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Biomedical subjects

D Harris

Publications and source records attributed to D Harris.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of acute myelogenous leukemia blast proliferation by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors.

Interleukin-1 (IL-1) has recently been reported to play an important role in acute myelogenous leukemia (AML) blast proliferation. We therefore investigated the effect of soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) on the growth of AML bone marrow blast progenitors from 25 patients. In the AML blast colony culture assay, sIL-1R and IL-1RA inhibited blast colony-forming cell replication in a dose-dependent fashion, at concentrations ranging from 10 to 500 ng/mL (sIL-1R) and 10 to 1,000 ng/mL (IL-1RA), and their inhibitory effect was partially reversed by IL-1 beta. A similar inhibitory effect was also noted with the use of anti-IL-1 beta neutralizing antibodies. When AML blast progenitors were grown either in the presence of fetal calf serum (FCS) alone or with one of the following: phytohemagglutinin leukocyte-conditioned medium (PHA-LCM), granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, interleukin-3 (IL-3), or stem cell factor (SCF), addition of 100 ng/mL sIL-1R or IL-1RA inhibited blast colony formation by 3% to 96% and 2% to 97%, respectively. In sharp contrast, neither of these IL-1-inhibitory molecules significantly inhibited proliferation of normal marrow hematopoietic progenitors. Lysates of 2 x 10(7) low-density AML marrow cells were tested for intrinsic IL-1 beta content using an enzyme-linked immunoadsorbant assay (ELISA). Samples from five of six patients showed high concentrations (ranging from 501 to 2,041 pg), whereas 2 x 10(7) cells from two normal marrow aspirates yielded 54.6 pg of IL-1 beta. AML blast colony-forming cells from all six patients were inhibited by sIL-1R, IL-1RA, or both. Incubation of nine samples of AML low-density cells with either sIL-1R or IL-1RA reduced GM-CSF concentrations in cell lysates, and supernatants from nine (P less than .01) and six samples (P less than .037), respectively, and G-CSF concentration in lysates from six of nine samples (P less than .03), and in supernatants from five of six samples (P less than .06) when studied by ELISAs. Our data implicate IL-1 in AML blast proliferation and suggest the potential benefits of using IL-1-inhibitory molecules in future therapies for AML.

Adult↗
PubMed1992

Drug delivery via the mucous membranes of the oral cavity.

The delivery of drugs via the mucous membranes lining the oral cavity (i.e., sublingual and buccal), with consideration of both systemic delivery and local therapy, is reviewed in this paper. The structure and composition of the mucosae at different sites in the oral cavity, factors affecting mucosal permeability, penetration enhancement, selection of appropriate experimental systems for studying mucosal permeability, and formulation factors relevant to the design of systems for oral mucosal delivery are discussed. Sublingual delivery gives rapid absorption and good bioavailability for some small permeants, although this site is not well suited to sustained-delivery systems. The buccal mucosa, by comparison, is considerably less permeable, but is probably better suited to the development of sustained-delivery systems. For these reasons, the buccal mucosa may have potential for delivering some of the growing number of peptide drugs, particularly those of low molecular weight, high potency, and/or long biological half-life. Development of safe and effective penetration enhancers will further expand the utility of this route. Local delivery is a relatively poorly studied area; in general, it is governed by many of the same considerations that apply to systemic delivery.

Administration, Buccal↗
PubMed1992

Microscopic epididymal sperm aspiration (MESA): a new option for treatment of the obstructive azoospermia associated with cystic fibrosis.

