Search PubMed⌕ Search

Biomedical subjects

C R White

Publications and source records attributed to C R White.

At least 55 records · Page 3Linked to original sources
PubMed1997

Angiomatoid melanoma: a case of metastatic melanoma mimicking a vascular malignancy.

We present a case of melanoma metastatic to forehead skin and sacral vertebra, without known primary, which, in the cutaneous metastasis, displayed striking histologic features suggesting vascular differentiation. Histopathologic examination of the lesion revealed a large, deeply extending spindle cell malignancy with numerous, cavernous, erythrocyte-filled spaces throughout and only scant melanin pigmentation, making initial diagnosis challenging. The neoplastic cells demonstrated positive staining with antibodies to S-100 protein, HMB 45, and vimentin. We suggest the term angiomatoid melanoma for this histopathologic variant.

Adult↗
PubMed1997

Immunoglobulin light chain alters mesangial cell calcium homeostasis.

This study examined the hypothesis that certain immunoglobulin light chains directly altered mesangial cell calcium homeostasis. Intracellular Ca2+ concentration (intracellular [Ca2+]) signaling was determined in suspensions of rat mesangial cells using the acetoxymethyl ester of fura 2 with a calcium removal/replacement protocol. Pretreatment of cultured rat mesangial cells with a glomerulopathic kappa-light chain (gle) produced reversible dose- and time-dependent attenuation of ATP- and thrombin-evoked [Ca2+] transients (189 +/- 24 vs. 126 +/- 10 nM, P < 0.05 with ATP; 198 +/- 5 vs. 117 +/- 3 nM, P < 0.05 with thrombin) and capacitative calcium influx (199 +/- 14 vs. 142 +/- 17 nM, P < 0.05 for ATP; 252 +/- 19 vs. 198 +/- 18 nM, P < 0.05 for thrombin). Mesangial cells treated with gle and supplemented with myo-inositol (450 microM) did not demonstrate the attenuation of the ATP-evoked [Ca2+] transient and capacitative calcium influx. Gle also decreased mean [Ca2+] transient (80 +/- 7 vs. 56 +/- 1 nM, P < 0.05) and capacitative calcium influx (306 +/- 10 vs. 241 +/- 4 nM, P < 0.05) in response to thapsigargin, a Ca2+-adenosinetriphosphatase inhibitor. This inhibition was not reversed by exogenous myo-inositol. Another kappa-light chain (10 microg/ml) did not affect mesangial cell calcium signaling. Deranged mesangial cell calcium homeostasis by certain light chains may play a central pathogenetic role in glomerulosclerosis associated with deposition of immunoglobulin light chains.

Adenosine Triphosphate↗
PubMed1996

Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits.

Reactive oxygen species play a central role in vascular inflammation and atherogenesis, with enhanced superoxide (O2.-) production contributing significantly to impairment of nitric oxide (.NO)-dependent relaxation of vessels from cholesterol-fed rabbits. We investigated potential sources of O2.- production, which contribute to this loss of endothelium-dependent vascular responses. The vasorelaxation elicited by acetylcholine (ACh) in phenylephrine-contracted, aortic ring segments was impaired by cholesterol feeding. Pretreatment of aortic vessels with either heparin, which competes with xanthine oxidase (XO) for binding to sulfated glycosaminoglycans, or the XO inhibitor allopurinol resulted in a partial restoration (36-40% at 1 muM ACh) of ACh-dependent relaxation. Furthermore, O2.(-)-dependent lucigenin chemiluminescence, measured in intact ring segments from hypercholesterolemic rabbits, was decreased by addition of heparin, allopurinol or a chimeric, heparin-binding superoxide dismutase. XO activity was elevated more than two-fold in plasma of hypercholesterolemic rabbits. Incubation of vascular rings from rabbits on a normal diet with purified XO (10 milliunits/ml) also impaired .NO-dependent relaxation but only in the presence of purine substrate. As with vessels from hypercholesterolemic rabbits, this effect was prevented by heparin and allopurinol treatment. We hypothesize that increases in plasma cholesterol induce the release of XO into the circulation, where it binds to endothelial cell glycosaminoglycans. Only in hypercholesterolemic vessels is sufficient substrate available to sustain the production of O2.- and impair NO-dependent vasorelaxation. Chronically, the continued production of peroxynitrite, (ONOO-) which the simultaneous generation of NO and O2.- implies, may irreversibly impair vessel function.

