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Biomedical subjects

S M Harris

Publications and source records attributed to S M Harris.

17 recordsLinked to original sources
PubMed2005

Antitumour activity of XR5944 in vitro and in vivo in combination with 5-fluorouracil and irinotecan in colon cancer cell lines.

XR5944 (MLN944), a novel bis-phenazine, has demonstrated potent cytotoxic activity against a variety of murine and human tumour models. In the present study, the antitumour activity of XR5944 was investigated in combination with 5-fluorouracil (5-FU) or irinotecan in human colon carcinoma cell lines and xenografts. In vitro cytotoxicity of the combinations following exposure to the drugs sequentially or simultaneously was evaluated by the sulphorhodamine-B assay and interactions were determined using median-effect analysis. Antagonism was observed (CI >1) following exposure of HT29 cells simultaneously to XR5944 and 5-FU or SN38 (active metabolite of irinotecan). In contrast, sequential exposure of either combination in either order demonstrated at least an additive response (CI< or =1). At least an additive response was also observed with these combinations in HCT116 cells regardless of schedule. Antitumour activity in HT29 xenografts in nude mice was enhanced by sequential administration of 5-FU (65 mg kg(-1)) or irinotecan (CPT-11) (35 mg kg(-1)) 48 h before XR5944 (5, 10, or 15 mg kg(-1)) compared to single agent treatment at the same or higher doses. Administration of irinotecan (35 mg kg(-1)) and XR5944 (15 mg kg(-1)) just 30 min apart yielded similar efficacy to sequential administration 48 h apart. All combinations were well tolerated. These data suggest that combinations of XR5944 with irinotecan or 5-FU are of significant interest in the treatment of colon cancer.

Animals↗
PubMed2001

Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators.

The comparative antihypertensive efficacy and tolerability of the angiotensin II receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine were evaluated in an 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study in 251 adult patients (45% women, 16% black) with mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period, patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily. After 4 weeks of double-blind treatment, patients were uptitrated to candesartan cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant differences between the candesartan cilexetil and amlodipine regimens for reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients on candesartan cilexetil and 87% of those on amlodipine were controlled (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil discontinued treatment, compared with 9.4% of patients on amlodipine, including 2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema, respectively. Peripheral edema, the prespecified primary tolerability end point, occurred with significantly greater frequency in patients on amlodipine (22.1%; mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and amlodipine are both highly effective in controlling BP in patients with mild hypertension. Candesartan cilexetil offers a significant tolerability advantage with respect to less risk of developing peripheral edema.

Amlodipine↗
PubMed2001

Antisocial personality, substance abuse, and exposure to parental violence in males referred for domestic violence.

This study investigated whether childhood disruptive behavior (hyperactivity, oppositional-defiance, conduct problems) plus adult psychopathic adjustment are associated with domestic violence. Adult males (n = 66) in diversion programs completed the Wender Utah Rating Scale (WURS), MMPI Psychopathic Deviate scale (PD), Conflict Tactics Scales representing themselves and their parents, and substance use measures. Substance use and lifespan antisocial personality (measured by high WURS and PD scores) were robust predictors of verbal and moderate physical domestic abuse. Violence in the family of origin was associated with abuse when tested alone, but failed to exhibit unique association with abuse when other predictors were taken into account. The possibility that antisocial batterers respond to contingencies by moderating physical harm, while persisting at psychological harm, is discussed.

Adolescent↗
PubMed2000

Save the young--the elderly have lived their lives: ageism in marriage and family therapy.

The paucity of literature addressing mental health issues concerning geriatric populations represents the perpetuation of ageist practices and beliefs in the field of marriage and family therapy. The purpose of this study was to assess whether client age and clinical training relate to the evaluation of couples who present for conjoint therapy. Written vignettes describing two couples, one older and one younger, who report issues involving the absence of sexual intimacy, increased frequency of arguments, and increased use of alcohol were evaluated by practicing marriage and family therapists, therapists-in-training, and individuals with no clinical background. It was hypothesized that respondents' views would vary in connection with the age of the couple and with the three levels of participant training. Results indicate that client age and participant training are associated with perceptions of individual and couple functioning. Our findings suggest that the relational and mental health concerns experienced by elder couples are not perceived as seriously as are identical concerns experienced by younger couples. Contrary to our expectations the observed differences between views of the two age conditions did not significantly differ between levels of participant training. Training and experience in marriage and family therapy may not significantly mitigate vulnerability to age-discrepant views.

