Biomedical subjects

W A Lee

Publications and source records attributed to W A Lee.

At least 19 recordsLinked to original sources

PubMed1992

Cluster analysis of the metastatic patterns of human immunodeficiency virus-associated Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a pleomorphic spindle cell lesion whose incidence has markedly increased among patients infected with the human immunodeficiency virus (HIV), especially among those whose primary risk factor is homo/bisexual transmission. The question as to whether KS is even a true neoplasm still remains largely unsettled due to the body of epidemiologic and histologic evidence suggesting an infectious etiology of the lesion. Accordingly, very few studies have been published regarding systemic distribution or patterns of metastatic progression of the lesion. In the past, such studies have been primarily hampered by inadequate sampling of different tissue specimens and by the lack of a method whereby the data could be rationally interpreted. In the present study we have reviewed the clinical and pathologic features of 169 autopsied patients with either documented HIV infection or the acquired immunodeficiency syndrome, among whom 28 patients were found to have KS. Using cluster analysis, we constructed a novel data structure, called a "dendrogram," whereby patterns of metastasis could be examined. Our results show at least three patterns of metastasis of the lesions, predominantly involving the skin, upper gastrointestinal tract, or midgastrointestinal tract, within this cohort of autopsied patients. These three patterns suggest that there is no single pathogenetic mechanism in the acquisition and dissemination of HIV-associated KS.

Adolescent↗

PubMed1992

Localization of the human cytomegalovirus 2.7-kb major early beta-gene transcripts by RNA in situ hybridization in permissive and nonpermissive infections.

During the early phase of a human cytomegalovirus (HCMV) infection, the 2.7-kb early gene is by far the most abundantly transcribed RNA. Using strand-specific 32P or digoxigenin-labeled riboprobes derived from a subgenomic fragment of the HCMV Towne 2.7-kb early gene, we have performed Northern blot analysis and RNA in situ hybridization on human and mouse fibroblasts infected with HCMV and on 23 formalin-fixed paraffin-embedded sections of tissue obtained at autopsy. By Northern blot analysis, expression of the 2.7 kb early gene was found only in permissive infections. In contrast, specific hybridization was detected in both permissive and nonpermissive cells by RNA in situ hybridization. In nonpermissive cells, hybridization was weak and predominantly nuclear. In permissive cells, strong nuclear and cytoplasmic hybridization was noted. Specific hybridization to cells with and without cytopathic changes was detected with the anti-sense probe in CMV infected tissue obtained at autopsy. When the sense riboprobe was employed, no specific hybridization was found under nondenaturing conditions. These results suggest that in situ hybridization with a probe directed at the 2.7-kb early gene is an effective method of detecting both permissive and nonpermissive HCMV infections in different stages of infection and in localizing the expression of the major early gene in various cell types.

Animals↗

PubMed1991

Intranasal bioavailability of insulin powder formulations: effect of permeation enhancer-to-protein ratio.

The intranasal administration of powder formulations containing insulin and the permeation enhancer sodium tauro-24,25-dihydrofusidate (STDHF) were investigated in the sheep model. Both the hypoglycemic response and the serum insulin levels increased as the mole ratio of STDHF to insulin was increased from 0 to 16.8. In vitro dissolution rates of the powders and the rapid tmax (approximately 5 min) observed after intranasal administration suggest that the absorption of insulin is not dissolution limited. The bioavailabilities (F) of the powder formulations ranged from 2.9 to 37.8%. In comparison, the F values for a solution formulation with a STDHF:insulin ratio of 8.4 administered as either drops or spray were 15.7 and 37.4%, respectively. The permeation enhancer STDHF increases mucosal permeability and reduces the average molecular weight of the insulin species.

Absorption↗

PubMed1991

Abundant expression of EBER1 small nuclear RNA in nasopharyngeal carcinoma. A morphologically distinctive target for detection of Epstein-Barr virus in formalin-fixed paraffin-embedded carcinoma specimens.

