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Biomedical subjects

J Wiley

Publications and source records attributed to J Wiley.

At least 55 records · Page 3Linked to original sources
PubMed1992

Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498.

The treatment of acute myeloid leukemia (AML) in children with Down's syndrome (DS) has engendered considerable controversy. Because of the concerns for toxicity and increased rate of infections, treatment approaches varied considerably in the past with mixed results. However, experience on the recently completed Pediatric Oncology Group (POG) 8498 AML study suggests that DS children with AML constitute a distinct subgroup that responds well to therapy. Twelve of 285 children on POG 8498 (protocol for newly diagnosed AML) had DS. Children with DS and AML were predominantly male (9 of 12) and were quite younger at diagnosis (< 24 months in 10). The white blood cell count was less than 50 x 10(3)/microL in all 12 and French-American-British types M6 and M7 were frequent (5 of 12). An abnormal cytogenetic marker, in addition to constitutional trisomy 21, was present in 9 of 12 and involved chromosome 8 in 4 of 9. All cases studied (n = 5) were positive for myeloid cell surface markers (CD33, CD13, or CD11b) and, interestingly, were also positive for the CD7 antigen. Chemotherapy included daunorubicin, cytarabine (Ara-C), and 6-thioguanine for remission induction and featured high-dose Ara-C (3 g/m2 per dose) with or without L-asparaginase early in remission. Compared with children without DS, children with DS had a superior event-free survival (EFS at 4 years 100% v 28% +/- 6.2%; P = .003). The EFS remained superior even when compared with non-DS children less than 2 years of age with a white blood cell count less than 10 x 100,000/microL (100% v 48% +/- 17.3%; P = .01).

Acute Disease↗
PubMed1992

Proof of differentiative mode of action of all-trans retinoic acid in acute promyelocytic leukemia using X-linked clonal analysis.

Using X-linked clonal analysis, mechanism of action of all-trans retinoic acid (ATRA) was sought in a 16-year-old female with relapsed clonally evolved acute promyelocytic leukemia (APL), who achieved complete remission. On ATRA, metamorphosis of peripheral blood leukemic promyelocytes to mature neutrophils was observed, despite the persistence of t(15;17) in 100% of bone marrow metaphases. DNA was extracted from fractionated serial blood specimens, collected at diagnosis, in first complete remission (CR), relapse, and during ATRA treatment. Using a phosphoglycerokinase (PGK) probe, the patient was heterozygous for both Bgl I and Bst XI PGK polymorphisms. Methylation analysis showed monoclonal leukemic promyelocytes with a polyclonal first CR achieved by standard chemotherapy. Subsequent examination, in relapse, of granulocytes appearing during ATRA treatment showed these to be monoclonal, proving these were derived from the neoplastic clone. The X-linked clonal analysis methodology has provided in vivo evidence of cellular differentiation as the mechanism of action of ATRA. Parallel studies of cytogenetic and clonal analysis showed a regression of the t(15;17) cytogenetic abnormality and return of a polyclonal PGK methylation pattern in 5 weeks, indicating a repopulation of marrow by normal stem cells. As standard cytogenetic techniques are inappropriate for nondividing cells, X-linked clonal analysis provides a marker system to allow insight into mechanism of drug action in malignant hematologic disease.

Adolescent↗
PubMed1992

Nicotinic receptor-evoked release of acetylcholine and somatostatin in the myenteric plexus is coupled to calcium influx via N-type calcium channels.

Entry of extracellular calcium (Ca++) via voltage-gated Ca++ channels is essential for neurotransmitter release. In this study, we examined whether nicotinic receptor-stimulated release of acetylcholine (ACh) and somatostatin (S14) are coupled to calcium influx via distinct calcium channel subtypes in the myenteric plexus. Isolated ganglia from the guinea pig ileal myenteric plexus were prepared and placed in perfusion chambers under standard conditions. The ganglionic agonist dimethylphenylpiperazinium (DMPP, 10(-6) to 10(-3) M) stimulated the release of [3H]ACh in a concentration-dependent manner. This release was blocked by hexamethonium or Ca(++)-free medium containing 1 mM EGTA and was antagonized by omega-conotoxin, a preferential N calcium channel blocker, but was not affected by nifedipine (L channel antagonist) or nickel (T calcium channel antagonist). DMPP-evoked release of somatostatin was also antagonized by omega-conotoxin, but was not affected by nifedipine or nickel. These observations indicate that neurosecretion of ACh and S14 evoked by DMPP is mediated by calcium entry via voltage-sensitive N-type Ca++ channels. To provide additional evidence that nicotinic receptor stimulation is associated with Ca++ entry via the N-type Ca++ channels, we examined the intracellular calcium [Ca++]i concentration of the myenteric plexus neurons using fura-2 microspectrofluorometry. Basal [Ca++]i of single ileal myenteric neurons was 65 +/- 5 nM. Perfusion with DMPP (10(-6) to 10(-3) M) caused a rapid, transient elevation in [Ca++]i which was abolished by Ca(++)-free medium containing 1 mM EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
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↗
PubMed1991

