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Biomedical subjects

L Davidson

Publications and source records attributed to L Davidson.

At least 37 records · Page 2Linked to original sources

Trabecular and cortical bone in the radii of women with parathyroid adenomata: a greater trabecular deficit, with a preliminary assessment of recovery after parathyroidectomy.

Radial bone mineral content (BMC) has been reported to be lower than normal in patients with hyperparathyroidism, but those measurements have been made with techniques which do not discriminate between trabecular and cortical bone. We have used a low radiation dose computed tomography technique to make differential measurements of trabecular and cortical bone in the radii of 18 out of 27 eligible female patients with surgically proven adenomata. Prior to parathyroidectomy there was a mean deficit of 40% (P less than 0.001) in trabecular bone density in the distal radius, and a deficit of 16% in cortical bone in the radius mid-shaft compared to normal values. Seventeen months after parathyroidectomy there was a small but significant increase in trabecular bone density in the distal radius in 13 of these patients, and no significant change in cortical bone. If these results represented the situation throughout the skeleton, it is possible that parathyroidectomy may provide some reduction in future risk of fracture in women with primary hyperparathyroidism.

Adult

Clinical significance and etiology of infected catheters used for total parenteral nutrition.

Catheter related sepsis (CRS) is the most serious complication of total parenteral nutrition. Frequently, however, low rates of CRS are associated with a high incidence of infection of the catheter tip, the clinical significance of which is unclear. The relationships between CRS, infection of the catheter tip and infection at the site of catheter insertion have been investigated in 283 catheters of 257 patients receiving total parenteral nutrition. CRS occurred in only ten patients (3.5 per cent) whereas organisms were isolated from 108 catheter tips (38.2 per cent). The most common organism isolated was Staphylococcus epidermidis (66.7 per cent). Eight catheter tips were colonized from a distant septic focus. Organisms were isolated from 90 catheter tips which were removed electively from patients who displayed no clinical evidence of sepsis. There was a poor correlation between infected catheter tips and infected catheter insertion sites. Asymptomatic infection of the catheter tip appears to be of little clinical relevance, resulting in no patient morbidity. Contamination of the catheter tip during or after removal seems to account for a significant proportion of these infections.

Bacteria

Comparative accuracy of computerized spatial vectorcardiography and standard electrocardiography for detection of myocardial infarction.

New computerized spatial vectorcardiographic variables were analyzed by discriminant analyses for group classification of 94 patients with acute myocardial infarction and 79 normal subjects. Using the integral of the sequential magnitudes of the spatial vectors during the period of initial abnormal depolarization (IAD) of the QRS at a discriminating value of 3 mv X msec., 87% of the subjects were correctly classified with a sensitivity of 85%; specificity of 88%; and an overall predictive accuracy of 87%, p less than .00001. The period of initial abnormal depolarization in which the vectors were integrated was determined by the first derivative of the sequential magnitudes of the spatial vectors of the QRS waveform (dm/dt). The mean value of dm/dt during the period of abnormal depolarization was a poor discriminating variable. The predictive accuracy of this new electrocardiographic criterion for diagnosis of myocardial infarction compared favorably with other computerized methods such as vectorcardiography, polarcardiography, Aitoff spatial trajectory, the 12-lead ECG derived by the Frank XYZ leads as well as the standard 12-lead ECG.

Computers

Sulphate conjugation limits fluctuations in free catecholamines in phaeochromocytoma.

More than 80% of total noradrenaline (NA) and adrenaline (A) and nearly 100% of dopamine (DA) circulate in blood as sulphates, and it has been proposed that sulphate conjugation contributes to the inactivation of catecholamines (CA). Sulphate conjugation rapidly responds to changes in sympathetic activity and may buffer the haemodynamic and metabolic consequences of wide fluctuations in CA release in phaeochromocytoma. This hypothesis was tested in seven patients with phaeochromocytoma by consecutive measurements of plasma-free and conjugated NA, under resting conditions, before operation and at least 4 weeks after tumour removal. Free and total (free + sulphates) NA were markedly elevated before compared with 1-4 months after surgery. Similar elevations were seen in free and total A and free DA. Before surgery consecutive measurements of total NA, 5 min apart, were markedly different (17 +/- 4.1 and 13.7 +/- 4.4 ng/ml, respectively), whereas only small differences in free NA levels were present (4.1 +/- 1.5 and 4.3 +/- 1.8 ng/ml). These differences between total and free levels were also apparent for A and DA, but to a lesser degree. In three patients, fluctuations in total NA concentration greater than 12 ng/ml were associated with either no change (one patient) or changes of 0.6 and 2.8 ng/ml in free levels for the other two patients, respectively. Mean blood pressure (BP) varied less than 8 mmHg in these patients. These findings suggest that sulphate conjugation is a dynamic process which may limit wide fluctuations in free CA concentration during episodic secretory activity in phaeochromocytoma.

