokinetic models of essential elements, drugs, imaging agents, and carcinogens. In this paper we review and analyse data on blood flow and identify representative percentages of cardiac output and absolute blood flow rates to organs and tissues of man for use as reference values for biokinetic models. To keep the review and analysis to a manageable size we have limited attention to the resting state and have suggested reference values for absolute and relative flow rates only for adult males and females.

Adult↗
PubMed1989

Optimal parameters for the histochemical demonstration of acetylcholinesterase in plastic sections of rat brain.

A modified method for improved preservation and optical resolution of acetylcholinesterase (AChE)-containing structures in adult rat brain is described. Optimal tissue preparation included fixation in paraformaldehyde 4%, glutaraldehyde 0.1%, and sucrose 7% in 0.1M Sorensen's phosphate buffer, pH 7.4, rinsing in buffer 50 mM with respect to NH4Cl and 2% with respect to sucrose, acetone dehydration, vacuum infiltration with LKB Historesin, and polymerization at 4 C, overnight incubation of 10 microns sections at 37 C in the AChE histochemical reaction mixture and silver intensification according to Hedreen et al. Demonstration of AChE enzyme activity in the cholinergic projection from the rat basal forebrain to the ipsilateral hippocampus exemplifies the usefulness of the technique. The method provides an excellent demonstration of AChE-positive axonal processes and enables the pharmacohistochemical visualization of cholinergic neurons. This procedure offers a convenient method for analysis of cholinergic neurons that avoids potential artifacts inherent in other AChE histochemical procedures.

Acetylcholinesterase↗
PubMed1988

Morphological response of axotomized septal neurons to nerve growth factor.

Septal efferent fibers from the neurons in the medial septal nucleus are destroyed by fimbria-fornix aspirative lesion. In the present study we used quantitative morphometric techniques to evaluate the response of these axotomized septal neurons to a constant infusion of nerve growth factor (NGF). By 2 weeks following the lesion, approximately 75% of the cholinergic neurons had degenerated in the untreated rats. The remaining cholinergic neurons showed few signs of the effect of the lesion when stained for a polyclonal antibody to ChAT and examined in 40-micron-thick sections. In 1-micron-thick sections the remaining ChAT-immunoreactive (IR) neurons also appeared no different from the intact ChAT neurons. However, non-ChAT-IR neurons had a shrunken nucleus, while all other morphometric parameters appeared normal. NGF infusion protected most of the ChAT-IR neurons from degenerating. The saved neurons had the same parameters as the undamaged ChAT-IR neurons when examined in either 40-micron- or 1-micron-thick sections. In addition, the shrunken appearance of the non-ChAT-IR neurons' nuclei was avoided by the NGF infusions. Enlarged ChAT-IR processes were evident in the dorsolateral quadrant of the septum following damage to the fimbria-fornix. NGF-infusions prevented the formation of these processes. Instead, in the treated animals the dorsal lateral quadrant contained a dense plexus of fine ChAT-IR varicosities. Taken together these results demonstrate that NGF not only can protect the cholinergic neurons from axotomy-induced degeneration but can also cause the saved neurons to maintain the same morphometric appearance as intact ChAT-IR neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Rat amnion membrane matrix as a substratum for regenerating axons from peripheral and central neurons: effects in a silicone chamber model.

An extracellular matrix preparation, the human amnion membrane matrix (hAMM) can serve as a neurite-promoting substratum for cultured peripheral and central neurons, and also as a support for axonal growth in experimentally injured adult brain in vivo. In the present study, we tested similar materials as bridges in a silicone chamber model for the regeneration of sciatic nerve in the adult rat. Since hAMM elicited an inflammatory response, we developed a rat amnion membrane matrix (rAMM), which proved to be an excellent neurite-promoting substratum for cultured ganglionic and spinal cord neurons. The rAMM was coiled and inserted in the 10 mm gap between the two nerve stumps from the silicone chambers. At 16 days after implantation, temporal progress of regeneration was grossly similar as in saline-prefilled control chambers. However, rAMM-prefilled chambers displayed significantly higher number of vessels and a markedly different geometry of the regenerate: an endoneurium, surrounded by a perineurial-like cell layer, was formed outside the largely preserved central portion of the rAMM coil. After longer regeneration times (28 days), a rAMM core was no longer detected, but some rAMM-like materials remained interspersed in the endoneurium. The overall organization of the regenerate and the number of myelinated axons at this time were similar to those of control chambers, although the endoneurial cross-sectional area was larger in the rAMM chambers. One specimen, however, displayed the very patterns for which the experiments were designed, namely an array of numerous, myelinated axons tracing the spiraling spaces between consecutive lamellae of the rAMM coil.

Amnion↗
PubMed1988

A biokinetic model for Rb in humans.

Although whole-body retention of Rb in humans has been characterized reasonably well, current biokinetic models for Rb do not provide detailed or accurate descriptions of the time-dependent distribution of this element within the body. In this paper we construct a physiologically descriptive biokinetic model that closely tracks the movement of Rb from the time of intake until virtually all of the ingested or injected quantity has been removed from the body. The selection process for model parameter values is described for a reference adult male, but we demonstrate how the model may be applied to non-reference humans, including young children. It is shown that the model accurately predicts long-term retention of Rb in both sexes and in different age groups and depicts changes with time in the internal distribution of Rb with sufficient accuracy to be suitable for dosimetric estimates even for the short-lived isotope 82Rb (T 1/2 = 75 s).

Adult↗
PubMed1988

Peripheral nerve regeneration in Gore-tex chambers.

Gore-tex chambers were used to bridge a 6 mm gap between the proximal and distal nerve stumps of a rat sciatic nerve. The wall structure of these chambers is characterized by "nodes" interconnected by smaller fibrils. Chambers with internodal distances of 5, 10 and 30 microns were used. Some 30 microns chambers were coated from the outside with Gore-tex (0.2 micron internodal distance) and others were coated from the inside. Regeneration after 12 weeks, as evidenced by muscle action potential recordings and light microscopy, was successful regardless of what type of chamber had been used. The organization of the nerve structure varied among different chamber types. A well organized coaxial nerve structure with myelinated axons was observed if inner-coated chambers were used. In chambers that were not coated or in outer-coated chambers tissue completely filled the chambers, and myelinated axons were arranged in mini-fascicles surrounded by loose connective tissue.

Animals↗
PubMed1988

Vein compression by arterial aneurysms.

This study was done to emphasize the importance of early, accurate diagnosis of arterial aneurysms that show the symptoms of venous obstruction. Fourteen patients were identified as having atherosclerotic aneurysms producing venous compression. Nine patients had popliteal aneurysms, causing popliteal vein thrombosis in three patients and vein compression without thrombosis in six patients. Five patients had iliac artery aneurysms, producing left iliac vein thrombosis in one patient and venous compression without thrombosis in four patients. In 10 patients the cause of the venous compression symptoms was correctly identified and appropriate revascularization was performed with successful results. In four patients, two with iliac artery aneurysms and two with popliteal artery aneurysms, the associated aneurysm was not identified. One patient died of a ruptured aneurysm and three patients had below-knee amputations because of untreatable distal ischemia. Inappropriate treatment of patients with venous obstruction from unrecognized arterial aneurysms is associated with unacceptable morbidity and mortality. Accurate diagnosis with timely aneurysm repair eliminates the risk of aneurysm rupture or thrombosis and simultaneously alleviates venous compression symptoms.

Aged↗