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Biomedical subjects

M Myers

Publications and source records attributed to M Myers.

At least 73 records · Page 4Linked to original sources
PubMed1995

Localization of amyloid P component in human brain: vascular staining patterns and association with Alzheimer's disease lesions.

Amyloid P component is a normal serum protein that is highly conserved across phylogeny. Although it resembles the classic acute-phase reactant C-reactive protein, and is considered to be a normal extracellular matrix component, its physiologic role in humans is unknown. Amyloid P component is also colocalized with accumulations of all recognized forms of amyloid. The present study uses light and electron microscopy to compare the cerebral localization of amyloid P component in cases with (n = 19) and without (n = 15) Alzheimer's disease (AD). In non-AD cases, amyloid P component was predominantly localized to the cerebrovasculature. Perivascular staining was observed in most cases, more so in the white than in the gray matter. In AD cases, amyloid P component was localized to all three characteristics histopathologic lesions, namely, neurofibrillary tangles, senile plaques, and amyloid angiopathy. Furthermore, in cases with prominent staining of gray matter parenchymal lesions, intravascular staining was decreased. Given the fixation and processing methods used, amyloid P component was never seen to be localized to the cerebrovascular basement membrane. These data argue against amyloid P component's postulated role as the anchor for vascular beta-amyloid deposition. Because there is no evidence for intrinsic amyloid P component production in brain, its perivascular and parenchymal distributions suggest either compromise of the blood-brain barrier or transport across vascular endothelium.

Adult↗
PubMed1995

High-dose nevirapine: safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection.

Nevirapine, a potent nonnucleoside reverse transcriptase inhibitor, produces a transient antiviral effect at < or = 200 mg/day due to the selection of resistant virus. To examine if higher levels of nevirapine could produce sustained antiviral activity, its safety, pharmacokinetics, and antiviral activity at 400 mg/day were studied in 21 patients. There was a rapid reduction in immune complex-dissociated p24 antigen and serum human immunodeficiency virus RNA concentration in all patients, and 8 of 10 patients had > 50% reduction at 8 weeks. Nevirapine-resistant virus was isolated from all subjects tested at 12 weeks: The mean plasma trough level (4.0 micrograms/mL [15.8 microM]) exceeded the mean IC50 of resistant virus. Rash developed in 48% of patients and was a dose-limiting toxicity factor in 6. These data suggest that clinical testing of potent antiviral compounds that select for drug-resistant virus is justified to determine if serum levels of drug sufficient to overcome resistant virus can be attained.

Adult↗
PubMed1995

Holmium-YAG laser for gall stone fragmentation: an endoscopic tool.

A systematic review of the 2.1 mu holmium-YAG laser for gall stone lithotripsy was undertaken. This infrared laser, which can be used endoscopically and percutaneously, has safety advantages over other lasers and has potential as a general purpose vascular and surgical tool. Twenty nine gall stones (mean mass 1.3 g) were fragmented in vitro using pulse energies of 114 to 159 mJ/pulse at 5 Hz with a 0.6 mm fibre, while being held in an endoscopy basket. All stones were successfully fragmented, requiring an average of 566 pulses with a 5 Hz pulse repetition frequency. The number of pulses required increased with gall stone size and mass (p < 0.01), and decreased with both pulse energy (p < 0.01) and operator experience (p < 0.05). The biochemical content of the stone did not significantly affect the number of pulses needed. The potential hazard of the laser to the biliary endothelium was investigated. At the pulse energies used, five pulses at close contact penetrated into the serosa of fresh gall bladder wall. No damage was seen when two pulses were fired. This laser shows considerable promise in gall stone lithotripsy. Until further safety data are available, however, its use with endoscopic vision is advised.

Cholelithiasis↗
PubMed1995

Smiling and fussing in seven-month-old preterm and full-term black infants in the still-face situation.

