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Biomedical subjects

R Owens

Publications and source records attributed to R Owens.

At least 37 records · Page 2Linked to original sources
PubMed1995

Autoregulatory circuits in myeloma. Tumor cell cytotoxicity mediated by soluble CD16.

BACKGROUND: Multiple myeloma remains an incurable malignancy due to marked resistance of the tumor to standard doses of chemotherapy. Treatment approaches, using chemotherapeutic dose escalation and hematopoietic stem cell support have resulted in significant augmentation of tumor mass reduction such that complete remissions are effected in approximately 50% of patients. These remissions are however, often not durable. In the setting of minimal residual disease, therefore, adjunctive immunotherapy may be useful. METHODS: Peripheral blood mononuclear cells were studied from 28 untreated patients with multiple myeloma (MM). Mononuclear cell CD16 (FcR gamma III) expression was determined by flow cytometry. The effect of lymphocyte-derived soluble CD16, isolated by affinity chromatography, on MM cell growth and differentiation was assessed. MM cell proliferation, viability, immunoglobulin production and gene expression was studied. RESULTS: Data are presented indicating that cells expressing CD16 are increased in untreated patients with IgG-secreting myeloma. The predominant phenotype of these cells is CD8+ or CD56+. These CD16+ cells can produce a soluble form of the Fc receptor (sFcR, sCD16) that can bind to surface Ig on cultured human IgG-secreting myeloma cells and effect suppression of tumor cell growth and Ig secretion. This effector function is accompanied by concomitant suppression of c-myc as well as IgH and IgL gene transcription. Finally, prolonged exposure to sCD16 causes myeloma tumor cell cytolysis. CONCLUSIONS: sCD16 and possibly other soluble FcR are candidate molecules for adjunctive immunotherapy of myeloma, once complete responses have been effected by intensive cytotoxic therapy, now possible in up to 50% of newly diagnosed patients.

Adult↗
PubMed1995

Psychological adjustment of children evaluated for short stature: a preliminary report.

Since synthetic growth hormone became available in the mid-1980s, there has been debate about its use for non-growth-hormone-deficient short children. Justification for this use of growth hormone often is based on a presumed association of short stature with significant psychosocial maladjustment. However, systematic evaluation of psychosocial functioning in short children has been limited, and our understanding of this area is scant. In this study, we have used a combination of interview and self-report measures to examine self-esteem, personality characteristics, affective functioning, coping style, and stature-related stresses in 41 children (5 to 16 years) referred to a pediatric endocrinology service because of short stature. Parent-report and child measures of self-esteem and psychological functioning indicated no evidence of maladjustment in comparison with norms. Furthermore, within the subject sample, the degree of short stature was not related to poor psychological functioning. We found limited evidence linking increased age with increased distress, suggesting that short stature may pose greater difficulties for children as they enter adolescence. Taken as a whole, however, the results do not support the contention that short stature is generally associated with psychosocial maladjustment in children referred for evaluation of their short stature.

Adaptation, Psychological↗
PubMed1995

Protein kinase C phosphorylates two of the four known syndecan cytoplasmic domains in vitro.

The transmembrane heparan sulfate proteoglycans of the syndecan family are implicated to participate in several cellular reactions which are dependent on protein kinase C. We have used an in vitro assay to assess whether any of the Peptides corresponding to the complete cytoplasmic domains of rat syndecans 1 through 4 were used as substrates for the enzyme. The syndecan-2 (fibroglycan) and syndecan-3 (N-syndecan) peptides were both found to be phosphorylated by protein kinase C with Kms of 15 +/- 3 microM and 85 +/- 25 microM, respectively, while the syndecan-1 and -4 peptides were not phosphorylated under the conditions used. The sites of in vitro phosphorylation for syndecans-2 and -3 were localized to ser-197 and ser-339, respectively. Thus, among 13 available sites (serines and threonines) in the four peptides, two were selectively modified by the enzyme. The specificity and the kinetics of the reactions indicate that the cytoplasmic domains of syndecan-2 and -3 are likely to be physiological substrates for protein kinase C.

Amino Acid Sequence↗
PubMed1994

Isotype choice for chimeric antibodies affects binding properties.