Adult↗
PubMed1999

Retrospective report on the effectiveness of a polyurethane football helmet cover on the repeated occurrence of cerebral concussions.

This report reviews the literature and unpublished data and presents survey results related to the use of a polyurethane football helmet cover. Two hundred forty-five individuals, identified by the helmet manufacturer as having purchased at least one device, were sent a survey after the 1992, 1993, and 1994 football seasons; 155 (63.3%) of the surveys were returned. The questionnaire, designed to be completed by the athlete, required a detailed history of concussions occurring both prior to and during the period the device was used. Individuals used the device as a result of having incurred at least one concussion. Rates of concussion reoccurrence while the device was worn were grouped by the number of previous concussions (1, 2, 3, or 4+) that occurred over a 4year period prior to use of the device. The rate of concussion reoccurrence was 2.4%, 7.3%, 15.8%, and 33.3%, respectively, over a 4-year period. The range appeared to reflect a parallel relationship between pre- and post-device concussion experiences: the more concussions experienced prior to adopting the device, the higher the rate of concussion reoccurrence while using the device. The natural history of repeated occurrences of concussive events may not be affected by the use of a polyurethane football helmet cover. We suggest that such a device not be routinely used prophylactically, but instead be reserved for individuals with 1 to 2 prior concussion injuries. However, at this time, we neither recommend nor discommend the device.

Adolescent↗
PubMed1998

Therapist physical attractiveness: an unexplored influence on client disclosure.

Existing research indicates that clients perceive facially attractive therapists as more competent, trustworthy, genuine, and effective than less attractive therapists. No studies exist to help explain how the therapist's attractiveness influences a client's self-disclosure. Participants (n = 241) were randomly assigned to one of eight experimental groups to test the interaction of the therapist's attractiveness, client's gender, the nature of presenting problem, and the client's comfort with disclosing in a hypothetical couple therapy scenario. Analysis of variance procedures established that most participants reported feeling more comfortable disclosing a benign (communication) problem than a potentially embarrassing (sexual) problem, and more comfortable disclosing problems to an attractive than to a less attractive female therapist. Therapists are encouraged to understand the power attractiveness may have in their own and their clients' lives.

Adolescent↗
PubMed1997

Stress and illness in adolescence: issues of race and gender.

There is an abundance of information on the association between stressful life events and illness within the adult population. In contrast, research on this relationship among adolescents is limited. This study evaluated the role of individual differences (gender and race) on the stress-illness relationship within the adolescent population. Participants were 119 adolescents (54 females and 65 males), recruited from two public high schools located in the southeast, who were administered four questionnaires designed to measure levels of stress, anxiety, and illness. Overall, correlational analysis revealed that stress and anxiety were positively correlated with reported illness. However, racial and gender differences did emerge. Although no gender differences were found with regard to the experience of stress, African-American athletes reported a higher frequency of stressful life events than did their Euro-American counterparts. Further, African-American adolescents reported a lower frequency of illness than did the Euro-Americans. Females reported more illnesses than did males. Possible explanations for individual differences in reported stress and illness are discussed.

Adolescent↗
PubMed1995

The receptor binding affinity of monocyclic [Ala3,Xaa11]endothelin-1 analogs correlates with inducible helix length.