Vascularity of tumors in children: evaluation with color Doppler imaging.

Twenty-one tumors in 20 children were evaluated with duplex and color Doppler imaging to determine the value of the technique in assessing the origin and pattern of vascular supply and the degree of neovascularity. The origin of the vascular supply was detected correctly in 12 of 13 tumors that were subsequently resected. In five children, this aided in determining the organ from which the tumor originated, and in one child, it established the presence of a tumor by showing blood flow in the center of a suspected abscess. In 18 tumors, color Doppler imaging showed the pattern of the vascular supply. Eleven had a peripheral pattern, and seven had a central, branching pattern. Although individual tumor types appeared to have characteristic patterns of vascular supply, these were not specific enough to aid in making a specific diagnosis. When the degree of intratumor neovascularity was graded on the basis of the findings on color Doppler imaging, it agreed with the results of histologic evaluation in 16 of 19 tumors. In one tumor, neovascularity was overestimated, and in two, it was markedly underestimated. Our experience suggests that color Doppler imaging is useful in detecting the origin and pattern of vascular supply and the degree of intratumoral blood flow in a variety of solid tumors in children.

Adolescent↗
PubMed1990

Mechanisms regulating somatostatin release and somatostatin-induced acetylcholine release from the myenteric plexus.

The present studies were performed to characterize the molecular form(s) of somatostatin present in the myenteric plexus and to examine some aspects of the regulatory mechanisms underlying somatostatin release and somatostatin-induced release of acetylcholine from this tissue. We observed the following: (1) Somatostatin-like immunoreactivity (SLI) is present in the myenteric plexus of the guinea pig ileum with somatostatin-14 being the predominant molecular form. (2) Somatostatin-like immunoreactivity is released from isolated myenteric ganglia after stimulation with veratridine or the ganglionic agonist dimethylphenylpiperazinium (DMPP). (3) Calcium entry via the N-type channel appears to play a dominant role in DMPP-induced release of SLI. (4) Somatostatin regulates its own release via a pertussis toxin-sensitive mechanism. (5) Under basal conditions somatostatin-14 stimulates release of acetylcholine in a concentration-dependent manner. (6) Calcium entry via L-type channels is associated with the release of acetylcholine evoked by somatostatin-14.

Acetylcholine↗
PubMed1989

Rare clonal karyotypic variants in primary cultures of human breast carcinoma cells.

Cytogenetic analyses were performed on 40 previously untreated primary human breast carcinomas, four untreated breast metastases, nine human breast fibroadenomas, and ten normal human mammary tissues, all in primary culture. The results revealed predominantly normal diploid cells with abnormal clones in two of 40 primary carcinomas and one of four metastases. 3p deletion [del(3)(p14-21)], similar to that associated with small cell lung cancer, was found in a primary tumor from a patient with bilateral breast cancer. In addition, a clone with t(1;4) was found in another primary breast carcinoma, while a t(1;5) clone was found in a metastatic tumor.

Breast↗
PubMed1989

Prostate-specific antigenic domain of human prostate specific antigen identified with monoclonal antibodies.

With the use of five murine monoclonal antibodies (1A5, 2A4, 3F1, F5 and 3A12) and an antigen-affinity purified goat polyclonal IgG antibody, the presence of a prostate-specific antigenic domain in human prostate-specific antigen molecule was identified. The results were based upon a series of quantitative competitive inhibition assays of each 125I-labeled monoclonal antibody and polyclonal antibody binding to prostate-specific antigen by unlabeled monoclonal antibodies as inhibitors, and immunohistochemical examination of an extensive panel of human tissue specimens. A cluster of two epitopes that are spatially related or in close topographical proximity and represent a prostate-specific antigenic domain are defined by the monoclonal antibodies 1A5, 2A4, 3F1, and F5, 3A12, respectively.

