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Biomedical subjects

M A Wright

Publications and source records attributed to M A Wright.

At least 19 recordsLinked to original sources
PubMed2005

People and guns involved in denied and completed handgun sales.

OBJECTIVE: Denial of handgun purchases by prohibited people and knowledge of the structure of gun commerce have helped to deter and prevent firearm violence. The authors hypothesize that handguns involved in a denied purchase would more closely resemble those used in crime compared with handguns sold. DESIGN: Cross sectional. SETTING: Denied and completed handgun sales in California, 1998-2000. MAIN OUTCOME MEASURES: Handgun and purchaser characteristics of denied and completed sales were compared. In particular, handgun characteristics most closely associated with crime guns (type, caliber, barrel length, price) were examined. RESULTS: Compared with handguns sold, handguns in denied sales were somewhat more likely to be semiautomatic pistols (74.6% v 69.4%), to have short barrels (25.9% v 22.2%), and be of medium caliber (48.9% v 37.3%). Ten percent of the handguns in denied sales and 3.4% of handguns sold were identified as inexpensive. CONCLUSIONS: The characteristics of denied handguns are similar to those seen among crime guns. Both groups of guns may reflect the desirability for criminal purposes of pistols, which have larger ammunition capacities than other handguns, and short barrels, which increase their ability to be concealed.

Adult↗
PubMed2005

Risk factors among handgun retailers for frequent and disproportionate sales of guns used in violent and firearm related crimes.

OBJECTIVE: To determine the retailer and community level factors associated with frequent and disproportionate sales of handguns that are later used in violent and firearm related crimes (VFC handguns). DESIGN: Cross sectional. The authors used California records to identify all handguns sold by study subjects during 1996-2000 and federal gun tracing records to determine which of these guns had been recovered by a police agency in the US or elsewhere and traced by 30 September 2003. SUBJECTS AND SETTING: The 421 licensed gun retailers in California selling at least 100 handguns annually during 1996-2000. MAIN OUTCOME MEASURE: The number of VFC handguns per 1000 gun years of exposure. Differences are expressed as incidence rate ratios (RR) with 95% confidence intervals (CI). RESULTS: Subjects accounted for 11.7% of California retailers with handgun sales, 81.5% of handgun sales, and 85.5% of VFC handguns. Among subjects, the 3426 VFC handguns accounted for 48.0% of all traced handguns and 65.0% of those linked to a specified crime. The median VFC handgun trace rate was 0.5/1000 gun years (range 0-8.8). In multivariate analysis, this rate increased substantially for each single-point increase in the percentage of proposed sales that were denied because the purchasers were prohibited from owning guns (RR 1.43; 95% CI 1.32 to 1.56), and was increased for pawnbrokers (RR 1.26; 95% CI 1.02 to 1.55). Community level crime rates and sociodemographics had little predictive value. CONCLUSIONS: Risk factors, largely determined at the retailer level, exist for frequent and disproportionate sales of handguns that are later used in violent and firearm related crimes. Screening to identify high risk retailers could be undertaken with data that are already available.

Adult↗
PubMed2003

Association between handgun purchase and mortality from firearm injury.

OBJECTIVE: To determine the association between mortality from violent or firearm related injury and previous handgun purchase. METHODS: Case-control study of 213 466 Californians ages 21 and older who died in 1998; cases were the 4728 violent or firearm related injury deaths, with subsets by specific cause and means of death, and controls were the 208 738 non-injury deaths. The exposure of interest was the purchase of a handgun during 1996-98. The main outcome measure was the odds ratio for handgun purchase, adjusted for age, sex, race, education, and marital status. RESULTS: Handgun purchase was more common among persons dying from suicide (odds ratio (OR) 6.8; 95% confidence interval (CI) 5.7 to 8.1) or homicide (OR 2.4, 95% CI 1.6 to 3.7), and particularly among those dying from gun suicide (OR 12.5; 95% CI 10.4 to 15.0) or gun homicide (OR 3.3; 95% CI 2.1 to 5.3), than among controls. No such differences were seen for non-gun suicide or homicide. Among women, those dying from gun suicide were much more likely than controls to have purchased a handgun (OR 109.8; 95% CI 61.6 to 195.7). Handgun purchasers accounted for less than 1% of the study population but 2.4% of gun homicides, 14.2% of gun suicides, and 16.7% of unintentional gun deaths. Gun suicide made up 18.9% of deaths among purchasers but only 0.6% of deaths among non-purchasers. CONCLUSION: Among adults who died in California in 1998, those dying from violence were more likely than those dying from non-injury causes to have purchased a handgun.

