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Biomedical subjects

M L Cooper

Publications and source records attributed to M L Cooper.

At least 55 records · Page 3Linked to original sources

Skin color, ancestry, and blood pressure among whites in Erie County, New York.

This study examines (1) the construct validity of a rank-order skin color measure and (2) interrelationships of skin color, ancestry, and blood pressure in a random survey of 763 white non-Hispanic and white Hispanic household residents in Erie County, NY. Skin color was significantly lighter among older respondents (P < .001) and among females (P < .0001). Skin color was lightest among Northern Europeans and darkest among Mediterraneans and white Hispanics (P < .0001). Higher systolic blood pressure was significantly associated with both darker skin color (P < .05) and northern European ancestry (P < .05). Several mechanisms to account for these findings are proposed.

Adult↗

Serotonin receptor subtype antagonists in the medial ventral medulla inhibit mesencephalic opiate analgesia.

Supraspinal opioid analgesia is mediated in part by connections between the midbrain periaqueductal gray (PAG) and the ventral-medial medulla, including the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis (NRGC). A serotonergic synapse appears to participate in this pathway since methysergide microinjected into the NRM-NRGC significantly reduced morphine analgesia elicited from the PAG. The present study evaluated the role of specific serotonin receptor subtypes by pretreating rats with microinjections of either the 5HT2 antagonist, ritanserin or the 5HT3 antagonist, ICS205930, into the NRM-NRGC and examining their effects upon morphine (2.5 micrograms) analgesia elicited from the PAG. Mesencephalic morphine analgesia was significantly reduced following pretreatment with both ritanserin (0.25-2.5 micrograms) on the tail-flick (81%) and jump (65%) tests and ICS205930 (0.25-5 micrograms) on the tail-flick (91%) and jump (63%) tests. Neither ritanserin nor ICS205930 altered basal nociceptive thresholds. Medullary placements ventral or lateral to the NRM/NRGC failed to support these antagonistic effects. These data indicate that ventro-medial medullary 5HT2 and 5HT3 serotonergic receptors modulate the transmission of opioid pain-inhibitory signals from the PAG.

Animals↗

Inhibition of mesencephalic morphine analgesia by methysergide in the medial ventral medulla of rats.

The neural substrates of endogenous supraspinal opioid pain inhibition are mediated in part by connections between the midbrain periaqueductal gray (PAG) and the ventral-medial medulla, including the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis (NRGC). To ascertain whether a serotonergic synapse participated in this pathway, the present study determined whether microinjections of methysergide into the NRM or NRGC would alter analgesia elicited by morphine microinjections into the PAG. Morphine (2.5 micrograms) in the PAG and immediately adjacent areas produced significant analgesia on the tail-flick and jump tests in rats. Pretreatment with the serotonin receptor antagonist methysergide (0.5-5 micrograms) in either the NRM or NRGC significantly reduced morphine analgesia elicited from the PAG by 69% on the tail-flick and by 50% on the jump tests without altering basal nociceptive thresholds. Medullary placements ventral or lateral to the NRM/NRGC failed to support this antagonistic effect. These data indicate that a ventro-medial medullary serotonergic synapse participates in the transmission of opioid pain-inhibitory signals from the PAG.

Animals↗

Stress and alcohol use: moderating effects of gender, coping, and alcohol expectancies.

A stressor vulnerability model of stress-induced drinking was tested in a stratified random sample of 1,316 Black and White adult drinkers. Stressors were highly predictive of both alcohol use and drinking problems among men who relied on avoidant forms of emotion coping or held strong positive expectancies for alcohol's effects and accounted for more than 35% of the variance in alcohol use among the subgroup of men who were high in both vulnerability factors. In contrast, stressors were negatively related among men who were low in both and were unrelated among women regardless of their coping or expectancies. These findings suggest that tension reduction theories of alcohol use are overly broad and that individual characteristics must be considered to account for stress-related effects on alcohol use and abuse.

Adaptation, Psychological↗

Antecedents and outcomes of work-family conflict: testing a model of the work-family interface.

A comprehensive model of the work-family interface was developed and tested. The proposed model extended prior research by explicitly distinguishing between work interfering with family and family interfering with work. This distinction allowed testing of hypotheses concerning the unique antecedents and outcomes of both forms of work-family conflict and a reciprocal relationship between them. The influence of gender, race, and job type on the generalizability of the model was also examined. Data were obtained through household interviews with a random sample of 631 individuals. The model was tested with structural equation modeling techniques. Results were strongly supportive. In addition, although the model was invariant across gender and race, there were differences across blue- and white-collar workers. Implications for future research on the work-family interface are discussed.

