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Biomedical subjects

R L Phillips

Publications and source records attributed to R L Phillips.

At least 19 recordsLinked to original sources
PubMed1992

Genetic control of murine hematopoietic stem cell pool sizes and cycling kinetics.

Bone marrow from each of two inbred mouse strains, C57BL/6J and DBA/2J, was highly enriched for stem cells using flow cytometry and was divided into two stem cell subpopulations using the mitochondrial dye rhodamine 123 (Rh-123). The Rh-123lo population was determined to be more primitive than Rh-123hi based on the expression of stem cell markers such as the c-kit protooncogene (stem cell factor receptor) and the Ly-6A/E stem cell antigen (Sca-1) as well as the lack of in vitro colony-forming ability. Compared to DBA/2J mice, marrow from the C57BL/6J strain consistently showed a higher proportion of "very primitive" (Rh-123lo) cells, suggesting that the sizes of functionally distinct stem cell subpopulations are maintained under precise genetic control. Marrow from both strains exposed to the cytotoxic drug 5-fluorouracil showed a dramatic increase in the proportion of Rh-123lo cells within 2 days as repopulation began. Marrow subpopulations returned to pretreatment proportions by the eighth day in DBA/2J mice but not until 14 days in C57BL/6J mice. This intrinsic difference in 5-fluorouracil recovery time was attributed to an increase rate of stem cell cycling in DBA/2J relative to C57BL/6J mice. When stem cell factor was injected into a C57BL/6J<-->DBA/2J allophenic mouse, blood cell chimerism shifted markedly but transiently toward the DBA/2J genotype, suggesting that the DBA/2J target population, because of an inherent kinetic advantage, was able to respond faster to the cytokine. A model is proposed that is based on these and our earlier observations to explain this strain-specific stem cell behavior and offer new insights into the genetic control of stem cell cycling and population dynamics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Allergy and cancer: organ site-specific results from the Adventist Health Study.

The relation between allergy and risk of cancer was evaluated in a cohort study of 34,198 Seventh-day Adventists in California. Information on prevalence of asthma, hay fever, and reactions to chemicals, medications, bee stings, and poison oak (or ivy) was obtained by questionnaire in 1976. The reported allergies must have been serious enough to require treatment by a physician. The cohort was then followed for 6 years (1977-1982). Both stratified analysis and Cox proportional hazards regression analyses were utilized to evaluate the relation of allergy to cancer after taking into account several potentially confounding variables. For all cancer sites combined in males, there was a 33% increased risk associated with reaction to medications. In contrast, among females, reaction to medications was associated with a 21% decrease in risk. Both results were statistically significant. Prostate and breast cancer risk were elevated in persons who reported any type of allergic history, as was risk of lymphatic or hematopoietic cancers and sarcoma. For each of these types of cancer, risk increased with increasing numbers of allergies. However, ovarian cancer risk was decreased in persons with any allergic history and increasing numbers of allergies was associated with decreasing risk of this form of cancer. These results suggest that the association between allergy and cancer is complex and depends on the specific allergy and the specific organ site under consideration.

California↗
PubMed1991

Cause-specific mortality among physicians with differing life-styles.

We compare the mortality experience of medical school graduates from Loma Linda University (LLU [n = 4342]) and the University of Southern California (USC [n = 2832]) with each other and with that of contemporaneous, white, American men. When compared with US white men from the general population, both USC and LLU graduates had below expected deaths for all causes (USC, standardized mortality ratio [SMR] = 76; LLU, SMR = 56), although deaths due to cerebrovascular disease, airplane accidents, and suicides were elevated for USC (SMRs = 132, 360, and 218, respectively). The LLU graduates had a risk similar to that of the USC graduates for fatal cancer, with a mortality ratio (MR) of 0.92 (95% confidence interval, 0.67 to 1.26); but half the risk of fatal atherosclerotic disease, with MRs of 0.58 (0.46 to 0.73) and 0.66 (0.43 to 0.99) for coronary and cerebrovascular disease, respectively; and three times the risk of fatal airplane accidents. The overall mortality rate of LLU physicians was only 75% as high as that of the USC physicians and only 56% as high as that of the US male population at large. We attribute this reduced mortality mainly to the low cardiovascular mortality rates, which may be accounted for by the life-style of the substantial proportion of Seventh-day Adventists among LLU graduates.

Accidents↗
PubMed1991

Diet and lung cancer in California Seventh-day Adventists.