Adult↗
PubMed2001

Subsequent criminal activity among violent misdemeanants who seek to purchase handguns: risk factors and effectiveness of denying handgun purchase.

CONTEXT: Some states prohibit the purchase of handguns by persons convicted of selected misdemeanor crimes, but most do not. California has denied handgun purchases by violent misdemeanants since 1991; the effectiveness of these policies is unknown. OBJECTIVE: To determine the risk factors for new criminal activity among violent misdemeanants who seek to purchase handguns and whether denial of handgun purchase by violent misdemeanants affects their risk of arrest for new crimes, particularly gun and/or violent crimes. DESIGN: Retrospective, population-based cohort study. SETTING AND SUBJECTS: Persons aged 21 to 34 years who sought to purchase a handgun through a licensed dealer in California during 1989-1991 and who had at least 1 violent misdemeanor conviction in the preceding 10 years. The study cohorts consisted of 986 persons whose purchase applications were made in 1991 and were denied (denied persons) and 787 persons whose purchase applications were made in 1989-1990 and were approved (purchasers). MAIN OUTCOME MEASURES: Incidence and relative risk of first arrest in California for new gun and/or violent crimes and for nongun, nonviolent crimes during a 3-year follow-up after actual or attempted handgun purchase. RESULTS: During the 3-year follow-up, 546 (33.0%) of 1654 subjects with follow-up information were arrested for a new crime, including 296 (31.9%) of 927 denied persons and 250 (34.4%) of 727 purchasers. After adjusting for differences in age, sex, and prior criminal history, purchasers were more likely than denied persons to be arrested for new gun and/or violent crimes (relative hazard [RH], 1.29; 95% confidence interval [CI], 1.04-1.60), but not for nongun, nonviolent crimes (RH, 0.96; 95% CI, 0.78-1.19). In both groups, risk of arrest was strongly related to age and number of convictions accrued prior to actual or attempted handgun purchase. CONCLUSION: Our results indicate that denial of handgun purchase to violent misdemeanants is associated with a specific decrease in risk of arrest for new gun and/or violent crimes.

Adult↗
PubMed2000

Polygalacturonase gene expression in kiwifruit: relationship to fruit softening and ethylene production.

In kiwifruit, much of the softening process occurs prior to the respiratory climacteric and production of ethylene. This fruit therefore represents an excellent model system for dissecting the process of softening in the absence of endogenous ethylene production. We have characterized the expression of three polygalacturonase (PG) cDNA clones (CkPGA, B and C) isolated from fruit of Actinidia chinensis. Expression of CkPGA and B was detected by northern analysis only in fruit producing endogenous ethylene, and by RT-PCR in other tissues including flower buds, petals at anthesis, and senescent petals. CkPGA promoter fragments of 1296, 860 and 467 bp fused to the beta-glucuronidase (uidA) reporter gene directed fruit-specific gene expression during the climacteric in transgenic tomato. CkPGC gene expression was observed in softening fruit, and reached maximum levels (50-fold higher than for CkPGA and B) as fruit passed through the climacteric. However, expression of this gene was also readily detected during fruit development and in fruit harvested prior to the onset of softening. Using RT-PCR, expression of CkPGC was also detected at low levels in root tips and in senescent petals. These results suggest that PG expression is required not only during periods of cell wall degeneration, but also during periods of cell wall turnover and expansion.

Amino Acid Sequence↗
PubMed2000

Vitamin D3 treatment to diminish the levels of immune suppressive CD34+ cells increases the effectiveness of adoptive immunotherapy.

