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D Siegel

Publications and source records attributed to D Siegel.

At least 19 recordsLinked to original sources
PubMed1992

Prevalence and correlates of herpes simplex infections. The population-based AIDS in Multiethnic Neighborhoods Study.

OBJECTIVE: To examine the extent and correlates of infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in an inner-city community, we studied the prevalence of antibodies to these viruses and their association with risk behaviors in a representative sample of unmarried white, black, and Hispanic adults living in San Francisco, Calif. DESIGN: Cross-sectional, community-based, random household survey. PARTICIPANTS: In 1988 and 1989, we surveyed 1770 unmarried men and women aged 20 to 44 years from three San Francisco neighborhoods of varying geographic and cultural characteristics. MAIN OUTCOME MEASURES: HSV-1 and HSV-2 antibodies based on an immunodot assay using type-specific glycoproteins gG-1 and gG-2. RESULTS: Of blood samples from 1212 participants available for testing, 750 (62%) had HSV-1 antibodies and 400 (33%) had HSV-2 antibodies. After controlling for other variables, HSV-1 antibody was significantly correlated (P less than .05) with older age (in heterosexual men, women, and homosexually active men), less education (in heterosexual men and women), and Hispanic (especially those not born in the United States) or black race. HSV-2 antibody was significantly correlated (P less than .05) with female gender, number of lifetime sexual partners and older age (in heterosexual men and women), and low levels of education and black or Hispanic race (in women). Among those with antibody to HSV-2, only 28 (19%) of 149 men and 32 (13%) of 251 women reported a history of genital herpes. However, most men (62%) and women (84%) who reported a history of genital herpes had HSV-2 antibodies. We observed a similar pattern (low sensitivity and moderate specificity) for a history of facial herpes and the presence of HSV-1 antibodies. After controlling for other variables, HSV-2 antibodies were associated with a lower frequency of HSV-1 antibodies among homosexual men infected with the human immunodeficiency virus. CONCLUSIONS: HSV-1 antibodies were found in nearly two thirds of single urban adults and were most common among Hispanics not born in the United States. HSV-2 antibodies were found in one third of this population and were associated with risk behaviors for sexually transmitted diseases. For both facial and genital herpes infections, self-reporting of infection was very insensitive and moderately specific.

Adult↗
PubMed1992

Elevated DT-diaphorase activity and messenger RNA content in human non-small cell lung carcinoma: relationship to the response of lung tumor xenografts to mitomycin Cł.

The enzyme DT-diaphorase (DTD; NAD(P)H:quinone oxidoreductase, EC 1.6.99.2), is an obligate two electron reductase which catalyzes reduction of a broad range of substrates, including quinones. We report here variations in DTD concentrations among different classes of lung tumors known also to vary in their responsiveness to cytotoxic agents. Small cell lung carcinomas (SCLCs) and cell lines derived from them have the low DTD activities and mRNA content characteristic of normal human lung, whereas non-small cell lung carcinomas (NSCLCs) have greatly elevated levels. DTD activity was increased up to 80-fold in NSCLC tumors relative to normal lung and 20-35-fold in NSCLC relative to SCLC cell lines. Increased DTD activity appeared to be a function of the NSCLC phenotype rather than a result of derivation from a cell type rich in DTD, since all histological classes of NSCLC showed this phenotype. In addition, where transfection of SCLC cell lines with the v-Ha-ras protooncogene caused a transition to a NSCLC phenotype, DTD activity was also elevated. Neuroendocrine-positive cells (SCLC, carcinoids, and a few NSCLC lines) typically had far lower DTD activities than did cell lines which lacked neuroendocrine markers (most NSCLC cells and mesotheliomas). High DTD activity may be exploited in the design of drugs which undergo bioreductive activation by this enzyme. Consistent with this, xenografts derived from NSCLC cell lines with high DTD that were grown in athymic nude mice were more susceptible to the antitumor quinone, mitomycin C, than were xenografts derived from SCLC cells containing low DTD. These data provide a mechanistic basis for the rational design of more effective bioreductive antitumor agents for use against NSCLC.

Animals↗
PubMed1992

Alteration in DNA cross-linking and sequence selectivity of a series of aziridinylbenzoquinones after enzymatic reduction by DT-diaphorase.