Acetylcholine↗
PubMed1996

Epidermotropically metastatic breast carcinomas. Rare histopathologic variants mimicking melanoma and Paget's disease.

Epidermotropic metastases from internal malignancies are exceedingly rare. We report two examples of epidermotropic metastatic breast carcinoma with striking intraepidermal involvement. The first case mimicked melanoma because the neoplastic cells contained melanin and were disposed both as single units and as nests at the dermoepidermal junction and throughout the epidermis. In the second case, the neoplastic cells were seen as isolated neoplastic cells with large, pale cytoplasm scattered throughout the epidermis, closely resembling extramammary Paget's disease. Immunohistochemical studies in both cases demonstrated the epithelial nature of intraepidermal neoplastic cells, which showed an immunophenotype identical to the neoplastic cells present in the dermis: positive staining with anti-cytokeratins, CEA, EMA, and GCDFP-15 and negative with anti-S-100 protein and HMB-45. These findings ruled out the possibility of a collision lesion, or simultaneous occurrence of melanoma and metastatic breast carcinoma. Pagetoid intraepidermal spread of metastatic breast carcinoma, as in our two cases, is exceptional. We also discuss the histogenetic similarities between our findings and those of mammary and extramammary Paget's disease, as well as the differential diagnosis of other cutaneous disorders characterized by pagetoid intraepidermal spread of neoplastic cells.

Aged↗
PubMed1996

Effects of maturation on cyclic GMP metabolism in ovine carotid arteries.

Previous studies suggest that elevated basal levels of cGMP in newborn arteries may help explain why vascular resistance is lower in newborns than adults. To explore the reasons why basal cGMP is higher in neonatal arteries, the present studies examined rates of cGMP synthesis and degradation in newborn and adult ovine common carotid arteries. The measurements were performed in both intact and homogenized arteries, and results were normalized relative to cell water to estimate intracellular concentrations and minimize errors due to compositional differences between newborn and adult arteries. Steady state levels of cGMP measured under baseline conditions averaged 0.11 +/- 0.02 microM in adult arteries and 0.59 +/- 0.11 microM in newborn arteries. These resting cGMP levels were unaffected by endothelium removal. Under baseline conditions, steady state rates of cGMP synthesis (mumol of cGMP/L of cell water/min) were higher in newborn (0.31 +/- 0.06) than in adult (0.15 +/- 0.04) arteries. Maximal rates of cGMP degradation (mumol of cGMP/L of cell water/min) measured in artery homogenates were also much higher in preparations of newborn (106 +/- 6) than of adult (78 +/- 6) arteries. Together, these data suggest that the reason resting cGMP concentrations were higher in newborn than in adult arteries was due at least in part to a higher basal rate of cGMP synthesis in the newborn. Estimates of apparent Km values for PDE were also greater in newborn (2.9 microM) than in adult (1.5 microM) preparations, suggesting that age-related differences in the Km for PDE may also contribute to the elevated basal concentration of cGMP observed in the newborn.

1-Methyl-3-isobutylxanthine↗
PubMed1995

A functional comparison of the rat type-1 angiotensin II receptors (AT1AR and AT1BR).

To evaluate and functionally compare the rat AT1A and AT1B receptor subtypes, stable Chinese hamster ovary (CHO) cell lines expressing either recombinant receptor in approximately equal numbers were generated. Radioligand binding data suggests that the recombinant AT1A receptor is pharmacologically similar to the recombinant AT1B receptor. Functional studies indicate that both receptor subtypes can independently activate the phospholipase C/IP3 and the dihydropyridine-sensitive voltage-dependent Ca2+ channel signal transduction pathways with equal efficiency, but are unable to modulate cAMP accumulation under our experimental conditions. Furthermore, both receptors can be directly involved in the cellular growth properties of AII. Slot-blot experiments clearly demonstrate that these receptors are expressed in a tissue-specific manner. A sequence comparison of the 5' flanking regions of these two genes shows that they have very little sequence homology (approximately 36%), suggesting that although the AT1A and AT1B receptors appear to be pharmacologically and functionally similar, the control of their expression seems to be governed by distinct transcription factors.