Animals↗
PubMed1989

Serum alpha-tocopherol levels of Mexican Americans, Cubans, and Puerto Ricans aged 4-74 y.

Data from the Hispanic Health and Nutrition Examination Survey were used to examine serum alpha-tocopherol levels (in subjects aged 4-74 y) and ratios of alpha-tocopherol to cholesterol plus triglyceride and to cholesterol (in subjects aged 20-74 y) of Mexican Americans (MA), Cubans, and Puerto Ricans (PR). Neither alpha-tocopherol nor the alpha-tocopherol-lipid ratios differed between sexes. PR had lower mean alpha-tocopherol and alpha-tocopherol-lipid ratios and higher prevalences of alpha-tocopherol less than 11.6 mumol/L than did MA or Cubans in several age groups. MA and Cuban adolescents had lower alpha-tocopherol levels than children had. Mean alpha-tocopherol levels and alpha-tocopherol-lipid ratios increased and prevalences of alpha-tocopherol less than 11.6 mumol/L decreased during adulthood in all three ethnic groups.

Adolescent↗
PubMed1988

Participation of gastric mechanoreceptors and intestinal chemoreceptors in the gastrocolonic response.

In this study we investigated the site and nature of the signal responsible for the generation of the gastrocolonic response at the rectosigmoid region. Sixteen healthy subjects participated in this study. Motor activities were recorded with pressure transducers placed in the rectosigmoid colon. Balloon distention of the stomach with 100, 200, or 300 ml of water caused a volume-dependent increase in rectosigmoid motility that was abolished by atropine. To investigate the intestinal phase of the gastrocolonic response, we infused into the duodenum isocaloric (178 kcal) solutions of normal saline, lipid, glucose, or essential amino acids at 1.5 ml/min for 30 min in random order on separate days. Only lipid infusion caused an increase in rectosigmoid pressure and this was accompanied by an elevation of plasma cholecystokinin from 1.2 +/- 0.1 to 4.3 +/- 1.0 fmol/ml. The increase in motility associated with lipid infusion was antagonized (58% +/- 7%) by atropine. To further investigate the possible role of cholecystokinin as a mediator of the gastrocolonic response, we infused cholecystokinin-octapeptide intravenously at doses of 5, 10, and 20 ng/kg.h. A significant increase in rectosigmoid motility was observed only at 20 ng/kg.h and this was accompanied by an increase in plasma cholecystokinin levels to 12 +/- 2 fmol/ml, a value threefold greater than that produced by lipid infusion. These studies demonstrate that gastric distention and intestinal lipid are potent stimuli for the generation of the gastrocolonic response involving the rectosigmoid region. The gastric phase can be generated by mechanoreceptors utilizing the cholinergic pathways, whereas the intestinal phase is nutrient-specific, partially atropine-sensitive, and independent of cholecystokinin.

Adolescent↗
PubMed1988

A comparison of alcohol and drug use patterns of homosexual and heterosexual men: the San Francisco Men's Health Study.

Very high prevalence rates for problem drinking and/or alcoholism have been estimated for homosexual male populations. Populations characterized by high prevalence rates for problematic drug or alcohol use are of special interest since study of such groups may help to provide insights regarding the processes associated with problematic substance use. However, prevalence estimates for problematic substance use within gay male populations have most typically relied on convenience samples and generally contain an over-representation of bar patrons. This study reports data from a large scale random household sample of homosexual and heterosexual men who live in an urban district of San Francisco, California. Few differences were noted in the drinking patterns of these men, although important differences were found in the prevalence of drug use over a 6-month period. Differences in the prevalence of at least weekly drug use were comparatively minor, however. Health policy implications of these findings are discussed.

Adult↗
PubMed1987

Neuropeptide Y inhibits cholinergic transmission in the isolated guinea pig colon: mediation through alpha-adrenergic receptors.

