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Biomedical subjects

E Lane

Publications and source records attributed to E Lane.

At least 37 records · Page 2Linked to original sources
PubMed1997

A conformation- and phosphorylation-dependent antibody recognizing the paired helical filaments of Alzheimer's disease.

Hyperphosphorylated tau (PHF-tau) is the major constituent of paired helical filaments (PHFs) from Alzheimer's disease (AD) brains. This conclusion has been based largely on the creation and characterization of monoclonal antibodies raised against PHFs, which can be classified in three categories: (a) those recognizing unmodified primary sequences of tau, (b) those recognizing phosphorylation-dependent epitopes on tau, and (c) those recognizing conformation-dependent epitopes on tau. Recent studies have suggested that the antibodies recognizing primary sequence and phosphorylation-dependent epitopes on tau are unable to distinguish between normal adult biopsy tau and PHF-tau. We now present evidence for a new fourth class of monoclonal antibodies recognizing conformation-dependent phosphoepitopes on tau, typified by TG-3, a monoclonal antibody raised to PHFs from AD brain homogenates. Studies using a series of deletional tau mutants, site-directed tau mutants, and synthetic peptides enable the precise epitope mapping of TG-3. Additional studies demonstrate that TG-3 reacts with neonatal mouse tau and PHF-tau but does not recognize adult mouse tau or tau derived from normal human autopsy or biopsy tissue. Further investigation reveals that TG-3 recognizes a unique conformation of tau found almost exclusively in PHFs from AD brains.

Adult↗
PubMed1997

Out of balance: consequences of a partial keratin 10 knockout.

Recently we generated keratin 10 knockout mice which provided a valuable model for the dominantly inherited skin disorder epidermolytic hyperkeratosis. Here we investigated the molecular basis for their phenotype. Hetero- and homozygotes expressed a truncated keratin 10 peptide which has been identified directly by microsequencing. Epitope mapping of monoclonal antibodies to keratin 10T enabled us to study its distribution relative to keratin 6, which is highly expressed in keratin 10 knockout mice, by double-immunogold electron microscopy. This revealed that keratin 10T was restricted to complexes with keratin 1 but did not mix with keratin 6. The latter did not form extended filaments with keratins 16/17 but aggregates. Keratins 6/16 were unable to compensate for the lack of normal keratin 1/10 filaments. Remarkably keratin 6 aggregates strictly colocalized with keratohyalin granules. Residual keratin 1/10T clumps were located in the cell periphery and at desmosomes which maintained a normal architecture. Surprisingly keratin 2e, a keratin tailored to sustain mechanical stress, was completely lost in paw sole epidermis of homozygous keratin 10 knockout mice, pointing to keratin 10 as its partner. The selective pairing of keratin 10T and the loss of keratin 2e indicate that in vivo keratins are less promiscuous than in vitro. Skin fragility in keratin 10 knockout mice and in epidermolytic hyperkeratosis is probably the consequence of two complementing mechanisms namely a decrease of normal keratin 1/10 filaments and an increase in keratins 6/16 with a poor filament-forming capacity.

Amino Acid Sequence↗
PubMed1996

Bioequivalence of two orally administered nicardipine products.