Endothelin-1, a bicyclic 21-amino acid peptide with disulfide bridges between cysteines 1 and 15 as well as between cysteines 3 and 11, has been reported to be partially helical based on both CD and NMR data. However, this remains an area of controversy with some claims that CD data indicate no alpha-helical structure (Calas, B.; Harricane, M.-C.; Gulmard, L.; Heitz, F.; Mendre, C.; Chabrier, P.E.; Bennes, R. Peptide Res. 1992, 5, 97) and a recent X-ray crystal structure placing the helix at a different locus (Janes, R.W.; Peapus, D.H.; Wallace, B.A. Structural Biology 1994, 1, 311). The CD studies reported herein indicate that the helical structures reported in NMR studies (e.g. Andersen, N.H.; Chen, C.; Marschner, T.M.; Krystek, Jr. S.R.; Bassolino, D.A. Biochemistry 1992, 31, 1280) apply to pure aqueous media as well. The helix located from Lys9 to the Cys15/His16 juncture is ca 75% populated in pH 4 aqueous buffer. Titration difference CDs reveal that the helix extent increases by one to two residues and that the 'helical conformation' is more completely populated upon addition of TFE to 50+ volume-%. Comparison with a more helical analog suggests that the helix propagates towards (but not to the end of) the C-terminus upon fluoroalcohol addition. A variety of monocyclic derivatives of [Nle7] ET-1 lacking the 3,11-disulfide were evaluated for biological activity and examined by TFE titration difference CD. The series included an Aib11 and a Pro11 analog. The helix promoting Aib analog was the most active while the Pro analog exhibited significantly lower vasoconstrictor activity and binding affinity for the ETA receptor. All of the monocyclic analogs became significantly more helical upon addition of fluoroalcohols. The inclusion of a proline residue at position 11 does not preclude helix formation upon addition of fluoroalcohols. Rather, helix formation is relatively easily induced but limited to a 5 residue span. Apparently this is insufficient to orient required side chains optimally for interaction with the ETA receptor. For the 1,15-monocyclic analogs differing only at position 11, ETA binding affinity and vasoconstrictor potency correlate with the facility which a 7-8 residue long helix can be induced. This presumably includes the segment Glu10-->Cys15 in all cases and may represent the full sequence from Lys9-->His16. CD studies also reveal that the C-terminal fragment of endothelins is not a fully disordered 'random coil' either alone or attached to the endothelin core.

Amino Acid Sequence↗
PubMed1994

Beta-structure in human amylin and two designer beta-peptides: CD and NMR spectroscopic comparisons suggest soluble beta-oligomers and the absence of significant populations of beta-strand dimers.

Intensity variation for the positive far UV CD band was observed for three 'beta-sheet' peptides. In 6% HFIP, an amyloidogenic species (human pancreatic amylin) displays, on standing, an extremely intense 192-nm band which diminishes upon physical agitation. A concurrently formed Tyr sidechain band at 274 nm disappears completely with agitation, linking the enhancement of the 192-nm band to the highly ordered stacking of beta-sheets. NMR studies indicate that the beta-states of the three peptides are oligomeric, not beta dimers. A membrane-forming EAK peptide displays NMR peaks due to the low concentration of 'random coil' monomers present in slow equilibrium with beta-oligomers; solutions of a more hydrophobic ELKA peptide, which displays an intense 195-nm band, contain only oligomeric species. NMR studies at 25% HFIP revealed the structural requirements for inhibition of beta-oligomer formation.

Amino Acid Sequence↗
PubMed1994

Racial differences in predictors of college women's body image attitudes.

African-American and Euro-American women from three predominantly Euro-American colleges in the southeast U.S. between 17 and 23 years of age completed instruments assessing body image attitudes, social competence, sex-role attitudes, racial identity, and a measure of family and personal characteristics. Analyses revealed race differences on all body image measures with the exception of appearance evaluation which was influenced by family income and race. Specifically, African-American women reported more satisfaction with and positive feelings towards their bodies and less dissatisfaction than Euro-American women. Unlike Euro-Americans, African-American women attached importance to fitness and health. The relationship between personal/physical factors and body image was stronger for African-American than Euro-American women. Additionally, personal/physical characteristics were the best model of appearance evaluation for African-American women, whereas personal/physical and sociodemographic factors best predicted this measure for Euro-American women. The results are discussed in relation to body image norms and standards of the African-American subculture and middle-class, Euro-American mainstream culture.

Adolescent↗
PubMed1993

Attenuation of AMPA-induced neurotoxicity by a calpain inhibitor.

The effects of a membrane-permeable inhibitor of calpain, Cbz-Val-Phe-H, were examined in an in vitro model of neurotoxicity. Cerebellar slices from young rats were treated with the glutamate receptor agonist, amino-3-hydroxy-5-methyl-4-isoazole propionic acid (AMPA), and cytotoxicity was quantified using conventional histological techniques. Slices treated with AMPA exhibited damage to 83.0% of cerebellar Purkinje cells. In contrast, only 23.6% of Purkinje cells were damaged in slices treated with Cbz-Val-Phe-H and AMPA. These findings indicate that calcium-activated proteolysis is a critical event in AMPA-induced toxicity, and provide evidence that calpain inhibitors are capable of attenuating this form of excitotoxic damage in the central nervous system.