Animals↗
PubMed1995

Juvenile xanthogranuloma: a clinical, histopathologic and immunohistochemical study.

Juvenile xanthogranuloma (JXG) is a benign histiocytic proliferation of uncertain histogenesis which usually resolves spontaneously. Histopathologically, classic lesions are characterized by diffuse proliferations of foamy histiocytes, many of which may be multinucleated (Touton cells), admixed with lymphocytes and eosinophils. Histologic variants of JXG, perhaps representing evolving lesions, may lack these typical histopathological features, showing diffuse infiltrates of non-foamy mononuclear histiocytes without Touton cells, posing problems in differentiation from other histiocytic or melanocytic proliferations. Immunohistochemically, JXG is characterized by variable expressions of several histiocytic markers as well as the absence of staining for S100 protein. To assess better the spectrum of histopathological and immunohistochemical features of JXG, we studied nine cases of classic or histologic variant of JXG. The cases were evaluated by light microscopy and with an extensive battery of antibodies. All 9 cases, regardless of their light microscopic appearance, showed markedly positive staining with histiocytic markers including CD68, HAM56, cathepsin B and vimentin, but did not stain for S100 protein. Antibodies to factor XIIIa stained positively in 8 cases while staining for other markers was variable. Our results suggest that the histiocytes in JXG lesions have macrophagic differentiation, probably representing a reactive process to an unknown stimulus.

Adult↗
PubMed1995

Hyperglycemia alters cytoplasmic Ca2+ responses to capacitative Ca2+ influx in rat aortic smooth muscle cells.

Concentrations of free cytoplasmic Ca2+ in rat aortic smooth muscle (RASM) cells were monitored using the ratiometric Ca2+ indicator fura 2-acetoxymethyl ester (AM). In RASM cells cultured in 5 mM Glc, incubation with angiotensin II, ATP, or thapsigargin [a selective inhibitor of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase] depleted SR Ca2+ stores and initiated a capacitative Ca2+ influx through the plasma membrane. This influx was resistant to verapamil, a selective inhibitor of L-type voltage-gated Ca2+ channels, but was sensitive to SKF-96365, an inhibitor of the receptor-operated Ca2+ entry pathway. RASM cells cultured in 25 mM Glc exhibited a significant decrease in cytoplasmic Ca2+ responses to agonist-induced Ca2+ release from SR stores and to subsequent capacitative Ca2+ entry. In addition, the cytoplasmic response to thapsigargin-induced release of Ca2+ from the SR in hyperglycemic cells peaked more sharply than in control cells and returned to baseline more rapidly. The effects of hyperglycemia were not overcome by myo-inositol supplementation.

Adenosine Triphosphate↗
PubMed1995

Calcium-sensitive chloride channels in vascular smooth muscle cells.

Chloride (Cl-) channels were characterized in vascular smooth muscle cells (VSMC) using radioisotope flux and patch-clamp electrophysiological techniques. Transmembrane 125iodine (125I) efflux from subcultured (Passage 1-5) rat aortic VSMCs was used as an indicator of Cl- movements to study the relationship between intracellular calcium concentration ([Ca2+]i) and Cl- channel activity. Angiotensin II (Ang II) (10(-7) M) and adenosine 5'-triphosphate (ATP) (10(-4) M) induced rapid increases (9.7- and 14.9-fold, respectively) in 125I efflux rates. We found that both Ang II- and ATP-stimulated 125I efflux and [Ca2+]i increases were completely abolished after brief incubation (20 microM, 20 min) with the acetoxymethyl ester of 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), a membrane-permeable Ca2+ chelator. However, when external EGTA was used to blunt agonist-stimulated Ca2+ influx, 125I efflux was still increased in response to Ang II and ATP. These data suggest that Ca2+ release from intracellular sites is sufficient to activate Cl- channels in response to Ang II and ATP. Using standard patch-clamp electrophysiological techniques, we found that Ang II, a Ca(2+)-mobilizing agonist, stimulated outward Cl- currents (gCl = 75 pS) in cell-attached (C/A) patches of primary and subcultured VSMCs. Collectively, these data suggest that Ang II and other vasoconstrictor agents stimulate Cl- channel activity via increases in [Ca2+]i. Cl- channel activation may help to depolarize the VSMC membrane leading to increased Ca2+ influx during agonist stimulation.