Adaptation, Psychological↗

Sociodemographic correlates of alcohol consumption among African-American and white women.

Correlates of abstention and heavier drinking were examined among 654 African-American and 474 white women, aged 19-70+, from a representative sample of households in Erie County, New York. Discriminant function analysis was employed to investigate the relationship between alcohol consumption and race, age, church attendance, family history of alcohol problems, household density, marriage, socioeconomic status (SES), employment and parity. Abstention was compared with drinking, and light/moderate drinking was compared with heavier drinking in the total sample and within each race. Compared to drinkers, abstainers were older, more religious, more likely to be African-American, or to be of lower SES. Racial differences in the correlates of abstention were found with respect to church attendance (positive association in African-Americans only), SES (negative association in African-Americans only), and household density (positive association in whites only). Compared to light/moderate drinkers, heavier drinking women were younger, less religious, more likely to be white, to have a positive family history, or to live in less crowded households. Racial differences in the correlates of heavier drinking were found with respect to church attendance (negative association in African-Americans only), parity (positive association in African-Americans only), and marital status (more heavier drinking among unmarried white women). Racial differences in the correlates of alcohol consumption document the need for further examination of the culture-specific determinants of women's drinking patterns.

Adult↗

Evaluation of a biodegradable matrix containing cultured human fibroblasts as a dermal replacement beneath meshed skin grafts on athymic mice.

Meshed, expanded split-thickness skin grafts (MSTSG) frequently achieve poor results when used to cover full-thickness wounds. Poor cosmetic and functional results occur in part because the epithelium that grows across the skin graft interstices lacks a dermis. We used a living dermal replacement composed of either polyglycolic acid (PGA) or polyglactin-910 (PGL) mesh containing confluent, cultured human fibroblasts. These grafts were applied to full-thickness wounds on athymic mice; widely expanded, 3:1 ratio human MSTSG was then placed over the dermal graft. Histologic examination of wounds during a 99-day period after graft placement showed that PGA/PGL-fibroblast grafts vascularized to the wound, and the MSTSG simultaneously vascularized to the PGA/PGL-fibroblast graft. Epithelialization from the MSTSG bridges proceeded rapidly across the surface of the PGA/PGL-fibroblast grafts, resulting in an epithelialized layer that covered a densely cellular substratum that resembled dermis. Basement membrane formation at the dermal-epidermal junction of the epithelialized interstices was confirmed by immunohistochemical microscopy. Minimal inflammatory reaction to the PGA/PGL-fibroblast grafts was seen. Grafts composed of PGA or PGL biodegradable meshes combined with cultured fibroblasts vascularize in full-thickness wounds, resulting in formation of organized tissue beneath the epithelialized surface that resembles dermis.

Animals↗

Prolonged course of bilateral acute idiopathic blind spot enlargement.

We report a patient with bilateral "acute idiopathic blind spot enlargement" (AIBSE) in whom visual symptoms and enlarged blind spots persisted for over 6 years and preceded the development of peripapillary hyperfluorescence on fluorescein angiography. These findings confirm the prolonged course that AIBSE can sometimes take and the suggestion that this rare disorder is due to peripapillary retinal dysfunction.

Acute Disease↗

Gender roles as mediators of sex differences in adolescent alcohol use and abuse.

This study tested the hypothesis that internalized gender-role personality attributes and gender-role ideology mediate sex differences in alcohol use and drinking problems in a random sample of 1,077 adolescents aged 13 to 19. Results indicated that gender roles substantially, although not completely, mediated the effects of sex on drinking patterns. The relationships between gender roles and alcohol use were largely consistent with the hypothesis that individuals with conventional gender identities conform more closely to cultural norms that condone drinking among males but not among females. However, effects of the gender-linked attributes of expressivity, emotional control, and instrumentality on drinking also may be interpreted within a framework that views them as functional coping styles. Finally, differences between Black and White teens in the relationships between alcohol use and the masculine attributes of instrumentality and emotional control suggest possible race differences in the functional value of these attributes.

Adolescent↗

Effects of topical antimicrobial agents on the human neutrophil respiratory burst.