Construction of a series of chimeric antibodies (murine variable region and human constant region) derived from the murine antibody BIRR1, which recognizes intercellular adhesion molecule 1 (ICAM-1), has revealed differences in the relative binding abilities of the chimeric antibody to antigen. The chimeric antibodies show a ranking of their ability to compete with BIRR1 for antigen on the surface of cells with the order BIRR1 = cIgG1 (100%) > cIgG4 (30%) > cIgG2 (10%) as demonstrated by solid-phase competitive enzyme-linked immunosorbent assay. Papain digestion yielded Fab fragments that were purified to homogeneity. Competitive enzyme-linked immunosorbent assay showed that the chimeric and murine Fab binding constants were equivalent. A solution-phase binding assay (analyzed by size exclusion high performance liquid chromatography) between the intact mAbs and recombinant soluble ICAM-1 further established that the binding constants involving the Fab arms of the two antibodies were equivalent. In summary, the murine and chimeric anti-ICAM-1 antibodies bind cellular ICAM-1 with equivalent affinities but with differing avidities.

Animals↗
PubMed1992

Molecular cloning of a novel hyaluronan receptor that mediates tumor cell motility.

A cDNA encoding a unique hyaluronan receptor has been molecularly cloned from a lambda GT11 3T3 cDNA expression library. Immunoblot analyses of cell lysates, using antibodies to peptides encoded in the cDNA, specifically react with a 58-kD protein. This protein is regulated by the mutant H-ras gene in cells containing a metallothionein promoter H-ras hybrid gene. Further, antibodies to peptide sequences encoded in the cDNA block the increase in locomotion resulting from induction of the mutant H-ras gene in this cell line. In a transblot assay, the bacterially expressed protein binds to biotinylated hyaluronan. Antibodies to peptides encoded in the cDNA react in immunoblot assays with the 58- and 52-kD proteins of a novel hyaluronan receptor complex previously implicated in cell locomotion. Furthermore, antibodies specific to the 58- and 52-kD proteins, which block ras-induced locomotion, also cross-react with the expressed, encoded protein. The gene product described here appears to be a new type of hyaluronan receptor that is involved in cell locomotion. It is named RHAMM, an acronym for receptor for hyaluronan-mediated motility.

3T3 Cells↗
PubMed1991

Toxicological investigation of liquid petroleum gas explosion: human model for propane/ethyl mercaptan exposures.

Four individuals died as the result of a propane explosion. As with many propane explosions, the question was raised as to the adequacy of the product's odorization after the autopsy studies had been conducted. In most cases, this question leads to litigation. Ethyl mercaptan is a widely used odorant for propane and was used in this instance. Three of the four victims had blood available at autopsy for study. Quantitative analyses of the victims' blood, obtained during autopsy, were performed using gas chromatography/mass spectrometry, without subjecting the samples to hydrolysis. These analyses determined the relative amounts of propane and ethyl mercaptan in the blood to be 90, 63, and 175 mL/m3 headspace, and 0.36, 0.34, and 0.77 microgram/L blood, respectively. Since mercaptans have been reported in human blood as products of metabolism, modeling studies were conducted to establish the validity of the autopsy data and to develop an autopsy toxicology protocol for investigating explosion deaths. When subjects were not exposed to an atmosphere containing ethyl mercaptan, dimethylsulfide was the only mercaptan detectable in their blood without severe hydrolysis prior to analysis. Metabolic ethyl mercaptan is sufficiently bound to be undetectable by the methods used without hydrolysis. Human subjects were exposed to a flammable mixture of air and propane odorized with ethyl mercaptan. The analyses of the blood from these subjects produced results which were comparable with those for the explosion victims, establishing that the question of odorant adequacy can be addressed at the autopsy of propane explosion victims. It is extremely important that the pathologist and toxicologist investigating gas explosion deaths recognize the valuable evidence existing in the victim's blood.

Autopsy↗
PubMed1990

AIDS and state developmental disability agencies: a national survey.

A survey of state developmental disability agencies was undertaken in October 1987 regarding AIDS policy development, education, and training and service provision. Of 44 states responding to the 27-item questionnaire, only 21 had formal AIDS policies. Policies varied considerably from state to state. Twenty-five of the responding states include information on AIDS in their staff training curriculum, with such training more likely to be provided to institutional staff than to community-based staff. Only 10 states reported AIDS prevention to be part of their client training programs, with training more likely to be found in institutional settings. Eleven states reported HIV positive cases, with such cases found more often in institutions than in community settings. Several states reported some type of segregation of HIV positive individuals. Policies, educational programming, and services to meet the special needs of persons with developmental disabilities are called for.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Experience with the sternocleidomastoid myoperiosteal flap for reconstruction of subglottic and tracheal defects: modification of technique and report of long-term results.

