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Biomedical subjects

H Peterson

Publications and source records attributed to H Peterson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Uptake, metabolism, and cytotoxicity of isomeric cholesterol-5,6-epoxides in rabbit aortic endothelial cells.

The isomeric cholesterol-5,6-epoxides represent two common cholesterol autoxidation products and along with their principal metabolic product, 3 beta,5 alpha,6 beta-cholestane triol, are purportedly angiotoxic. The uptake and cytotoxic action of these compounds was examined in cultured rabbit aortic endothelial cells emphasizing mechanisms of uptake and metabolic fate. The isomeric cholesterol epoxides are incorporated with equal facility and in a dose-dependent manner. The pattern of uptake, which is markedly influenced by media serum concentration and by temperature, suggests that these compounds are partly incorporated through association with serum lipoproteins. After incorporation, both epoxide isomers are rapidly converted to cholestane triol which readily exits the cells. Cholestane triol is further metabolized to an ester-type product representing up to 10% of the added cholesterol epoxides by 24 h of incubation. The order of cytotoxic potency of these cholesterol oxides is: cholestane triol greater than cholesterol-beta-epoxide greater than cholesterol-alpha-epoxide, with LD50 concentrations ranging from 23 to greater than 150 microM in confluent cells. Cholestane triol and cholesterol-beta-epoxide are twice as cytotoxic to subconfluent cells as compared to confluent cells, whereas cholesterol-alpha-epoxide is essentially equitoxic to confluent and subconfluent cells. Cholesterol epoxide cytotoxicity is significantly reduced by treatments in the absence of serum in accord with substantial reduction in uptake when incubations are performed in serum-free media. Our findings show that these cytotoxic cholesterol oxides are incorporated by endothelial cells through a combination of receptor-mediated and nonspecific or passive mechanisms; however, the efficacy of uptake and resulting toxicity is substantially influenced by serum lipoproteins.

Animals↗
PubMed1990

Cutaneous vasculitis associated with pheochromocytoma.

We describe a patient who presented with constitutional symptoms, severe hypertension, and purpuric lesions over the knees, thighs, and penis. The patient was eventually diagnosed as having multiple endocrine neoplasia type II, with cutaneous leukocytoclastic vasculitis. The cutaneous vasculitis persisted despite treatment with high-dose systemic corticosteroids, but rapidly resolved after the removal of bilateral pheochromocytomas. This case demonstrates cutaneous leukocytoclastic vasculitis in association with pheochromocytoma.

Adrenal Cortex Hormones↗
PubMed1989

Incorporation of arachidonic, dihomogamma linolenic and eicosapentaenoic acids into cultured V79 cells.

The uptake and distribution of three common dietary polyunsaturated fatty acids was studied using Chinese hamster lung fibroblasts (V79 cells). Treatment of V79 cells with arachidonic (20:4), eicosapentaenoic (20:5) and dihomogammalinolenic (20.3) acids for 24 hr produced a marked uptake of 20:3 and 20:4, both of which were assimilated to a considerably greater degree than 20:5. All polyunsaturated fatty acids were incorporated primarily into phospholipids; however, there were considerable differences in their distribution into individual phospholipid species. Although 20:4 was incorporated primarily into phosphatidylcholine, 20:3 entered largely into phosphatidylethanolamine and phosphatidylglycerol, and 20:5 was distributed about equally between phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol. A marked conversion of 20:3 to 20:4 was found after 24 hr and, in several phospholipids, there was as much derived-radiolabeled 20:4 as there was radiolabeled 20:3. There was little evidence of 20:4 and 20:5 metabolism. V79 cells undergo substantial changes in phospholipid fatty acid composition following supplementation with these polyunsaturated fatty acids; however, these fatty acids are assimilated to different degrees and their distribution among cellular phospholipids is distinct, suggesting incorporation via independent mechanisms.

8,11,14-Eicosatrienoic Acid↗
PubMed1989

Induction of cytotoxicity and mutagenesis is facilitated by fatty acid hydroperoxidase activity in Chinese hamster lung fibroblasts (V79 cells).