DT-diaphorase (DTD) mediated reduction of a series of 2,5-bis-substituted-3,6-diaziridinyl-1,4-benzoquinones was found to increase the level of DNA interstrand cross-linking (ISC) formed at neutral pH with an enhancement observed as the pH was decreased to 5.8. The analogues used were symmetrically alkyl-substituted carbamoyl ester analogues of AZQ (D1-D7), 3,6-diaziridinyl-1,4-benzoquinone (DZQ), the 2,5-dimethyl derivative (MeDZQ), and a 2,5-bis[(2-hydroxyethyl)amino] analogue (BZQ). At pH 5.8, the level of DNA ISC induced by enzymatic reduction was as follows: DZQ greater than MeDZQ much greater than D1 (methyl) greater than D3 (n-propyl) greater than D2 (AZQ; ethyl) greater than D5 (n-butyl) greater than D7 (sec-butyl) greater than D4 (isopropyl) D6 greater than (isobutyl). A similar trend was observed at pH 7.2. The level of DNA ISC induced by BZQ, which is not a substrate for DTD, was not increased by enzymatic reduction. Dicumarol, a known inhibitor of DTD, was capable of inhibiting the DNA ISC induced by these quinones upon enzymatic reduction. MeDZQ and DZQ reacted with guanines, as measured by Maxam and Gilbert sequencing, with a sequence selectivity similar to that of the nitrogen mustard class of antitumor agents. Enzymatic reduction of DZQ and MeDZQ by DTD was found to alter their sequence-selective alkylation. Reduced DZQ showed enhanced guanine alkylation in 5'-GC-3' sequences and new sites of adenine alkylation in 5'-(A/T)AA-3' sequences. Reduced MeDZQ only showed new sites of adenine alkylation at 5'-(A/T)AA-3' sequences but no enhancement of guanine alkylation. The new sites of adenine alkylation were found to be inhibited in the presence of magnesium and rapidly converted into apurinic sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylation↗
PubMed1992

Mitomycin C.

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Animals↗
PubMed1992

Relationship between DT-diaphorase-mediated metabolism of a series of aziridinylbenzoquinones and DNA damage and cytotoxicity.

A series of 2,5-bis-substituted 3,6-diaziridinyl-1,4-benzoquinones have been tested for their ability to be reduced by the two-electron NAD(P)H:(quinone acceptor) oxidoreductase [DT-diaphorase (DTD); EC 1.6.99.2]. Symmetrically alkyl-substituted carbamoyl ester analogs of 2,5-ethyl(carboethoxyamino)3,6-diaziridinyl-1,4- benzoquinone [AZQ], 3,6-diaziridinyl-1,4-benzoquinone (DZQ), and its 2,5-dimethyl derivative (MeDZQ) were tested. The rate of reduction by DTD was DZQ greater than MeDZQ greater than n-butyl- (D5) greater than sec-butyl- (D7) greater than n-propyl- (D3) greater than methyl- (D1) greater than ethyl- (AZQ) greater than i-butyl- (D6) greater than i-propyl- (D4) substituted derivatives. The hydroxyethylamino analog (BZQ) was not a substrate for DTD. The order of toxicity to HT-29 human colon carcinoma cells (at 1-log cell kill) was MeDZQ greater than DZQ greater than BZQ greater than D1 greater than D5 greater than AZQ greater than D7 greater than D3 greater than D6 greater than D4. Dicumarol, a known inhibitor of DTD, was capable of inhibiting the cytotoxicity of DZQ, MeDZQ, AZQ, D3, D4, D5, D6, and D7, with little inhibition of D1 cytotoxicity. Alkaline elution assays suggested that DZQ induced DNA strand breaks, whereas MeDZQ induced DNA interstrand crosslinks in HT-29 cells. The formation of both classes of lesions was inhibited by dicumarol. DZQ and MeDZQ were 5-6-fold less cytotoxic to the DTD-deficient BE cell line, whereas BZQ was more cytotoxic to this cell line than the HT-29 cell line. BZQ was capable of inducing dicumarol-insensitive DNA interstrand crosslinks in both cell lines. In summary, these data show a trend between the rate of reduction by DTD of an analog and its ability to induce cytotoxicity in HT-29 cells, and they support a role for DTD in the bioreductive activation of AZQ and its analogs.