The highly restricted expression of the Epstein-Barr virus (EBV) genome in malignancy has limited the use of EBV detection methods applicable to formalin-fixed paraffin-embedded carcinoma specimens. In EBV-transformed lymphocytes very short nonprotein coding EBV transcripts (EBERs) are expressed in much higher abundance (10(7) copies per cell) than other EBV latency transcripts. Using a 3H riboprobe, the authors demonstrated EBER1 expression in NASOPHARYNGEAL CARCINOMAS (NPCs) as well as in parotid salivary gland. Recognition of EBER1 expression was facilitated by the intensity of hybridization and its characteristic morphology (nuclear with nucleolar sparing). EBER1 expression was not demonstrated in other epithelial malignancies arising from mucosal surfaces (oropharynx, uterine cervix) from which EBV shedding has been detected. Repeat study of the NPC specimens with digoxigenin-labeled probe yielded hybridization signal with subcellular morphologic detail and without background in a 12-hour procedure. Thus the EBER1 transcript is an appropriate target for in situ hybridization detection of EBV in formalin-fixed paraffin-embedded carcinoma specimens.

Carcinoma↗

PubMed1990

Anesthesia influences the outcome from experimental spinal cord injury.

The effect of anesthesia upon the functional outcome after experimental spinal cord injury (SCI) was studied in 221 rats subjected to graded weight drop contusion in the thoracic cord. Neurologic function was assessed in a blinded fashion for one week after injury using a modification of the method of Tarlov. The post-mortem concentrations of serotonin and its metabolite were measured in injured and surrounding spinal tissues in a subset of animals in order to estimate the survival of descending long-tract axons. In initial studies using non-ventilated animals where body temperature was not controlled (n = 130), halothane anesthesia was associated with significantly better neurologic scores at all levels of injury (50, 100 and 250 g.cm) in comparison to pentobarbital. In a second experiment under these conditions (n = 53) the effect of halothane was observed after a 50 g.cm injury in comparison to both pentobarbital and nitrous oxide. Improved neurologic recovery was accompanied by the preservation of normal serotonin and metabolite concentrations in spinal tissue caudal to the site of injury. These values did not differ from those measured in sham-operated animals. Separate experiments (n = 12) revealed halothane's preservation of somatosensory-evoked responses during the early postinjury period in animals showing improved neurologic recovery. Subsequent experiments (n = 12) were performed to assess the effect of oxygen supplementation and the control of rectal temperature and a separate series of acute experiments (n = 14) examined arterial blood pressure responses to injury in halothane- and pentobarbital-anesthetized animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1990

The organization of torque and EMG activity during bilateral handle pulls by standing humans.

This study examined whether the torques and EMG activity that precede and accompany bilateral arm pulls made by standing humans demonstrate a pulse height form of organization. Nine adults made abrupt bilateral pulls in the sagittal plane against a handle, to force targets equal to 5, 10, 20, 40, 60, 80 and 95% of their maximal pulling force (%MPF). The force applied at the handle, ground reaction forces, the center of pressure (CP), and EMG activity in gastrocnemius (GS), biceps femoris (BF), tibialis anterior (TA) and quadriceps (QD) muscles were recorded. Our analysis divided the action into a pre-pull phase (events prior to the increase of handle force) and a pulling phase (while handle force was greater than zero). We evaluated the effects of %MPF on the durations and peak amplitudes of the pre-pull and pulling angular impulses about the ankle joint and on pre-pull EMG patterns. The results showed that the angular impulse associated with the pulling torque (due to the reactive force on the body during the pull) had a pulse height organization: peak torque increased linearly with %MPF, and the durations of the pulling torque were relatively constant. In contrast, a pulse height organization did not characterize the pre-pull period for either the angular impulse associated with ankle torque (due to net ground reaction force) or EMG activity in the leg muscles. Rather, peak ankle torque typically increased up to some submaximal %MPF and then plateaued, perhaps due to a constraining effect on foot length on CP. The durations of pre-pull ankle torques increased over the whole range of %MPF, thereby compensating for the limit on ankle torque. Depending on the subject, the muscles were recruited in two different orders: GS-BF-TA-QD, or GS-TA-BF-QD. As the %MPF increased, the EMG onset times of all four muscles occurred earlier, and there was a greater likelihood that the BF, TA and QD muscles would be recruited on a given trial. The changes in the ankle torque and EMG patterns were gradual, suggesting that the pre-pull phase could have one underlying form of organization, with parameters that are tuned to task goals and anatomical constraints.