The metabolic activation of benzo[a]pyrene and 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene was studied in V79 Chinese hamster fibroblasts after supplementations with arachidonic acid or treatments with linoleic acid hydroperoxide. The extent of metabolic activation was estimated using cytotoxicity and mutagenesis as endpoints. Pretreatment of cells with arachidonic acid for 24 h resulted in significant elevations in the content of this fatty acid in cell phospholipids and increased prostaglandin synthesis. Arachidonic acid and linoleic acid hydroperoxide facilitated 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene cytotoxicity and mutagenesis, and to a lesser extent increased the cytotoxicity and mutagenicity of benzo[a]pyrene. No other compounds tested were mutagenic under these conditions, however, linoleic acid hydroperoxide markedly increased their cytotoxicity. Arachidonic acid-facilitated toxicity and mutagenesis was inhibited by indomethacin, whereas no inhibition was seen when linoleic acid hydroperoxide was used. Nordihyroquairaretic acid abolished the cytotoxicity and mutagenesis facilitated by arachidonic acid and linoleic acid hydroperoxide. Our findings demonstrate that induction of cytotoxicity and mutagenesis following treatment of V79 cells with carcinogens may be limited by low levels of arachidonic acid in these cells. A peroxidatic mechanism is proposed, with limited substrate specificity, for the metabolic activation of chemicals in V79 cells.

Animals↗
PubMed1988

Mutagenic characterization of cholesterol epoxides in Chinese hamster V79 cells.

The uptake, metabolism and alkylating properties of the diastereomeric cholesterol epoxides were studied using Chinese hamster lung fibroblasts (V79 cells). Specific emphasis is given to the comparative cyto- and geno-toxic effects of cholesterol 5 beta,6 beta-epoxide (beta CE) and cholesterol 5 alpha,6 alpha-epoxide (alpha CE) and data are provided for the first time indicating that beta CE can induce more 6-thioguanine-resistant cells than alpha CE. Cholesterol 5 beta,6 beta-epoxide induced colonies of cells resistant to 6-thioguanine at 2-3-fold the frequencies observed with the alpha-isomer, but neither compound produced ouabain-resistant colonies. The cytotoxicity (LD50) of alpha CE was estimated to be 45-50 microM whereas beta CE displayed an LD50 of 25-29 microM. Inhibition of DNA synthesis (IC50) was observed over the same dose ranges as the LD50 for each epoxide isomer. The epoxides were assimilated by cells to an equal extent, however, beta CE was metabolized to cholestane 3 beta,5 alpha-6 beta-triol twice as rapidly as the alpha-isomer. Both epoxides reacted with 4-(4'-nitrobenzyl)-pyridine to a similar extent, and with identical nucleophilic selectivity at pH 7.4, but their alkylating activity was estimated on this basis to be two orders of magnitude less than methyl methanesulfonate. Binding experiments with the DNA or cultured V79 cells or with calf-thymus DNA indicated that interactions were noncovalent and DNA binding did not correlate with the potency of the epoxides to induce the 6-thioguanine-resistant phenotype. Our results could be interpreted as indicating that both cholesterol epoxide isomers are weak mutagens or that they might induce some epigenetic event repressing the hypoxanthine guanine-phosphoribosyltransferase gene. The similarity of the epoxides' alkylating activity and their DNA-binding properties are inconsistent with their different potencies in inducing the 6-thioguanine-resistant phenotype, suggesting that the mechanism leading to this phenotype is not necessarily the result of DNA alkylation.

Alkylating Agents↗
PubMed1986

Poly(ADP-ribose) synthesis and inhibition of DNA synthesis in Chinese hamster cells treated with methylating agents and thymidine.

A possible role of poly(ADP-ribose) synthesis in modulating the response of V79 cells to DNA damage induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and methyl methanesulfonate (MMS) was investigated. Inhibition of [3H]thymidine (dThd) incorporation into DNA and lowering of NAD+ levels in intact cells were employed as parameters of DNA-synthesis inhibition and poly(ADP-ribose) synthesis, respectively. Dose responses of these parameters were studied in cells 2 and 24 h after treatment with the methylating agents in medium with or without dThd. The initial inhibition of DNA synthesis was uniformly associated with stimulation of poly(ADP-ribose) synthesis whether the cells were treated with MNNG or MMS, incubated with or without 20 microM dThd which did not inhibit poly(ADP-ribose) synthesis, or incubated with 3 mM dThd which did inhibit the latter synthesis. By contrast, the DNA-synthesis inhibition detected 24 h after treatment with MNNG was not associated with poly(ADP-ribose) synthesis. These data suggest that (i) the mechanism of this later inhibition of DNA synthesis is different from that of the initial inhibition, (ii) DNA-synthesis inhibition does not stimulate poly(ADP-ribose) synthesis, and (iii) single-strand breaks, resulting from N-methylation of the DNA, stimulate poly(ADP-ribose) synthesis, which may produce the initial inhibition of DNA synthesis. The initial inhibition of DNA synthesis was not uniformly associated with mutagenesis and dThd facilitation of MNNG-induced cytotoxicity and mutagenesis. This indicates that O-methylation of DNA does not stimulate poly(ADP-ribose) synthesis. Our data suggest that, in V79 cells treated with methylating agents, poly(ADP-ribose) synthesis is stimulated by single-strand breaks, inhibits DNA synthesis, and thereby serves to allow time for repair of the DNA prior to replication.

