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Biomedical subjects

D A Lewis

Publications and source records attributed to D A Lewis.

At least 271 records · Page 15Linked to original sources

Tritiated imipramine binding distinguishes among subtypes of depression.

We studied 45 depressed patients and 20 healthy controls in order to determine if tritiated imipramine binding distinguished among subtypes of primary major depressive disorder. Mean (+/- standard deviation) values for maximal concentration of tritiated imipramine binding sites on platelet membranes were significantly lower in patients with bipolar and familial pure depressive disease (754 +/- 149 and 870 +/- 241 femtomoles [fmole]/mg of protein, respectively) than in patients with depressive spectrum and sporadic depressive disease (1,236 +/- 241 and 1,188 +/- 325 fmole/mg of protein, respectively), neither of which differed from healthy controls (1,238 +/- 201 fmole/mg of protein). Multiple linear regression analysis revealed that these differences could not be attributed to differences in age, sex, Hamilton Rating Scale score, presence of psychotic features, hospitalization status, or medication history. This association of a biological finding with distinct clinically defined subtypes of depression may lead to a classification of affective disorders useful in further research.

Adult↗

In-vitro inhibition of glucosyltransferase from the dental plaque bacterium Streptococcus mutans by common beverages and food extracts.

Some fruit juices and beverages inhibit the glucosyltransferases of Streptococcus mutans. Inhibition by cocoa, coffee and tea was due partly to gelatin-precipitable tannins and partly to components that exhibited properties of monomeric polyphenols. Charcoal treatment removed all inhibitory activity. Catechin, a known constituent of these beverages, was an effective inhibitor of the enzymes. The effects of the fruit juices were attributable mainly to the inhibition of the glucosyltransferases by the endogenous fructose and glucose. The findings show that naturally-occurring constituents of foods can inhibit extracellular polysaccharide formation from sucrose. Such constituents may play a role in regulating dental plaque formation in vivo and, thereby, may have long-term effects on the development of dental caries.

Beverages↗

Tritiated imipramine binding to platelets in manic subjects.

We studied 21 patients with bipolar affective disorder and 25 healthy controls in order to determine if tritiated imipramine binding to platelets distinguished the manic from the depressed phase of bipolar disorder. Depressed patients had a significantly lower mean Bmax value (754 +/- 149 fmole/mg protein) than the manic and control groups (1112 +/- 248 and 1237 +/- 201 fmole/mg protein, respectively), which did not differ from each other. These differences could not be attributed to differences in age, sex, menopausal status, the presence of psychotic features or medication history among the subject groups. These findings confirm that decreased imipramine binding to platelets is a state marker for bipolar depression and not a trait marker of bipolar disorder.

Adult↗

Tritiated imipramine binding to platelets is decreased in patients with agoraphobia.

Controversy exists regarding the relationship between anxiety states and major depression. We studied the binding of tritiated imipramine to platelet membranes in order to determine if patients with agoraphobia and panic attacks differed from depressed subjects or healthy volunteers on this biological parameter. Mean (+/- SD) Bmax and Kd values were significantly lower in patients with agoraphobia and panic attacks (787 +/- 276 fmole/mg protein and 0.35 +/- 0.14 nM, respectively) than in healthy volunteers (1237 +/- 201 fmole/mg protein and 0.71 +/- 0.37 nM, respectively). In addition, patients with agoraphobia and panic attacks had binding parameters that were similar to those of patients with bipolar or familial pure depressive disorder, but significantly lower than those of patients with depressive spectrum or sporadic depressive disorder. These findings have implications for both the nosology and pathophysiology of anxiety disorders.

Adolescent↗

Characterization of a renal cell carcinoma cell line suitable as a target for immunological studies in vitro and in the nu/nu mouse.