Adrenal Gland Neoplasms

A new human ovarian carcinoma cell line: establishment and analysis of tumor-associated markers.

In the present study we describe the establishment and characteristics of a new human tumor cell line (OV-1063) positive for carcinoembryonic antigen (CEA) originating from ovarian metastatic tumor cells. Analysis of the cultured cells during their in vitro adaptation period revealed while the primary culture exhibited a low proportion of CEA-positive cells, this proportion increased with culture passages and eventually more than 90% of the cells in the established line were CEA-positive. Thus, during the period of adaptation to in vitro growth, a selection for CEA-positive cells took place but the amount of CEA secreted per each positive cell seemed to be constant. Several tumor-associated characteristics were found positive on the established OV-1063 cell line. The in vitro growing cell line exhibited an abnormal chromosome pattern with a near-trisomy karyotype for some chromosomes, colony formation in soft agar as well as positive staining with a monoclonal antibody B38.1. Culture supernatants of the OV-1063 cells contained significant amounts of CEA as well as CA-125 antigen which is an ovarian-carcinoma-associated antigen.

Agar

[3H]GABA binding in brains from Huntington's chorea patients: altered regulation by phospholipids?

Binding sites for tritum-labeled gamma-aminobutyric acid (GABA) in cerebellar cortex of Huntington's chorea patients have an increased affinity but unaltered maximum capacity as compared to binding sites in tissue from control patients. A similar binding pattern is produced in control membranes by treatment with Triton X-100, phospholipase C, or glycerophosphoethanolamine. Thus, it is likely that phospholipids or their metabolites regulate the accessibility of the GABA binding site and that this regulation is abnormal in Huntington's chorea.

Cerebellar Cortex

Sodium-independent, high-affinity binding of [3H]gamma-aminobutyric acid in human neurological disorders.

With respect to [3H]GABA-binding in material prepared from human post-mortem brain, the following observations have been made: (1) The [3H]GABA binding site in the cerebellum has the pharmacological characteristics of the physiological GABA-receptor observed in other species. Together with the post-mortem stability exhibited for [3H]GABA-binding, this provides an approach for determining the functional state of the GABA-receptor in various disease states; (2) In Parkinson's disease [3H]GABA-binding in the substantia nigra is significantly decreased whereas that in the putamen and caudate nucleus is unaltered. The former finding likely indicates that GABA binding sites (receptors) occur on nigral dopaminergic cell bodies and/or dendrites. The latter finding may signify that relatively few of the striatal [3H]GABA binding sites occur on dopaminergic nerve terminals in the human caudate or putamen; (3) In Huntington's disease [3H]GABA binding was decreased in the caudate nucleus and putamen, in parallel wih the massive cell loss and gliosis observed in this condition. Membranes prepared from cerebellar tissue of these patients possessed an increased affinity for [3H]GABA-binding; (4) Pre-treatment of cerebellar membranes from control brains with Triton-X-100 (0.02%) or phospholipase-C (0.001 units) results in kinetic changes very similar to those observed in Huntington's brains. In contrast, such treatment was virtually without effect on the IC50 or KD for [3H]GABA on cerebellar membranes prepared from Huntington's brains; (5) These results imply that a phospholipid, possibly related to phosphoglycerolethanolamine, is altered in the membrranes of Huntington's patients and that this phospholipid normally has a role in controlling accessibility to the GABA-receptor.

Binding, Competitive

Tumor inhibitory and non-tumor inhibitory L-asparaginases from Pseudomonas geniculata.