Neuropeptide Y, a member of the pancreatic polypeptide family, caused dose-dependent relaxation of guinea pig colon longitudinal muscle. This inhibitory effect was unaffected by hexamethonium but was abolished by atropine and tetrodotoxin, suggesting that neuropeptide Y is acting via postganglionic cholinergic neurons. Studies utilizing alpha-adrenergic and dopamine receptor antagonists revealed that neuropeptide Y-mediated relaxation was blocked only by the alpha 2 antagonist yohimbine. Neuropeptide Y also antagonized muscle response to electric field stimulation that was reversed by yohimbine. Additional studies with muscle slices incubated with [3H]norepinephrine or [3H]choline showed that neuropeptide Y stimulated norepinephrine release from sympathetic nerves, which, in turn, inhibited the release of acetylcholine via alpha 2 receptors located on postganglionic nerves. This pathway provides a mechanism for neuropeptide modulation of classical neurotransmitter function.

Acetylcholine↗
PubMed1987

Participation of serotonin and substance P in the action of cholecystokinin on colonic motility.

Cholecystokinin (CCK) has a potent stimulatory effect on gastrointestinal motility. The mechanism of CCK-generated contractions in the colon is unknown. We explored the possibility that CCK-mediated contractions in the guinea pig colon occur via a serotonin and/or substance P pathway. In the circular layer, octapeptide of CCK (CCK-8) had no effect under basal conditions, but after treatment with tetrodotoxin the peptide generated dose-dependent contractions (ED50 6 X 10(-8) M). In the longitudinal layer, CCK-8 produced dose-related contractions (ED50 6 X 10(-9) M) blocked by tetrodotoxin and markedly inhibited by the substance P antagonist, Spantide. The effect of substance P was not significantly antagonized by tetrodotoxin but was markedly attenuated by Spantide. Serotonin produced dose-dependent contractions in the longitudinal layer (ED50 4 X 10(-8) M). Desensitization to serotonin antagonized the action of CCK-8 but had no effect on substance P-mediated contractions. Pretreatment with the serotonin antagonist mianserin inhibited CCK-8- but not substance P-generated contractions. In contrast, the stimulatory effect of serotonin was antagonized by Spantide. These studies suggest that in the circular layer of the guinea pig colon CCK-8 has no effect under basal conditions, but after removal of tonic inhibition, the peptide produced a direct stimulatory effect. In contrast, CCK-8 generated contractions in guinea pig colon longitudinal layer, mediated by a pathway involving serotonin and substance P.

Animals↗
PubMed1987

Somatostatin inhibits cAMP-mediated cholinergic transmission in the myenteric plexus.

The mechanism by which somatostatin acts to modulate cholinergic transmission is not clear. In this study we investigated the role of the adenosine 3',5'-cyclic monophosphate (cAMP) system in mediating cholinergic transmission in the guinea pig myenteric plexus and examined the ability of somatostatin to alter acetylcholine (ACh) release stimulated by various cAMP agonists. Forskolin, 8-bromo-cAMP, vasoactive intestinal peptide (VIP), and cholera toxin each stimulated the release of [3H]ACh in a dose-related manner. Addition of theophylline enhanced the release of [3H]ACh stimulated by these cAMP agonists. In contrast 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, antagonized the action of forskolin, VIP, and cholera toxin but had no effect on that evoked by 8-bromo-cAMP. These observations suggest that cAMP may serve as a physiological mediator for ACh release from myenteric neurons. Somatostatin inhibited release of [3H]ACh evoked by various cAMP agonists in a dose-related manner. Maximal inhibition, observed in the presence of 10(-6) M somatostatin was 48 +/- 5, 47 +/- 9, and 43 +/- 12% of control for forskolin-, VIP-, and cholera toxin-evoked release of [3H]ACh. In contrast somatostatin at 10(-6) M inhibited only 20 +/- 5% of the release of [3H]ACh stimulated by 8-bromo-cAMP. Pretreatment with pertussis toxin antagonized the inhibitory effect of somatostatin on the release of [3H]ACh evoked by forskolin, VIP, or cholera toxin but had no effect on the inhibitory action of somatostatin on the release of [3H]ACh evoked by 8-bromo-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Dopaminergic modulation of rectosigmoid motility: action of domperidone.