Adult↗

PubMed1990

Bioavailability improvement of mycophenolic acid through amino ester derivatization.

The potential bioavailability improvement of mycophenolic acid (MPA), 1, through ester derivatization was evaluated in monkeys at a dose of 20 mg/kg in this study. The acetyl solketal ester 3 was found to have excellent partition properties but poor aqueous solubility. Thus, even though it can be converted rapidly to MPA by plasma and liver enzymes, it showed poor oral bioavailability (56% of MPA) in monkeys. The bioavailability of the morpholinoethyl ester 4 and the acetyl morpholinoethyl ester 5, on the other hand, was found to be 236 and 150% that of MPA, respectively. Since ester 5 has greater aqueous solubility, but similar chemical stability and enzymatic hydrolysis rates compared to ester 4, the better bioavailability of ester 4 may result from its greater partitioning into the gastrointestinal membranes.

Administration, Oral↗

PubMed1990

The effects of permeation enhancers on the surface morphology of the rat nasal mucosa: a scanning electron microscopy study.

A rat model has been developed to compare relative morphological changes in the nasal mucosa after exposure to potential membrane permeation enhancers. Scanning electron microscopy was used to characterize gross structural and specific cellular changes following exposure. Micrographs of the rat nasal mucosa were scored in four categories: (1) mucosal surface integrity, (2) ciliary morphology, (3) mucus/extracellular debris, and (4) presence of red blood cells. The order of increasing morphological damage resulting from a 5-min exposure to each surfactant was 0.5% Solulan C-24 congruent to 0.5% Solulan C-24/0.5% sodium tauro-24,25-dihydrofusidate (STDHF) less than 0.5% STDHF less than 1.0% STDHF much less than 1.0% Laureth-9 less than 1.0% sodium taurodeoxycholate congruent to 1.0% sodium deoxycholate. The changes observed in the mucosal morphology after exposure to the various surfactants are in general agreement with data in the literature. This model is able to compare rapidly the relative morphological effects on the mucosal membrane of different nasal formulations.

Animals↗

PubMed1990

The effects of contrast dye on bacterial growth: an in vitro model.

We devised an in vitro model to examine the effects of Conray 60 contrast dye on microorganisms commonly found in septic arthritis. Using 42 culture plates in aerobic and anaerobic environments, we found no adverse effect on bacterial growth using 30, 7.5, 3.75, and 1.875% concentrations of Conray 60 contrast dye on cultures of Staphylococcus aureus, Hemophilus influenza, and Streptococcus pneumonia.

Arthritis, Infectious↗

PubMed1989

Wipe and flexion withdrawal reflexes display different EMG patterns prior to movement onset in the spinalized frog.

We investigated the hypotheses (1) that the initial flexion part of the wipe reflex elicited in the spinalized frog has the same EMG pattern for wipes to different target locations (Berkinblit et al. 1986), thereby reducing the complexity of the control of this task, and (2) that this initial flexion is the same as occurs in the flexion withdrawal reflex (Easton 1972). The activities of seven muscles of the hindlimb of the spinal frog were recorded via intramuscular electromyograms (EMGs) during the wipe reflex to two target locations and during the flexion withdrawal reflex. The EMGs were analyzed during the interval between stimulus placement and movement onset for mean integrated EMG and duration from EMG onset to movement onset. This analysis revealed significant differences (p less than 0.0001) in the EMG patterns that preceded the initial flexion posture for all three movements. These findings suggest that the spinal circuitry coordinating the initial flexion part of the wipe reflex to different target locations and the flexion withdrawal reflex may not be uniformly shared.

Animals↗

PubMed1989

A control systems framework for understanding normal and abnormal posture.

