PubMed Health⌕ Search

Biomedical subjects

S A Norman

Publications and source records attributed to S A Norman.

At least 19 recordsLinked to original sources
PubMed2005

Reproductive factors and subtypes of breast cancer defined by hormone receptor and histology.

Reproductive factors are associated with reduced risk of breast cancer, but less is known about whether there is differential protection against subtypes of breast cancer. Assuming reproductive factors act through hormonal mechanisms they should protect predominantly against cancers expressing oestrogen (ER) and progesterone (PR) receptors. We examined the effect of reproductive factors on subgroups of tumours defined by hormone receptor status as well as histology using data from the NIHCD Women's Contraceptive and Reproductive Experiences (CARE) Study, a multicenter case-control study of breast cancer. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risk using multivariate unconditional logistic regression methods. Multiparity and early age at first birth were associated with reduced relative risk of ER + PR + tumours (P for trend=0.0001 and 0.01, respectively), but not of ER - PR - tumours (P for trend=0.27 and 0.85), whereas duration of breastfeeding was associated with lower relative risk of both receptor-positive (P for trend=0.0002) and receptor-negative tumours (P=0.0004). Our results were consistent across subgroups of women based on age and ethnicity. We found few significant differences by histologic subtype, although the strongest protective effect of multiparity was seen for mixed ductolobular tumours. Our results indicate that parity and age at first birth are associated with reduced risk of receptor-positive tumours only, while lactation is associated with reduced risk of both receptor-positive and -negative tumours. This suggests that parity and lactation act through different mechanisms. This study also suggests that reproductive factors have similar protective effects on breast tumours of lobular and ductal origin.

Adult↗
PubMed2001

Development and validation of a telephone questionnaire to characterize lymphedema in women treated for breast cancer.

BACKGROUND AND PURPOSE: Accurate and economical characterization of lymphedema is needed for population-based studies of incidence and risk. The purpose of this study was to develop and validate a telephone questionnaire for characterizing lymphedema. SUBJECTS: Forty-three women who were treated previously for breast cancer and who were recruited from physical therapy practices and a cancer support organization were studied. METHODS: Questionnaire assessment of the presence and degree of lymphedema was compared with physical therapists' diagnoses, based primarily on circumferential measurements. Twenty-five of the 43 subjects were measured independently by 2 physical therapists to assess interobserver agreement. RESULTS: Interobserver agreement on clinical assessments of the presence and degree of lymphedema was high (20/25, weighted kappa=.80); all of the disagreements were between judgments of whether there was no lymphedema or mild lymphedema. For the diagnosis of at least moderate lymphedema (differential in the circumferences of the upper extremities greater than 2 cm), sensitivity of the questionnaire varied from 0.86 to 0.92 and specificity was 0.90. However, sensitivity (varying from 0.93 to 0.96) was higher than specificity (varying from 0.69 to 0.75) for the diagnosis of any lymphedema. DISCUSSION AND CONCLUSION: A few straightforward questions exhibited excellent agreement with physical therapists' assessments for identifying at least moderate lymphedema.

Adult↗
PubMed2000

Identification of transforming growth factor-beta1-binding protein overexpression in carmustine-resistant glioma cells by MRNA differential display.

BACKGROUND: The authors previously demonstrated the presence of cells in primary human malignant gliomas that intrinsically are resistant to carmustine (BCNU). Numerous studies have identified mechanisms of therapy resistance in these cells; however, the authors' work and that of others suggest that additional mechanisms of resistance exist. METHODS: The authors identified a glioma cell line that lacks detectable methylguanine methyltransferase expression and does not alter its expression of glutathione-S-transferase-pi in response to BCNU chemotherapy. This cell line was used in mRNA differential display experiments to identify genes involved in what to the authors' knowledge were previously undescribed mechanisms of resistance. RESULTS: The overexpression of the gene encoding the transforming growth factor latency binding protein was demonstrated in glioma cells selected for resistance to BCNU, compared with their parental unselected cells. CONCLUSIONS: Transforming growth factor-beta1 has pleiotropic functions in transformed and normal cells. Although activation of TGF-beta1 does not appear to be a causative factor in BCNU resistance in the current study, it may be involved in the growth of these resistant cells.