Cystic fibrosis is a life-threatening disease. Only recently has the prognosis improved. In the male patient there is an almost invariable absence or maldevelopment of the vas deferens, creating a situation of obstructive azoospermia. Consequently, their fertility potential has been considered nonexistent. Having gained experience in microscopic epididymal sperm aspiration coupled with the advanced reproductive technologies for the treatment of congenital absence of the vasa, we sought to extend this treatment option to the male cystic fibrosis population. An Indian male with clinically evident and genetically confirmed cystic fibrosis underwent microscopic retrieval of epididymal sperm. The anatomy of the epididymis and the quality of sperm obtained were similar to those patients with congenital absence of the vas deferens. After appropriate spousal genetic testing, superovulation, and transvaginal oocyte retrieval, in vitro insemination of sperm was performed. Fifty percent of the oocytes were subjected to partial zona dissection and a single embryo resulted. Subsequent to transfer, no conception was realized but the effort expanded the clinical usefulness of microscopic epididymal sperm aspiration. This should open up an avenue of treatment for couples in whom only the most dire predictions for fertility have been made to date.

Adult↗
PubMed1992

Localization of sequence-determined neoepitopes and neutrophil digestion fragments of C-reactive protein utilizing monoclonal antibodies and synthetic peptides.

We recently described 17 anti-CRP mAb, seven to native- (or conformational) and 10 to neo- (or sequence-determined) epitopes, including several anti-neo-CRP mAb specific for CRP peptide 199-206. In the present study, four new anti-native- and four new anti-neo-CRP mAb were generated and characterized by ELISA reactivity with native and modified human and rabbit CRP, as well as binding to pronase fragments of human CRP in Western blots. Assays with 17 synthetic CRP peptides identified anti-neo-CRP mAb specific for peptides 1-16, 14-24 and 137-152, respectively. The anti-neo-CRP mAb were reacted with fragments obtained by digesting CRP with multiple additional enzymes, including Staphylococcal V8 protease, trypsin, elastase, plasmin, thrombin and alpha-chymotrypsin. Native CRP was remarkably resistant to enzymic digestion, particularly in the presence of calcium, but was readily cleavable upon denaturation. Twenty-three informative fragments served to further distinguish mAb reactivity with at least four additional neo-CRP epitopes, which presumptively included residues in the regions of amino acids 22-45, 41-61, 114-121 and 130-138, respectively. The eight epitopes identified corresponded well with predicted regions of CRP antigenicity. In addition, at least six distinct native or conformation-determined epitopes were delineated. Reactivity of the anti-neo-CRP mAb with fragments of CRP generated by PMN enzymes indicated that regions sensitive to cleavage by neutrophil enzymes are located at approximately 3, 10 and 16 kD from the amino terminus of the CRP subunit. We expect that the anti-CRP mAb described and mapped herein will be useful tools for the elucidation of CRP structure and function.

Antibodies, Monoclonal↗
PubMed1992

Morningness versus eveningness arousal patterns in young adults.

The preference for morning versus evening time for activities requiring alertness was investigated. Responses from 9 individuals categorized as "owls" and 7 classed as "larks" based on their scores on the Morningness Versus Eveningness Questionnaire were compared to a group of 11 classified as "neither" on measures of sleep attitude and personality factors of arousal. No statistically significant differences were found; however, an item analysis yielded a statistically significant difference among the groups' responses on questions involving personal choices of sleep/wake schedules. This distinguishing aspect between the groups denotes the utility of subjective measures of preference. Our findings complement those from other subjective and experimental studies of "owls" and "larks" and add the important dimension of inquiring about personal preferences of subjects.

Adolescent↗
PubMed1992

Lingual vibrotactile threshold and suprathreshold responses of normal-speaking black and white young adults.

A paradigm for studying oral sensory tactile function through use of single frequency vibration applied to the dorsal surface of the tongue was administered to a group of 10 young black women and 10 young white normal-speaking women. Analyses showed no differences between groups with regard to lingual vibrotactile threshold of sensitivity or suprathreshold magnitude-estimation scaling responses.

Adult↗
PubMed1992

Hearing threshold shift during auditory magnitude estimation.