A continuous human renal carcinoma cell line designated RPMI-SE was established from a patient with a poorly to moderately differentiated renal cell carcinoma. The cells are anchorage dependent, have a well defined globular shape with pseudopod-like structures, a doubling time in vitro of 24 hr. and are able to grow subcutaneously in female ICR Swiss nu/nu mice. RPMI-SE cells obtained from tissue culture and the nude mouse had the chromosome number of near-tetraploidy. Common morphologic rearrangements were present in both the cell line and nu/nu mouse tumor. RPMI-SE was evaluated as a target cell line in an in vitro Indium-111 release assay. Three patterns of cytotoxicity were observed at an effector to target cell ratio of 100:1. The highest degree of cytotoxicity (75 per cent) was obtained with autologous lymphocytes. An intermediate level of cytotoxicity (50 per cent) was obtained with allogeneic lymphocytes. The lowest level of cytotoxicity (27 per cent) was obtained with normal lymphocytes and was comparable to the level of cytotoxicity observed with the NK sensitive K562 target cell line. Morphologic data and chromosomal analysis indicate that the RPMI-SE cell line has maintained characteristics of the original tumor. This cell line will be useful for immunological studies as a target cell line in vitro as well as in vivo in the nude mouse.

Animals↗

[3H]cortivazol: a unique high affinity ligand for the glucocorticoid receptor.

Cortivazol (CVZ) and deacylcortivazol (DAC) are pyrazolosteroids with potent glucocorticoid activity. In previous work we showed that DAC is 40-fold more potent than dexamethasone (DEX) in lysing leukemic lymphoblasts. To assess the interaction between these atypical steroids and the glucocorticoid receptor, we examined the binding of [3H]CVZ to cytosol from glucocorticoid-sensitive and -resistant variants of the human leukemic cell line CEM C7. In glucocorticoid-sensitive cells [3H]CVZ causes a 2-fold induction of glutamine synthetase and binds to a protein in the 4.6 S region of high salt sucrose gradients. On DEAE-cellulose chromatography, [3H]CVZ-receptor complexes show a shift from high (0.25 M KP) to low salt (0.09 M KP) eluting forms upon activation. CVZ competes for a 97,000-dalton protein labeled by [3H]dexamethasone mesylate. Scatchard analysis of the binding of [3H]CVZ in glucocorticoid-sensitive cells revealed a curvilinear plot which resolved into high (0.4 nM) and low (11 nM) affinity components. The receptor concentration of the low affinity site (0.30 pmol/mg protein) was approximately twice that of the high affinity site (0.14 pmol/mg protein). Dissociation experiments with dilution and/or excess unlabeled CVZ supported the presence of independent sites. In contrast, the binding of [3H]DEX to C7 cytosol revealed a single class of binding sites (Kd = 1.9 nM; receptor concentration, 0.46 pmol/mg protein). Examination of the binding of [3H]CVZ using 10(-5) M DEX as the competing ligand showed that DEX binds only to the low affinity site detected by [3H]CVZ. In cytosol from a glucocorticoid-resistant cell line with virtually no [3H]DEX binding, [3H]CVZ detected a single high affinity binding site that was similar in dissociation constant (0.8 nM) and receptor concentration (0.13 pmol/mg protein) to the high affinity site detected in the glucocorticoid-sensitive cell line C7.

Binding, Competitive↗

Oxytocin does not influence adrenocorticotropin secretion in man.

Recent studies suggest that oxytocin inhibits ACTH secretion in normal men, whereas previous animal studies indicate that oxytocin is a weak secretagogue of ACTH. We studied the effect of oxytocin on plasma ACTH and cortisol in normal men under three conditions. Using four different doses of oxytocin (30, 60, 90, and 120 mU/kg), given by iv bolus injection, we found no difference in the effect of oxytocin on morning ACTH and cortisol levels compared with the effect of a placebo. A prolonged infusion of oxytocin (90 mU/kg . h) given from 0300-0600 h did not suppress basal ACTH or cortisol levels or delay or blunt their normal circadian rise. In addition, pretreatment with oxytocin (50 mU/kg, iv bolus dose, followed by an infusion of 50 mU/kg . h) did not alter the ACTH and cortisol responses to vasopressin. We conclude that oxytocin is not a major regulator of pituitary-adrenal activity in normal men.

Adrenocorticotropic Hormone↗

Serotonergic regulation of prolactin and growth hormone secretion in man.

Controversy still exists regarding the role of serotonin in the regulation of prolactin (Prl) and growth hormone (GH) secretion in man. We gave healthy male volunteers three oral doses (0.5, 1.0 and 1.5 mg/kg) of fenfluramine, a serotonin-releasing agent and uptake inhibitor, and a corresponding placebo. There was a significant dose-response effect of fenfluramine on Prl but not on GH levels. Following the highest dose of fenfluramine, mean Prl levels increased from 9.7 ng/ml to 42.3 ng/ml. In a separate study, subjects were pre-treated with cyproheptadine, a serotonin antagonist, before the administration of fenfluramine. Cyproheptadine did not significantly affect basal Prl or GH levels, but it did blunt the response of Prl to fenfluramine. Cyproheptadine pre-treatment did not alter plasma levels of fenfluramine. Our findings support a stimulatory role for serotonin in the regulation of Prl secretion in man. They also suggest that serotonin does not have a major influence on GH secretion in man.