Aged↗
PubMed1998

Expression of a receptor protein tyrosine phosphatase in human glial tumors.

We have analyzed expression of a receptor protein tyrosine phosphatase (RPTPzeta/beta) in tissue samples from 23 human gliomas. Using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we assayed for the presence or absence of mRNA transcripts encoding the intact receptor and 2 alternatively spliced forms of RPTPzeta/beta. Transcripts encoding the intact and truncated receptors were expressed in all of the lower grade gliomas (WHO grade 1-3) analyzed, but not in 55% of the grade 4 glioblastomas multiforme (GBM). However, this subset of GBMs did express an alternatively spliced secreted form comprised of only the RPTPzeta/beta extracellular domain. Our data suggests there may be a correlation between the loss of transcripts encoding the receptor forms of RPTPzeta/beta and progression from low to high grade gliomas. This work provides additional evidence for the importance of phosphatase isoform expression in human tumors.

Adolescent↗
PubMed1998

Altered gene expression in human astrocytoma cells selected for migration: I. Thromboxane synthase.

Human glioma cells from a long-term cell line were selected for their ability to migrate on a glioma-derived extracellular matrix. When tested over 28 serial passages, the migration-selected strain showed a genetically stable, enhanced migration rate compared with the parental cells. Proliferation studies demonstrated that the growth rate of migration-selected cells was slightly arrested. Both the selected strain and the parental culture showed anchorage-independent growth in soft agarose and were tumorigenic in athymic mice. Using molecular genetic strategies' display to isolate genes expressed differentially between the 2 populations, a 300-bp sequence homologous to thromboxane synthase was upregulated in the migration-selected cells relative to the parental cells. Expression levels of thromboxane synthase were highly elevated in the migration-selected cells when assessed by RNAse-protection assay and by flow cytometry. Two specific thromboxane synthase inhibitors, Dazmegrel and Furegrelate, reduced the migration rate of the migration-selected cells to a rate equal to or less than the rate exhibited by the parental cells, respectively. The inhibitors effect on the parental cells was inconsequential. These results suggest that aberrations in the regulation of thromboxane synthase expression or activity may influence the motility of human glioma cells.

Animals↗
PubMed1997

Expression of the genes encoding myelin basic protein and proteolipid protein in human malignant gliomas.

Pathological differentiation of oligodendroglioma and mixed oligoastrocytoma from astrocytoma is difficult, relying on morphological characteristics due to the lack of reliable immunohistochemical stains. Oligodendrocytes, the presumed cell of origin of oligodendrogliomas, highly express the genes encoding myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the expression of these genes to determine whether they might be useful molecular markers of oligodendrocytic tumors. MBP and PLP were highly expressed in all oligodendrogliomas and minimally expressed in glioblastomas multiforme. MBP was highly expressed in mixed oligoastrocytomas, whereas PLP expression was minimal. The association between tumor classification and expression of the MBP and PLP genes was statistically significant. Expression of these genes may serve as a useful molecular marker for some subtypes of human gliomas.

Adult↗
PubMed1996

Contrasting migratory response of astrocytoma cells to tenascin mediated by different integrins.

Tenascin, an extracellular matrix protein, is expressed in human gliomas in vitro and in vivo. The distribution of tenascin at the invasive edge of these tumors, even surrounding solitary invading cells, suggests a role for this protein as a regulator of glioma cell migration. We tested whether purified tenascin, passively deposited on surfaces, influenced the adhesion or migration of a human gliomaderived cell line, SF-767. Adhesion of glioma cells to tenascin increased in a dose-dependent fashion up to a coating concentration of 10 micrograms/ml. Higher coating concentrations resulted in progressively fewer cells attaching. Cell adhesion could be blocked to basal levels using anti-beta 1 integrin antibodies. In contrast, when anti-alpha v antibodies were added to the medium of cells on tenascin, cell adhesion was enhanced slightly. Using a microliter scale migration assay, we found that cell motility on tenascin was dose dependently stimulated at coating concentrations of 1 and 3 micrograms/ml, but migration was inhibited below levels of non-specific motility when tested at coating concentrations of 30 and 100 micrograms/ml. Migration on permissive concentrations of tenascin could be reversibly inhibited with anti-beta 1, while treatment with anti-alpha v antibodies increased migration rates. We conclude that SF-767 glioma cells express two separate integrin receptors that mediate contrasting adhesive and migratory responses to tenascin.