The relative bioavailabilities of orally administered nicardipine (Zenith Laboratories) and nicardipine (Cardene Syntex Laboratories) were compared following a single 30 mg dose under fasted conditions using a two-way crossover study with 34 healthy adult male subjects. In a separate study the effect of food on the relative bioavailabilities of these products was assessed following an identical dose by comparing the Zenith product under fasted conditions, the Zenith product under fed conditions, and the Syntex product under fed conditions using a three-way crossover study with 17 healthy adult male subjects. In the fasted study, 90% confidence intervals surrounding ratios (Zenith/Syntex) of least-squares means derived from 1n-transformed data were 0.84-1.02 for AUCt, 0.85-1.04 for AUCinfinity, and 0.86-1.05 for Cmax, clearly demonstrating bioequivalence of the two products. In the food-effect study ratios of least-squares means (Zenith under fed conditions/Zenith under fasted conditions) were 0.62 for AUCt, 0.65 for AUCinfinity, and 0.40 for Cmax, with tmax delayed from 0.906 +/- 0.337 h (Zenith under fasted conditions) to 2.33 +/- 0.717 h (Zenith under fed conditions) and 2.84 +/- 0.834 h (Syntex under fed conditions). Findings indicate that the presence of food in the gastrointestinal tract reduces the bioavailability of orally administered nicardipine. However, ratios under fed conditions (Zenith/Syntex) were very close to unity for each metric, suggesting that the observed food effect is independent of the product formulation. Findings further suggested that food effects on conventional pharmacokinetic metrics might be attributed to alteration of extent, rather than rate, of gastrointestinal absorption. Finally, these results question the applicability of the peak plasma concentration (Cmax) as an index of absorption rate in nicardipine studies.

Administration, Oral↗
PubMed1996

Cutaneous permeability barrier repair following various types of insults: kinetics and effects of occlusion.

Previous studies have shown that acute disruption of the cutaneous permeability barrier by acetone results in an initial rapid phase of repair followed by a later, slower phase. In the present study, we demonstrate that manipulations which disrupt the barrier by other mechanisms, such as tape stripping or detergent treatment, have a similar pattern of barrier repair. In all three models, the return of lipid to the stratum corneum parallels the normalization of barrier function, and occlusion immediately after disrupting the barrier blocks both the return of lipid and the normalization of function. Moreover, occlusion beginning 6-8 h following barrier disruption blocks the late, slower phase of repair, indicating that the late phase can be inhibited independently of the initial phase. Lastly, both severe and relatively minor perturbations of the barrier elicit a repair response with a similar kinetic pattern. In summary, the present study demonstrates that barrier repair responses are similar regardless of the etiology or extent of barrier disruption.

Acetone↗
PubMed1995

Fluvoxamine treatment of alcoholic amnestic disorder.

The serotonin uptake inhibitor fluvoxamine was assessed in treatment of alcohol-induced Korsakoff's syndrome (KS) using fixed (4 weeks, 200 mg/day) or individualized (6 weeks, plasma concentration > or = 400 ng/ml) dosing in randomized placebo-controlled double-blind crossover studies. Cognitive functions and concentrations of the major cerebrospinal fluid (CSF) metabolites of serotonin (5-HIAA), norepinephrine (MHPG), and dopamine (HVA) were determined in abstinent, nondepressed KS patients (aged 45-75), at baseline and placebo (3-4 weeks), and after 3-4 (n = 10) or 6 (n = 4) weeks of fluvoxamine administration. Fluvoxamine decreased CSF 5-HIAA compared to placebo (P < 0.003) without consistent changes in HVA or MHPG. Reductions in 5-HIAA correlated with improvements on the Wechsler Memory Scale Memory Quotient (P < 0.05), independent of effects on attention/vigilance or Beck Depression Inventory scores. Reductions in 5-HIAA correlated with plasma fluvoxamine (P < 0.03) only for fluvoxamine concentrations below 450 ng/ml. These findings suggest improvement of memory consolidation and/or retrieval in patients with Korsakoff's syndrome by fluvoxamine via serotonergic mechanisms.

Aged↗
PubMed1993

High-resolution CT in simple coal workers' pneumoconiosis. Lack of correlation with pulmonary function tests and arterial blood gas values.