We investigated emotional responses to the still-face paradigm in 7-month-old preterm and full-term black infants. Baby FACS criteria were used to code the duration and intensity of infant smiles and the presence or absence of cry faces and fussy vocalizations within each episode. Infants in both groups showed the still-face effect: a significant reduction in smiling from episode 1 (baseline) to episode 2 (maternal still-face) and partial return to baseline in episode 3 (recovery). A multivariate analysis of covariance (MANCOVA) for big smiles yielded significant main effects for group and episode and a significant group x episode interaction. Preterm infants spent less time than full-term infants displaying big smiles in episode 1 and a less pronounced decrease in big smiles in episode 2. Maternal depressive symptoms did not differ significantly between groups. Counter to our expectations, depressive symptoms were positively associated with small-to-medium smiles in the baseline episode but not with big smiles in any episode. These findings confirm the robustness of the still-face paradigm and its potential usefulness for research on individual as well as group differences in affective communication in infants.

Affect↗
PubMed1994

Comparison of the coated-vesicle and synaptic-vesicle vacuolar (H+)-ATPases.

The V-ATPases are a novel class of ATP-dependent proton pumps responsible for acidification of intracellular compartments in eukaryotic cells. They play an important role in receptor-mediated endocytosis, intracellular membrane traffic, macromolecular processing and degradation and coupled transport, as well as functioning in the plasma membrane of certain specialized cell types. The V-ATPases are multisubunit complexes that are organized into a peripheral V1 complex responsible for ATP hydrolysis and an integral V0 domain responsible for proton translocation. Regulation of vacuolar acidification is critical to its role in membrane traffic and other cellular processes. We are currently investigating several mechanisms of regulation of vacuolar acidification, including disulfide bond formation between cysteine residues located at the catalytic site, control of assembly of the peripheral and integral domains, and differential targeting of V-ATPases to different intracellular destinations using their interaction with organelle-specific adaptin complexes.

Animals↗
PubMed1994

Comparison in humans of the potency and pharmacokinetics of intravenously injected cocaethylene and cocaine.

Cocaethylene (the ethyl ester of benzoylecgonine) is a product of the interaction between ethanol and cocaine. The results of preclinical studies and of a pilot clinical study have shown cocaethylene to produce pharmacologic effects similar to those of cocaine. However, no information is available concerning the potency and pharmacokinetics of cocaethylene in comparison to those of cocaine in humans. We report the results of a single-blind, crossover study in which six male, healthy, paid volunteers, who were moderate users of cocaine, were intravenously injected with the water soluble fumarate salt of cocaethylene (0.25 mg/kg cocaethylene base) or an equivalent dose of the water soluble hydrochloride salt of cocaine (0.25 mg/kg cocaine base). Each dose was dissolved in normal saline and injected over a 1-min interval. Test sessions were separated by a 1-week interval. The variables measured were: cocaine and cocaethylene plasma concentrations, subjective and cardiovascular effects. The results indicate, that in comparison to cocaine, cocaethylene had a significant smaller elimination rate constant (0.42 versus 0.67 l/h), had a longer elimination half-life (1.68 versus 1.07 h), and induced ratings of "high" and changes in heart rate that were of lower magnitude (65%, and 43%, respectively). During the period of time that pharmacologic effects were present the plasma concentrations of cocaine and cocaethylene were statistically indistinguishable. This finding supports the conclusion that in humans cocaethylene is less potent than cocaine.

Adult↗
PubMed1994

Suppression of B-cell mediated immunity in juvenile chinook salmon (Oncorhynchus tshawytscha) after exposure to either a polycyclic aromatic hydrocarbon or to polychlorinated biphenyls.

