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Biomedical subjects

C R White

Publications and source records attributed to C R White.

At least 73 records · Page 4Linked to original sources

Endothelium-derived relaxing factor and cyclic GMP-dependent vasorelaxation in human chorionic plate arteries.

Endothelium derived relaxing factor (EDRF), now widely believed to be nitric oxide (NO), may play an important part in the control of fetoplacental vascular tone. To further explore this role we have determined the relaxation responses to exogenous NO and examined the temporal relationship between intracellular concentrations of cyclic GMP and vascular tone in isolated ring segments of human chorionic plate arteries. We have also determined the dose relations for the contractile agonists serotonin and the thromboxane analog U46619. Lastly, we have explored the relaxation responses to a wide range of agents known to elicit EDRF release in other vascular beds. Chorionic plate arteries relaxed significantly to exogenous NO with concomitant increases in cyclic guanosine monophosphate over basal values. ED50s for serotonin and U46619 were 1.48 x 10(-6) M and 3.39 x 10(-8) M respectively. The ED50 for NO derived from S-nitroso-N-acetyl-penicillamine was 1.28 x 10(-6) M. Endothelium-intact segments of chorionic plate arteries pre-contracted with either serotonin or U46619 failed to relax significantly to acetylcholine, adenosine diphosphate, A23187, bradykinin, and histamine and only minimally to substance P. We suggest that EDRF is likely to be important in the control of placental vascular tone, but that it is not possible to demonstrate its action in an unperfused experimental system.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Parachordoma.

Parachordomas are rare soft-tissue neoplasms that are histologically similar to chordomas. They typically develop adjacent to tendon, synovium, or osseous structures within extremities and present as slowly growing, locally destructive, lobulated neoplasms that are prone to recurrence if incompletely excised. We report a parachordoma occurring in the right middle finger of a 25-year-old man. The neoplasm had been present for 5 years, and the patient had sustained repeated injuries to the area. Histologically, the lesion was characterized by well-circumscribed lobules composed of small cellular aggregates, some in "alveolar" distribution, and single, large, vacuolated (physalipherous) cells embedded within a hyalin and chondroid matrix divided by fibrous trabeculae. Immunohistochemically, the parachordoma stained positively for the S-100 protein, vimentin, and cytokeratin.

Adult↗

Effects of maturation on cyclic GMP-dependent vasodilation in ovine basilar and carotid arteries.

The present experiments examine the effects of maturation on cyclic GMP (cGMP)-mediated vasodilation in 688 segments of common carotid (COM) and basilar (BAS) arteries taken from newborn (3- to 7-d-old) and nonpregnant adult sheep. The main finding is that maximum efficacy for relaxation decreased with maturation in both artery types for the nitric oxide releasing vasodilators S-nitroso-N-acetyl-penicillamine and nitroglycerin. These decreases could not be explained by changes in the -log ED50 concentrations for either vasodilator. Determination of the time course of cGMP responses to S-nitroso-N-acetyl-penicillamine or nitroglycerin at 10 microM revealed that the peak cGMP responses to these agents (range: 5.3 +/- 0.8 to 8.3 +/- 1.6 pmol/mg of protein) also did not vary significantly with age. However, cGMP attained peak values more rapidly in adult (COM: 50 s; BAS 30 s) than in newborn (COM: 60-80 s: BAS, 40-60 s) segments and returned to baseline more slowly in newborn than in adult segments, suggesting that maturation accelerates cGMP turnover. Correspondingly, baseline levels of cGMP were higher in newborn (COM: 1.0 +/- 0.1; BAS: 3.3 +/- 0.5 pmol/mg of protein) than in adult (COM: 0.3 +/- 0.1; BAS: 1.7 +/- 0.2 pmol/mg of protein) segments. Despite these differences in cGMP time course, rates of relaxation in response to S-nitroso-N-acetyl-penicillamine and nitroglycerin did not vary significantly with age, indicating that the temporal relation between cGMP and relaxation is different in newborn and adult arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry.

Oxidation of lipoproteins is important for the initiation and propagation of the atherosclerotic lesion and may involve secondary oxidants derived from nitric oxide. Nitric oxide (NO) reacts at near diffusion limited rates with superoxide (O2-.) to form the strong oxidant, peroxynitrite (ONOO-). Nitration on the ortho position of tyrosine is a major product of peroxynitrite attack on proteins. Nitrotyrosine was detected in atherosclerotic lesions of formalin-fixed human coronary arteries with polyclonal and monoclonal antibodies. Binding was pronounced in and around foamy macrophages within the atheroma deposits. Nitration was also observed in early subintimal fatty streaks. Antibody binding was completely blocked by co-incubation with 10mM nitrotyrosine, but not by equivalent concentrations of aminotyrosine or phosphotyrosine. The presence of nitrotyrosine indicates that oxidants derived from nitric oxide such as peroxynitrite are generated in human atherosclerosis and may be involved in its pathogenesis.

