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D Young

Publications and source records attributed to D Young.

At least 379 records · Page 21Linked to original sources
PubMed1991

Genetic analysis of superoxide dismutase, the 23 kilodalton antigen of Mycobacterium tuberculosis.

The gene encoding a 23 kilodalton protein antigen has been cloned from Mycobacterium tuberculosis by screening of a recombinant DNA library with monoclonal antibodies. The product of the gene has been identified as the superoxide dismutase (SOD) of M. tuberculosis on the basis of sequence comparison and by expression of the recombinant protein in a functionally active form. The derived amino acid sequence of M. tuberculosis SOD reveals a close similarity to manganese-containing SODs from other organisms, in spite of the fact that previous studies using the purified enzyme have identified iron as the preferred metal ion ligand. SOD is present in the extracellular fluid of logarithmic-phase cultures of M. tuberculosis, but the structural gene is not preceded by a signal peptide sequence. Insertion of the M. tuberculosis SOD gene into a novel shuttle vector demonstrated the mycobacteria but is ineffective in Escherichia coli.

Amino Acid Sequence↗
PubMed1991

Suicide, stressors, and the life cycle.

OBJECTIVE: Relationships between stressors and suicide might be expected to vary with stages of the life cycle. The purpose of this study was to examine this possibility. METHOD: The authors examined the first 204 consecutive cases from the San Diego Suicide Study, a federally funded investigation of 283 suicides, for possible relationships between suicide and age and the frequency of specific stressors. Information was gathered from family members, spouses, acquaintances, employers, other witnesses, physicians, and other professionals by trained interviewers using a structured format. Hospital, physician, therapist, school, and police records were also included when available. DSM-III diagnoses were made by consensus of two investigators. Life events information was also reviewed independently by the investigators to determine stressors (if any) for each case. RESULTS: Of the 202 subjects for whom data were available, 195 (97%) had one or more stressors; 137 male subjects had a total of 272 stressors, and 58 female subjects had a total of 115 stressors. The authors found predictable patterns of the three most common stressor groups--conflict-separation-rejection, economic problems, and medical illness. The majority of the stressors among subjects 80 years old or older were illnesses. The only significant difference between the sexes was that more men than women had economic problems as a stressor. CONCLUSIONS: The variations in the patterns of stressors found in this study of suicides coincide with adult development theory. The lack of population comparison subjects and stressor scoring validation, however, limits the predictive value of these data in assessing suicidal persons.

Adolescent↗
PubMed1991

Diapause and quiescence in Lutzomyia diabolica (Diptera:Psychodidae).

Gravid, laboratory-reared Lutzomyia diabolica from Garner State Park, Texas, oviposited from May to December in an outdoor colony cage at Gainesville, Florida. Egg batches contained 100% fast-developing (nondiapause) eggs, a mixture of fast-developing and slow-developing (diapause) eggs, or 100% slow-developing eggs, depending on the time of year laid. The percent diapause eggs per batch increased from 0% in early October to 100% by December. These observations suggest that Lu. diabolica is a long-day species, depositing diapause eggs in response to shorter day length. Temperature may also modify the degree of diapause response by altering the calendar position of the critical day length. Termination of the winter diapause is probably temperature dependent. Quiescence was observed in 3rd and 4th stage larvae in both indoor and outdoor cultures and was usually associated with adverse conditions such as excessive moisture, extreme temperatures, or poor diet.

Animals↗
PubMed1991

Characterization of prominent protein antigens from mycobacteria.

Detailed analysis of mycobacterial proteins originally identified by their prominent interaction with the host immune system reveals a number of interesting biochemical characteristics. M. tuberculosis antigens with molecular weights of 71, 65 and 12 kilodaltons (kD) belong to highly conserved heat shock protein families. A group of closely related antigens with molecular weights around 30 kD are major secreted antigens which share the ability to bind to fibronectin. Antigens with molecular weights of 38 kD and 19 kD are probably lipoproteins with a role in nutrient transport, while the 23 kD antigen is the superoxide dismutase enzyme of M. tuberculosis. It is anticipated that further studies along these lines will generate information of importance to the understanding of the lifestyle of mycobacteria in vivo and also to the elucidation of immune mechanisms in mycobacterial disease.

Antigens, Bacterial↗
PubMed1991

The troubled adolescent.

The general practitioner has to establish whether the alleged 'troubled adolescent' is showing normal or abnormal behaviour. It is necessary to interview the adolescent separately and to act as his or her advocate. A history and a physical examination from an important therapeutic baseline. An understanding of the concerns and developmental tasks of adolescence is vital. Early referral for more complex problems is advisable.

Adolescent↗
PubMed1990

Recognition of a peptide antigen by heat shock--reactive gamma delta T lymphocytes.

