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Biomedical subjects

M Gold

Publications and source records attributed to M Gold.

At least 127 records · Page 7Linked to original sources
PubMed1994

A new procedure for the purification of the bacteriophage lambda terminase enzyme and its subunits. Properties of gene product A, the large subunit.

New methods for the purification of highly active bacteriophage lambda terminase holoenzyme, and its individual subunits, gene products (gp) A and gpNu1, have been developed. These methods are rapid, simple, reproducible, and give high yields of unaggregated protein from small volumes of culture. The procedures involve fractionation of extracts of Escherichia coli strains harboring plasmids engineered to overproduce the respective proteins. All purified proteins exist as monomers or dimers at moderate concentrations. At concentrations where holoenzyme efficiently promotes in vitro cosN-cleavage and lambda DNA packaging, gpA displays neither of these activities unless supplemented with gpNu1 and the E. coli protein integration host factor. At high protein concentrations, however, gpA can promote cos-cleavage by itself. Although gpNu1 itself cannot promote either cosN-cleavage or DNA packaging, it does modulate these activities of gpA. GpA is a DNA-stimulated ATPase whose catalytic parameters closely resemble those of the holoenzyme. Like the holoenzyme, gpA displays a DNA helicase activity which is able to melt the annealed cosN overhangs. Certain preparations of gpA appear to undergo a time-dependent amino-terminal clipping at discrete sites even in the presence of as many as four protease inhibitors and at low temperature.

Adenosine Triphosphatases↗
PubMed1994

The in vitro endonuclease activity of gene product A, the large subunit of the bacteriophage lambda terminase, and its relationship to the endonuclease activity of the holoenzyme.

The reaction requirements and kinetic properties of the in vitro endonuclease activity of the bacteriophage lambda terminase and its large subunit, gene product (gp) A, have been analyzed. Optimal cleavage reaction activity for both proteins requires Mg2+, a pH between 8.5 and 9.0, and is enhanced by ATP or ATP analogs. Under these conditions both terminase and gpA generate aberrant nicks in and around cosN. Optimal nicking specificity of terminase is observed under conditions of 50-100 mM salt, 5 mM spermidine, 1.5 mM ATP, and a pH between 7.0 and 7.5. Specific activity of terminase is greatly reduced under these conditions, and gpA is completely inactive at all protein concentrations tested. Under optimal reaction conditions, gpA endonuclease activity differs from that of the holoenzyme in that it can only be detected at high concentrations, is strongly protein concentration-dependent, and can not be stimulated by the Escherichia coli protein integration host factor. Addition of purified gpNu1 partially, but not completely, minimized these differences, suggesting that the role of gpNu1 in the holoenzyme is to modulate the basal endonuclease of gpA.

Bacteriophage lambda↗
PubMed1994

The in vitro ATPases of bacteriophage lambda terminase and its large subunit, gene product A. The relationship with their DNA helicase and packaging activities.

The bacteriophage lambda terminase is composed of two subunits, gpNu1 and gpA. In vitro, the holoenzyme is a site-specific endonuclease, helicase, ATPase, and can package lambda DNA into proheads. gpA possesses ATPase and helicase activities which are similar to those of the holoenzyme. Both terminase and gpA can hydrolyze a wide range of deoxyribo- and ribonucleoside triphosphates to inorganic phosphate and the corresponding diphosphate. Nucleoside diphosphates are not substrates for either protein. ATPase of both proteins is stimulated by double-stranded DNA. The ATPase of gpA is protein concentration-dependent, while that of terminase is not. Helicase activity of both proteins is not concentration-dependent, and requires a hydrolyzable triphosphate. ATP, dATP, and GTP supported helicase activity, while adenosine 5'-(beta, gamma-methylene)triphosphate, adenosine 5'-3-O-(thio)triphosphate, ADP, CTP, and UTP did not. The kinetic parameters of ATPase and helicase activities were similar for both proteins, but packaging with terminase was optimal only at a significantly higher level of ATP. Packaging was detectable at significant levels with CTP and UTP, but not with GTP. Packaging also differed from ATPase and helicase in the utilization of divalent metal cations and susceptibility to various inhibitors.

Adenosine Triphosphatases↗
PubMed1994

A home-based geriatric assessment, follow-up and health promotion program: design, methods, and baseline findings from a 3-year randomized clinical trial.