We examined 21 miners by means of standard chest radiography, high-resolution computerized tomography (HRCT), pulmonary function tests, and resting arterial blood gas levels. Using the ILO/UC classification of pneumoconiosis, 7 miners had category 1/0 or 2/1 simple coal workers' pneumoconiosis (CWP). By HRCT, nodules were identified in 12 miners; 4 of 9 were classified as category 0/0 CWP; 2 of 5, 0/1 CWP; 5 of 6, 1/0 CWP; and 1 of 1, 2/1 CWP by chest radiograph. Focal emphysema was identified by HRCT in 7 miners; 4 of 9 were classified as 0/0 CWP; 2 of 5, 0/1 CWP; and 1 of 6, 1/0 CWP by standard chest radiography. Four miners with definite nodules confirmed by HRCT had focal emphysema, while three without nodules had focal emphysema. Pulmonary function testing was not different between miners with or without CWP by standard chest radiography, nor was it different between miners with or without definite nodules evidenced by HRCT. No difference in resting oxygenation was found between any group of miners. The presence of focal emphysema confirmed by HRCT did not significantly affect pulmonary function tests on resting arterial blood gas values. There was, however, a significantly lower FEV1 and mean forced expiratory flow during the middle half of forced vital capacity with lifetime nonsmoking miners. The presence of CWP on chest radiography was significantly correlated with smoking cigarettes but not the years of mining. The presence of nodules on HRCT approached a significant correlation with cigarette smoking, but focal emphysema did not. For detecting evidence of coal dust accumulation in lung parenchyma and identifying focal emphysema, HRCT was more sensitive than standard chest radiography. However, despite earlier detection of parenchymal abnormalities, abnormal pulmonary function attributable to coal dust could not be identified.

Blood Gas Analysis↗
PubMed1993

Effects of fluvoxamine, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers.

The effects of fluvoxamine (50 or 100 mg), alone and in combination with ethanol (0.8 g/kg), on psychomotor and cognitive performance and on autonomic nervous system reactivity were studied in healthy male volunteers. Fluvoxamine produced neither serious psychomotor or cognitive impairment nor alterations in autonomic nervous system functioning at these doses. There was no evidence that fluvoxamine exacerbated, or improved, ethanol-induced impairments of memory or any other measures evaluated. Fluvoxamine tended to improve recognition, but not free recall, of words.

Adult↗
PubMed1990

Effects of adinazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers.

Effects on psychomotor and cognitive performance of adinazolam (15 or 30 mg), alone and in combination with ethanol (0.8 g/kg), were studied in healthy male volunteers and compared to effects of 10 mg diazepam. Adinazolam 30 mg produced relatively long-lasting impairments on tests of tracking, attention, verbal and nonverbal information processing, and memory. Adinazolam 15 mg resulted in descreased visual information processing. Adinazolam decreased supine mean arterial pressure, but only the 15 mg resulted in a tendency for decreased plasma norepinephrine concentrations. After standing for 5 min, 30 mg adinazolam was associated with increased heart rate. Although ethanol consumption produced additive decrements on a continuous performance task, there was little evidence to support a synergistic effect. Adinazolam 30 mg was accompanied by increased self-reports of side effects, especially drowsiness.

Adult↗
PubMed1990

Effects of single doses of alprazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers.

Effects of alprazolam, alone and in combination with ethanol, on psychomotor and cognitive performance were studied in healthy male volunteers and compared to effects of diazepam. Alprazolam 2 mg produced relatively long-lasting impairments on tests of tracking, verbal and nonverbal information processing, and memory, and decreased blood pressure without a change in heart rate or plasma norepinephrine levels. Although ethanol consumption was demonstrated to produce additive decrements in performance on certain tasks, there was little evidence to support a synergistic effect. Alprazolam 2 mg was accompanied by increased self-reports of side effects, especially drowsiness. Low dose alprazolam, diazepam, and ethanol produced significantly fewer side effects than 2 mg alprazolam, but significantly more than placebo.

Adult↗
PubMed1990

Abnormal neuroendocrine responsivity to acute i.v. clomipramine challenge in depressed patients.