Small synthetic peptides that correspond to different portions of the 65-kilodalton mycobacterial heat shock protein (Hsp65) were used to identify a putative antigenic epitope for gamma delta cells. Weaker gamma delta responses to the equivalent portion of the autologous homolog, mouse Hsp63, were also seen. The stimulatory epitope overlaps with an epitope recognized by arthritogenic alpha beta T cell clones. The data suggest that gamma delta cells have a role in autoimmune disorders and imply that these cells recognize ligands by a mechanism similar to that of alpha beta T lymphocytes, that is, in the form of small processed protein fragments bound to antigen-presenting molecules.

Amino Acid Sequence↗
PubMed1990

Quantitation of the antitumour agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in plasma by high-performance liquid chromatography.

N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide is a new experimental antitumour agent which has excellent in vivo activity against the Lewis lung tumour in mice. A reversed-phase high-performance liquid chromatographic method is described for the measurement of this agent in plasma. The internal standard was N-[2-(diethylamino)ethyl]acridine-4-carboxamide. The compounds of interest were extracted from plasma (0.2 ml) with acetonitrile and further purified on C18 solid-phase extraction Bond Elut columns. After elution with acetonitrile-ammonium acetate buffer and evaporation, the final separation was carried out on a C18 muBondapak column with fluorimetric detection. Over the plasma concentration range 100-5000 nM, the intra- and inter-assay coefficients of variation were less than 4.1 and 7.7%, respectively. The accuracy of the method varied from 97 to 105% of the theoretical values. The lowest concentration which could be measured with acceptable accuracy (+/- 10%) and precision (coefficient of variation less than 10%) was 10 nM. The method was sufficiently sensitive to allow pharmacokinetic analyses of 30 mumol/kg doses for more than six half-lives (t1/2) in rabbits (t1/2 = 4) and mice (t1/2 = 1.3 h).

Acridines↗
PubMed1990

Is DNA ploidy an independent prognostic indicator in infiltrative node-negative breast adenocarcinoma?

To evaluate DNA content as an independent, long-term prognostic indicator in infiltrative, node-negative adenocarcinoma of the breast, flow cytometric DNA analyses were performed retrospectively in 165 patients. The exclusive use of paraffin-embedded tissue permitted the study of patients for whom 3 to 15 years' follow-up was available. Other investigators have shown a relationship between DNA nuclear content and well-known prognostic indicators of breast carcinoma, such as estrogen receptors, age, menopausal status, and stage of tumor. However, very few of these studies were based on patients with long-term clinical follow-up and investigated the independent prognostic value of DNA nuclear content. The frequency of aneuploidy in the patients in this study was 57%, with DNA indices ranging from 0.73 to 2.59. Survival in patients with localized breast carcinoma with DNA aneuploid tumors was 84.1% at 5 years and 75.5% at 10 years. Those with diploid tumors showed survival of 87.8% at 5 years and 73.4% at 10 years. These data show no independent prognostic value for DNA nuclear content. The relationship between DNA content, tumor histologic type, and age was also investigated. High-grade tumors were more often aneuploid. There was no association between DNA content and age. Of 165 patients, information regarding estrogen receptor status was available in only 77; 45% of those with aneuploid tumors and 35% with diploid tumors were estrogen receptor-negative. This difference was not significant. The authors conclude that simple determination of DNA ploidy fails to indicate prognosis for infiltrative, node-negative breast carcinoma.

Adenocarcinoma↗
PubMed1990

Disposition of amsacrine and its analogue 9-([2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino)-N,5-dimethyl-4- acridinecarboxamide (CI-921) in plasma, liver, and Lewis lung tumors in mice.

9-([2-Methoxy-4-[(methylsulfonyl)amino]phenyl]amino)-N,5-dimethyl-4- acridinecarboxamide (CI-921), an analogue of the clinical antileukemia drug amsacrine with improved solid tumor activity in mice, is currently being evaluated in patients. In order to determine whether CI-921 possesses any advantages over amsacrine in terms of tissue delivery, the pharmacokinetics of amsacrine and CI-921 were determined following i.v. injection in male B6D2F1 mice. Plasma kinetics in normal mice were measured following administration of 14.4, 28.9, and 57.7 mumol/kg. The kinetics in s.c. Lewis lung tumors, and in plasma and livers of normal and tumor-bearing mice were measured following administration of 57.7 mumol/kg. CI-921 and amsacrine were quantitated by high-performance liquid chromatography after extraction from plasma and from liver and tumor homogenates. In experiments with appropriate 3H-labeled compounds, both total and covalently bound radioactivity (determined after precipitation and washing with acetonitrile) were measured in plasma and in liver homogenates. Over this dose range, nonlinear kinetics were observed in plasma for unchanged CI-921 and amsacrine, and a reasonable fit was obtained with Michaelis-Menten kinetics to a one-compartment model for CI-921 (Km 3.7 mumol/liter; Vmax 18 mumol/h/kg; V ss 3.3 liter/kg) and a two-compartment model for amsacrine (Km 3.6 mumol/liter; Vmax 76 mumol/h/kg; Vss 4.8 liter/kg). The area under the concentration-time curve (AUC) for plasma following a dose of 57.7 mumol/kg was 31 mumol.h/liter for CI-921 and 6.3 mumol.h/liter for amsacrine. However, equilibrium dialysis measurements indicated high plasma protein binding with free drug fractions for CI-921 and amsacrine of 0.63 and 6.7%, respectively. In the liver, unchanged drug concentrations and total radioactivity for both compounds were approximately 10-fold those in plasma, and the tissue half-life of CI-921 was approximately 4-fold longer for CI-921 than for amsacrine. Plasma and liver kinetics in mice with s.c. Lewis lung tumors were similar to those in normal mice. Tumor half-lives of unchanged CI-921 and amsacrine were 3.9 and 2.7 h, respectively, considerably longer than those for plasma (1.2 and 0.30 h respectively) or liver (1.2 and 0.28 h, respectively). Tumor AUC values for CI-921 and amsacrine were 68 and 37 mumol.h/liter, respectively, as compared to the calculated AUC values for free drug in plasma of 0.19 and 0.42 mumol.h/liter, respectively. It is concluded that the uptake into tumors from the plasma free drug fraction is more efficient for CI-921 than for amsacrine.