To investigate the role of dopamine in the modulation of colonic motility we evaluated the effect of dopamine on basal rectosigmoid motor activity before and after treatment with domperidone, phentolamine, propranolol, atropine or placebo in 12 healthy subjects. We also investigated the role of dopamine on the postprandial gastrocolic response. Basal motility index was 126 +/- 38. Dopamine (5-100 micrograms/kg) generated dose-dependent contractions with a frequency of 3 cpm. At 50 micrograms/kg dopamine produced a motility index of 2066 +/- 631. Pretreatment with domperidone (0.4 mg/kg) significantly decreased the amplitude of contractions induced by dopamine but had no effect on the frequency. The motility index was reduced to 668 +/- 148. In contrast atropine, phentolamine and propranolol had no effect on dopamine-stimulated motility. Furthermore, domperidone significantly attenuated the postprandial gastrocolic response compared to placebo. The motility indices of the early and late gastrocolic response were reduced by 65 +/- 12 and 70 +/- 10% of control, respectively. These studies indicate that dopamine stimulates rectosigmoid motility in contrast to its known inhibitory effect on upper gastrointestinal motility. This appears to be mediated by specific dopamine receptors.

Adolescent↗
PubMed1986

Alcohol and drug use during sexual activity and compliance with safe sex guidelines for AIDS: the AIDS Behavioral Research Project.

This article describes the association between drug and alcohol use during sexual activity and high-risk sex for AIDS. Data to test this association are drawn from a prospective study of the behavioral changes made by gay men in San Francisco in response to the AIDS epidemic. Findings drawn from the May, 1984 and May 1985 waves of data collection are described. The cross-sectional analysis showed that use of particular drugs during sex, the number of drugs used during such activity, and the frequency of combining drugs and sex are all positively associated with risky sexual activity for AIDS. The retrospective data showed that men who currently abstained from combining drug use with sexual activity were likely to have been at no risk for AIDS over two measurement points during the previous year. The men who currently combined drug use with sex were most likely to have a history of high-risk sexual activity over the previous year. These findings show a strong relationship between drug and alcohol use during sex and non-compliance with safe sex techniques to prevent the spread of AIDS. Implications of this relationship for AIDS health education efforts are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Mutagenicity of cyclopenta-fused isomers of benz(a)anthracene in bacterial and rodent cells and identification of the major rat liver microsomal metabolites.

The microsomal metabolites and mutagenic activity of four cyclopenta-fused benz(a)anthracenes, benz(j)aceanthrylene [B(j)A], benz(e)aceanthrylene [B(e)A], benz(l)aceanthrylene [B(l)A], and benz(k)acephenanthrylene [B(k)A], have been studied. Aroclor 1254-induced rat liver microsomes metabolized B(j)A to B(j)A-1,2-dihydrodiol, B(j)A-9,10-dihydrodiol, B(j)A-11,12-dihydrodiol, and 10-hydroxy-B(j)A; B(e)A-1,2-dihydrodiol, B(e)A-3,4-dihydrodiol, and B(e)A-5,6-dihydrodiol; B(l)A to B(l)A-1,2-dihydrodiol, B(l)A-4,5-dihydrodiol, and B(l)A-7,8-dihydrodiol; and B(k)A to B(k)A-4,5-dihydrodiol and B(k)A-8,9-dihydrodiol. With each polycyclic aromatic hydrocarbon, metabolism occurred on the cyclopenta ring. All four isomers were active as gene mutagens in Salmonella typhimurium and in Chinese hamster V79 cells. In the S. typhimurium mutation studies, using Aroclor 1254-induced rat liver S9, B(j)A, B(e)A, and B(l)A required significantly less microsomal protein for maximal mutation response than B(k)A and B(a)P, suggesting a one-step activation mechanism, presumably on the cyclopenta-fused ring. B(j)A, B(e)A, and B(l)A were significantly more mutagenic than B(k)A and B(a)P in S. typhimurium. In the Aroclor 1254-induced rat liver S9-mediated V79 mutagenesis system, all four isomers were active, with B(l)A the most active. When Syrian hamster embryo cells were used as the metabolic activation component for V79 cells, only B(l)A produced a significant response and was equivalent in activity to B(a)P. A helical configuration for B(l)A is inferred from the identification of two trans-B(l)A-1,2-dihydrodiols, syn and anti, which have been synthesized, separated, and characterized. The metabolically formed dihydrodiol is anti-trans-B(l)A-1,2-dihydrodiol, and experimental evidence suggests that the metabolically formed B(l)A-1,2-oxide is the anti-isomer. Synthetic B(l)A-1,2-oxide was found to be a direct-acting mutagen in S. typhimurium and Chinese hamster V79 cells and is estimated to account for up to 40% of the mutagenic activity of the parent hydrocarbon. Therefore, certain cyclopenta-ring fusions on benz(a)anthracene appear to markedly increase its genotoxic and carcinogenic activities.

Animals↗