Animals↗
PubMed1986

Growing pains.

In the investigation of children with leg aches, it is essential to identify any underlying organic disease. Growing pain is a poorly named, nebulous entity that can be diagnosed only by exclusion. The greatest diagnostic error is to make a diagnosis of growing pains while overlooking some serious underlying condition.

Adolescent↗
PubMed1985

Primary pulmonary lymphoma. A clinical and immunohistochemical study of six cases.

Six patients with lymphomatous lesions primarily involving the pulmonary parenchyma were studied. In these patients, both the history and physical findings were vague and minimal. The laboratory findings also were nonspecific, although the findings of large multiple lesions in the lungs and pleural adhesion or effusion were more consistent with lymphoma. Histologic examination revealed lymphocytic infiltration of the pulmonary parenchyma in all six patients and presence of germinal or growth centers in some areas of the lesions in four. The hilar or mediastinal lymph nodes were not involved in five patients so examined. Immunocytochemical study of cytoplasmic immunoglobulin revealed monoclonal lymphocytic proliferation in five patients and negative staining in one patient. Clinical, histologic, or immunohistochemical studies alone may not be sufficient to detect all of the lymphomatous lesions. The combined use of all of these parameters is more advantageous for accurate diagnosis of these lesions. Treatment is surgical resection. Radiotherapy or chemotherapy are used when residual disease is present after surgery. Three patients died of disseminated lymphoma 96, 42, and 8 months after diagnosis, respectively, and three patients are still alive at 18, 24, and 4 months, respectively.

Aged↗
PubMed1985

Deoxyribonucleoside-induced selective modulation of cytotoxicity and mutagenesis.

Treatment of Chinese hamster V79 cells with dThd, dCyd, or dThd plus dCyd increased MNNG-induced AGr-, TGr-, and Ouar-mutant frequencies but did not significantly increase background mutant frequencies. All the AGr colonies that were isolated possessed phenotypes characteristic of HGPRT-deficient mutants, and the deoxyribonucleosides did not selectively affect the growth of the mutants, nor the selecting efficiency of AG, and did not significantly enhance background mutagenesis. These data show that both dThd and dCyd facilitated MNNG-induced mutagenesis. This facilitation was maximal when cells were exposed to the deoxyribonucleosides throughout the first doubling time (24 h) after treatment with MNNG and for 4 more doubling times prior to mutant selection with AG. This indicates that one round of DNA replication was sufficient for mispairing of methylated bases in the DNA with the C and T provided by the deoxyribonucleosides, and that 4-6 doublings prior to mutant selection with AG were necessary to deplete pre-existing hypoxanthine: guanine phosphoribosyl transferase in newly mutated cells. The dCyd facilitated mutagenesis by FdUrd, which was not mutagenic without dCyd, indicating that increased dCTP:dTTP ratios were mutagenic. Treatment with FdUrd plus dCyd also induced FdUrdr cells, suggesting that inhibition of dCyd utilization may prevent the development of FdUrd-resistance in cancer chemotherapy. Although dCyd and dThd facilitated mutagenesis in cells treated with monofunctional alkylating agents that methylate DNA oxygens, facilitation of mutagenesis did not occur in cells treated with BCNU, which cross links DNA, nor with benzo(a)pyrene and aflatoxin B1, which are frame shift mutagens, nor with MMS, which produces barely detectable levels of O-methylation in DNA. Virtually non toxic concentrations of dThd potentiated the cytotoxicity of MNNG more than 10-fold but that of MMS was potentiated only about 2-fold showing that O-alkylation of DNA was associated not only with the facilitation of mutagenesis but also with the potentiation of cytotoxicity. The potentiation of MNNG-induced cytotoxicity was maximal in V79 and L1210 cells after only 2 h treatment with dThd, showing that not even one round of DNA replication was necessary for this potentiation. Moreover, dCyd abolished the potentiation, and, at equitoxic concentrations, MNNG induced higher mutant frequencies than did MMS. These data show that the mechanisms by which methylating agents plus dThd induce mutagenesis are fundamentally different from their mechanisms of cytotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkylating Agents↗
PubMed1984

Mortality among young black women using contraceptives.