Tumor growth can increase the number of immature bone marrow-derived CD34+ cells that exhibit natural suppressor (NS) activity toward T-cell function. Using a metastatic Lewis lung carcinoma (LLC-LN7) tumor model, these CD34+ NS cells were shown to be present within the s.c. primary tumor tissue, but their levels declined after treatment with the inducer of myeloid cell differentiation, vitamin D3. Therefore, studies determined whether vitamin D3 treatment to diminish the CD34+ NS cell levels in LLC-LN7-bearing mice would enhance (a) intratumoral immune reactivity and (b) the antitumor activity of adoptive therapy consisting of tumor-reactive lymph node cells. The results showed that vitamin D3 treatment alone increased the intratumoral CD8+ cell content and the activity of the intratumoral infiltrate, as detected by production of interferon-gamma and expression of the p55 IL-2 receptor. Although vitamin D3 treatment had no effect on the size of the primary tumor, it lessened the extent of tumor metastasis. Treating mice with the combination of vitamin D3 and adoptive immunotherapy significantly reduced metastasis in mice with established tumors, and reduced both metastasis and locoregional recurrence after surgical excision of the primary tumor. These studies demonstrate that vitamin D3 treatment increases intratumoral T-cell immune reactivity, and that coupling vitamin D3 treatment to diminish levels of CD34+ NS cells with adoptive immunotherapy enhances the effectiveness of the adoptively transferred tumor-reactive lymph node cells at limiting both metastasis and locoregional tumor recurrence.

Animals↗
PubMed1999

Increased resistance to apoptosis by bone marrow CD34(+)progenitor cells from tumor-bearing mice.

Tumors, such as the murine Lewis lung carcinoma (LLC), produce granulocyte-macrophage colony-stimulating factor (GM-CSF), which increases the proportion of CD34(+) hematopoietic progenitor cells in the bone marrow and in the periphery. This increase in peripheral CD34(+) cells had been attributed to the growth-promoting and mobilizing effects of the tumor-derived GM-CSF. However, the possibility that the CD34(+) cells of tumor bearers might have enhanced survival abilities had not been considered. The present studies showed a significant baseline level of apoptotic cells in short-term (5-day) cultures of normal CD34(+) cells containing GM-CSF plus stem cell factor (SCF), and a markedly greater level of apoptosis in cytokine-deficient cultures. In contrast, CD34(+) cells from tumor bearers did not undergo such levels of apoptosis, even in the absence of cytokines. This resistance to apoptosis could be conferred to normal CD34(+) cells by culture with LLC-conditioned medium. Studies to elucidate possible mechanisms for the resistance to apoptosis by tumor-exposed CD34(+) cells showed increased levels of the pro-life gene product bcl-2. Finally, the resistance of tumor-exposed CD34(+) cells to ligation of the Fas receptor, a known apoptotic trigger in hematopoietic cells, was compared with that of control CD34(+) cultures. Whereas approximately half of the normal CD34(+) cells underwent apoptosis in response to Fas ligation, the tumor-exposed CD34(+) cells resisted apoptosis, even though their surface Fas expression was greater than that of normal CD34(+) cells. Thus, our results show that the increased level of CD34(+) cells in tumor bearers is due not only to an increased growth and mobilization of CD34(+) cells as previously thought, but also may be due to an increased resistance to apoptosis that is conferred by tumor-derived products and is associated with increased expression of bcl-2.

Animals↗
PubMed1999

Dendritic cell differentiation pathways of CD34+ cells from the peripheral blood of head and neck cancer patients.

Patients with head and neck squamous cell carcinoma (HNSCC) have increased levels of immune-suppressive peripheral blood CD34+ cells. This study showed that the peripheral blood CD34+ cells of HNSCC patients are capable of differentiating into dendritic cells. Because CD34+ cells can differentiate through several pathways into dendritic cell subpopulations, the intermediate cells through which the blood CD34+ cells of HNSCC patients differentiate were identified. After 6-7 days of culturing the CD34+ cells of HNSCC patients with granulocyte-macrophage colony-stimulating factor, stem cell factor, and tumor necrosis factor at, there appeared CD14+CD1a+ and a lesser proportion of CD14(-)CD1a+ cells resembling the precursor cells of the bipotential and committed dendritic cell differentiation pathways that have been described for cord blood CD34+ cells. To functionally analyze whether these populations were in fact precursor cells, they were isolated and cultured for an additional 10-12 days. Each of these populations was shown to function as precursor cells because they were able to develop into cells that resembled dendritic cells, although a higher proportion developed from the CD14-CD1a+ cells. In contrast, expression of the dendritic activation/maturation marker CD83 was highest on the cells that developed from CD14+CD1a+ cells. Thus, the CD34+ cells whose levels are increased in HNSCC patients can develop into both committed and bipotential dendritic precursor cells, which can subsequently give rise to dendritic cells.