Juvenile chinook salmon (Oncorhynchus tshawytscha) were injected intraperitoneally with either the polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (DMBA)1 or with the commercial polychlorinated biphenyl (PCB) mixture, Aroclor 1254, to assess effects on the B-cell mediated immune response. B-cell mediated immunity was assessed by examination of the primary and secondary plaque-forming cell (PFC) responses of anterior kidney and splenic leukocytes to a T-independent antigen, TNP-keyhole limpet hemocyanin (TNP-KLH). Salmon exposed to DMBA at dosages of 20% or 1% of the 96 hr LD50 (12.7 mg and 0.6 mg/kg of salmon, respectively) or to PCBs at a dosage of 20% of the 96 hr LD50 (54.0 mg/kg of salmon) exhibited a suppressed PFC response. The secondary PFC response of anterior kidney and splenic leukocytes to both antigens and the primary splenic PFC response to TNP-LPS were suppressed in salmon exposed to either DMBA or PCBs. However, only the primary PFC response of anterior kidney leukocytes to TNP-LPS was suppressed in salmon exposed to PCBs and no suppression of this response was observed in salmon exposed to DMBA. Neither anterior kidney or splenic leukocytes from salmon exposed to DMBA or PCBs showed an altered primary PFC response to the T-dependent antigen, TNP-KLH. These results suggest that B-cell mediated immunity in salmon is suppressed by known mammalian immunosuppressants and that suppression of the PFC response observed previously in salmon from an urban estuary may be due to contaminant exposure.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

The coated vesicle vacuolar (H+)-ATPase associates with and is phosphorylated by the 50-kDa polypeptide of the clathrin assembly protein AP-2.

We have previously noted a 50-kDa polypeptide (p50) co-purifying with preparations of the bovine brain clathrin-coated vesicle vacuolar (H+)-ATPase (V-ATPase) (Zhang, J., Myers, M., and Forgac, M. (1992) J. Biol. Chem. 267, 9773-9778). We show that p50 is also immunoprecipitated with the V-ATPase, further suggesting its specific association with the proton pump. To determine the identity of this 50-kDa polypeptide and the stoichiometry of its association with the V-ATPase, we performed N-terminal amino acid sequencing and quantitative amino acid analysis of the gel-purified protein. These results revealed the unknown polypeptide to be the 50-kDa subunit of the clathrin assembly protein AP-2 (AP50); we estimate the stoichiometry of association is one AP50 per V-ATPase complex. AP50 is an N-ethylmaleimide (NEM)-inhibitable autokinase and incubation of purified V-ATPase with [gamma-32P]ATP resulted in the NEM-sensitive phosphorylation of AP50 and the B subunit of the V-ATPase. The same phosphorylation pattern is seen if the labeling reaction is done with intact clathrin-coated vesicles and the V-ATPase subsequently immunoprecipitated from the solubilized vesicles. This represents the first report of phosphorylation of one of the V-ATPase subunits. The functional significance of this phosphorylation for regulation or targeting of the V-ATPase in vivo remains to be determined.

Adaptor Protein Complex 2↗
PubMed1993

Assembly of the peripheral domain of the bovine vacuolar H(+)-adenosine triphosphatase.

The biosynthesis and assembly of the peripheral sector (V1) of the vacuolar proton-translocating adenosine triphosphatase (V-ATPase) was studied in a bovine kidney epithelial cell line. Monolayer cultures of cells were metabolically radiolabeled with Tran35S-label and the V-ATPase subsequently immunoprecipitated using a monoclonal antibody raised against the bovine brain-coated vesicle proton pump. The V-ATPase immunoprecipitated from the bovine kidney cell line has a subunit composition very similar to that of the bovine brain-coated vesicle proton pump and the V-ATPase prepared from other kidney tissues. Radiolabeling the cells for increasing times showed that the V1 or peripheral portion of the V-ATPase is assembled within 10-15 min; the intact V1V0 complex is also detectable within 10-15 min. Fractionation of the cells into cytosolic and membrane components prior to immunoprecipitation revealed that there is a significant pool of V1 in the cytosol; a similar complex is also found in bovine brain cytosol. Pulse-chase studies suggest that this cytosolic pool is not an obligate precursor for membrane-bound V1V0 and does not exchange with the membrane V1 population at later times. No qualitative differences in assembly were observed when pulse-chase studies were performed at 15 degrees C or in the presence of brefeldin A. This suggests that assembly of V1V0 is probably completed in the endoplasmic reticulum prior to distribution of the enzyme throughout the cell, with a cytosolic pool of V1 of unknown function existing in parallel with the fully assembled complex.