Data on the risk of death associated with various contraceptive methods are incomplete. Therefore, we analyzed the mortality rates for young, black inner-city women who used one of four methods of contraception--oral contraceptives, depomedroxyprogesterone acetate, intrauterine (contraceptive) devices, and barrier methods. The subjects were 30,580 15- to 44-year-old women who enrolled at a family planning clinic between 1967 and 1972 and who were observed by monitoring death certificates through the end of 1977. Forty percent of the 218 deaths observed were from accidents and violence. Use of this family planning clinic greatly reduced the risk of death from childbearing; only two deaths were associated with pregnancy and childbirth, compared with the 24 deaths expected. Overall, users of the four methods died at similar, low rates. Given that this study involves considerable loss to follow-up, possible acute effects of contraceptives (eg, infections or thrombosis) are more accurately estimated than possible long-term effects (eg, cancer).

Adolescent↗
PubMed1984

Results, charges, and benefits of intensive care for critically ill patients: update 1983.

Objective and quantitative methods were used to measure severity of illness and outcome of intensive care in critically ill patients, in terms of success or failure of therapy within the ICU, survival or death at 1 yr, quality of life in survivors, and utilization of resources. One hundred ninety-nine consecutive Class IV critically ill surgical patients hospitalized between 1977 and 1978 at the Massachusetts General Hospital comprised the study population. Although the mortality rate of 69% was close to the 73% rate we recorded for 1972-1973, the survivors' quality of life was significantly better. Hospitalization costs increased from $15,000 to $22,000 per patient, almost consistent with the inflation rate between 1973 and 1978. Survival rates and quality of life in survivors did not vary with age. The disease process for which the patient was hospitalized was an important determinant of outcome. Intensive care medicine for critically ill surgical patients does prolong life and enable some patients to return to a productive lifestyle; however, the costs of these benefits are extremely high.

Adult↗
PubMed1984

Objective, quantitative measurement of severity of illness in critically ill patients.

Severity of illness must be quantitated in critically ill patients if studies of outcome and therapeutic efficacy are to be meaningful. Objective physiologic indicators of critical illness, such as pertinent laboratory values, can be quantitated using the Therapeutic Intervention Scoring System--TISS. TISS data were obtained for 199 consecutive Class IV critically ill surgical ICU patients and compared to the same data obtained in less critically ill Class II and III ICU patients who served as the control group. For the physiologic indicators of critical illness, a wide range of normal values was established prospectively. The actual values generated by Class IV patients were compared to values of the same indicators as measured in Class II and III ICU patients. Of all objective indicators of critical illness, 55% were either outside the normal range or more than 2 SD away from the mean value of objective indicators for Class II and III ICU patients; 49% were beyond the normal range or more than 3 SD away. Of all TISS indicators, 73% were abnormal, and 36% of all physiologic indicators were still abnormal despite massive therapeutic support when compared to Class II or III ICU patients. Those patients who had more than 40% of their physiologic indicators abnormal were more likely to die. However, the percentage of abnormal TISS indicators did not discriminate between patients who died and those who lived, because almost all patients received massive support.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical Care↗
PubMed1983

Induction of mutations by 5-fluorodeoxyuridine: a mechanism of self-potentiated drug resistance?

In medium containing concentrations of deoxycytidine that occur in vivo, 5-fluorodeoxyuridine induced mutation frequencies 6-90 fold greater than spontaneous mutant frequencies at two genetic loci in Chinese hamster cells. In medium lacking deoxycytidine, 5-fluorodeoxyuridine was more cytotoxic but induced no mutants. Hence, the effectiveness of cancer therapy with 5-fluorodeoxyuridine may be limited by self potentiated development of 5-fluorodeoxyuridine-resistant mutants and enhanced and prolonged by manipulating deoxycytidine metabolism.

Animals↗
PubMed1983

Sleep studies in the subject's home.

Because the ambient environment affects sleep duration and sequence, sleep in the subject's home may be more valid than in a laboratory. Telephone polysomnogram transmission (TPSM) and portable electromagnetic tape recordings offer recordings in the subject's bedroom. Ten subjects were recorded in the laboratory and at home by TPSM and portable recording. Overall sleep patterns were similar with all three techniques, but sleep and REM latency were much shorter and REM duration much longer, and time awake after sleep onset was longer with laboratory recordings. These data show that sleep patterns in the home differ from recordings in the laboratory. Portable recordings provide the additional benefit of monitoring daytime cycles. TPSM affords seven or eight channels for more precise recording and sleep staging.

Adolescent↗