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Biomedical subjects

J Cummings

Publications and source records attributed to J Cummings.

At least 163 records · Page 9Linked to original sources

Determination of adriamycin, adriamycinol and their 7-deoxyaglycones in human serum by high-performance liquid chromatography.

A reversed-phase isocratic high-performance liquid chromatographic assay is described for the measurement of adriamycin, adriamycinol and their 7-deoxyaglycones in human serum. The lower limit of detection in serum is 3 ng/ml for adriamycin and 1 ng/ml for adriamycinol and the 7-deoxyaglycones with coefficients of variation for k' of less than 5% throughout the day. An extraction technique for serum is described which is capable of an almost equal recovery (greater than 77%) of adriamycin, metabolites and daunorubicin (the internal standard) without interference from endogenous components of serum. Serum concentrations of metabolites 15 min after intravenous bolus administration of 40 mg/m2 adriamycin in two different patients were 26.5 and 16.6 ng/ml for adriamycinol; 109.8 and 5.8 ng/ml for the adriamycinol 7-deoxyaglycone and 21.4 and 17.1 ng/ml for the adriamycin 7-deoxyaglycone. A total of six metabolites of adriamycin were detected in the two patients using this methodology.

Chemical Phenomena↗

Kinetic studies of latent microsomal UDP-glucuronyltransferases. Kinetics of glucuronidation in intact and perturbant-treated membranes.

Double-reciprocal plots (with UDP-glucuronate as varied substrate) of the rate of glucuronidation of p-nitrophenol by the latent UDP-glucuronyltransferases of intact guinea pig and rat liver microsomal membranes (prepared with 154 mM KCl and 0.25 M sucrose) were continuously curved concave-downwards. Good fits to the kinetic data were obtained by using two different calculation methods which assume that two forms (high K and low K) of the transferase catalyse the reaction simultaneously. No evidence of cooperativity in binding of UDP-glucuronate to the enzyme was found. When latency of the enzymes of these preparations was destroyed by disrupting the membranes with Triton X-100 or lysophosphatidylcholine, double-reciprocal plots were linear. With guinea pig membranes, lysophosphatidylcholine generated an activated single-enzyme form obeying the simple Michaelis-Menten rate law; K for the activated species was close to that (K1) for the native low K form and its value of V was greater than the combined maximum velocities (V1 + V2) of the two forms in intact membranes. With rat membranes, both perturbants produced a single activated form also with V greater than (V1 + V2) and with K2 greater than K greater than K1. These results are discussed and are consistent with the view of transferase latency which envisages that there are two populations (buried and exposed) of enzyme molecules in intact microsomal membranes. The effects of membrane perturbants on the kinetic parameters of the two native transferase forms were assessed by accounting for the possibility that the reactivity of the buried transferase is controlled by the rate of transport of UDP-glucuronate across the membrane matrix. The data are compatible with a model which supposes that UDP-glucuronate gains access to the buried population by a process with the kinetic characteristics of a facilitated transport system.

Animals↗

Defective Schwann cell function in canine inherited hypertrophic neuropathy.

Segments of peripheral nerve from dogs with canine inherited hypertrophic neuropathy ( CIHN ) were transplanted to the transected sciatic nerve of immuno incompetent mice. Regenerating mouse axons penetrated the grafts and were myelinated by dog Schwann cells. In grafts collected 3 or more months after transplantation, filamentous or granular material, identical to that occurring in nerves of affected dogs, accumulated in myelinating Schwann cells. Demyelinated fibers were only rarely found in grafted segments of affected nerve. Neither filamentous accumulations nor demyelination were observed in grafts of control canine nerve. These results indicate that CIHN is associated with a defect in Schwann cell function, and the abnormal accumulations of filaments suggest that the defect may be in the cytoskeleton. The rarity of demyelination in grafts suggests that some factor in addition to the Schwann cell defect is required to precipitate myelin destruction.

Animals↗

Effect of a subcutaneously growing Walker 256 carcinosarcoma on host tissue mitochondrial function and magnesium content.