Antigens, CD1↗
PubMed1999

The impact of childhood foster care and other out-of-home placement on homeless women and their children.

OBJECTIVE: This study compares homeless women who had childhood histories of foster care or other out-of-home placement to those who have not. METHOD: A countywide probability sample of homeless women (n = 179) received structured interviews. RESULTS: One-third of homeless women reported being raised apart from their parents. Among women with children under age 18, most (61.5%) had children who had lived in foster care or other out-of-home placements. Variables associated with homeless mothers' children living in foster care or other out-of-home placements were: Child was school-age, mother was age 35 or older, mother had a current alcohol or drug use disorder, mother experienced childhood sexual abuse, and mother ran away from home (when under age 18). CONCLUSIONS: Parenting is difficult for homeless mothers who may need to place their children with others to facilitate school attendance. Parent-child interaction may be problematic in family shelters where privacy is rare. Thus, programs promoting family preservation for homeless mothers should provide parenting support as well as permanent housing.

Adult↗
PubMed1999

Skewed differentiation of bone marrow CD34+ cells of tumor bearers from dendritic toward monocytic cells, and the redirection of differentiation toward dendritic cells by 1alpha,25-dihydroxyvitamin D3.

Tumor presence is detrimental to the development of antigen-presenting dendritic cells. Since dendritic cells can arise from CD34+ precursor cells, the present study assessed the capacity of bone marrow CD34+ cells from tumor bearers to develop into dendritic cells when cultured in the absence of either tumor cells or their products. Culturing bone marrow CD34+ cells from mice bearing Lewis lung carcinomas yielded a lower number of dendritic cells than arose from CD34+ cells of normal mice. This reduced yield of dendritic cells was associated with a shift to development of monocytic cells and a reduced antigen presenting capability by the cultures. When the CD34+ cell cultures from tumor bearers were supplemented with the differentiation-inducing hormone 1alpha,25-dihydroxyvitamin D3, there was the restoration of dendritic cell development and antigen presenting ability. These results show that CD34+ cells from tumor bearers remain defective in their development into dendritic cells even when cultured outside the tumor environment, but development of dendritic cells can be restored with 1alpha,25-dihydroxyvitamin D3.

Animals↗
PubMed1999

Cultures derived from peripheral blood CD34+ progenitor cells of head and neck cancer patients and from cord blood are functionally different.

Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune defects mediated, in part, by an increased number of immune suppressive CD34+ progenitor cells in their peripheral blood and tumor. One means of overcoming this immune suppression is to stimulate the CD34+ cells to differentiate into more mature, nonsuppressive progeny such as dendritic cells or monocytes. This study determined that CD34+ cells from the peripheral blood of HNSCC patients have the same potential to differentiate into dendritic cells as do human umbilical cord blood CD34+ cells following 12-16 days of culture with a cytokine cocktail. When compared functionally, the cultures that developed from CD34+ cells of cord blood were able to induce an allostimulatory response in naive T-cells, while the cultures that developed from patient CD34+ cells lacked allostimulatory ability. Both cultures expressed class II MHC (HLA-DR), but the proportion of cells expressing the costimulatory molecules CD80 and CD86 was significantly less in cultures that developed from HNSCC-patient CD34+ cells. Therefore, although the CD34+ cells from the peripheral blood of HNSCC patients can differentiate into dendritic cells, their allostimulatory capabilities are impaired, raising the question of their potential effectiveness in stimulating antitumor immune responses.

Antigens, CD34↗
PubMed1999

Chemoattraction of femoral CD34+ progenitor cells by tumor-derived vascular endothelial cell growth factor.