This paper presents a brief overview of a control systems framework for understanding normal and abnormal posture, with a special emphasis on postural control during arm movements. The need for meaningful and valid definitions of postural output is discussed. A distinction is drawn between the joint posture and balance outputs of the system. The roles of commands and perturbing inputs in controlling and disturbing joint posture and balance are described. The effects of initial conditions on command inputs and postural outputs are considered. Mechanisms for correcting postural errors are described, with a major focus on active closed-loop and open-loop control processes. The method of objectively describing system behavior by the gains, time delays, and thresholds of input-output functions is presented. All concepts are developed in relation to their clinical implications.

Arm↗

PubMed1988

Quantitative and clinical measures of static standing balance in hemiparetic and normal subjects.

Static standing balance was compared in 10 subjects with hemiparesis resulting from a cerebrovascular accident (33-71 years of age), 10 young normal subjects (22-40 years of age), and 10 older normal subjects (48-78 years of age) using a quantitative maximal load test and a clinical evaluation. The maximal load test required subjects to maintain a standing position against static loads applied at the waist (sagittal and frontal planes). Maximal loads were recorded as a percentage of body weight at the point when subjects could no longer hold the initial standing position. Effects of mechanical and cognitive factors were minimized in the maximal load test. Hemiparetic subjects had significantly lower maximal loads and clinical balance scores than both normal subject groups. Maximal loads of the young and older normal subjects were comparable, but the older subjects had lower clinical scores than the young subjects. Low correlations between subjects' scores on the two tests imply that each test yielded different information about static balance. Implications of the study results for the evaluation and treatment of balance deficits in hemiparetic persons are discussed.

Adult↗

PubMed1987

Effects of arm acceleration and behavioral conditions on the organization of postural adjustments during arm flexion.

Nine standing subjects performed unilateral arm flexion movements over an eight-fold range of speeds, under two behavioral conditions. In the visually-guided condition, a visual target informed subjects about the correct movement speed. Seven subjects also made movements of different speeds during a self-paced condition, without a visual target. Angular displacement and acceleration of the arm, and EMG activity from the hamstrings (HM), erector spinae (ES) and the anterior deltoid (AD) muscles were measured. The following results were observed. Mean rectified amplitudes of EMG activity in HM and ES were typically correlated with the average arm acceleration and presumably the disturbance to posture and/or balance. HM and ES amplitudes were correlated for only six subjects. Functions relating the ratios of HM/ES EMG amplitudes to acceleration varied between subjects. HM onset latencies were highly variable for slow movements and usually lagged movement. For movements above a threshold-like point in acceleration, HM latencies were correlated with arm acceleration and recruited before movement. ES latencies were constant for fast movements, and negatively correlated with acceleration for slower movements. The recruitment order of HM and AD was influenced by the behavioral condition but not by arm acceleration for fast movements. HM and AD were recruited coincidentally for visually-guided movements, while for self-paced movements, HM was recruited before AD. We conclude that for the arm flexion task: HM and ES are not tightly coupled; both behavioral and mechanical conditions affect the recruitment of postural muscles; and postural and focal components of the movement are probably organized by parallel processes.

Acceleration↗

PubMed1987

Absence of stretch reflex gain enhancement in voluntarily activated spastic muscle.

Static and dynamic stiffnesses of voluntarily activated elbow muscles were compared in spastic and contralateral arms of 15 subjects with spastic hemiparesis. Stiffnesses were estimated from the positional deflections induced by applying load perturbations to each forearm. In 11/15 subjects (73%), stiffness were comparable on the two sides. In the remaining 4/15 subjects (27%), stiffness were consistently greater on the spastic side, however, EMG recordings from these spastic muscles were of much smaller amplitude than those of the contralateral muscles, indicating that this increase was probably caused by changes in the mechanical properties of elbow muscles, rather than by stretch reflex enhancement. We conclude that for voluntarily activated muscles of spastic hemiparetic subjects, reflex stiffness (and presumably stretch reflex gain), of spastic and contralateral limbs is not significantly different. These findings impose important constraints upon theories attempting to explain spastic hypertonia, and they also provide guidelines for clinical quantification of spasticity.

Adult↗

PubMed1987

Therapeutic model for experimental spinal cord injury in the rat: I. Mortality and motor deficit.