Cell Nucleus↗

Immunophenotypic and genotypic analysis in cutaneous lymphoid hyperplasias.

BACKGROUND: The clinical utility of immunophenotyping and Southern blot analysis in the evaluation of patients with cutaneous lymphoid hyperplasia (CLH) is controversial. OBJECTIVE: Our purpose was to determine whether adjunctive immunophenotyping and Southern blot analysis are of diagnostic and prognostic value in patients with CLH. METHODS: Immunophenotyping was performed on skin biopsy specimens from 26 patients with a routine histologic diagnosis of CLH. Southern blot analysis for immunoglobulin (Ig) gene rearrangements was done on 13 of 26 cases. RESULTS: Twenty-four of 26 patients had polyclonal CLH on immunophenotyping: 2 of 26 had monoclonal lymphoma. Two of 11 patients with polyclonal CLH studied by Southern blot analysis had clonal Ig gene rearrangements. In both, lymphoma developed within 1 to 6 years; comparison of CLH and malignant lymphoma demonstrated overlapping and different clonal bands. Two additional patients with polyclonal CLH developed lymphoma. No clonal gene rearrangements were detected in the CLH or lymphoma from one; the other was not studied. CONCLUSION: Immunophenotyping will identify some patients with lymphoma with nondiagnostic histologic features. Southern blot analysis will predict some patients with polyclonal CLH in whom malignant lymphoma will develop and who may benefit from definitive therapy.

Adult↗

Heterosexually acquired human immunodeficiency virus infection and the United States blood supply: considerations for screening of potential blood donors. HIV Blood Donor Study Group.

The impact of heterosexual transmission of the human immunodeficiency virus (HIV) on the United States blood supply was assessed, and deferral criteria that may exclude potential donors who are at high risk for heterosexually acquired HIV infection were evaluated. Interviews were conducted with 508 HIV-seropositive blood donors from May 1, 1988, to August 31, 1989 (Phase 1), and with 472 donors from January 1, 1990, to May 31, 1991 (Phase 2), at 20 blood centers. From Phase 1 to Phase 2, the overall HIV prevalence decreased from 0.021 to 0.018 percent (p < 0.001). HIV risk factors among HIV-1-seropositive donors were similar during both study phases. Eleven percent of the men and 56 percent of the women reported as their only risk that they had a heterosexual partner who was at increased risk for HIV or was known to have HIV. These percentages were similar during both study periods. During Phase 2, 13 percent of the men and 17 percent of the women with heterosexual transmission risk had a positive serologic test for syphilis, hepatitis B core antibody, or hepatitis C antibody. Among HIV-1-seropositive donors reporting heterosexual risk, the median numbers of previous-year and lifetime sex partners for men were 2 and 30, respectively; for women, those numbers were 1 and 7, respectively. Thirty-one percent of the men and 6 percent of the women reporting heterosexual transmission risk also reported having had syphilis or gonorrhea within 3 years of donation. It is concluded that the impact of heterosexual transmission of HIV infection on transfusion safety is not worsening at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Banks↗

DNA determination in dysplastic nevi. A comparative study between flow cytometry and image analysis.

Dysplastic nevi (DN), described in 1978, have been associated with increased risk of melanoma, but the role of DN as precursors of melanoma is still controversial. Recent studies have shown that DN are very common in the general population, bringing into question this purported association. Numerous investigations have attempted to correlate the presence of DN in individuals with specific phenotypic and genotypic features, including the presence of abnormal DNA content. Because the occurrence of such abnormal DNA stemlines in neoplasms may be associated with malignant behavior, we studied 38 biopsies from 19 patients that histologically fulfilled criteria for DN in order to ascertain characteristics of DNA content. Nuclear suspensions made from paraffin-embedded tissue were evaluated by both flow cytometry and image analysis techniques. All cases demonstrated diploid populations by both DNA measurement methods. Our results contradict previous reports of aneuploid populations in these melanocytic lesions.

Adolescent↗

Cutaneous acanthamoeba infection associated with leukocytoclastic vasculitis in an AIDS patient.

Cutaneous Acanthamoeba infection is a rare complication of immunocompromised individuals including those having acquired immunodeficiency syndrome (AIDS), who often have concurrent central nervous system involvement. Acanthamoeba typically involves the skin and central nervous system by disseminating from a primary focus in the lungs or sinuses. We report an unusual patient with AIDS who developed cutaneous infection with Acanthamoeba, apparently without CNS infection but with sinus involvement. Histologically, the purpuric lesions showed prominent leukocytoclastic vasculitis as well as myriads of organisms.

