Biomedical subjects

M R Clark

Publications and source records attributed to M R Clark.

204 records · Page 12Linked to original sources

PubMedDate not supplied

Monoclonal antibodies derived from hybrid myelomas.

The hybrid myeloma technique for the production of monoclonal antibodies has been widely applied in many areas of biological and medical research. The strategy for derivation of monoclonal antibodies requires careful consideration of factors such as the initial immunization with antigen, choice of myeloma cell line, and method of assay for the desired antibodies. Once the hybrid lines have been isolated and established in culture they will continue to secrete the monoclonal antibody indefinitely, providing routine cloning is carried out to eliminate the accumulation of variants. Production of human monoclonal antibodies is at present limited by the lack of suitable parental myeloma cell lines although some success has been reported using both mouse and human cell lines. Under many assay conditions monoclonal antibodies behave differently to antisera directed against the same antigen but some of these differences are eliminated when two or more monoclonal antibodies are mixed. The unique properties of monoclonal antibodies also may allow subtle distinctions to be made between closely related antigens.

Animals↗

PubMedDate not supplied

Psychiatric and medical factors associated with disability in patients with dizziness.

Dizziness is a common patient symptom and often remains medically unexplained even after an extensive work-up. The otologic disorders, psychiatric disorders, and functional disability of 75 patients presenting with dizziness to a community otolaryngology practice were assessed in 1991. The patients were classified according to the presence or absence of at least one current DSM-III-R psychiatric disorder and the presence or absence of a peripheral vestibular disorder. Decrements in mental health and role functioning, and increases in bodily pain and hypochondriacal focus were significantly associated with the presence of a psychiatric disorder and whether the etiology of dizziness was due to a peripheral vestibular dysfunction.

Depressive Disorder↗

PubMedDate not supplied

A conceptual structure and methodology for the systematic approach to the evaluation and treatment of patients with chronic dizziness.

The patient with chronic dizziness should never be labeled with psychogenic dizziness. Chronic does not mean psychogenic. Chronic means that health care has been unsuccessful. A systematic approach that yields a comprehensive formulation and rational treatment plan will increase the probability of a successful outcome and return to health. The four perspectives of diseases, life stories, dimensions, and behaviors provide a comprehensive yet flexible methodology for the evaluation of the patient in distress with chronic and disabling dizziness. The design of a comprehensive treatment plan involves the determination of each perspective's contribution to the patient's distress and to what relative degree. This process recognizes that the perspectives are distinct from one another but complementary in illuminating the various reasons for a patient's distress. The perspectives come together as the formulation of the patient's case and offer a recipe for treatment rather than just a list of ingredients such as bio, psycho, and social.

Anxiety Disorders↗

PubMedDate not supplied

Rheological properties of antibody-coated red cells.

In vivo and in vitro antibody-coated nonspherocytic red cells have normal deformability in iso-osmolar media, and their isolated membranes have normal mechanical stability as measured in the ektacytometer, a laser visco-diffractometer. The deformability of red cells from patients with hemolytic anemia was proportionately reduced with the degree of spherocytosis irrespective of whether the direct antiglobulin test was positive. However, when antibody-sensitized nonspherocytic cells were suspended in hyperosmolar media and exposed to constant shear stress in the ektacytometer, they showed reduction of their deformability index in the presence of polyvinylpyrrolidone (PVP; 360,000 Daltons) but not dextran. This reduction was not due to alterations in cell water or cation content. Also, when incubated at 37 degrees C, sensitized red cells reacted specifically with PVP, and underwent a decrease in cell deformability. This appears to be the result of changes either in red cell membrane rigidity or membrane viscosity. The PVP effect was reproducible, time- and temperature-dependent, and predicted reliably the Rh phenotype. These observations were used to develop a novel approach to the antiglobulin test in the blood bank.

Anemia, Hemolytic, Autoimmune↗

PubMedDate not supplied

Could gut-liver function derangements cause chronic venous insufficiency?

Upregulation of adhesion molecules and neutrophil infiltration of venous valve cusps may be risk factors for chronic venous insufficiency. But studies that focus on the target organ (vein) fail to consider the influence of systemic inflammation on WBC behavior in the microcirculation. This study probes the gut-liver axis as a potential source of gut-derived oxidative stress and free radical production leading to white blood cell activation in chronic venous insufficiency. Venous hemodynamics (ambulatory venous pressure, air plethysmography, duplex) and gut-derived oxidative stress markers were studied in nine patients with chronic venous insufficiency (group I) and nine age- and sex-matched control subjects with no venous disease (group II). Group I had healed venous ulcers (class 5, CEAP) but near-normal ambulatory venous pressure, to eliminate high ambulatory venous pressure as a chronic venous insufficiency risk factor. Markers of gut-derived oxidative stress included: stool analysis; intestinal permeability; hepatic detoxification challenges with caffeine, salicylate, and acetaminophen; and urine lipid peroxides. Ambulatory venous pressure did not significantly differ (group I, 42.5 +/- 5.3 mm Hg; group II, 35.5 +/- 5.5 mm Hg; p = NS). Candida overgrowth in stool distinguished group I from group II (7/9 pts vs 1/9 pts, respectively; p = 0.015). Increased intestinal permeability (lactulose/mannitol ratio) was prevalent in both groups (group I 0.07 +/- 0.02, group II 0.17 +/- 0.08, p = NS; normal range, 0.01-0.03). Both groups showed similar incidence of elevated urine lipid peroxides (5/9 pts vs 6/9 pts, respectively; p = NS), yet group I exhibited underfunction of both sulfation (group I 16.8 +/- 2.9%, group II 43.3 +/- 11%, p<0.03; normal acetaminophen recovery 16-36%) and glucuronidation (group I 30.4 +/- 4.1%, group II 64.1 +/- 14.4%, p<0.04; normal acetaminophen recovery 27%-56%) relative to oxidative stress, perhaps an indicator of diminished antioxidant capacity in patients with chronic venous insufficiency. Gut dysbiosis (as indicated by stool yeast) and hepatic detoxification challenge pathway exhaustion may lead to subclinical, systemic inflammation and peripheral white blood cell adhesion in chronic venous insufficiency. Further exploration of the relationship between oxidative stress and venous disease is needed.

Adult↗

PubMedDate not supplied

The effect of abnormal hemoglobins on the membrane regulation of cell hydration.

Several hemoglobinopathies are associated with abnormalities in the permeability of the red cell membrane, in some cases leading to permanent alterations of the intracellular milieu. Homozygous sickle cell disease is the most thoroughly studied example. Deoxygenation of sickle cells causes a transient increase in the permeability to monovalent cations and Ca; prolonged deoxygenation can lead to a permanent accumulation of Ca and loss of total cations and water. Although the mechanisms for the permeability changes are not yet defined, mechanical stress on the membrane, with subsequent damages by excess Ca or membrane-associated hemoglobin have been suggested to play a role. Loss of cell water and increase in mean cell hemoglobin concentration causes massive reduction of cell deformability in the oxygenated state and makes the hemoglobin more likely to undergo sickling because of the strong concentration dependence of the sickling process. Limited evidence suggests the occurrence of permeability defects in other hemoglobinopathies and the thalassemias. The suggested alterations range from a slight increase in K permeability of incubated thalassemia cells to substantial dehydration of cells from patients with homozygous hemoglobin C disease. Oxidative damage to the membrane, involving an abnormal hemoglobin-membrane association, may underly the permeability changes in these cells.

Adenosine Triphosphate↗