The neutrophil oxidative burst plays an important role in killing intracellular microorganisms. We studied the effects of topical antimicrobial agents on the N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated oxidative burst of human peripheral blood neutrophils, using a flow cytometric assay. Mafenide acetate, sulfadiazine silver, gentamicin sulfate, neomycin sulfate-polymyxin B sulfate (Neosporin GU irrigant), acetic acid, amphotericin B, and povidone-iodine inhibited the neutrophil oxidative burst at or below clinical concentrations, while 0.25% modified diluted sodium hypochlorite (Dakin's) solution caused cell death. Bacitracin-polymyxin B sulfate (Polysporin) greatly augmented the respiratory burst; this effect was due to the bacitracin component. Diluted gentamicin and acetic acid also augmented intracellular hydrogen peroxide production, but to a lesser extent than Polysporin. Inhibition of the respiratory burst of neutrophils might be considered when these agents are used for topical wound care, although clinical correlates of these effects have not been determined.

Acetates↗

In vivo optimization of a living dermal substitute employing cultured human fibroblasts on a biodegradable polyglycolic acid or polyglactin mesh.

The design of a skin-substitute must address the need for a dermal component, as this mesenchymally-derived tissue is important in maintaining the integrity and function of skin. An in vivo study was undertaken to assess the use of two biodegradable meshes, polyglycolic acid and polyglactin-910, as carriers for cultured human fibroblasts in a living dermal replacement. The consistent vascularization and epithelialization of these grafts placed on athymic mice showed that this has potential in re-creating the dermis in a skin-substitute.

Animals↗

The cytotoxic effects of commonly used topical antimicrobial agents on human fibroblasts and keratinocytes.

This study evaluated the cytotoxicity of commonly used topical agents to human dermal fibroblasts and epidermal keratinocytes, which play a prominent role in wound healing. The effects of these topical agents were assessed using two separate assays for the fibroblasts--tritiated thymidine incorporation and the uptake of a vital dye (neutral red). Keratinocytes were evaluated with the neutral red assay. Serial dilutions of each of 10 commonly used topical agents produced decreases in both the uptake of neutral red and the incorporation of thymidine at clinically relevant doses. Only Neosporin G.U. irrigant showed no significant difference compared with controls in the assays for both the fibroblasts and the keratinocytes. Careful attention must be paid to which agent is used in the clinical setting, since many of these can have profound effects on cells that influence wound healing.

Acetates↗

Reconstitution of the histologic characteristics of a giant congenital nevomelanocytic nevus employing the athymic mouse and a cultured skin substitute.

This study addresses the development of an animal model for human giant congenital nevomelanocytic nevi (GCNN). Skin grafts were made from 1) non-involved split-thickness skin from a 12-month-old GCNN patient, 2) nevus split-thickness skin from the same GCNN patient, 3) nevus full-thickness skin, and 4) cadaveric human split-thickness skin. For groups 1) and 2), human epidermal and dermal cells were enzymatically isolated and expanded in tissue culture. Composite grafts were made by placing the cultured dermal cells into a collagen-glycosaminoglycan (GAG) matrix, followed by placement of the epidermal cells onto the opposite, laminated side of the matrix. All grafts were placed onto full-thickness wounds of athymic mice and biopsies were obtained from 6 to 38 weeks later for light microscopy including S-100 immunoperoxidase staining, and electron microscopy. The GCNN cultured skin mice (group 2) developed black, raised skin in the healed wounds. None of the group 1 mice developed lesions, grossly or histologically. All of the nevus full-thickness mice retained the nevus grossly. Histopathologic examination at 38 weeks of the black, raised plaques of group 2 demonstrated a reconstituted dermis similar to group 3. Nevus cells were larger and more epithelioid in the upper dermis, as seen with true GCNN. These nevomelanocytes were not seen in the dermis at 24 weeks, suggesting that the nevus cells migrated from the epidermal component of the cultured graft to the dermis during this time frame (24-38 weeks). The melanocyte identity of these cells was confirmed with S-100 immunoperoxidase staining and electron microscopy. These findings are unique to this composite cultured graft system. The ability to culture specific types of melanocytes and place them int skin substitutes on athymic mice provides a basis for the study of GCNN and melanocyte biology in vivo.

Animals↗

Alcohol drinking patterns and blood pressure.

BACKGROUND: Although blood pressure tends to increase with average alcohol consumption, little is known about the effects of drinking patterns on blood pressure. Therefore, the effects of average drinks per day and drinking pattern (defined as the independent and interactive effects of quantity and frequency) on blood pressure were compared. METHODS: Data were obtained from a random sample survey of 1,635 household residents in Erie County, New York. Alcohol-blood pressure relationships were examined using multiple regression analyses that controlled for the potentially confounding influence of 13 additional risk factors for elevated blood pressure. RESULTS: Consistent with prior research, a positive relationship was found between average drinks per day and diastolic and systolic blood pressure. Analyses examining the effect of drinking pattern indicated that drinking frequency had a positive effect on both diastolic and systolic blood pressure, whereas drinking quantity did not affect either. Furthermore, there was little evidence that the frequency-by-quantity interaction affected blood pressure. CONCLUSIONS: Low average alcohol intake and low blood pressure were associated with infrequent drinking, rather than with frequent drinking of small amounts of alcohol. Results suggest that the standard practice of averaging alcohol consumption may obscure important effects of drinking frequency on health.