In the course of establishing a therapeutic model for experimental spinal cord injury in the rat, we determined the effects of trauma dose (20, 30, 40, 50, and 60 g-cm) on the mortality and motor deficit in the 4 weeks following injury. Mortality was dependent upon the trauma dose: 20 g-cm, 11%; 30 g-cm, 14%; 40 g-cm, 27%; 50 g-cm, 32%; 60 g-cm, 41%. Statistical analysis by linear regression is highly significant for increasing mortality with increasing trauma dose. The motor deficit determined by a modified Tarlov scale also was dependent upon trauma dose. A trauma dose-response curve based on this study indicates that a drug which reduces the motor deficit from that found at 40 g-cm to that at 30 g-cm may be detected at a significant level of 0.05 with a power of 0.8 if 30 rats are included in each of placebo and treated groups. The same sample size would detect a significant reduction of mortality from that of 40 g-cm to 30 g-cm.

Animals↗

PubMed1986

The pH dependence of the mechanism of reaction of hydrogen peroxide with a nonaggregating, non-mu-oxo dimer-forming iron (III) porphyrin in water.

The reaction of hydrogen peroxide with 5, 10,15,20-tetrakis(2,6-dimethyl-3-sulfonatophenyl)porphinato- iron(III) hydrate [(P)FeIII(H2O)] has been investigated in water between pH 1 and pH 12. The water-soluble (P)FeIII(H2O) neither aggregates nor forms a mu-oxo dimer. The pH dependence and rate-limiting second-order rate constants (kly) for oxygen transfer from H2O2 and HO2- to the iron(III) porphyrin were determined by trapping of the resultant higher-valent iron-oxo porphyrin species with 2,2'-azinodi(3-ethylbenzthiazoline)-6-sulfonate (ABTS). Reactions were monitored spectrophometrically by following the appearance of the radical ABTS.+. From a plot of the logarithm of the determined second-order rate constants for reaction of hydrogen peroxide with iron(III) porphyrin vs. pH, the composition of the transition states can be assigned for the three reactions that result in oxygen transfer to yield a higher-valent iron-oxo porphyrin species. The latter not only reacts with ABTS to provide ABTS.+ in a peroxidase-type reaction but also reacts with hydrogen peroxide to provide O2 in a catalase-type reaction. The nitrogen base 2,4,6-collidine serves as a catalyst for oxygen transfer from hydrogen peroxide to the (P)FeIII-(H2O) and (P)FeIII(HO) species. The preferred mechanism involves a 1,2-proton shift concerted with heterolytic cleavage of the peroxide O-O bond. An analogous mechanism is believed to occur in the peroxidase enzymes.

Catalysis↗

PubMed1985

Stabilization of higher-valent states of iron porphyrin by hydroxide and methoxide ligands: electrochemical generation of iron(IV)-oxo porphyrins.

An electrochemical study of hydroxide- and methoxide-ligated iron(III) tetraphenylporphyrins possessing ortho-phenyl substituents that block mu-oxo dimer formation has been carried out. Ligation by these strongly basic oxyanions promotes the formation of iron(IV)-oxo porphyrins upon one-electron oxidation. Further one-electron oxidation of the latter provides the iron(IV)-oxo porphyrin pi-cation radical. These results are discussed in terms of chemical model studies and the enzymatic intermediate compounds I and II of the peroxidases.

Chlorides↗

PubMed1985

Alteration of thromboxane and prostacyclin levels in experimental spinal cord injury.

We measured levels of thromboxane B2 and 6-keto-PGF1 alpha in rabbit spinal cord and cat CSF after impact injury to spinal cord. Rabbit tissue thromboxane B2 levels increased more than 6-keto-PGF1 alpha. In cat, CSF thromboxane B2 was higher the first hour postinjury; CSF 6-keto-PGF1 alpha also increased, but less so. These results imply activation of arachidonic acid metabolism. The relatively greater increase of thromboxane B2 suggests that thromboxane-prostacyclin imbalance may contribute to post-traumatic ischemia.

6-Ketoprostaglandin F1 alpha↗