The neuroendocrine responsivity to an acute serotonergic challenge with low-dose i.v. clomipramine was studied in seven drug-free depressed patients and seven age-matched healthy control subjects. The depressed patients had higher baseline prolactin concentrations than the healthy subjects, and their prolactin response to clomipramine, assessed as either the percent of baseline or the log-transformed concentration, was significantly different (delayed and blunted peak response) compared to healthy controls. The growth hormone response was exaggerated in the depressed patients, and there were also trends toward blunting in their cortisol and adrenocorticotropic hormone responses. These results are consistent with previous findings of altered neuroendocrine responses to a variety of putative serotonin agonists in depressed patients.

Adrenocorticotropic Hormone↗
PubMed1990

Rapid diagnosis of typhoid fever through identification of Salmonella typhi within 18 hours of specimen acquisition by culture of the mononuclear cell-platelet fraction of blood.

Detection of Salmonella typhi in blood by culture of the mononuclear cell-platelet layer was compared with other methods currently used for the diagnosis of typhoid fever. Colonies of S. typhi were present in all mononuclear cell-platelet layer-positive cultures within 18 h of plating and were identified within an additional 10 min by a coagglutination technique. In contrast, identification of all positive cultures by conventional blood culture required 3 days.

Agglutination Tests↗
PubMed1990

The use of a coagglutination test to presumptively identify Salmonella typhi in bone marrow-oxgall medium cultures from typhoid fever patients.

A study was conducted to test a coagglutination procedure for detection of Salmonella typhi in bone marrow cultures from suspected typhoid patients admitted to Friendship Hospital, Jakarta, Indonesia. The results of the coagglutination tests were compared to the results from standard cultural isolation and identification. Bone marrow aspirates (356) were cultured in oxgall medium and aliquots subcultured daily for 7 days while simultaneously testing for the presence of Salmonella group D and Vi antigens using coagglutination (COAG). S. typhi was isolated from 220 (62%) of the cultures and the D- and Vi-COAG tests were positive for those same cultures. The COAG test was also negative for 6 cultures containing S. paratyphi A. The COAG results were available within 10 minutes after 18 to 24 hours incubation of the primary cultures whereas the isolation and confirmed identification took 2 to 3 days longer. The COAG test is valuable as an aid to rapidly identify S. typhi in bone marrow-oxgall cultures.

Agglutination Tests↗
PubMed1989

Use of a DNA probe to detect Salmonella typhi in the blood of patients with typhoid fever.

A DNA probe was used to detect Salmonella typhi from blood samples from 14 of 33 patients with culture-confirmed typhoid fever, using the equivalent of 2.5 ml of blood. In contrast, S. typhi was detected in 17 of the same 33 patients by culture of 8 ml of blood. The probe hybridized to blood samples of 4 of 47 patients from whom S. typhi was not isolated.

Autoradiography↗
PubMed1989

The effects of intravenous clomipramine on neurohormones in normal subjects.

The neuroendocrine effects of iv administration of clomipramine (CMI), a serotonin reuptake inhibitor, were studied in normal subjects. Under double blind, placebo-controlled conditions, single 10- and 20-mg doses of CMI were administered. Ten milligrams of CMI led to significant increases in plasma PRL and cortisol concentrations; plasma ACTH increased slightly but not significantly. In contrast, plasma GH, melatonin, and norepinephrine concentrations did not increase. Plasma PRL, ACTH, and cortisol levels increased significantly after 20 mg CMI; again, there were no significant changes in plasma GH, melatonin, or norepinephrine concentrations. All subjects tolerated the 10-mg dose well, but the 20-mg dose caused nausea in three of six subjects. Desmethylclomipramine, a metabolite that inhibits reuptake of norepinephrine, was not detectable in plasma after either CMI dose. These results support the hypothesis that serotonin is involved in the regulation of PRL, cortisol, and ACTH in humans.

Adrenocorticotropic Hormone↗
PubMed1988

Growth inhibition of transformed mouse fibroblasts by adenine nucleotides occurs via generation of extracellular adenosine.