Astrocytoma↗
PubMed1996

Biological and molecular analysis of a low-grade recurrence of a glioblastoma multiforme.

We and others have reported that human malignant gliomas demonstrate intratumor heterogeneity in which many regions may be benign; however, the presence of regions of increased malignancy in these same tumors is generally indicative of poor patient prognosis. These data suggested that tumor progression may be a local phenomenon, resulting in regions that progress to a more malignant type prior to the progression of the entire tumor. Implicit in this premise is the idea that molecular markers of tumor progression may be detectable prior to histological evidence of progression. This report details analyses performed on a primary and recurrent tumor obtained from the same patient in which the primary tumor was of a higher histological grade than the recurrent tumor. Results of molecular, cytogenetic, flow cytometric, and histological analyses of the primary tumor were indicative of a grade 4 glioblastoma multiforme. Standard cytogenetic and flow cytometric analyses demonstrated that the cells were near-diploid with a stem line population of 46,XX normal G-banded karyotypes. In contrast, tissue resected from the recurrent tumor 5 months later was histologically less malignant; however, the molecular, cytogenetic, and flow cytometric analyses of this sample demonstrated the presence of specific genetic abnormalities typically found in more malignant tumors. These data demonstrate that specific molecular and/or genetic changes leading to tumor progression may become detectable in a glioma prior to the appearance of histological features of a higher grade tumor.

Adult↗
PubMed1995

Cancer incidence in a group of workers potentially exposed to ethylene oxide.

BACKGROUND: Cytogenetic changes associated with ethylene oxide (ETO) exposure at a worksite prompted a study of cancer incidence in that cohort. METHOD: Cancer incidence through 31 December 1987 was ascertained in a cohort of 1132 individuals employed at the worksite at any time from 1 July 1974 through 30 September 1980, the period of potential exposure to ETO at the plant. The number of observed cancers was compared with that expected based on age- and sex-specific incidence rates reported by the National Cancer Institute's Surveillance Epidemiology and End Results Program. Standardized morbidity ratios (SMR) were calculated separately for regular and temporary employees. RESULTS: Of the 28 cancers observed in the cohort, 12 were breast cancers. The SMR for breast cancer among regular female employees ranged from 2.55 (95% CI: 1.31-4.98, P = 0.02) to 1.70 (95% CI: 0.89-3.23, P = 0.09) depending on calendar year of follow-up, assumptions about completeness of follow-up, and the reference rates used. The excess of breast cancer over expected in regular female employees diminished over time. No statistically significant excess of breast cancer was noted for temporary female employees at any point during follow-up. No increase in cancer incidence was found over that expected for any cancer sites associated with ETO in previous studies--leukaemia, brain, pancreas and stomach. CONCLUSIONS: Factors such as appropriateness of latency periods, length of follow-up and lack of a common histopathological type need to be considered in evaluating the excesses in observed breast cancer incidence, which diminished over time.

Adult↗
PubMed1994

Molecular cloning and chromosomal localization of a human skeletal muscle PP-1 gamma 1 cDNA.

Type-1-protein phosphatase (PP-1) activity is reduced in skeletal muscle from human subjects with insulin resistance (Kida et al. 1990). This reduced phosphatase activity probably leads to the abnormal insulin action for glucose storage observed in insulin-resistant subjects. In the present study, a human homolog of rat liver PP-1 gamma 1 cDNA was isolated from human skeletal muscle. The nucleotide sequence contains a 957-nucleotide open reading frame encoding an amino acid sequence identical to that encoded by rat liver PP-1 gamma 1 cDNA. Northern blot analysis shows PP-1 gamma 1-specific mRNA is expressed in human heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas. PP-1 gamma 1 was localized to human Chromosome 12.