Amsacrine↗
PubMed1990

Neonatal dopamine lesion in the rat results in enhanced adenylate cyclase activity without altering dopamine receptor binding or dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP-32) immunoreactivity.

Newborn male Sprague-Dawley rats were treated neonatally with an intracisternal injection of 75 micrograms 6-hydroxydopamine (6-OHDA) following desipramine pretreatment in order to induce a permanent selective dopamine (DA) lesion. At 60-70 days of age a massive loss of tyrosine hydroxylase (TH) immunoreactive (IR) cells was seen in substantia nigra. The TH-IR terminal density was reduced by 92% in striatum, 77% in nucleus accumbens and by 72% in tuberculum olfactorium. Quantitative autoradiography using 3H-SCH-23390 and 3H-spiperone did not reveal any alteration of DA D1 and D2 receptor binding in the denervated regions studied. Furthermore, no change in the Bmax or Kd of 3H-SCH-23390 or 3H-spiperone in vitro binding was observed in membrane preparations of striatum following the neonatal DA lesion. Basal and DA-stimulated accumulation of cAMP was increased in striatal membrane preparations of the neonatally DA-lesioned rats. No alteration of the immunoreactivity of the D1 receptor associated phosphoprotein dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP-32), was observed as visualized using quantitative immunohistochemistry. Thus, neonatal DA lesions seem to induce a selective functional supersensitivity reflected by an enhanced activity of D1 receptor-coupled adenylate cyclase, without any alteration in the number of affinity of D1 and D2 receptor sites. Furthermore, the appearance of DARPP-32 seems to be independent of intact DA input during development.

Adenylyl Cyclases↗
PubMed1990

Biliary excretion of reduced haloperidol glucuronide.

The biliary excretion of haloperidol and reduced haloperidol were investigated in the guinea pig. Bile duct cannulated guinea pigs were administered a single intraperitoneal dose of haloperidol (1 mg/kg). Bile was continually collected over a 12-h period. Aliquots of the bile samples were analyzed by HPLC for free haloperidol and reduced haloperidol. The remaining portions of the bile samples were incubated with beta glucuronidase and reanalyzed for haloperidol and reduced haloperidol. Although no significant amount of haloperidol glucuronide was detected in the bile, a new metabolite of reduced haloperidol, reduced haloperidol glucuronide, was found. The amount of reduced haloperidol excreted in the bile as the glucuronide conjugate was significantly higher than the amount of haloperidol or reduced haloperidol. These results imply that reduced haloperidol glucuronide may play a role in the disposition of haloperidol and/or its metabolite, reduced haloperidol.

Animals↗
PubMed1990

Cloning of three human multifunctional de novo purine biosynthetic genes by functional complementation of yeast mutations.

Functional complementation of mutations in the yeast Saccharomyces cerevisiae has been used to clone three multifunctional human genes involved in de novo purine biosynthesis. A HepG2 cDNA library constructed in a yeast expression vector was used to transform yeast strains with mutations in adenine biosynthetic genes. Clones were isolated that complement mutations in the yeast ADE2, ADE3, and ADE8 genes. The cDNA that complemented the ade8 (phosphoribosylglycinamide formyltransferase, GART) mutation, also complemented the ade5 (phosphoribosylglycinamide synthetase) and ade7 [phosphoribosylaminoimidazole synthetase (AIRS; also known as PAIS)] mutations, indicating that it is the human trifunctional GART gene. Supporting data include homology between the AIRS and GART domains of this gene and the published sequence of these domains from other organisms, and localization of the cloned gene to human chromosome 21, where the GART gene has been shown to map. The cDNA that complemented ade2 (phosphoribosylaminoimidazole carboxylase) also complemented ade1 (phosphoribosylaminoimidazole succinocarboxamide synthetase), supporting earlier data suggesting that in some organisms these functions are part of a bifunctional protein. The cDNA that complemented ade3 (formyltetrahydrofolate synthetase) is different from the recently isolated human cDNA encoding this enzyme and instead appears to encode a related mitochondrial enzyme.

Acyltransferases↗