The growth of transformed mouse fibroblasts (3T6 cells) in medium containing 5% fetal bovine serum was inhibited after treatment with concentrations greater than 50 microM ATP, ADP, or AMP. Adenosine, the common catabolite of the nucleotides, had no effect on cell growth at concentrations below 1 mM. However, the following results indicate that the toxicity of ATP, ADP, and AMP is mediated by serum- and cell-associated hydrolysis of the nucleotides to adenosine. 1) ADP and AMP, but not ATP, were toxic to 3T6 cells grown in serum-free medium or medium in which phosphohydrolase activity of serum was inactivated. Under these conditions, the cells exhibited cell-associated ADPase and 5'-nucleotidase activity, but little ecto-ATPase activity. 2) Inhibition of adenosine transport in 3T6 cells by dipyridamole or S-(p-nitrobenzyl)-6-thioinosine prevented the toxicity of ATP in serum-containing medium and of ADP and AMP in serum-free medium. 3) A 16-24-h exposure to 125 microM AMP or ATP was needed to inhibit cell growth under conditions where serum- and cell-associated hydrolysis of the nucleotides generated adenosine in the medium continuously over the same time period. In contrast, 125 microM adenosine was completely degraded to inosine and hypoxanthine within 8-10 h. Furthermore, multiple doses of adenosine added to the cells at regular intervals over a 16-h period were significantly more toxic than an equivalent amount of adenosine added in one dose. Treatment of 3T6 cells with AMP elevated intracellular ATP and ADP levels and reduced intracellular UTP levels, effects which were inhibited by extracellular uridine. Uridine also prevented growth inhibition by ATP, ADP, and AMP. These and other results indicate that serum- and cell-associated hydrolysis of adenine nucleotides to adenosine suppresses growth by adenosine-dependent pyrimidine starvation.

5'-Nucleotidase↗
PubMed1987

Normal cerebral asymmetry in bipolar patients.

Reversal of normal cerebral asymmetry has been reported to be more frequent in children with higher cortical dysfunction and in schizophrenics, in whom it has clinical significance as well. As there are few studies of bipolar patients, we attempted to determine if significant reversal would be found in a clearly diagnosed sample of bipolar patients. As technical differences may account for varying results, we used two previously reported methods and a modified technique. Correlations of computed tomography (CT) findings with neuropsychological variables (Halstead Reitan Battery and WAIS subtests) were also studied. Bipolars and controls did not differ on any CT measure, nor were there meaningful correlations between asymmetry and neuropsychological variables. If if is confirmed that schizophrenics have increased reversed cerebral asymmetry but bipolars do not, it may point to an important difference, as all other CT abnormalities initially described in schizophrenics are now also noted in bipolar patients.

Adult↗
PubMed1986

Treatment of childhood hyperactivity with desipramine: plasma drug concentration, cardiovascular effects, plasma and urinary catecholamine levels, and clinical response.

Twenty-nine boys with attention deficit disorder/hyperactivity were randomly assigned to receive desipramine (DMI; n = 17) or placebo (n = 12) for 14 days in a noncrossover, double-blind study. There was immediate behavioral improvement with DMI at day 3 that was sustained for 2 weeks; behavioral improvement did not correlate with plasma concentrations of DMI, hydroxy-DMI, or their sum at either days 3 or 14. There were no untoward side effects; there was a drug-induced increase in pulse and diastolic blood pressure. During drug therapy, the urinary excretion of norepinephrine, vanillymandelic acid, and 3-methoxy-4-hydroxyphenylglycol (MHPG) was decreased at both days 3 and 14. The plasma MHPG level was decreased at days 3 and 14 and (standing) plasma NE levels increased at day 14. The decreases in both urinary and plasma MHPG levels showed significant correlations with behavioral improvement during the second week. These data corroborate previous findings on sympathomimetic effects of tricyclic antidepressants in children and support a noradrenergic mechanism in the mediation of drug effects on attention deficit disorder/hyperactivity.

Administration, Oral↗