Subglottic or tracheal reconstruction may be required in cases of subglottic stenosis, invasive thyroid carcinoma, or trauma. The sternocleidomastoid myoperiosteal flap uses clavicular periosteum on a muscle pedicle to provide vascularity. Clavicular periosteum is fibrous, durable, and will conform to the shape of the trachea, forming bone to provide stability to the airway. The procedure is relatively simple and involves single-staged reconstruction. After 4 years' experience with this flap, we present the results from a series of 11 patients who underwent subglottic or tracheal reconstruction with the sternocleidomastoid myoperiosteal flap. Ten of 11 patients were successfully decannulated. The average time from reconstruction to decannulation was 50.3 days. Follow-up ranged from 12 to 40 months. We also describe modifications of the initial technique that have been introduced to improve the flap's versatility and effectiveness.

Adult↗
PubMed1988

Ultrasound findings in the adreno-genital syndrome (congenital adrenal hyperplasia).

The adreno-genital syndrome (congenital adrenal hyperplasia) is caused by deficiency of an enzyme (usually C-21 hydroxylase) necessary for adrenal production of cortisol, which results in excessive accumulation of androgenic precursors. It is the most common cause of female pseudohermaphroditism. There have been a few sporadic reports of ultrasonic demonstration of enlarged adrenals in the adreno-genital syndrome. To determine whether ultrasonography could be used to establish or exclude the diagnosis, ultrasonic examinations were performed on eight newborn infants with ambiguous genitalia who were subsequently proven to have the adreno-genital syndrome. The adrenals were found to be enlarged in three patients, at the upper limit of normal in three patients, and in two infants the adrenals were well within normal limits in size. The uterus was identified in seven of the eight patients, but was not seen for technical reasons in one. It is concluded that ultrasound is useful in the evaluation of infants with congenital adrenal hyperplasia to establish the presence of a uterus and to demonstrate enlargement of the adrenals, but it should be cautioned that finding adrenals of normal size does not exclude the diagnosis. Key words ultrasound, adreno-genital syndrome, congenital adrenal hyperplasia.

Adrenal Glands↗
PubMed1987

The effect of in utero exposure to hexachlorobenzene on the developing immune response of BALB/c mice.

BALB/c mice were exposed to 0.0, 0.5 and 5.0 mg/kg maternal body weight hexachlorobenzene (HCB) throughout gestation by daily per os dosing of the females. At 45 days of age selected immune functions of the offspring were assessed. The delayed-type hypersensitivity (DTH) response to oxazolone was severely depressed in animals exposed to either 0.5 or 5.0 mg/kg HCB, however, only those animals exposed to 5.0 mg/kg HCB showed a significant decrease in their mixed lymphocyte response (MLR) levels. The ability of isolated spleen cells to undergo a blastogenic response to concanavalin A (ConA), phytohemagglutinin (PHA) and lipopolysaccharide (LPS) showed no significant changes due to HCB exposure. Similarly, no significant difference in the induction of direct hemolytic plaque-forming cells was seen. A significant increase in the relative distribution of splenic T cells and a significant decrease in splenic B cells was measured in the offspring of HCB-treated females. These results suggest that HCB is capable of affecting the development or maturation of the immune response in mice, perhaps at the T cell level.

Animals↗
PubMed1985

Therapeutic implications of hypertension-induced glomerular injury. Comparison of enalapril and a combination of hydralazine, reserpine, and hydrochlorothiazide in an experimental model.

Systemic hypertension does not always reflect concomitant glomerular hypertension. At similar levels of systemic hypertension, glomerular injury occurs only in kidneys that lack protective preglomerular vasoconstriction, which results in glomerular hypertension. indeed, glomerular hypertension and glomerular injury do not develop in rats with spontaneous hypertension that have effective preglomerular vasoconstriction. In the experiments reported herein, the normal adaptive response (afferent arteriolar dilation) to a reduction of one and five-sixths of the renal mass in rats with spontaneous hypertension was examined to ascertain whether that response would expose the remaining nephrons to the injurious effects of high perfusion pressure. In addition, the efficacies of two different antihypertensive regimens were compared. Rats with spontaneous hypertension received either no therapy, or a combination of hydralazine, reserpine, and hydrochlorothiazide, or the angiotensin converting enzyme inhibitor enalapril. Three weeks after ablation of one and five-sixths of the renal mass, blood pressure, glomerular filtration rate, urinary protein excretion, and histologic injury scores for mesangial expansion and glomerulosclerosis were determined. Untreated rats with hypertension had severe glomerulosclerosis and mesangial expansion. Both antihypertensive regimens normalized systemic blood pressure and reduced glomerulosclerosis. However, enalapril was more effective than the combination of hydralazine, reserpine, and hydrochlorothiazide in reducing the exaggerated glomerular filtration rate (0.52 +/- 0.40 versus 0.82 +/- 0.10 ml per minute; p less than 0.05), the injury score for mesangial expansion (79 versus 103; p less than 0.05), and the degree of proteinuria (32 +/- 4 versus 42 +/- 3 mg per 24 hours; p less than 0.05). Persistence of hyperfiltration accompanied by increased mesangial expansion, may lead to progression of glomerular damage despite "adequate" control of systemic hypertension, as observed in rats treated with a combination of hydralazine, reserpine, and hydrochlorothiazide.