Mitochondria were prepared from the liver, kidneys, and skeletal muscle of rats at 1, 6, 12, 18, and 26 days after inoculation with Walker 256 cells or sterile 0.9% NaCl solution and assessed for structural and functional integrity. Using polarography to measure respiration, it was found that all tissue mitochondria from both controls and tumor-bearing animals prepared 1 day after inoculations were damaged and had impaired respiratory function. This effect was believed to be caused by the presence of anesthetic molecules in the mitochondrial membranes rather than by tumor. On Day 6, all tissue mitochondria were respiring properly; no evidence of membrane disruption was apparent. From Day 12 onwards, mitochondria from the tumor-bearing animals would not consume oxygen unless magnesium ions were added to incubation media. Kidney required by far the greatest amount of magnesium, in one case, 10 mM MgCl2. The requirement of the liver never exceeded 3 mM MgCl2, and with the muscle no dependency developed. The quantity of magnesium ions necessary to restore normal kidney mitochondrial function increased with tumor size (r = 0.83). From Day 12 onwards, mitochondria prepared from the control animals respired normally, and all mitochondria from the controls and the tumor-bearing rats were structurally intact. When the magnesium content of the abnormal mitochondria prepared from the animals inoculated with tumor cells was measured by atomic absorption spectrophotometry, the mitochondria were found to be deficient by 18% for kidney (p less than 0.01) and 20% for liver (p less than 0.01) compared to controls (Student's t test).

Animals↗

Reversible dementia. Illustrative cases, definition, and review.

The pitfalls of overlooking correctable causes of progressive intellectual deterioration are illustrated by live patients whose conditions were originally diagnosed as primary dementia. In each case careful evaluation disclosed a reversible process. Treatable intracranial conditions, systemic illnesses, endocrinopathies, deficiency states, collagen-vascular disorders, heavy-metal intoxications, exposure to industrial agents, infections, and the effects of drugs must all be considered in the evaluation of the patient with dementia. Such conditions are less likely to go undiagnosed when dementia is regarded as a nonspecific syndrome of progressive intellectual compromise rather than a specific diagnosis.

Aged↗

The phospholipid-dependence of uridine diphosphate glucuronyltransferase. Temperature-dependence of microsomal enzyme activity (reverse reaction).

Arrhenius plots of the non-latent UDP-glucuronlytransferase reverse reaction (p-nitrophenyl glucuronide donor) activity of guinea-pig microsomal membranes prepared with 15 mM-KCl were linear from 5 to 40 degrees C. These plots for other preparations from guinea-pig and rat liver (i.e. preparations that show transferase latency) exhibited two linear regions intersecting at a transition point near 19--21 degrees C. This discontinuity was abolished when latency was removed by treating the membranes with perturbants of phospholipid-bilayer structure. Thus the temperature-depdendnces of the reverse reaction catalysed by the enzymes of these various preparations are similar to those of the corresponding forward reactions [Pechey, Graham & Wood (1978) Biochem. J. 175, 115--1124]. Perturbants activated the enzyme of KCl-prepared guinea-pig microsomal membranes only slightly and caused no significant alteration to Arrhenius plots of its forward or reverse reaction activities. These results support the 'compartmentation' theory of UDP-glucuronyltransferase lactency.

Animals↗

Nonaphasic misnaming and other neurobehavioral features of an unusual toxic encephalopathy: case study.

A patient with propranolol-induced mental status changes was studied during and after the period of propranolol intoxication. While intoxicated he manifested the syndrome of "non-aphasic misnaming," did poorly on the nonverbal portions of the WAIS, and exhibited perseveration and variability of performance. Our observations clarify the nature of the neurobehavioral disturbances in toxic-metabolic encephalopathies.

Aged↗

Recurrent transitional cell carcinoma in an ileal conduit.

A patient with recurrent transitional cell carcinoma involving an ileal conduit is reported. This case is unusual for the following reasons: the malignancy was located in an area where there was no transitional epithelium; a "napkin ring" deformity was present; there was a 6-year interval between the initial cystectomy and the recurrence of the malignancy.

Aged↗

Staffing patterns and team composition.

The authors describe the work of a Veterans Administration task force in developing guidelines for staffing patterns and team composition on a hospital inpatient ward. The task force first defined the objectives of treatment, and then proceeded to define the needs of patients and their families, the types of professionals constituting the mental health team, and the functions they performed. It also identified the specific activities required in providing patient care, the staff involved in them, and those who could be involved, in some cases with more training.

Hospitals, Veterans↗