Adult↗

Skin wound closure in athymic mice with cultured human cells, biopolymers, and growth factors.

Skin wound closure remains a major problem in acute and reconstructive skin grafting after large burns because of limited availability of donor skin. This report evaluates six protocols for preparation in vitro of skin substitutes composed of cultured human cells, biopolymers, and growth factors for wound closure. Full-thickness wounds in athymic mice treated in a single procedure with cultured skin substitutes were compared directly to treatments with murine skin autograft, human skin xenograft, or no graft. Rectilinear planimetry of healed wounds 6 weeks after surgery showed that skin substitutes cultured in serum-free medium, and for 24 hours before surgery in defined medium with basic fibroblast growth factor (100 ng/ml), were not statistically different (p less than 0.05) in size from treatment with human skin xenograft. Acceptance and persistence of skin substitutes cultured in serum-free media were 70% at 6 weeks after surgery, as determined by staining of healed skin with a fluorescein-labeled monoclonal antibody against human HLA-ABC antigens. Ultrastructural examination of wounds with cultured human skin 6 weeks after treatment showed complete basement membrane, including anchoring fibrils, presence of melanocytes and pigment transfer to keratinocytes, and innervation of healed skin adjacent to basement membrane. These findings demonstrate effectiveness of cultured skin substitutes for closure of skin wounds and illustrate important capabilities to modulate the natural processes of wound repair, to increase supply of materials used for wound repair, and to enhance quality of wound healing.

Animals↗

Use of a composite skin graft composed of cultured human keratinocytes and fibroblasts and a collagen-GAG matrix to cover full-thickness wounds on athymic mice.

In patients with extensive full-thickness burns, wound coverage may be accelerated if skin can be expanded to produce a skin replacement that reproducibly supplies blood to the wound and has good structural qualities. In addition, development of skin replacements may benefit patients who require reconstruction or replacement of large areas of abnormal skin. We have developed a composite skin replacement composed of cultured human keratinocytes (HK) and fibroblasts. Cultured human fibroblasts are seeded into the interstices, and cultured HKs are applied to the surface of a matrix composed of type I collagen crosslinked with a glycosaminoglycan, which has a defined physical structure. After HKs reach confluence on the matrix surface, the composite grafts are placed on full-thickness wounds on the dorsum of athymic mice. Graft acceptance, confirmed by positive staining with antibodies specific for human HLA-ABC antigens on HKs, is approximately 90%. A defined skin structure is present histologically by day 10 after grafting, with a differentiated epithelium and a subepidermal layer densely populated by fibroblasts and capillaries without evidence of inflammation. Fluorescent light microscopy to identify laminin and type IV collagen and electron microscopy confirm the presence of basement membrane components by 10 days after grafting. Attachment of the graft to the wound is similar with and without the addition of human basic fibroblast growth factor, a potent angiogenic agent, to the skin replacement before graft placement on wounds.

Animals↗

Cytotoxicity to cultured human keratinocytes of topical antimicrobial agents.

Cultured skin grafts administered clinically for closure of burn wounds may be contacted by topically applied antimicrobial agents. A study was performed to assess whether commonly used topical antimicrobial agents are toxic to cultured human keratinocytes (HK) in vitro. Serum-free MCDB 153 culture medium containing Neosporin G.U. irrigant (Neomycin, 40 micrograms/ml-polymyxin B sulfate, 200 units/ml) and a standard tissue culture antimicrobial agent of penicillin (10,000 units/ml)-streptomycin (10,000 micrograms/ml)-amphotericin B (25 micrograms/ml) had no effect on the keratinocyte growth rates when compared to standard MCDB 153 medium without antibiotics. Medium containing Sulfamylon (mafenide acetate, 0.85%), Polysporin (polymyxin B sulfate, 1 x 10(4) units/ml-bacitracin, 500 units/ml), gentamicin sulfate (0.1%), modified Dakins solution (25%), and acetic acid (0.25%) all showed statistically significant (P less than 0.01) decreases in keratinocyte growth rates. This data suggests that commonly applied antimicrobials may not be appropriate for cultured grafts in the concentrations that are used clinically.

Acetates↗