Two enzymes that catalyze the hydrolysis of l-asparagine have been isolated from extracts of Pseudomonas geniculata. After initial salt fractionation, the enzymes were separated by chromatography on diethylaminoethyl-Sephadex and purified to homogeneity by gel filtration, ion-exchange chromatography, and preparative polyacrylamide electrophoresis. The enzymes differ markedly in physicochemical properties. One enzyme, termed asparaginase A, has a molecular weight of approximately 96,000 whereas the other, termed asparaginase AG, has a molecular weight of approximately 135,000. Both enzymes are tetrameric. The asparaginase A shows activity only with l-asparagine as substrate, whereas the asparaginase AG hydrolyzes l-asparagine and l-glutamine at approximately equal rates and it is also active with d-asparagine and d-glutamine as substrates. The asparaginase A was found to be devoid of antitumor activity in mice, whereas the asparaginase AG was effective in increasing the mean survival times of both C3H mice carrying the asparagine-requiring Gardner 6C3HED tumor line and Swiss mice bearing the glutamine-requiring Ehrlich ascites tumor line. These differences in antitumor activity were related to differences in the K(m) values for l-asparagine for the two enzymes. The asparaginase A has a K(m) value of 1 x 10(-3) M for this substrate whereas the corresponding value for the AG enzyme is 1.5 x 10(-5) M. Thus the concentration of asparagine necessary for maximal activity of the asparaginase A is very high compared with that of the normal plasma level of asparagine, which is approximately 50 muM.

Animals

American Burkitt's lymphoma-hand-mirror variant. A detailed investigation of cytologic, ultrastructural, and immunologic features.

Previous studies of patients with lymphoid malignancies have suggested a relationship between survival and the presence of more than 40% hard-mirror cells in the bone marrow. This report represents the first detailed study of a patient with American Burkitt's lymphoma with numerous hand-mirror cells in the bone marrow during the course of the disease. The Burkitt cells were atypical because of their hand-mirror configuration in the bone marrow, the presence of cytoplasmic glycogen, the finding of an IgG surface marker, and a strongly positive acid phosphatase staining reaction. The presence of increased numbers of hand-mirror forms in the bone marrow during the course of the patient's illness may have clinical significance, because they were replaced by non-hand-mirror Burkitt cells in the terminal phase. More reports and investigations of patients with large numbers of hand-mirror forms in the bone marrow are needed to elucidate the full significance of this unusual cellular phenomenon.

Adult

L-Asparagainases from Citrobacter freundii.

Three enzymes which catalyze the hydrolysis of L-asparagine have been identified in extracts of Citrobacter freundii. One of these (asparaginase-glutaminase (EC 3.5.1.1) also shows substantial glutaminase activity. This enzyme is extremely labile, is sensitive to inactivation by p-chloromercuribenzoate, and is not protected by dithiothreitol. A second enzyme (asparaginase B) is also sensitive to mercurials but is protected from inactivation by dithiothreitol. This enzyme has a relatively low affinity for L-asparagine (Km = 1.7-10(-3) M). The third enzyme (asparaginase A) is insensitive to inactivation by mercurials, is stable upon long term storage and has a relatively high affinity for L-asparagine (Km = 2.9-10(-5) M). This enzyme has been purified to homogeneity and has a molecular weight of approx. 140 000; the subunit weight being approx. 33 000. The C. freundii asparaginase A produced significant increases in the survival time of C3H/HE mice carrying the 6C3HED lymphoma tumor.

Amino Acids

Purification and properties of L-glutaminase-L-asparaginase from Pseudomonas acidovorans.

An enzyme that catalyzes the hydrolysis of both glutamine and asparagine has been purified to homogeneity from extracts of Pseudomonas acidovorans. The enzyme having a ratio of glutaminase to asparaginase of 1.45:1.0 can be purified by a relatively simple procedure and is stable upon storage. The glutaminase-asparaginase has a relatively high affinity for L-asparagine (Km=1.5 X 10(-5) M) and L-glutamine (Km=2.2 X 10(-5) M) and has a molecular weight of approximately 156,000 the subunit molecular weight being approximately 39,000. Injections of the enzyme produced only slight increases in the survival time of C3H/HE mice carrying the asparagine-requiring 6C2HED Gardner lymphoma and of white Swiss mice carrying the glutamine-requiring Ehrlich lymphoma.