AIDS-Related Opportunistic Infections↗

Recombinant human granulocyte colony-stimulating factor promotes wound healing in a patient with congenital neutropenia.

We report a patient with congenital neutropenia or Kostmann's Syndrome who suffered many complications after presenting with Clostridium septicum enterocolitis, including absence of wound healing. Because of several reports of the use of granulocyte colony-stimulating factor (G-CSF) in patients with various complications of neutropenia, we treated this patient with recombinant human (rh) G-CSF. We found that once rhG-CSF restored neutrophil counts to normal, progressive wound healing followed. Thus, rhG-CSF therapy may be useful in treating neutropenic patients with wound complications.

Adolescent↗

Simulation of emergency medical service scheduling.

Efficient allocation of resources is essential in any activity, but experimenting to determine appropriate levels risks a reduction in services that could be dangerous in a healthcare operation. Computer simulations offer a risk-free environment for testing alternate resource levels and balancing costs and services. This article describes the use of a simulation to determine appropriate staffing levels for an emergency medical service.

Alabama↗

Chronic verrucous varicella-zoster virus infection in patients with the acquired immunodeficiency syndrome (AIDS). Histologic and molecular biologic findings.

Verrucous skin lesions have been attributed to various herpes viruses in immunosuppressed patients, including those with human immunodeficiency virus infection (HIV). We examined such lesions from six HIV-infected patients to determine the range of microscopic findings present and to establish which herpesviruses were present. Verrucous epidermal hyperplasia, pseudocarcinomatous hyperplasia, and massive hyperkeratosis correlate with the warty clinical appearance of the lesions. Herpetic cytopathic changes, including multinucleated epidermal giant cells, steel-gray nuclei, necrotic acantholytic keratinocytes, and Cowdry type A nuclear inclusions were seen most prominently in the dells between papillations and in adnexal epithelium. In two cases, increased numbers of spindled cells were seen in the dermis. Immunoperoxidase staining with anti-type IV collagen antibodies demonstrated that these findings were not those of Kaposi's sarcoma, but represent a fibrotic reaction to the infection. Viral cultures of four of the cases demonstrated the presence of varicella-zoster virus, whose presence was detected by the polymerase chain reaction in paraffin-embedded lesional tissue from all six cases. Polymerase chain reaction did not show the presence of cytomegalovirus, herpes simplex, Epstein-Barr, or human papillomavirus. We conclude that these unusual verrucous lesions are a chronic manifestation of herpes zoster infection and that the reported presence of other agents in such lesions is probably coincidental.

Acquired Immunodeficiency Syndrome↗

Evolution of B-cell lymphoma from pseudolymphoma. A multidisciplinary approach using histology, immunohistochemistry, and Southern blot analysis.

Cutaneous B-cell lymphomas are rare neoplasms that can present as lesions involving solely the skin or develop in association with a systemic lymphoma. Histologically they are often difficult to differentiate from pseudolymphomas, and the use of immunohistochemistry may be necessary to correctly classify them. We report a study of multiple skin lesions in a patient who initially presented with multiple pseudolymphomas, apparently associated with an immune response to the dye of his tattoos. Over a period of 4 years his skin lesions evolved from histologically benign and immunologically polyclonal pseudolymphomas to a histologically malignant and immunologically monoclonal B-cell large cell lymphoma. Genotypic analysis with a probe for the heavy-chain immunoglobulin gene demonstrated the presence of clonal B-cell populations in all of the pseudolymphoma biopsy samples as well as in the subsequent lymphoma tissue samples, with a pattern of clonal bands suggestive of evolution of the B-cell clones. These findings suggest that the development of B-cell lymphoma in this patient was related to a persistent abnormal immune response to the chronic antigenic stimulus of the dye of the tattoo. The presence of clonal B-cell populations in pseudolymphoma by Southern blot analysis may be useful in predicting those patients who will subsequently develop overt lymphoma.

Blotting, Southern↗

Comparison of image analysis with flow cytometry for DNA content analysis in pigmented lesions of the skin.

The DNA ploidy of 85 melanocytic skin lesions was determined by flow cytometry (FCM) and interactive image analysis (IA) using nuclear extracts of paraffin-embedded tissue. Of the 85 lesions analyzed, 43 were malignant melanomas in different stages of evolution, 15 were dysplastic nevi, 11 were Spitz nevi, and 16 were other types of nevi. Some of the last had features of congenital nevi. Within the melanoma category, there was 42% aneuploidy by FCM versus 56% by IA. Of those melanomas aneuploid by FCM, all but one were aneuploid by IA. All dysplastic nevi, 10/11 Spitz nevi and 15/16 other nevi were diploid by both methods. One of the 16 nevi from the "other types" category was tetraploid by IA but diploid by FCM. A single Spitz nevus was tetraploid by FCM but diploid by image analysis. While our results suggest that interactive IA is potentially a more sensitive method than FCM for detecting aneuploidy in cutaneous pigmented lesions, it remains to be shown whether this will translate into better prognostic assessment of the biologic behavior of melanocytic neoplasms than provided by flow cytometric ploidy analysis.