Animals↗
PubMed1983

Use of clonal assay in determination of urothelial drug sensitivity in carcinoma in situ of the bladder: clinical correlations in 5 patients.

Five patients with carcinoma in situ of the bladder, including 4 with associated grossly apparent tumors, were followed for 2 years or until invasive disease appeared while receiving intravesical chemotherapy. In vitro drug sensitivity determinations were made using the clonal assay. Of 9 retrospective and prospective in vitro/in vivo drug sensitivity correlations 7 proved correct. However, in vitro growth occurred in only 50 per cent of the urothelial samplings in which adequate cells were present. The assay has some potential use in selecting agents for intravesical chemotherapy but the problem of unpredictable and limited in vitro growth must be overcome.

Administration, Topical↗
PubMed1983

Red cell folate levels, food antibodies and reticulin antibodies in farmer's lung--is there an association with coeliac disease?

Indirect evidence of enteropathy has been sought in a group of 57 subjects with farmer's lung (FL) by clinical questionnaire, estimation of red cell folate levels, the presence of precipitating antibodies to various food antigens and detection of reticulin antibodies. One subject was found who had villous atrophy and responded clinically to gluten withdrawal. There were two subjects with low red cell folate levels and multiple food antibodies, and one subject with reticulin antibodies and multiple food antibodies. Enteropathy is infrequent in subjects diagnosed clinically as having farmer's lung but seems to be more common than would be expected by chance. The mechanism has yet to be elucidated.

Adolescent↗
PubMed1981

The effects of denervation on contractile properties or rat skeletal muscle.

1. Isometric contractions of fast and slow twitch muscles of rats were recorded 1-42 days after denervation. 2. The major changes occurred over the period from 2 to 6 days after denervation. These changes were qualitatively similar in the two types of muscle. The most important effects were on the twitch: times to peak and half relaxation were prolonged, active tension and peak rate of rise of tension were increased. Tetanic tension per unit cross-sectional area and the maximum rate of rise of tension decreased during this period but, in the second week, the tension recovered substantially and the maximum rate recovered completely. 3. Very small differences were seen between muscles denervated with short and long nerve stumps at day 4. 4. In the late stage of denervation (7-42 days) twitch and tetanic tension fell more than cross-sectional area, but this may have been due to greater atrophy of fibres compared with other muscle tissue. 5. Apart from this tension fall, there were only small changes in the fast muscle in the late stage of denervation. These were a fall in twitch-tetanus ratio and a prolongation of relaxation. 6. In more than half of the soleus muscles there was a late reversal of some of the denervation changes, and these muscles showed a greater degree of atrophy. The less atrophied soleus muscles maintained a prolonged twitch and a low rate of development of tension. 7. It is concluded that denervation affects the contractile properties of muscle as early and as abruptly as it does the membrane properties, and that most of the contractile changes are a direct consequence of changes in excitation-contraction coupling alone.

Animals↗
PubMed1980

Carbon dioxide laser treatment of laryngeal stenosis.

Six patients ranging from 3 to 67 years of age were treated for acquired laryngeal stenosis. Five of these patients were considered failures from conventional surgical techniques including multiple open endolaryngeal procedures and repeated dilations. Using the carbon dioxide laser, the various obstructing lesions were excised microendoscopically and injected with interstitial steroids. After one to six procedures, all of these patients now have adequate airways and serviceable voices.

Adult↗
PubMed1980

Personality adjustment of children and adolescents with hypopituitarism.

Sixteen children and adolescents with extreme short stature secondary to hypopituitarism were compared to a matched group of physically healthy peers on a variety of psychological tests assessing general adjustment, body image, sex role development, sex-related fantasy, and reactions to frustration. With the exception of their reactions to frustrations, the psychological adjustment of children with hypopituitarism compared favorably with that of normal children. Children with hypopituitarism typically perceived less adaptive, mature solutions to frustrating situations than did peers of average stature. Anticipatory guidance for children with extreme short stature might help facilitate more adaptive responses to the difficult and inevitable frustrations imposed by short stature. Evaluations of intervention directed toward the enhancement of coping skills and life adjustment of children with small stature due to hypopituitarism is seen as a focus for future research with this population.

Adaptation, Psychological↗