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Biomedical subjects

P C Brown

Publications and source records attributed to P C Brown.

At least 19 recordsLinked to original sources
PubMed1992

Social influence, marriage, and the heart: cardiovascular consequences of interpersonal control in husbands and wives.

Human and experimental animal research suggests that social stress in general--and chronic, effortful attempts to exert social control in particular--may contribute to cardiovascular disease. We examined the effects of exerting social influence or control on cardiovascular responses in married couples. Compared to husbands discussing a problem with their wives, husbands attempting to influence or persuade their wives displayed larger increases in systolic blood pressure (SBP) before and during the discussion. Furthermore, these physiological effects were accompanied by increases in anger and a more hostile and coldly assertive interpersonal style. Although wives who engaged in social influence attempts displayed generally similar behavior, they did not show the elevated SBP response or anger. We discuss the results in terms of the social context of cardiovascular reactivity and potential marital factors in cardiovascular health.

Adaptation, Psychological↗
PubMed1992

Ultrastructural changes in acquired perforating dermatosis.

We performed ultrastructural studies of skin lesions in seven adults with acquired perforating dermatosis. Three of the patients had diabetes mellitus and two were undergoing hemodialysis. Lesions in an early stage showed exocytosis of inflammatory cells and alteration of elastic fibers. Lesions in an intermediate stage featured discontinuities of the basement membrane and aggregates of electron-dense material lateral to the perforated focus, together with dermal edema, scattered macrophages, and densely aggregated collagen fibers that focally filled the papillary dermis. Later-stage lesions showed fibroblasts in the dermis and degenerated elastic fibers within transepidermal channels. In most cases there was a single large epidermal channel lined by flattened epithelial cells, and containing a variety of cellular and extracellular materials. Small "secondary" channels without abnormal keratinization were also observed within the epidermis. The findings suggest that altered keratinization is limited to the immediate vicinity of well-formed transepidermal channels, and that exocytosis of inflammatory cells and alterations of elastica are early and possibly key changes in lesion development. The unexpected discovery of hair fragments in one case suggests that curled hairs may play a role in the pathogenesis of some cases of acquired perforating dermatosis.

Adult↗
PubMed1992

Comparison of iohexol 300 and diatrizoate meglumine 60 for body CT: image quality, adverse reactions, and aborted/repeated examinations.

Six hundred patients were prospectively randomized and given either diatrizoate meglumine 60 or iohexol 300 during dynamic contrast-enhanced body CT in order to compare image quality, contrast reactions, and the number of aborted studies or studies in which images had to be repeated. Three hundred two patients received iohexol 300, and 298 patients received diatrizoate meglumine 60. Thirty-nine percent (119/302) of the patients given iohexol 300 and 63% (188/298) of the patients given diatrizoate meglumine 60 had at least one adverse reaction thought to be related to contrast material during, or within 24 hr of, the body CT scan. When reactions of discomfort (heat or warmth, flushing, bad taste) were excluded, 16% (48/302) of the patients who received iohexol and 33% (99/298) of the patients who were given diatrizoate meglumine 60 had at least one adverse reaction. The differences in both types of reactions between the two agents were significant (p less than .001). Among scans evaluated for study quality, 71% (214/302) of the iohexol 300 group and 62% (184/298) of the diatrizoate meglumine 60 group had optimal enhancement (p = .02). However, when the optimal and adequate categories were combined, 301 of 302 patients given iohexol 300 and 292 of 298 patients given diatrizoate meglumine 60 had diagnostic-quality studies (no statistical difference). Studies were not terminated nor were images repeated in 97% (292/302) of the patients given iohexol 300 and in 94% (280/298) of those given diatrizoate meglumine 60. The CT study was repeated because of movement during the contrast injection or aborted because of contrast-related reactions in 0.7% of the patients given iohexol 300 and in 3.0% of the patients given diatrizoate meglumine 60. This difference was statistically significant (p = .04). Our results suggest that the difference in image quality, number of adverse reactions, and number of aborted/repeated CT scans performed with iohexol 300 or diatrizoate meglumine 60 are not sufficiently different to warrant conversion to nonionic agents for body CT scans.

Diatrizoate Meglumine↗
PubMed1991

The toxicity of menadione (2-methyl-1,4-naphthoquinone) and two thioether conjugates studied with isolated renal epithelial cells.