Controlled trials in a number of countries have documented benefits from different types of in-home assessment and treatment programs for various subgroups of elderly persons. We have developed a program to test, using a randomized controlled design, the concepts of in-home comprehensive geriatric assessment (CGA) coupled with follow-up, health education, and preventive care in an urban United States community. The intervention includes yearly in-home CGA by geriatric nurse practitioners (GNPs), who provide, following discussions with physician geriatricians, lists of specific recommendations for health and well-being enhancement. The GNPs provide follow-up visits quarterly and regular telephone contacts to improve compliance. We recruited for our trial 414 home-living subjects aged 75 years and over, 215 randomized to the intervention group and 199 to the control group. Subjects were generally representative of the overall elderly population of the city of Santa Monica, a seaside suburb of Los Angeles. Extensive baseline data (medical, functional, psychosocial and environmental) were collected from subjects prior to randomization, using validated instruments whenever possible. Follow-up data were collected from each subject every 4 months by trained research assistants throughout the 3-year intervention follow-up period. Our study was designed to assess effects of the intervention on the hypothesized outcomes of health status, functional status, psychosocial parameters, and service utilization. Careful documentation of the intervention will enhance our ability to make process-outcome comparisons. Preliminary analysis reveals that the in-home CGA uncovered many important health deficits for most subjects resulting in a number of substantial recommendations. We are confident that when it is completed, this study will succeed in answering important remaining questions about the feasibility and effectiveness of establishing a geriatric in-home prevention and health promotion program in the United States based on principles of CGA.

Aged↗
PubMed1994

Non-Mendelian mitochondrial inheritance as a cause of progressive genetic sensorineural hearing loss.

Awareness of non-Mendelian mitochondrial inheritance and of its role as an agent of genetic sensorineural hearing loss (SNHL) is recent. Mitochondria are passed on exclusively from the ovum to all the offspring of both sexes, a novel pattern of inheritance. Owing to the critical role of mitochondria in cellular energy metabolism, deletions or point mutations of the mitochondrial DNA often cause progressive SNHL and a variety of disorders in other organ systems (mitochondrial cytopathies). The clinical expression of mitochondrial diseases varies and depends on the proportion of mutated mitochondria in various body tissues, as well as the nature of the mutation or deletion. In order to determine how often SNHL occurs in mitochondrial diseases and what is its presenting symptom, and also whether SNHL is a marker for particular phenotypes, we carried out a review of published case reports of patients with an established diagnosis of mitochondrial disease. The review indicates that SNHL occurs at all ages and in virtually all variants of mitochondrial diseases. It is not clear whether SNHL is a marker for a more severe and more rapid course of disease; the lower prevalence of SNHL in descriptions of live patients than of those who had died may be an artifact of case selection reported in the literature. Mitochondrial disease needs to be considered in progressive hearing loss and better longitudinal audiometric study of established cases will be required to answer these questions.

Age of Onset↗
PubMed1994

Acyclovir neurotoxicity: clinical experience and review of the literature.

Acyclovir produces neurologic symptoms that resemble extension of viral infection into the central nervous system. We discuss our observations in the cases of two patients with acyclovir neurotoxicity and review the findings of all previous reports in the English language literature. Systemic disease, most commonly renal dysfunction, preceded all 30 reported cases of acyclovir neurotoxicity. The most common symptoms were mental status disorder and involuntary movements. Measurement of serum acyclovir levels substantiated the diagnosis in only a subset of patients. Although all patients recovered, hemodialysis hastened the rate of recovery.

Acyclovir↗
PubMed1994

Proximal intentional neglect: a case study.

Although neglect has been demonstrated in the horizontal, vertical, and radial planes of space and has been attributed to sensory-attentional, motor-intentional, and representational deficits, motor intentional neglect in the radial plane has not been previously described. A patient who had a right parietal infarct was tested with a modified cancellation task that uses a fixed window, thereby controlling attentional demands and allowing one to dissociate between intentional and representational neglect. This patient showed proximal (radial) intentional neglect (a failure to move towards or in proximal space). Unlike controls whose search times decreased with increasing window size, our patient showed no change in search time as a function of window size. This pattern of behaviour suggests that the patient's search strategy does not incorporate factors such as the relation between a fixed target space and a variably sized aperture, but rather was based on the allocation of a certain amount of resources for a fixed period of time after which, regardless of performance, the patient would stop searching.

Aged↗
PubMed1994

Anosognosia for hemiplegia: an electrophysiologic investigation of the feed-forward hypothesis.

The cause of anosognosia for hemiplegia (AHP) remains unclear. Weakness is detected when there is a mismatch between the expectancy of movement and the sensory perception of movement. The feed-forward hypothesis of AHP posits that there is a failure of detection because there is a loss of motor intention and expectancy of movement. We tested motor intention by measuring the activation of proximal muscles (pectoralis majoris) while subjects squeezed a dynamometer with each hand. We tested a group of normal controls, a group of patients with hemiparesis, a patient with neglect, a patient with resolved AHP, and a patient with persistent AHP. The patient with AHP did not contract either of his pectoralis muscles when asked to squeeze with his contralesional, paretic hand, yet he contracted both of them when squeezing the dynamometer with his ipsilesional hand. Normal controls, hemiparetic controls, and the patient with hemispatial neglect contracted both pectorales when asked to squeeze with each hand. The pattern of activation seen in the patients with persistent AHP and resolved AHP demonstrates a loss of motor intention and lends support to the feed-forward hypothesis of AHP.