Amidohydrolases

Catecholamine and octopamine concentrations in brains of patients with Reye syndrome.

Dopamine, norepinephrine, and octopamine levels were estimated in regions of brains obtained postmortem from children who died with Reye syndrome and from age-matched controls. Hypothalamic norepinephrine levels were greatly decreased (to 30 percent of control, p less than 0.02) and octopamine levels were increased (to 700 percent of control, p less than 0.01). Levodopa had little effect on the physiologic condition of the patients. However, CNS dopamine and homovanillic concentrations were not elevated by levodopa, indicating that in the present cases levodopa was not metabolized to its catecholamine products. The findings indicate that the encephalopathy of Reye syndrome (as in other types of hepatic coma) may be linked to the presence of false transmitters in the brain and that levodopa is a rational therapy if administered before irreversible CNS changes occur.

Brain Chemistry

The interaction of an anionic photoreactive probe with the anion transport system of the human red blood cell.

N-(4-azido-2-nitrophenyl)-2-aminoethyl[35S]sulfonate is employed as a photoreactive probe for the anion transport system in the human erythrocyte. In the dark and at 37 degrees C the probe penetrates the membrane via a pathway sensitive to specific inhibitors of anion permeability. It reversibly inhibits sulfate and chloride fluxes but the inhibition is reduced by higher concentrations of sulfate. Upon photolysis to produce a reactive nitrene (at 0 degrees C to minimize penetration), the probe inhibition of anion permeability. Under appropriate conditions the degree of inhibition after photoactivation (irreversible) is almost the same as that in the dark (reversible). The binding sites for the radioactive probe are largely found in proteins of 95 000 apparent molecular weight (band 3). After pronase treatment of the labelled cells, most of the probe is found in a 65 000 molecular weight segment derived from the 95 000 molecular weight protein. In this respect the photoreactive probe resembles another potent irreversible inhibitor of anion transport, 4, 4'-diisothiocyano-2, 2' stilbene disulfonate. In fact, most of the binding sites for each probe are common to both. Thus, in the dark, the azido derivative protects the anion system from inhibition by DIDS and substantially reduces the binding of DIDS to band 3 protein. Conversely, pretreatment with DIDS substantially reduces the binding of the photoreactive probe to the same protein. The fact that an apparent substrate for the anion permeation system competes for binding sites with a specific non-penetrating inhibitor of anion permeability suggests that the inhibitory and transport sites may be closely related and implicates the 95 000 molecular weight protein as the element of the anion transport system which contains the substrate binding site.

Biological Transport

Mitosis and early meiosis in Tetrahymena pyriformis and the evolution of mitosis in the phylum Ciliophora.

The micronuclear mitotic spindle of Tetrahymena pyriformis contains several distinctive elements. The 150 or so continuous microtubules (MTs) form a peripheral sheath just inside the inner nuclear membrane while the kinetochore bundles traverse the center of the nucleoplasm. A new set of microtubules, the separation spindle, appears during the 10-fold nuclear elongation which occurs during the late anaphase. Both the separation spindle and peripheral sheath MTs are present in the macronucleus during macronuclear division but there are no definite kinetochore MTs. In the cresent stage of meiotic prophase both peripheral sheath and kinetochore MTs are present in the micronucleus. By using our own, and other workers', data in conjunction with the phylogenetic scheme for the ciliates which has been designed by Corliss (1974, 1975), we have attempted to trace out the evolutionary history of the various elements of the ciliate mitotic spindle. For example, the micronuclear separation spindle can be followed, from its point of origin within the primitive gymnostomes, throughout the phylum. The separation spindle of the macronucleus, by contrast, is lost at the level of the heterotrichs. Similarly, the anaphase breakdown and reconstitution of the nuclear envelope, which occurs in the primitive Loxodes magnus, can be followed up some phyletic branches, such as the heterotrichs, but in the suctorians and some other groups this feature seems to have been lost. Tracing the evolution of the ciliate mitotic spindle is made very difficult both by the incompleteness of the data and by what appear to be a number of cases of secondary reduction and parallel evolution. In general, however, the evolution of mitosis correlates well with the phylogeny of the ciliates constructed by Corliss and we consider this an independent substantiation of the general correctness of his phylogeny.

Biological Evolution