Animals↗
PubMed1993

Peritoneal fluid in children with intussusception: its sonographic detection and relationship to successful reduction.

A retrospective review of the abdominal/pelvic ultrasound (US) examinations in 21 consecutive children with intussusception proven on barium enema was performed to determine what is the incidence of US detected peritoneal fluid in this population and to see if the rate of reduction was different in this subset. Twelve of the 21 children (57%) had free fluid demonstrated with US. Eight of these 12 (67%) had successful reduction. Six of the nine children (67%) without free fluid were also successfully reduced.

Ascitic Fluid↗
PubMed1993

Modification of cardiac Na+ channels by batrachotoxin: effects on gating, kinetics, and local anesthetic binding.

The purpose of the present study was to examine the characteristics of Na+ channel modification by batrachotoxin (BTX) in cardiac cells, including changes in channel gating and kinetics as well as susceptibility to block by local anesthetic agents. We used the whole cell configuration of the patch clamp technique to measure Na+ current in guinea pig myocytes. Extracellular Na+ concentration and temperature were lowered (5-10 mM, 17 degrees C) in order to maintain good voltage control. Our results demonstrated that 1) BTX modifies cardiac INa, causing a substantial steady-state (noninactivating) component of INa, 2) modification of cardiac Na+ channels by BTX shifts activation to more negative potentials and reduces both maximal gNa and selectivity for Na+; 3) binding of BTX to its receptor in the cardiac Na+ channel reduces the affinity of local anesthetics for their binding site; and 4) BTX-modified channels show use-dependent block by local anesthetics. The reduced blocking potency of local anesthetics for BTX-modified Na+ channels probably results from an allosteric interaction between BTX and local anesthetics for their respective binding sites in the Na+ channel. Our observations that use-dependent block by local anesthetics persists in BTX-modified Na+ channels suggest that this form of extra block can occur in the virtual absence of the inactivated state. Thus, the development of use-dependent block appears to rely primarily on local anesthetic binding to activated Na+ channels under these conditions.

Animals↗
PubMed1993

A complete description of the EGF-receptor exon structure: implication in oncogenic activation and domain evolution.

In this paper, we report that the chicken Epidermal Growth Factor Receptor (EGF-R), encoded by the proto-oncogene c-erbB, is comprised of 28 exons and spans over 75 Kb. The four previously identified domains which make up the extracellular ligand binding region of the receptor are coded for by two copies of a 300 amino acid repeat. We have demonstrated that the 3' end of each repeat coincides with the 3' end of the last exon making up the repeat. This alignment suggests that an exon-duplication may have occurred in the ligand-binding region of the gene. The transmembrane domain is encoded within a single exon and the exon boundaries of the catalytic domain closely match those defined by structural homology with other kinases. Along with the 54 chicken splice sites, the region 5' to the first exon was also sequenced. The proposed promoter region is greater than 70% GC, contains five repeats of the consensus Sp1 binding sequence and does not have a CCATT or TATA box. In addition to the presence of these characteristic housekeeping features, expression analysis confirms the promoter activity of this region and four sets of TCC repeats similar to those found in the human EGF-R promoter have been identified. To our knowledge this represents the first complete description of the exon-intron structure of the EGF-receptor family. The elucidation of the EGF-R exon structure provides insight into the domain evolution of the receptor-kinases and the mechanisms for the oncogenic conversion of EGF-R in erythroleukemias and glioblastomas.

Amino Acid Sequence↗