Animals↗
PubMed1995

Rapid development of disseminated superficial porokeratosis after transplant induction therapy.

Disseminated superficial actinic porokeratosis (DSAP) is a cutaneous disorder, usually inherited in an autosomal dominant fashion, characterized by numerous annular papules with subtle raised hyperkeratotic borders and slightly atrophic centers. While the precise pathophysiologic mechanisms underlying the development of DSAP are unknown, one hypothesis is multifocal expansion of atypical clones of keratinocytes, perhaps unmasked by actinic damage, as implied by its name. Although primarily of cosmetic concern, there is an increased risk of squamous cell carcinoma of the skin developing within DSAP lesions, which often show histologic keratinocytic atypia centrally. Immunosuppression, which is a significant risk factor for secondary malignancies including cutaneous squamous cell carcinoma, is also a well-documented precipitant of porokeratosis. We report a 62-year-old man who developed DSAP in a widely and rapidly progressive manner within days of receiving total body radiation and high-dose induction chemotherapy as planned preparative therapy for an autologous peripheral blood stem cell transplant for relapsed high grade lymphoma. Our patient's eruption of DSAP highlights a little recognized cutaneous manifestation of aggressive bone marrow transplant induction therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Subtle clues to the diagnosis of the herpesvirus by light microscopy. Herpetic syringitis.

Among the numerous infections to which AIDS patients are susceptible, those caused by herpesvirus (simplex and varicella/zoster) are among the most common. Because herpetic infections may be the first manifestations of AIDS and often are associated with poor prognosis, rapid and accurate diagnosis of them is imperative. Herpesvirus infection may be diagnosed histopathologically by the presence of ballooned, acantholytic, and multinucleated keratinocytes; intranuclear eosinophilic viral inclusions; steel gray color of affected keratinocytic cytoplasm and nuclei, chromatin margination, and necrotic acantholytic keratinocytes in older lesions. These changes are often limited to the epidermis, but there may frequently be involvement of epithelia of follicles (herpetic folliculitis) and sebaceous glands as well. Similar changes, although seldom noted, may be present in eccrine ducts and glands (herpetic syringitis). Recognition of subtle histologic clues concerning the secretory and ductal components of sweat glands in an unusual case of herpes infection facilitated rapid diagnosis in an AIDS patient, allowing appropriate treatment.

AIDS-Related Opportunistic Infections↗
PubMed1994

Human immunodeficiency virus infection among health care workers who donate blood.