Patients and animals with GM-CSF-producing tumors have an increased number of mobilized CD34+ progenitor cells within their peripheral blood and tumor tissue. These CD34+ cells are inhibitory to the activity of intratumoral T-cells. The present study used the murine Lewis lung carcinoma (LLC) model to assess mechanisms that could lead to the accumulation of CD34+ cells within the tumor tissue. In vitro analyses showed that LLC tumor explants released chemoattractants for normal femoral CD34+ cells. The LLC tumor cells contributed to the production of this activity since CD34+ cell chemoattractants were also released by cultured LLC cells. Antibody neutralization studies showed that most, although not all, of the chemotactic activity that was produced by LLC cells could be attributed to VEGF. In vivo studies with fluorescent-tagged CD34+ cells showed their accumulation within the tumor tissue, but not within the lungs, spleen or bone marrow, suggesting a selective accumulation within the tumor. Whether or not VEGF could chemoattract CD34+ cells in vivo was measured with a VEGF-containing Matrigel plug assay. Infusion of fluorescent-tagged CD34+ cells into mice after the plugs became vascularized revealed the accumulation of fluorescent-tagged cells within the plugs. However, these CD34+ cells failed to accumulate within the VEGF-containing Matrigel plugs when they were infused together with neutralizing anti-VEGF antibody. Through a combination of in vitro and in vivo analyses, the LLC cells were shown to be capable of chemoattracting CD34+ cells, with most of the tumor-derived chemotactic activity being due to tumor release of VEGF.

Animals↗
PubMed1999

Effectiveness of denial of handgun purchase to persons believed to be at high risk for firearm violence.

OBJECTIVES: The purpose of this study was to determine whether denial of handgun purchase is an effective violence prevention strategy. METHODS: Individuals denied handgun purchase because of a prior felony conviction and handgun purchasers with a felony arrest at time of purchase were examined. RESULTS: Relative to those denied purchase, handgun purchasers were found to be at greater risk for subsequent offenses involving a gun (relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.08, 1.36) or violence (RR = 1.24, 95% CI = 1.11, 1.39), after adjustment for number of prepurchase weapon/violence charges. CONCLUSIONS: Denial of handgun purchase to persons with a prior felony conviction may lower their rate of subsequent criminal activity.

Adult↗
PubMed1998

Stimulation of immune suppressive CD34+ cells from normal bone marrow by Lewis lung carcinoma tumors.

Progressive growth of metastatic Lewis lung carcinoma (LLC-LN7) tumors is associated with increased levels of bone-marrow-derived CD34+ cells having natural suppressor (NS) activity toward T cells. The present studies determined whether tumor-derived products are responsible for this induction of NS activity. Culturing normal bone marrow cells with LLC-LN7-conditioned medium (LLC-CM) or with recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) resulted in the appearance of NS activity. The development of NS activity coincided with a prominent increase in the levels of CD34+ cells. That the CD34+ cells were responsible for the NS activity of the bone marrow cultures containing LLC-CM was shown by the loss of NS activity when CD34+ cells were depleted. The stimulation of CD34+ NS cells by LLC-CM was attributed to tumor production of GM-CSF, since neutralization of GM-CSF within the LLC-CM reduced its capacity to increase CD34+ cell levels. Studies also showed that the induction of CD34+ NS cells by LLC-CM and GM-CSF could be overcome by including in the cultures an inducer of myeloid differentiation, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]. These results demonstrate that the mechanism by which the LLC-LN7 tumors stimulate increased levels of CD34+ NS cells from normal bone marrow is by their production of GM-CSF and that this can be blocked with the myeloid differentiation inducer 1,25(OH)2D3.

Animals↗
PubMed1998

Criminal activity and assault-type handguns: a study of young adults.

STUDY OBJECTIVE: We studied a population of young adults who legally purchased handguns to determine whether an association exists between the purchase of an assault-type handgun and prior or subsequent criminal activity. METHODS: We conducted a longitudinal study of 5,360 legally authorized purchasers of handguns in California in 1988 who were younger than 25 years at the time of purchase. Our main outcome measures were (1) adjusted relative risk (RR) for the purchase of an assault-type handgun for subjects with a criminal history compared with subjects without such a history and (2) adjusted RR for new criminal activity during the 3 years after handgun purchase for purchasers of assault-type handguns compared with purchasers of other handguns. RRs were adjusted for sex and race/ethnicity. RESULTS: Handgun purchasers with a criminal history were more likely than those with no criminal history to purchase assault-type handguns (4.6% and 2.0%, respectively; RR = 2.0; 95% confidence interval [CI] 1.5 to 2.8). Among handgun purchasers who had a criminal history, purchasers of assault-type handguns were more likely than purchasers of other handguns to be charged with new offenses (RR = 1.5; 95% CI, 1.3 to 1.9), including offenses involving firearms of violence (RR = 1.7; 95% CI, 1.3 to 2.20. Among those who had previously been charged with Violent Crime Index offenses (murder, rape, robbery, aggravated assault), those who purchased assault-type handguns were more than twice as likely as purchasers of other handguns to be charged with a new offense (RR = 2.3; 95% CI, 1.5 to 3.4) and three times as likely to be charged with a new offense involving firearms or violence (RR = 3.0, 95% CI, 1.9 to 4.6). CONCLUSION: In this population, the purchase of an assault-type handgun was associated with both prior and subsequent criminal activity.