Aneuploidy↗

Oculocutaneous manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum.

Although they were once believed to be distinct diseases, many observers currently consider erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis to represent a mild-to-severe continuum of the same process. Each shares certain clinical, histologic, and etiologic characteristics; among the latter two are frequent ocular involvement. Because long-term ophthalmic sequelae may be catastrophic, early recognition and therapy of this acute oculocutaneous disease spectrum are critically important.

Conjunctivitis↗

Human immunodeficiency virus type 1-infected blood donors: behavioral characteristics and reasons for donation. The HIV Blood Donor Study Group.

Between May 1988 and September 1989, 829 human immunodeficiency virus type 1 (HIV-1)-seropositive donors were identified from 3,919,000 units of blood donated at 20 United States (US) blood centers. Of the 829,512 (62%) were interviewed to assess behavioral characteristics of the largest subgroup, men reporting sex with men, use of the confidential unit exclusion (CUE) and reasons for donation among all donors. Among 216 men reporting sex with men, 97 percent had male and 72 percent had female sexual contact since 1978. The majority identified themselves as bisexual (29%) or heterosexual (26%). Although 61 percent of 512 donors were aware of their risk behavior at donation, including 57 percent of those infected through heterosexual transmission, only 5 percent used the CUE. Reasons for donation included failure to read carefully (46%) or comprehend (15%) the deferral materials, pressure to donate (27%), a desire to be tested for HIV-1 (15%), and a reliance on screening to identify infected blood (10%). Reasons given for a perception of being at low risk included no recent risk behaviors, infrequent risk behaviors, or modification of risk behaviors. To reach high-risk donors, centers should assess whether referral materials provide necessary medical information and are clearly written for persons with diverse cultural and language backgrounds. Staff should be encouraged to avoid the use of culturally stigmatized terms and behaviors that may be perceived as high pressure.

Blood Donors↗

Spontaneous rhythmic contractile behaviour of aortic ring segments isolated from pressure loaded regions of the vasculature.

STUDY OBJECTIVE: The aim was to study contractile responses of segments of rat arteries taken from pressure loaded and pressure protected regions and to examine the role of endothelial derived factors on the spontaneous activity of pressure loaded ring segments. DESIGN: Rats were subjected to complete aortic coarctation between the origins of the renal arteries and allowed to recover for 8 d. After 8 d arterial pressures were measured in awake animals from the pressure loaded and pressure protected regions simultaneously. Ring segments (2-3 mm) were taken from the two regions and mounted in a tissue bath for isometric force measurements. Similar studies were conducted in sham animals and in animals in which the kidney distal to the coarctation had been removed. EXPERIMENTAL MATERIAL: Female Sprague-Dawley rats, weight 200-250 g, were used. MEASUREMENTS AND MAIN RESULTS: Eight days after coarctation mean aortic pressure proximal to the occlusion was 168(SEM 1.29) mm Hg (n = 104) while distally it was 38(2.42) (n = 40). Of the rings tested 96% showed spontaneous rhythmic activity, having a mean frequency of 3.94(0.17) cycles.min-1. Spontaneous activity was not present in the pressure protected segments taken from the same animals. Rats with the distal kidney removed (n = 25) failed to become hypertensive and similarly prepared ring segments failed to show spontaneous rhythmic activity. Prior removal of the endothelial layer had no effect on the spontaneous contractile responses in pressure loaded segments. Histological examination showed that the media to lumen ratio was increased in coarcted rats in both pressure loaded and pressure protected regions compared to similar regions in sham operated animals. CONCLUSIONS: Pressure loaded arterial segments show spontaneous contractile activity when compared to sham segments by mechanisms not dependent on endothelial derived factors. The increase in pressure proximal to the occlusion is dependent on the renin-angiotensin system, since pressure was not increased when the distal kidney was removed. We hypothesise that the chronic pressure load induces fundamental changes in membrane permeability which leads to spontaneous contractile activity.

Acetylcholine↗

Rhabdomyoma of the tongue.

Rhabdomyomas, which are rare striated muscle neoplasms, may occur on oral or genital mucosal surfaces as well as on the skin. Little discussion of rhabdomyomas occurs in any dermatology or dermatopathology literature. We report an 84-year-old patient who had a rhabdomyoma of her lateral tongue and discuss the clinical and histologic characteristics of this unusual type of benign neoplasm.

Aged↗