The Adventist Health Study, a cohort study of 34,198 California Seventh-day Adventists, identified 61 cases of new primary lung cancer over 6 years of follow-up (1977-1982). The population studied was unique in that only 4% admitted to current cigarette smoking and about half were lacto-ovovegetarians. A total of 36% of the lung tumors were adenocarcinomas, and 19% were squamous cell carcinomas. The expected associations with cigarette smoking were noted for Kreyberg group I tumors (squamous cell, large cell, and small cell carcinoma; relative risk (RR) = 53.2 for current smokers and 7.07 for past smokers), but much lesser associations were noted for Kreyberg group II tumors (adenocarcinoma and bronchoalveolar carcinoma; RR = 1.99 for current smokers and 1.59 for past smokers). In this study, fruit consumption was the dietary constituent that showed a strong, statistically significant protective association with lung cancer that was independent of smoking (fruit consumption less than 3 times/week, RR = 1.0; 3-7 times/week, RR = 0.30; greater than or equal to 2 times/day, RR = 0.26). This association was somewhat stronger for Kreyberg group II tumors, but similar trends were also noted for Kreyberg group I tumors. Confounding with smoking seems unlikely in a population with very few current smokers and where both stratification and Cox modeling methods of analysis led to similar conclusions.

Adenocarcinoma↗
PubMed1991

Bladder cancer in a low risk population: results from the Adventist Health Study.

A cohort study of bladder cancer was conducted in a population of California Seventh-day Adventists. Most Seventh-day Adventists use neither tobacco nor alcohol yet experience a large degree of variation in dietary habits. Therefore, diet and other lifestyle habits were evaluated in this unique population. In 1976, 34,198 non-Hispanic white Seventh-day Adventists in California completed a detailed lifestyle questionnaire which included a 51-item food frequency section. This cohort was then followed until the end of 1982 during which time all newly diagnosed malignancies were detected. In order to evaluate the relation between several variables hypothesized to be associated with altered bladder cancer risk, age-, sex-, and smoking-adjusted relative risks (incidence rate ratios) were calculated using the method of Mantel-Haenszel adopted for person-time data. Multivariate analyses were conducted using the Cox Proportional Hazards Regression model. Between the return of the questionnaire and the end of follow-up, there were 52 histologically confirmed bladder cancers detected in the cohort. Increasing age, male gender, and a history of cigarette smoking were all significantly associated with increased bladder cancer risk. In addition, residence in a rural area was associated with significantly increased risk (relative risk (RR) = 1.80) as was high consumption of meat, poultry, and fish (RR = 2.57).

California↗
PubMed1991

Neutrophils and mast cells: nedocromil sodium inhibits the generation of neutrophil-derived histamine-releasing activity (HRA-N).

The effect of nedocromil sodium on the generation of neutrophil-derived histamine-releasing activity (HRA-N) from human peripheral blood neutrophils and on the secretory effects of HRA-N and anti-IgE on rat basophil leukemia (RBL) cells was studied. Nedocromil sodium caused dose-related inhibition of HRA-N generation by human neutrophils (10(-7) to 10(-4) mol/L; inhibitory concentration of 50%, 1.5 x 10(-8) mol/L). In contrast, the presence of nedocromil sodium had no effect on HRA-N-mediated serotonin release from RBL cells. In five experiments, with one crude and four partially purified HRA-N preparations, serotonin release from RBL cells exposed to native HRA-N or HRA-N in the presence of nedocromil sodium (10(-4) mol/L) was 28% +/- 6% and 26% +/- 5%, respectively. Similar results were found with all concentrations of nedocromil sodium studied. Preincubation of RBL cells with nedocromil sodium (10(-4) mol/L) for 0 to 60 minutes also did not affect HRA-N-mediated serotonin release. Likewise, nedocromil sodium (10(-7) to 10(-4) mol/L) had no effect on anti-IgE-induced serotonin release from RBL cells. In 10 experiments, anti-IgE alone or in the presence of nedocromil sodium (10(-4) mol/L) induced 32% +/- 6% and 32% +/- 5% serotonin release, respectively. Preincubation of RBL cells with nedocromil sodium before anti-IgE exposure had no further effect. This is the first study of pharmacologic manipulation of the generation of a histamine-releasing factor. It is hypothesized that one possible mechanism whereby nedocromil sodium protects against asthma and allergic rhinitis is through inhibition of HRA-N generation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Analysis of maize brittle-1 alleles and a defective Suppressor-mutator-induced mutable allele.