Adolescent↗
PubMed1998

Apple ACC-oxidase and polygalacturonase: ripening-specific gene expression and promoter analysis in transgenic tomato.

Levels of 1-aminocyclopropane-1-carboxylate (ACC) oxidase and polygalacturonase (PG) mRNAs were characterized during ripening of Royal Gala, Braeburn and Granny Smith apples. Both ACC-oxidase and PG mRNAs were up-regulated in ripening fruit of all three cultivars. Expression in Royal Gala was detected earlier than in Braeburn and Granny Smith, relative to internal ethylene concentration. Genomic clones corresponding to the ACC-oxidase and PG mRNAs expressed in ripe apple fruit were isolated and ca. 2 kb of each promoter was sequenced. The start point of transcription in each gene was mapped by primer extension, and sequences homologous to elements in other ethylene-responsive or PG promoters were identified. The fruit specificity of the apple ACC-oxidase and PG promoters was investigated in transgenic tomato plants using a nested set of promoter fragments fused to the beta-glucuronidase (gusA) reporter gene. For the ACC-oxidase gene, 450 bp of 5' promoter sequence was sufficient to drive GUS expression, although this expression was not specific to ripening fruit. Larger fragments of 1966 and 1159 bp showed both fruit and ripening specificity. For the PG gene, promoter fragments of 1460 and 532 bp conferred ripening-specific expression in transgenic tomato fruit. However GUS expression was down-regulated by 2356 bp of promoter, suggesting the presence of a negative regulatory element between positions -1460 and -2356.

Amino Acid Oxidoreductases↗
PubMed1998

Failure of tumor-reactive lymph node cells to kill tumor in the presence of immune-suppressive CD34+ cells can be overcome with vitamin D3 treatment to diminish CD34+ cell levels.

Growth of Lewis lung carcinoma (LLC-LN7) tumors results in an increase in CD34+ granulocyte-macrophage progenitor cells having natural suppressor (NS) activity. These CD34+ NS cells were capable of inhibiting the cytotoxic activity of tumor-reactive lymph node cells. In vivo studies showed that adoptive treatment of LLC-LN7 tumor-bearing mice with tumor-reactive lymph node cells plus IL-2 failed to reduce the development of metastases. Studies were conducted to determine if diminishing the levels of CD34+ NS cells would allow for improved anti-tumor effectiveness of the adoptively transferred cells. The suppressive activity of CD34+ cells toward the cytolytic activity of tumor-reactive lymph node cells could be blocked by in vitro culture of CD34+ cells with the differentiation-inducing hormone 1alpha,25-dihydroxyvitamin D3. Similarly, treatment of LLC-LN7-bearing mice with vitamin D3 alone diminished the levels of CD34+ NS cells within regional lymph nodes, spleens and tumors. This treatment resulted in an increased immune reactivity to autologous tumor, as shown by the production of IFN-gamma by lymph node cells in response to the presence of LLC-LN7 cells. The extent of tumor metastasis in mice receiving vitamin D3 treatment was also reduced. When tumor-reactive lymph node cells were adoptively transferred into these LLC-LN7-bearing mice that were receiving vitamin D3 treatment, there resulted a pronounced synergistic reduction in tumor metastasis. The results of this study show that treatment of tumor bearers with vitamin D3 to eliminate CD34+ NS cells improves the anti-tumor effectiveness of adoptively transferred tumor-reactive lymph node cells.

Animals↗