Menadione (2-methyl-1,4-naphthoquinone) was used as a model compound to test the hypothesis that thioether conjugates of quinones can be toxic to tissues associated with their elimination through a mechanism involving oxidative stress. Unlike menadione, the glutathione (2-methyl-3-(glutathion-S-yl)-1,4-naphthoquinone; MGNQ) and N-acetyl-L-cysteine (2-methyl-3-(N-acetylcysteine-S-yl)-1,4-naphthoquinone; M(NAC)NQ) thioether conjugates were not able to arylate protein thiols but were still able to redox cycle with cytochrome c reductase/NADH and rat kidney microsomes and mitochondria. Interestingly, menadione and M(NAC)NQ were equally toxic to isolated rat renal epithelial cells (IREC) while MGNQ was nontoxic. The toxicity of both menadione and M(NAC)NQ was preceded by a rapid depletion of soluble thiols and was associated with a depletion of soluble thiols and was associated with a depletion of protein thiols. Treatment of IREC with the glutathione reductase inhibitor, 1,3-bis(2-chloroethyl)-1-nitrosourea, potentiated the thiol depletion and toxicity observed with menadione and M(NAC)NQ indicating the involvement of oxidative stress in this model of renal cell toxicity. The lack of MGNQ toxicity can be attributed to an intramolecular cyclization reaction which destroys the quinone nucleus and therefore eliminates its ability to redox cycle. These findings have important implications with regard to our understanding of the toxic potential of quinone thioether conjugates and of quinone toxicity in general.

Animals↗
PubMed1991

Cynical hostility, attempts to exert social control, and cardiovascular reactivity in married couples.

Chronically hostile persons may be at greater risk of cardiovascular illness, perhaps because of their more pronounced physiologic responses to interpersonal stressors. The present study of married couples examined the association between Cook and Medley Hostility (Ho) Scale scores and cardiovascular reactivity while couples were engaged in a discussion task with or without an incentive to exert control over their partner. Cynical hostility was associated with greater heart rate (HR) reactivity among husbands in both conditions and with greater systolic blood pressure (SBP) reactivity among husbands attempting to influence their wives. Further, husbands' cynical hostility was associated with greater SBP reactivity in their wives. Wives' cynical hostility was unrelated to their own or their husbands' reactivity. These results underscore the importance of social contexts in the association between hostility and psychophysiologic processes and suggest that the motive to exert social control may be important for hostile persons.

Adult↗
PubMed1991

Effect of allyl alcohol on xanthine dehydrogenase activity in the perfused rat liver.

Xanthine oxidase has been implicated in the production of reactive oxygen species and cell injury produced by various toxic compounds. Since allyl alcohol injuries the liver by an oxygen-dependent mechanism, we examined the actions of this hepatotoxicant on the conversion of xanthine dehydrogenase into xanthine oxidase in perfused livers. A microassay for NAD(+)-dependent xanthine dehydrogenase, based on measuring the production of NADH fluorometrically under anaerobic conditions, was developed and used to examine the actions of allyl alcohol on this activity in periportal and pericentral regions of the liver lobule. The oxygen-dependent activity, xanthine oxidase, was monitored in whole liver homogenates by uric acid formation at 302 nm under aerobic conditions. Perfusion of the liver with allyl alcohol (350 microM) increased xanthine oxidase and decreased xanthine dehydrogenase in whole liver consistent with the hypothesis that allyl alcohol enhanced calcium-dependent proteolytic conversion of the NAD(+)-dependent to the O2-dependent form. Xanthine dehydrogenase was higher in pericentral than in periportal regions of the liver lobule and tended to decrease selectively in periportal zones of livers exposed to allyl alcohol. O2 uptake was stimulated transiently by allyl alcohol followed by subsequent inhibition of respiration. These results are consistent with the idea that conversion of NAD(+)-dependent xanthine dehydrogenase to xanthine oxidase is involved in the zone-specific hepatotoxicity of allyl alcohol.

1-Propanol↗
PubMed1990

The mechanism of cysteine conjugate cytotoxicity in renal epithelial cells. Covalent binding leads to thiol depletion and lipid peroxidation.