Adult↗

Effect of particle size of dried mycobacteria on adjuvant induced arthritis in the rat.

Freund's complete adjuvant prepared by grinding dried, heat killed Mycobacterium tuberculosis with liquid paraffin was investigated for particle size-weight distribution. Variations in the grinding times and preparative procedure had a marked effect on the arthritogenic action of the adjuvant in the rat. A satisfactory response in the injected foot was found only when the particle size was less than 19 microns and a secondary response in the non-injected foot required particles less than 10 microns in diameter.

Animals↗

Rabbit monoarticular arthritis as a model for intra-articular drug injections. The local action of administered cortisol and alpha-1 proteinase inhibitor.

Monoarticular arthritis in the rabbit has been used to study the effect of intra-articular administration of cortisol-21-phosphate and alpha-1-proteinase inhibitor. The preparations were administered both separately and in combination. All treatments improved parameters associated with joint biochemistry and histopathology, but the greatest effect was found when steroid was combined with anti-proteinase. Cortisol-21-phosphate had both an anti-inflammatory and anti-arthritic action, whereas alpha-1-proteinase inhibitor showed little anti-inflammatory action but had some anti-arthritic effect. Alpha-1-proteinase inhibitor had no anti-inflammatory action against carrageenan induced oedema in the rat, but was anti-arthritic against adjuvant induced arthritis in the rat where it reduced both primary and secondary arthritis.

Acid Phosphatase↗

Neutral protease, collagenase and elastase activities in synovial fluids from arthritic patients.

Neutral protease, collagenase and elastase activities were high in synovial fluids from inflammatory arthritic diseases such as gout, active rheumatoid arthritis and ankylosing spondylitis. The activities correlated well with biochemical parameters such as CRP, ESR and total protein. Values were much lower in a non-inflammatory fluid from a patient with osteoarthrosis. Treatment of fluids with trypsin released both collagenase and elastase. The fluids possessed reserve inhibitory action against these enzymes presumably due to plasma antiproteases being present. The collagenase present was found to possess a MW of 32,700 daltons.

Arthritis↗

Collagenase and elastase in the serum of adjuvant arthritic rats.

Collagenase and elastase activities in the serum of adjuvant arthritic rats declined with time as the disease progressed and did not parallel increases in alpha 1-macroglobulin or alpha 2-acute phase globulin levels. The fall in collagenase and elastase activities was accompanied by a decline in serum alpha 1-proteinase inhibitor levels. It was concluded that the fall in collagenase and elastase activities in serum was due to inactivation by serum anti-proteases.

Animals↗

Influence of age on the cortisol response to dexamethasone.

Controversy exists regarding the association of age with postdexamethasone serum cortisol levels. We evaluated this relationship in 95 patients with major depressive disorder and 49 healthy controls. Age and 8 a.m. postdexamethasone cortisol levels were not correlated among the healthy controls, but were positively associated among the depressives. There was also a trend for age and 4 p.m. postdexamethasone cortisol levels to be positively associated in depressives. Multiple linear regression analyses revealed that these associations could not be explained by other variables such as sex, psychotic features, or familial subtype of depression. Several hypotheses that might account for these associations are examined.

Adult↗

Prevention of bacterial colonization of wounds at operation: comparison of iodine-impregnated ('Ioban') drapes with conventional methods.

Forty-five patients undergoing clean elective inguinal surgery were randomly allocated to receive one of three skin preparations, (1) alcoholic povidone-iodine ('Betadine') alone, (2) the same covered with an incise drape ('Steri-Drape'), or (3) an iodine-containing incise drape ('Ioban') alone. The first two preparations were superior in reducing bacterial colony counts measured on skin with cotton swabs and impression cultures. There were no clinical postoperative wound infections in any group but it is suggested that although the use of an iodine-containing incise drape alone is attractive, its bactericidal action is inferior to conventional preparations.

Disinfection↗