A mutant allele of the maize brittle-1 (bt1) locus, brittle-1-mutable (bt1-m), was shown genetically and molecularly to result from the insertion of a defective Suppressor-mutator (dSpm) transposable element. An Spm-hybridizing restriction enzyme fragment, which cosegregates with the bt1-m allele and is absent from wild-type revertants of bt1-m, was identified and cloned. Non-Spm portions of it were used as probes to identify wild-type (Bt1) cDNAs in an endosperm library. The 4.3-kb bt1-m genomic clone contains a 3.3-kb dSpm, which is inserted in an exon and is composed of Spm termini flanking non-Spm sequences. RNA gel blot analyses, using a cloned Bt1 cDNA probe, indicated that Bt1 mRNA is present in the endosperm of developing kernels and is absent from embryo or leaf tissues. Several transcripts are produced by bt1-m. The deduced translation product from a 1.7-kb Bt1 cDNA clone has an apparent plastid transit peptide at its amino terminus and sequence similarity to several mitochondrial inner-envelope translocator proteins, suggesting a possible role in amyloplast membrane transport.

Alleles↗
PubMed1990

History of cigarette smoking and risk of leukemia and myeloma: results from the Adventist health study.

The risks of leukemia and myeloma associated with cigarette smoking were evaluated in a cohort study of 34,000 Seventh-day Adventists. Although Seventh-day Adventists do not smoke by church proscription, many are adult converts who smoked cigarettes prior to their baptism into the church. In comparison with those who never smoked, ex-smokers experience a relative risk of 2.00 (95% confidence interval = 1.01-3.95) for leukemia and 3.01 (95% confidence interval = 1.13-8.05) for myeloma. Risks increased in a dose-response fashion with increasing numbers of cigarettes smoked daily for both leukemia (trend P = .009) and myeloma (trend P = .005). Also, the risks of both leukemia and myeloma increased with the total duration of cigarette smoking. The cigarette smoking-leukemia relationship was strongest for myeloid leukemia, for which ex-smokers experienced a relative risk of 2.24 (95% confidence interval = 0.91-5.53). These data lend support to the hypothesis that cigarette smoke may induce malignant degeneration in bone marrow and its products.

California↗
PubMed1990

Cocaine-induced reduction of glucose utilization in human brain. A study using positron emission tomography and [fluorine 18]-fluorodeoxyglucose.

We examined the effects of cocaine hydrochloride (40 mg intravenously) on regional cerebral metabolic rates for glucose and on subjective self-reports of eight polydrug abusers in a double-blind, placebo-controlled, crossover study. The regional cerebral metabolic rate for glucose was measured by the [fluorine 18]-fluorodeoxyglucose method, using positron emission tomography. With eyes covered, subjects listened to a tape that presented white noise, "beep" prompts, and questions about subjective effects of cocaine or saline. Cocaine produced euphoria and reduced glucose utilization globally (mean reduction, 14%). Twenty-six of 29 brain regions (all neocortical areas, basal ganglia, portions of the hippocampal formation, thalamus, and midbrain) showed significant decrements (5% to 26%) in the regional cerebral metabolic rate for glucose. No significant effects of cocaine were observed in the pons, the cerebellar cortex, or the vermis. Right-greater-than-left hemispheric asymmetry of regional cerebral metabolic rates for glucose occurred in the lateral thalamus. The findings demonstrate that reduced cerebral metabolism is associated with cocaine-induced euphoria.

Adult↗
PubMed1990

Hypertension, antihypertensive medication and risk of renal carcinoma in California Seventh-Day Adventists.

A longitudinal study of 34 198 non-Hispanic white California Seventh-day Adventists identified incident cases of renal carcinoma over six years of follow-up. The use of antihypertensive medications and self-reported hypertension had estimated age-sex adjusted incidence rate ratios of 4.51 and 2.90 respectively. These were relatively unchanged by stratifying on additional variables that may have been confounders. Cases diagnosed later during the follow-up period had the strongest association with hypertension, making the alternative explanation that the cancer may have caused the hypertension less likely. Being married in 1976 (amongst females at least) was also associated with a marked elevation of risk. Point estimates of effect suggested that frequent (greater than or equal to 3 week) consumption of fruit (RR = 0.21) and salad vegetables (RR = 0.34) may be protective for this cancer, although the 95% confidence interval did not quite exclude the null value.