Nephrotoxic cysteine conjugates kill cells after they are metabolized by the enzyme cysteine conjugate beta-lyase to reactive fragments which bind to cellular macromolecules. We have investigated the cellular events which occur after the binding and lead ultimately to cell death in renal epithelial cells. Using S-(1,2-dichlorovinyl)-L-cysteine (DCVC) as a model conjugate, we found that the phenolic antioxidants N,N'-diphenyl-p-phenylenediamine (DPPD), butylated hydroxyanisole, butylated hydroxytoluene, propyl galate, and butylated hydroxyquinone, and the iron chelator deferoxamine inhibited the cytotoxicity significantly. Among the five antioxidants, DPPD was most potent. DPPD blocked DCVC toxicity over an extended time period, and the rescued cells remained functional as measured by protein synthetic activity. DPPD was able to block the toxicity of two other toxic cysteine conjugates S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine and S-(1,1,2,2-tetrafluoroethyl)-L-cysteine. In addition to LLC-PK1 cells, DPPD also protected freshly isolated rat kidney epithelial cells in suspension and in primary culture. In suspension cells, DPPD was effective at low doses of DCVC (25-50 microM) but not at high concentrations (250-500 microM). DPPD inhibition was not due to an inactivation of beta-lyase or a decrease in the binding of [35S]DCVC metabolites to cellular macromolecules and occurred at a step after the activation of the toxins. During DCVC treatment, lipid peroxidation products were detectable prior to cell death. DPPD blocked lipid peroxidation over the whole time course. Depletion of nonprotein thiols also occurred prior to cell death. DPPD did not prevent the loss of nonprotein thiols. However, the sulfhydryl-reducing agent DTT blocked lipid peroxidation and toxicity at a step after the activation of DCVC. Therefore, it appears that cysteine conjugates kill renal epithelial cells by a combination of covalent binding, depletion of nonprotein thiols, and lipid peroxidation.

Animals↗
PubMed1989

Infection-induced panniculitis.

We evaluated the histopathologic findings in 15 cases of panniculitis due to infection. Organisms were identified by special staining in 14 cases, and in 6 of these the etiologic agent was confirmed by culture studies. In one additional case, lesional culture was positive despite negative special staining. Eight cases were caused by gram positive or gram negative bacteria, 2 by atypical mycobacteria, 2 by Nocardia, and 3 by fungi (Candida and Fusarium species). Most patients had conditions or were receiving therapies predisposing to immunosuppression, but at least 2 individuals had no other major medical problems. There were some variability in microscopic findings and overlap with established forms of panniculitis; 3 cases (2 due to bacteria and 1 to Fusarium) resembled acute, "neutrophilic" erythema nodosum, and evidence of vasculitis was seen in septicemias due to Pseudomonas, Nocardia, and Fusarium. Nevertheless, several distinctive features associated with infectious panniculitis of diverse etiologies included: epidermal alterations such as acanthosis and parakeratosis; dermal edema with a diffuse or perivascular neutrophilic infiltrate; and mixed septal-lobular panniculitis with neutrophilic infiltration, vascular proliferation and hemorrhage, and necrosis. Infection should be suspected in virtually any case of panniculitis, particularly when occurring in an immunosuppressed patients, but the microscopic features enumerated above should arouse particular suspicion of an infectious process.

Adult↗
PubMed1987

The role of preoperative colonoscopy in colorectal cancer.

Routine preoperative colonoscopy has been recommended for those patients with the diagnosis of colorectal cancer to identify synchronous polyps and/or cancers which might otherwise be undetected on barium enema or at the time of operation. It has been suggested that this approach may alter surgical therapy or follow-up. The charts of 98 patients who underwent preoperative colonoscopy solely for the purpose of detecting additional polyps or cancers prior to open surgical resection for colorectal cancer were retrospectively reviewed. All patients had biopsy or barium-enema evidence of colorectal cancer. Patients with familial polyposis or chronic ulcerative colitis were excluded. Synchronous cancers were detected in 7.1 percent of patients, and synchronous neoplastic polyps in 29 percent. Forty-three percent of synchronous cancers and 73 percent of synchronous neoplastic polyps would not have been included in the standard surgical resection for the index cancer if the additional information provided by colonoscopy had not been available. Surgical treatment and/or follow-up were altered in 33 percent of patients as a consequence of the colonoscopic evaluation. Colonoscopy prior to surgery for colorectal carcinoma is highly desirable and may potentially improve long-term survival.