Agnosia↗
PubMed1994

Motor neglect associated with a discrete parietal lesion.

The syndrome of motor neglect may follow brain lesions affecting frontal, subcortical, and parietal structures. However, pure motor neglect has not been previously associated with a lesion confined to the parietal lobe. We observed a 79-year-old right-handed man with right-sided limb akinesia and motor neglect without concomitant sensory or visuospatial neglect. MRI showed a left posterior parietal infarct sparing the primary sensorimotor cortex. Transcranial magnetic stimulation showed comparable thresholds for electromyographic activation of the muscles of the right and left arm and normal central motor conduction times, indicating functional integrity of the motor cortex. This case demonstrates that a discrete parietal lesion can produce a pure intentional disorder, independent of sensory or visuospatial neglect.

Aged↗
PubMed1993

Threonine 246 at the active site of the L-lactate dehydrogenase of Bacillus stearothermophilus is important for catalysis but not for substrate binding.

Threonine 246 is an active site residue that is conserved in all known L-lactate dehydrogenase (LDH; EC 1.1.1.27) sequences. In order to investigate the role of Thr246 in Bacillus stearothermophilus LDH, this residue was altered by site-directed mutagenesis to valine, alanine, leucine, and serine, respectively. The effects of these mutations, as observed in both steady-state and single-turnover kinetic measurements with different substrates, demonstrated the importance for catalysis of a hydroxyl group in the 246 amino acid residue. In contrast, no significant contribution of the OH group of Thr246 to productive pyruvate binding was observed. Instead, it is proposed that the role of Thr246 may be to facilitate hydride transfer from the nicotinamide ring of the NADH cofactor to the pyruvate carbonyl group.

Base Sequence↗
PubMed1993

Health maintenance organizations: critical issues raised by restructuring delivery for health systems reform.

In sum, the potential that managed care will grow under health systems reform creates an opportunity for the HMO industry but also serves as a challenge and a threat. Faced with greater scrutiny and growing demands, HMOs increasingly are being forced to demonstrate their potential and live up to their expectation. At the same time, the changing nature of the health care system creates a challenge for HMOs. Cost pressures create needs to review the entire delivery system, including the ambulatory component, with a focus on enhancing cost-effectiveness. Greater visibility also creates demands; growing market penetration argues for the creation of a new paradigm to define an appropriate structure for public accountability and management. Finally, the transformation of an HMO industry into a managed care industry is not without its risks as HMO performance becomes evaluated not only against itself but as part of the performance of the broader managed care industry in which HMOs have become embedded.

Health Maintenance Organizations↗
PubMed1993

Comparison of the efficacy and safety of inhaled fluticasone propionate 200 micrograms/day with inhaled beclomethasone dipropionate 400 micrograms/day in mild and moderate asthma.

This study was designed to compare the efficacy and safety of a new inhaled corticosteroid, fluticasone propionate at a total daily dose of 200 micrograms, with beclomethasone dipropionate 400 micrograms/day in childhood asthma. A total of 398 asthmatic children (aged 4-19 years) were randomised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler. During the study the patients recorded morning and evening peak expiratory flow rate (PEFR), symptom scores, and use of beta 2 agonist rescue medication. In addition, clinic visit PEFR and forced expiratory volume in one second were measured. Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment. For the purposes of analysis the diary card data were grouped into three periods: week 3 (days 15-21), week 6 (days 36-42), and weeks 1-6 (days 1-42). The results showed no significant difference between treatments on most efficacy parameters. However, there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 (fluticasone propionate 6.1%, beclomethasone dipropionate 3.9%) and at week 6 (fluticasone propionate 8.3%, beclomethasone dipropionate 5. 9%) and % predicted evening PEFR at week 6 (fluticasone propionate 7.3%, beclomethasone dipropionate 4.9% and over weeks 1-6 (fluticasone propionate 5.5%, beclomethasone dipropionate 3.6%. Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 81%) and % days without rescue medication at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 80%) and over weeks 1-6 (fluticasone propionate 80%, beclomethasone dipropionate 73%). Except for a higher incidence of sore throat in the fluticasone propionate group, the two treatments did not differ with regard to safety. There was no evidence of adrenal suppression with either treatment. In conclusion, fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma.

Administration, Inhalation↗