Base Sequence↗
PubMed1993

Selection of neighborhood controls for a study of factors related to the diagnosis of cervical cancer.

The level of effort required to generate neighborhood controls for a statewide matched case-control study of cervical cancer was investigated, with the aim of identifying hard-to-reach demographic subgroups. Cross reference telephone directories were used to identify households on the same street as the case. Letters were then sent to the households, followed by 'phone calls. A total of 2920 households were contacted to obtain 147 controls. Overall, 63.6% of age-eligible contacts participated in the study. In 49.3% of all households the major reason for not obtaining a control was "no age-eligible women". Level of effort required to obtain a matched control was greater for black women than for white women--on average 24 letters and 40 'phone calls for black women vs 12 letters and 20 calls for white women. Fewer eligible younger women refused to be interviewed than older. No marked differences were noted when the data were stratified by urban-rural area of residence.

Adult↗
PubMed1992

Oxygenation and ventilation during cardiopulmonary resuscitation utilizing continuous oxygen delivery via a modified pharyngeal-tracheal lumened airway.

Use of continuous transtracheal oxygen delivery systems combined with rhythmic chest compressions can provide excellent oxygenation and ventilation during cardiopulmonary resuscitation. However, occasional displacement of the transtracheal catheter results in life-threatening pneumomediastinal complications. We investigated using the pharyngeal lumen of a pharyngeal-tracheal lumened airway (PtL) as an alternative delivery system for continuous oxygen flow in 21 large mongrel dogs. Excellent ventilation was possible in anesthetized, apneic, and paralyzed dogs in normal sinus rhythm from the "bellows" effect of chest compressions. The hypercapnia and respiratory acidemia resulting from 5 min of complete apnea in ten dogs during normal sinus rhythm was readily corrected (p less than 0.01). In an additional 11 dogs, external chest compressions were performed and oxygen was delivered continuously via the PtL during 20 min of ventricular fibrillation. During this period of cardiac arrest, pH declined (7.38 +/- 0.01 vs 7.19 +/- 0.02; p less than 0.01), but PaCO2 (35 +/- 1 vs 38 +/- 3 mm Hg) and PaO2 (67 +/- 2 vs 68 +/- 3 mm Hg) were not significantly different from prearrest values. Successful resuscitation was achieved in 8 of 11 (73 percent) animals, which is similar to the results in historical controls with endotracheal intubation. No pneumomediastinal complications were seen with use of the PtL. We conclude that using the pharyngeal lumen of the PtL for continuous delivery of oxygen combined with external chest compressions can provide a safe and effective mode of oxygenation and ventilation during cardiac arrest.

Animals↗
PubMed1991

Diet and the risk of in situ cervical cancer among white women in the United States.

A case-control study of women with incident in situ and invasive cervical cancer was conducted during 1982-83 in five US areas reporting to the Comprehensive Cancer Patient Data System: Birmingham, AL; Chicago, IL; Denver, CO; Miami, FL; and Philadelphia, PA. Controls were selected by random-digit dialing and matched to invasive cases on age, race, and telephone exchange. Of the white non-Hispanic in situ cases and controls identified, 229 (78 percent) and 502 (74 percent) were successfully interviewed. Diet was assessed by asking about the usual adult frequency of consumption of 75 food items and the use of vitamin supplements. Included were the major sources of the four micronutrients postulated to reduce the risk of cervical cancer: carotenoids, vitamin A, vitamin C, and folate. Weak inverse associations between risk of in situ disease and intake of carotenoids, vitamin C, folate, fruit, and vegetables/fruits were noted but, with further analysis, these seemed attributable to residual confounding by the multiple lifestyle-related risk factors for this disease and possibly to selection bias. Vitamin A and vegetable intake were unrelated to risk. Dark yellow-orange vegetable consumption and duration of multivitamin use were each strongly related to reduced risk of in situ disease (P for trend = 0.02 and 0.002, respectively) and need to be evaluated in other studies. The absence of persuasive protective effects for the four micronutrients and the similar findings from our analysis of invasive cervical cancer do not concur with other epidemiologic studies and suggest that the role of diet and nutrition in the etiology of cervical cancer is not yet resolved.