Adult↗
PubMed1987

Pancreatic lymphoma, diagnosis and management.

Eleven cases of non-Hodgkin's lymphoma were referred as patients thought to have pancreatic cancer. It was impossible to make the diagnosis in this particular group of patients preoperatively, by imaging techniques and needle biopsy. For this reason we favor laparotomy for staging followed by Roux-en-Y choledochojejunostomy for those patients with obstructive jaundice because this approach both rapidly resolves the jaundice and enables a more accurate diagnosis. We do not feel that non-surgical means of decompression of the biliary tree by transhepatic or endoscopically placed stents are as safe or effective for patients who are potentially curable because the diagnosis may not be made early enough. We call this group of patients to your attention because recent reports indicate that over 30% of such patients can be cured by chemotherapy. Thus these lesions should be differentiated from others at this location.

Adult↗
PubMed1987

Potentially curable masses in the pancreas.

Twenty patients with intraabdominal non-Hodgkin's lymphoma localized to the peripancreatic area were reviewed. Appropriate diagnosis and staging required exploratory laparotomy and biopsy. With appropriate chemotherapy and radiotherapy, 40 percent of these patients were alive 3 years after diagnosis without evidence of disease. It is for this reason that we have adopted an aggressive approach in obtaining histologic diagnoses for all pancreatic masses.

Adenocarcinoma↗
PubMed1985

Mechanisms of 3-hydroxy-3-methylglutaryl coenzyme A reductase overaccumulation in three compactin-resistant cell lines.

We have isolated three mammalian cell lines which are resistant to compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The drug resistance in all three cell lines is due to an increase of HMG-CoA reductase activity. Two of the three cell lines overaccumulate HMG-CoA reductase messenger RNA when grown in the presence of compactin. DNA hybridization experiments indicate that both a baby hamster kidney-derived compactin-resistant cell line, C100, and a cell line derived from mouse 3T6 cells, 3T6-40, exhibit amplifications of the HMG-CoA reductase gene. A third compactin-resistant cell line derived from Chinese hamster ovary cells, ML100, does not exhibit an amplification of the HMG-CoA reductase gene, nor does it show an elevated level of HMG-CoA reductase mRNA, comparable to that seen in the other cell lines.

Animals↗
PubMed1979

Coordinated modulation of albumin synthesis and mRNA levels in cultured hepatoma cells by hydrocortisone and cyclic AMP analogs.

The treatment of Hepa-2 cells, a permanent mouse hepatoma cell line, for 72 h with hydrocortisone (10(-6) M), N6,O2-dibutyryl cyclic AMP (10(-3) M), or 8-bromocyclic AMP (10(-3) M) results in a 2-,3- or 4-fold increase, respectively, in rates of synthesis and secretion of mouse serum albumin. Simultaneous treatment with hydrocortisone and N6,O2-dibutyryl cyclic AMP results in a 10-fold stimulation in these parameters, an effect that is significantly more than additive for the two compounds tested. The number of albumin mRNA sequences, determined by hybridization of total cell RNA to albumin complementary DNA, was increased in direct proportion to the increases in albumin synthesis in all experiments. The relative rate of albumin synthesis approaches in vivo levels in cells treated simultaneously with hydrocortisone and N6,O2-dibutyryl cyclic AMP. We propose that these factors may be necessary to maintain the maximal level of differentiated function in the continuous culture of Hepa-2 cells.

Animals↗
PubMed1979

Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes.

Selection of mammalian cells in progressively increasing concentrations of methotrexate results in selective amplification of DNA sequences coding for dihydrofolate reductase (tetrahydrofolate dehydrogenase, 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 1.5.1.3). In some cell variants the amplified genes are stable with growth in the absence of methotrexate, whereas in other variants the amplified genes are lost from the population. We have previously reported that in a stably amplified variant of Chinese hamster ovary cells, the genes are localized to a single chromosome. Herein we report that in mouse S-180 and L5178Y cell lines unstably amplified dihydrofolate reductase DNA sequences are associated with small, paired chromosomal elements denoted "double minute chromosomes," whereas in stably amplified cells of the same origin, the genes are associated with large chromosomes.

Animals↗