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M Bothwell

Publications and source records attributed to M Bothwell.

75 records · Page 5Linked to original sources

Pathways of assembly of aspartate transcarbamoylase from catalytic and regulatory subunits.

A scheme for the assembly of aspartate transcarbamoylase (EC 2.1.3.2; carbamoylphosphate:L-aspartate carbamoyltransferase) from catalytic and regulatory subunits is presented along with a technique for detecting intermediates and measuring the kinetics of assembly at protein concentrations of about 10 nM. (125)I-labeled subunits (10(6) cpm/mug) were used, and the reaction was "topped"at specific times with an appropriate "chase" followed by electrophoretic separation and measurement of the amounts of the various species. Two intermediates were identified. A stable enzyme complex lacking one regulatory subunit is the principal product when catalytic subunits are in excess. A transiently stable complex lacking one catalytic subunit is the principal species when regulatory subunits are in excess. Measurements with mixtures of the purified regulatory-deficient molecules and free regulatory subunits gave a second-order rate constant of 10(5) 10(5) M(-1) sec(-1) for the formation of bonding domains between catalytic and regulatory chains. No data for the rate of rupture of these bonds are available, but the kinetics of the assembly of the enzyme in vitro can be accounted for if this value is about 10(-2) sec(-1). Assembly from subunits occurs in seconds at concentrations equivalent to those that would exist in vitro even if there were only enzyme molecule per cell.

Allosteric Regulation↗

Actinomycosis: a potential complication of head and neck surgery.

Actinomycosis is a granulomatous infection occasionally found in the head and neck region that potentially may complicate a major head and neck oncologic surgical procedure. A case presentation, a review of the pertinent literature, and the treatment of this infectious complication are the primary elements of this report. A chronic infection of the neck caused by Actinomyces ssp developed postoperatively in a patient treated for head and neck cancer. Despite relapse after an initial course of long-term antibiotic therapy, the infection was successfully eradicated. Actinomycosis after surgery for head and neck cancer is unusual. However, the etiologic agent, Actinomyces ssp, is a common, potential microbial contaminant of head and neck surgery characterized by oral cavity or pharyngeal entry. Recognition of the typical manifestation of this infection in the neck facilitates prompt, appropriate treatment.

Actinomycosis↗

Nerve growth factor receptor and choline acetyltransferase remain colocalized in the nucleus basalis (Ch4) of Alzheimer's patients.

Previous investigations have demonstrated an almost exclusive "coupling" between the receptor for nerve growth factor and cholinergic neurons within the basal forebrain. The present series of experiments were carried out to address two questions. First, what is the status of nerve growth factor receptor-containing neurons within the basal forebrain of patients with histopathologically confirmed diagnoses of Alzheimer's disease (AD)? More importantly, the second experiment assesses the degree to which the receptor for nerve growth factor and choline acetyltransferase remain colocalized within AD basal forebrain. A "decoupling" of this relationship, in which nerve growth factor receptors are no longer present upon magnocellular cholinergic neurons, would suggest that a loss of trophic support is functionally antecedent to the neuronal shrinkage and neuronal death seen in the basal forebrain in AD. Data obtained from six AD cases and four normal controls demonstrated an extensive reduction in number and shrinkage in size of nerve growth factor receptor containing neurons within the Ch4 region of the basal forebrain. Double label studies using either immunofluorescence or immunoperoxidase techniques demonstrated that the receptor for nerve growth factor and choline acetyltransferase remain colocalized in AD patients. This was true for neurons exhibiting either healthy or dystrophic morphological profiles. These data confirm previous studies, demonstrating that both a loss and shrinkage of cholinergic neurons occurs within the AD basal forebrain. The results of the present immunohistochemical investigation suggest that the degenerative changes associated with these neurons do not result from impaired trophic support related to a loss of NGF receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