Animals↗
PubMed1992

Risk for AIDS in multiethnic neighborhoods in San Francisco, California. The population-based AMEN Study.

To examine the actual and potential spread of human immunodeficiency virus (HIV) from an acquired immunodeficiency syndrome (AIDS) epicenter to surrounding neighborhoods, we studied the prevalence of the viral infection and AIDS risk behaviors from 1988 to 1989 in a representative sample of unmarried whites, African Americans, and Hispanics living in San Francisco. We surveyed 1,770 single men and women aged 20 to 44 years (a 64% response rate) in a random household sample drawn from 3 neighborhoods of varying geographic and cultural proximity to the Castro District where the San Francisco epidemic began. Of 1,369 with blood tests, 69 (5%) had HIV antibodies; all but 5 of these reported either homosexual activity (32% HIV-positive; 95% confidence interval [CI] = 23%, 41%), injection drug use (5% HIV-positive; CI = 1%, 14%), or both (59% HIV-positive; CI 42%, 74%). Homosexual activity was more common among white men than among African-American or Hispanic men, but the proportion of those infected was similar in the 3 races. Both the prevalence of homosexually active men and the proportion infected were much lower in the 2 more outlying neighborhoods. Risk behaviors in the past year for acquiring HIV heterosexually--sex with an HIV-infected person or homosexually active man or injection drug user, unprotected sexual intercourse with more than 4 partners, and (as a proxy) having a sexually transmitted disease--were assessed in 1,573 neighborhood residents who were themselves neither homosexually active men nor injection drug users. The prevalence of reporting at least 1 of these risk behaviors was 12% overall, and race-gender estimates ranged from 5% among Hispanic women to 21% among white women. We conclude that in San Francisco, infection with HIV is rare among people who are neither homosexually active nor injection drug users, but the potential for the use spread of infection is substantial, as 12% of this group reported important risk behaviors for acquiring the virus heterosexually.

Acquired Immunodeficiency Syndrome↗
PubMed1979

An improved program to calculate intrapulmonary shunting.

A computer program was developed to calculate intrapulmonary venous admixture on a Texas Instruments TI 59 programmable calculator. The program incorporates the following characteristics: 1) a correction for saturated water vapor pressure which varies with body temperature; 2) a mathematical model of the standard oxyhemoglobin dissociation curve; and 3) correction factors for shifts of the dissociation curve due to variations in pH and carbon dioxide tension. It also corrects oxygen tensions obtained at electrode temperature to those at patient temperature, and calculates variations of the Bunsen solubility coefficient of oxygen in blood with body temperature.

Bionics↗
PubMed1977

Pharmacokinetic study of netilmicin.

Netilmicin at a dose of 2 mg/kg was infused intravenously into 10 healthy volunteers. A peak serum concentration of 16.56 mug/ml was obtained at the end of the infusion. Thirty-nine percent of the infused dose was excreted in the urine during the first 8 h after infusion. The pharmacokinetic parameters of netilmicin were derived by analyzing the elimination data according to a two-compartment model.

Adult↗
PubMed1977

Hepatic dysfunction in acute measles infection of adults.

Hepatitis has rarely been recognized as a complication of acute measles infection. Two adult patients are reported in whom abnormal liver function was a prominent clinical feature during acute measles infection. Hepatic function returned to normal in both patients as the measles infection resolved. Hepatitis may be a salient clinical manifestation of acute measles infection of adults.

Acute Disease↗
PubMed1975

Human therapeutic and agricultural uses of antibacterial drugs and resistance of the enteric flora of humans.

Fecal samples were collected from five groups of people differing in the manner of their exposure to antibacterial drugs. The groups included: (i) people working on farms who were continuously in contact with the predominantly resistant florae of farm animals receiving rations containing antibacterial drugs, (ii) people residing on the same farms with no direct exposure to the farm animals, (iii) people treated with antibacterial drugs, (iv) untreated people residing with treated individuals, and (v) untreated people with no exposure to farm animals or treated individuals. The samples were examined by quantitative plating for proportions of antibiotic-resistant, gram-negative enteric organisms. Individual isolates were also examined for their susceptibility to 11 different antibacterial drugs. The results indicate that enteric florae unexposed directly to the selective effects of antibacterial drugs may be affected by contact with predominantly resistant florae directly exposed to antibacterial drugs.

Agriculture↗