The purpose of the present experiment was to determine the extent of hearing threshold shift that may occur during an auditory magnitude-estimation task involving stimulus intensities as great as 80 dB sensation level. Also, possible influences of hearing threshold shift on numerical magnitude-estimation responses and magnitude-function slopes were investigated. Results indicated that hearing threshold shift was insignificant (1-2 dB). Consistent small increases in numerical magnitude responses were observed on a magnitude-estimation task where hearing thresholds were retested between stimulus presentations versus a magnitude-estimation task where hearing thresholds were not retested. The stability of auditory magnitude functions across different conditions in the current investigation was in agreement with vibrotactile magnitude-scaling behavior observed by Fucci, et al. in 1989 and 1991. The over-all results supported the concept of an absolute, internal sensory-scaling mechanism being operable during magnitude estimation of auditory stimuli as discussed by Zwislocki and Goodman in 1980.

Adolescent↗
PubMed1991

Suppression of chronic myelogenous leukemia colony growth by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors: a novel application for inhibitors of IL-1 activity.

In this study, we investigated the role of interleukin-1 beta (IL-1 beta) in the malignant evolution of chronic myelogenous leukemia (CML) and the functional activity of IL-1 inhibitors. Bone marrow (BM) and peripheral blood (PB) low-density cells from 38 CML patients were studied in the colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte colony culture assay. Samples from patients with early stage, interferon-alpha (IFN)-sensitive disease formed hematopoietic colonies in the presence of fetal calf serum (FCS), erythropoietin (Epo), and one of the following: granulocyte-macrophage colony-stimulating factor (10 ng/mL), IL-3 (15 ng/mL), both, or phytohemagglutinin-conditioned medium. The addition of IL-1 beta augmented IFN-sensitive CML colony growth in a dose-dependent manner at concentrations of 10 to 100 U/mL. In sharp contrast, addition of the above growth factors did not augment the colony growth-promoting effect of FCS and Epo in samples from IFN-resistant patients; further, adherent cell fractionation or T-lymphocyte depletion attenuated the "autonomous" colony growth. Lysates of 2.5 x 10(7) low-density cells from each of six IFN-resistant and six IFN-sensitive CML patients and three normal volunteers were tested for intrinsic IL-1 beta content in an enzyme-linked immunosorbent assay and yielded a mean of 610 pg, 54.6 pg, and 49.4 pg of IL-1 beta, respectively (P less than .045). Interestingly, both soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) at concentrations of 5 to 100 ng/mL (sIL-1R) and 10 to 500 ng/mL (IL-1RA) inhibited CML colony growth in a dose-dependent fashion, with maximal inhibition of 64% and 65%, respectively. A similar effect was noted with the use of anti-IL-1 beta neutralizing antibodies. These data implicate IL-1 beta in CML disease progression and suggest that the inhibitory effects of molecules such as sIL-1R and IL-1RA could conceivably be the basis of a novel therapeutic strategy against this disorder.

Adolescent↗
PubMed1991

Magnitude estimation and cross-modal matching of auditory and lingual vibrotactile sensation by normal speakers and stutterers.

The present experiment was a preliminary attempt to employ the psychophysical scaling methods of magnitude estimation and cross-modal matching to investigate suprathreshold auditory and lingual vibrotactile sensation magnitude responses for normal-speaking young adults (N = 20) and young adult stutterers (N = 7). A 1000-Hz binaural auditory stimulus and a 250-Hz lingual vibrotactile stimulus were employed for both procedures. Results indicated that the stutterers tended to use more restricted response ranges than the normal speakers for auditory magnitude scaling, and lower response ranges than the normal speakers for lingual vibrotactile magnitude scaling.

Adolescent↗
PubMed1991

The effects of two anti-vertigo drugs (betahistine and prochlorperazine) on driving skills.

1. The effects of betahistine 72 mg three times daily, prochlorperazine 5 mg three times daily and placebo taken for 3 days before testing were compared on two actual driving tasks (weaving and gap estimation) and two psychomotor tasks (reaction time and kinetic visual acuity) in normal subjects in a double-blind prospectively randomised cross-over study. 2. The psychomotor effects of betahistine could not be distinguished from those of placebo. 3. Prochlorperazine impaired driving performance causing increased carelessness and slowing on the weaving test. 4. There was little subjective appreciation of impairment whilst taking prochlorperazine.

Adult↗