OBJECTIVE: To estimate the prevalence of human immunodeficiency virus (HIV) infection among health care workers who donate blood. DESIGN: Point prevalence survey of blood donors. SETTING: 20 U.S. blood centers that participate in an ongoing interview study of HIV-seropositive blood donors. MEASUREMENTS: Prevalence rates for HIV in persons who reported being health care workers were measured directly for 6 of the 20 blood centers. For the other 14 centers, we derived the numerator from the interview study in the same manner used for the 6 centers; we estimated the denominator using blood collection logs at those centers and extrapolations from the survey completed at the 6 blood centers. RESULTS: Between March 1990 and August 1991, 8519 health care workers donated blood at 6 hospitals and other medical facilities. Three persons were HIV seropositive: Two reported being health care workers and having nonoccupational risk factors for HIV infection; the occupation and other possible risk factors of the third seropositive donor could not be determined. Therefore, the highest overall prevalence of HIV infection among health care worker donors at these 6 centers was 0.04% (3 of 8519; upper limit of 95% CI, 0.1%). We estimated that during the same period, approximately 36,329 health care workers were tested for HIV at all 20 centers. Twenty-seven persons infected with HIV who donated at hospitals were identified; 7 did not return for interviews, so their health care occupations could not be verified. Thus, the highest estimated overall prevalence of HIV infection among health care worker donors at the 20 centers was 0.07% (27 of 36,329; upper limit of CI, 0.1%). Of the 20 known health care worker donors, 11 reported nonoccupational risks for HIV infection; 3 of the remaining 9 health care workers described occupational blood exposures that could have resulted in transmission of HIV. CONCLUSIONS: Blood donors can serve as a sentinel cohort when evaluating the risk for occupationally acquired HIV infection. These findings suggest that among the many health care worker donors in this study, HIV infection attributable to occupational exposure was uncommon.

Adult↗
PubMed1994

Superoxide and peroxynitrite in atherosclerosis.

The role of reactive oxygen species in the vascular pathology associated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (.NO) with superoxide (O2-), yielding the oxidant peroxynitrite (ONOO-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to critical sites of .NO reaction with O2-. Intravenously injected liposomes (3000 units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed group to a greater extent than in controls. Quantitative immunocytochemistry demonstrated enhanced distribution of SOD in both endothelial and vascular smooth muscle cells as well as in the extracellular matrix. SOD activity in vessel homogenates of liposome-treated rabbits was also increased. Incubation of beta very low density lipoprotein with ONOO- resulted in the rapid formation of conjugated dienes and thiobarbituric acid-reactive substances. Our results suggest that the reaction of O2- with .NO is involved in the development of atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation, as well as by limiting .NO stimulation of vascular smooth muscle guanylate cyclase activity.

Acetylcholine↗
PubMed1994

Pyoderma gangrenosum in association with psoriatic arthritis.

We present a patient with psoriasis and psoriatic arthritis who developed multiple large, painful ulcers that were scattered over his anterior lower legs and were characteristic of pyoderma gangrenosum (PG). This association has not previously been described. We review other forms of arthritis that usually occur with PG and discuss them in light of this observation.

Arthritis, Psoriatic↗
PubMed1994

Calcium-mobilizing agonists stimulate anion fluxes in cultured endothelial cells from human umbilical vein.

The goal of the present studies was to determine whether anion fluxes are involved in thrombin- and histamine-activated signal transduction pathways in human umbilical vein endothelial cells (HUVECs). 125Iodine (125I) efflux techniques were used to test the sensitivity of anion fluxes to increases in [Ca2+]i and activation of protein kinase C. HUVECs exhibited constant 125I efflux rates under basal conditions. Administration of thrombin or histamine stimulated an increase in 125I efflux rates which returned to control values after approximately 1-2 min. Since both agonists stimulate increases in [Ca2+]i, we tested the hypothesis that 125I efflux was sensitive to changes in [Ca2+]i. When HUVECs were exposed to ionomycin or thapsigargin, the 125I efflux rate increased and remained elevated for several minutes. In subsequent experiments, HUVECs were incubated with the cell permanent Ca2+ chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, to buffer changes in [Ca2+]i. This treatment reduced both basal and thrombin-stimulated 125I efflux. However, when Ca2+ was removed from the efflux buffer and replaced with EGTA, peak thrombin-stimulated 125I efflux remained unchanged. This anion efflux was also sensitive to activation of protein kinase C since phorbol 12-myristate 13-acetate and phorbol, 12,13-dibutyrate blunted thrombin-mediated increases in 125I efflux. Preincubation of HUVECs with protein kinase C inhibitor peptide [19-36] antagonized the phorbol ester-mediated decrease in thrombin-stimulated 125I efflux. We suggest that 125I efflux in HUVECs represents a Ca(2+)-sensitive anion conductance and that intracellular Ca2+ release, but not extracellular Ca2+ influx, is sufficient to initiate channel activity.

Anions↗