Adult↗
PubMed1991

The relationship of Papanicolaou testing and contacts with the medical care system to stage at diagnosis of cervical cancer.

The relationship of Papanicolaou (Pap) testing and physician visits to stage at diagnosis of cervical cancer was assessed by interviews with 149 women with invasive cervical cancer and 214 women with in situ cervical cancer. A significantly smaller percent of study subjects with invasive disease than in situ disease had at least one Pap test in the 3 years prior to diagnosis (age- and race-adjusted odds ratio: 3.38). The two groups did not differ in visits to a physician for other reasons during this period. Pap testing decreased with increasing age for both groups, but not physician visits. While 65% percent of the subjects with invasive disease aged between 65 and 79 years had never had a Pap test until diagnosis, 88% had seen a physician in the preceding 3 years. Women with regional or distant invasive disease were least likely to have had Pap tests, and, within this group, those aged between 35 and 64 years were also least likely to have seen a physician. Strategies for early detection must reflect missed opportunities and the need to bring those not receiving care into the system.

Adult↗
PubMed1990

Diet and the risk of invasive cervical cancer among white women in the United States.

A case-control study of incident invasive cervical cancer was conducted in Birmingham, Alabama; Chicago, Illinois; Denver, Colorado; Miami, Florida; and Philadelphia, Pennsylvania, during 1982-1983. Controls were selected by random-digit dialing and were matched to cases by age, race, and telephone exchange. Of the white, non-Hispanic cases and controls identified, 271 (73%) and 502 (74%), respectively, were successfully interviewed. Diet was assessed by asking about the usual adult frequency of consumption of 75 food items and the use of vitamin supplements. Included were the major sources of the four micronutrients believed to reduce the risk of cervical cancer: carotenoids, vitamin A, vitamin C, and folate. Women in the highest quartiles of intake of each of these micronutrients had adjusted relative risks of invasive squamous cell cervical cancer comparable to those of women in the lowest quartiles, although their micronutrient intake was estimated to be 3-4 times as high. Risk was not affected by increased consumption of vegetables, dark green vegetables, dark yellow-orange vegetables, fruits, or legumes, or by high intake of the basic food groups. These generally negative findings stand in contrast to findings in previous epidemiologic studies, and the discrepancy is not readily explained by bias, uncontrolled confounding, or inadequate power. The question of the role of diet and nutrition in the etiology of cervical cancer is not yet resolved.

Adult↗
PubMed1990

A survey of exposures, practices and recommendations of surgeons in the care of patients with human immunodeficiency virus.

Policy makers face a conflict between satisfying concerns of health care workers (HCW) about the occupational risk of human immunodeficiency virus (HIV) infection and ensuring adequate care for patients. This conflict is particularly severe in the field of surgery. We mailed a questionnaire on the surgical care of patients infected with HIV to 1,461 surgeons in New York City and Philadelphia, and 551 (37.7 per cent) responded. Although 1.9 per cent currently were testing all patients for HIV, 42.6 per cent of surgeons believed that all patients in their hospital should be tested. Of the surgeons who responded, 6.3 per cent refused to treat any patient infected with HIV. Less than 50 per cent recommended the use of barrier precautions on all patients in their hospital. Surgeons in New York City were significantly more likely than those in Philadelphia to favor separate facilities for HIV-infected patients. Surgeons considering themselves at higher occupational risk were more likely than those at lower risk to favor widespread testing, separate facilities and use of precautions. Surgeons reported a wide range of opinions. Their approach to the use of barrier precautions differs from the Centers for Disease Control recommendations. The patterns observed suggest that distinct policies may be appropriate for different hospitals.

Female↗