Amino Acid Sequence↗
PubMed1988

Thyrotropin releasing hormone, cholecystokinin and endogenous opioids in the modulation of spinal reflexes in the rabbit.

Electrical stimulation of the sural nerve of the rabbit evokes reflexes in the ipsilateral ankle extensor gastrocnemius medialis and in the knee flexor semitendinosus which are differentially modulated by endogenous opioids. Intravenous injection of the putative functional opioid antagonist, thyrotropin releasing hormone (TRH) or its analogue RX77368, caused the extensor response to double in size and the flexor reflex to increase to 1.5-1.7 times pre-drug controls. The opioid RX77368 had no effect on the naloxone-reversible inhibition of the gastrocnemius reflex which followed tetanic stimulation of the fine afferent fibres of the common peroneal or sural nerves. The cholecystokinin antagonist proglumide, which has been shown to enhance the actions of endogenous opioids in some species, had no effects on either reflex. It is possible that TRH acts as an excitatory neurotransmitter or modulator in the spinal cord of the rabbit opposing, but not blocking, the actions of endogenous opioids.

Animals↗
PubMed1983

Synapsin I (Protein I), a nerve terminal-specific phosphoprotein. II. Its specific association with synaptic vesicles demonstrated by immunocytochemistry in agarose-embedded synaptosomes.

Synapsin I (protein I) is a major neuron-specific endogenous substrate for cAMP-dependent and Ca/calmodulin-dependent protein kinases that is widely distributed in synapses of the central and peripheral nervous system (De Camilli, P., R. Cameron, and P. Greengard, 1983, J. Cell Biol. 96:1337-1354). We have now carried out a detailed analysis of the ultrastructural localization of synapsin I in the synapse. For this purpose we have developed a novel immunocytochemical technique that involves the labeling of isolated synaptosomes immobilized in a thin agarose gel. Special fixation conditions were designed to maximize accessibility of synapsin I to marker molecules. Immunoferritin and immunoperoxidase studies of this preparation indicated that synapsin I is localized in the presynaptic compartment and that it is present in close to 100% of all nerve endings. Immunoferritin labeling also indicated that, inside the nerve ending, synapsin I is specifically associated with the cytoplasmic surface of synaptic vesicles. In agreement with these immunoferritin results, the labeling produced by immunoperoxidase was compatible with a specific association of synapsin I with synaptic vesicle membranes. However, at variance with the very specific distribution of immunoferritin, immunoperoxidase reaction product was also found on other membranes of the terminals, presumably as a result of its diffusion over a short distance from the synaptic vesicles. Anti-synapsin I immunoperoxidase staining of tissue sections for electron microscopy produced an uneven labeling of terminals of the neuropile, in agreement with results of a previous study (Bloom, F. E., T. Ueda, E. Battenberg, and P. Greengard, 1979, Proc. Natl. Acad. Sci. USA. 76:5982-5986). A comparison with results obtained in isolated synapses indicates that the limited labeling of nerve endings in tissue sections results from limited and uneven penetration by marker molecules. The specific association of synapsin 1 with synaptic vesicle membranes in the great majority of nerve terminals suggests a prominent role for this phosphoprotein in the regulation of synaptic vesicle function.

Agar↗
PubMed1975

Palytoxin: effects on contractility and 45Ca2+ uptake in isolated ventricle strips.

Palytoxin (PTX) inhibited phasic tension production and initiated tonic contracture in isolated paced ventricle strips at concentrations greater than 10(-10) M. PTX-induced contracture was associated with increased 45Ca2+ uptake. PTX-induced additional 45Ca2+ uptake was completely blocked by 2 mM La3+. All observed PTX effects were enhanced by elevation of [Ca2+] o from 1.9 to 6 mM and this threefold increase in [Ca2+] o resulted in a threefold increase in isotope-determined Ca2+ uptake in presence of 10(-8) M PTX. It is concluded that the observed effects of PTX could be mediated by an increase in calcium permeability of myocardial cells.

Acrylamides↗