Aged↗
PubMed1990

Program for PET image alignment: effects on calculated differences in cerebral metabolic rates for glucose.

A program was developed to align positron emission tomography images from multiple studies on the same subject. The program allowed alignment of two images with a fineness of one-tenth the width of a pixel. The indications and effects of misalignment were assessed in eight subjects from a placebo-controlled double-blind crossover study on the effects of cocaine on regional cerebral metabolic rates for glucose. Visual examination of a difference image provided a sensitive and accurate tool for assessing image alignment. Image alignment within 2.8 mm was essential to reduce variability of measured cerebral metabolic rates for glucose. Misalignment by this amount introduced errors on the order of 20% in the computed metabolic rate for glucose. These errors propagate to the difference between metabolic rates for a subject measured in basal versus perturbed states.

Brain↗
PubMed1989

Chronic disease among Seventh-day Adventists, a low-risk group. Rationale, methodology, and description of the population.

The Adventist Health Study is a prospective cohort study of 34,198 non-Hispanic white Seventh-day Adventists (13,857 men; 20,341 women, age 25-100 years) followed for 6 years (1977-1982). Within this population, 55.2% were lacto-ovovegetarian (consumed meat, poultry, or fish less than one time per week with no restrictions as to egg or dairy product consumption) in 1976 and most abstained from alcohol, tobacco, and pork products. Baseline data included demographic variables, information on current and past dietary habits, exercise patterns, use of prescription drugs, use of alcohol and tobacco, measures of religiosity, occupation and residential histories, anthropometric data, and menstrual and reproductive histories. Nonfatal case ascertainment was completed through review of self-reported hospitalizations obtained from annual self-administered mailed questionnaires and through computerized record linkage with two California population-based tumor registries. Fatal case ascertainment was completed via record linkage with computerized California state death certificate files, the National Death Index, and individual follow-up. During the 6 years of follow-up, 52.8% of the 34,198 study subjects reported at least one hospitalization. A total of 20,702 medical charts were reviewed for cancer and cardiovascular disease incidence and 1406 incident cancer cases and 2716 deaths from all causes were identified after baseline data collection.

Adult↗
PubMed1989

Dietary habits and breast cancer incidence among Seventh-day Adventists.

Breast cancer incidence was monitored in a cohort of 20,341 California Seventh-day Adventist women who completed a detailed lifestyle questionnaire in 1976, and who were followed for 6 years. There were 215 histologically confirmed primary breast cancer detected among some 115,000 person-years of follow-up. Mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. Established risk factors for breast cancer showed strong relationships to risk in these data. Age at first live birth, maternal history of breast cancer, age at menopause, educational attainment, and obesity were all significantly related to risk. However, increasing consumption of high fat animal products was not associated with increased risk of breast cancer in a consistent fashion. Nor were childhood and early teenage dietary habits (vegetarian versus nonvegetarian) related to subsequent, adult risk of developing breast cancer. Also, a derived index of percent of calories from animal fat in the adult years was not significantly related to risk. These results persisted after simultaneously controlling for other, potentially confounding variables, utilizing Cox proportional hazard regression models.

Adult↗
PubMed1989

Prospective study of exogenous hormone use and breast cancer in Seventh-day Adventists.

Exogenous hormone use as either oral contraceptives (OC) or hormone replacement therapy (HRT) was evaluated in reference to subsequent breast cancer risk in a cohort study of 20,341 Seventh-day Adventist women, residing in California, who completed a detailed lifestyle questionnaire in 1976 and who were followed for 6 years. During the follow-up period, 215 histologically confirmed primary breast cancers were detected in the cohort. The mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. In this cohort, after taking into account potentially confounding variables, current use of HRT (in 1976) was associated with a 69% increase in breast cancer risk, which was statistically significant (RR = 1.69; CI = 1.12-2.55). However, there was no strong increase in risk with increasing duration of use of HRT. Subgroups of women who did experience HRT associated increases in breast cancer risk included those women who had ever used HRT (RR = 1.39; CI = 1.00-1.94) and those with no history of maternal breast cancer (RR = 1.45), those women with prior benign breast disease (RR = 2.80), and those women who experienced menopause at 44 years of age or later (RR = 1.56). There was no substantial increase in breast cancer risk associated with use of OC in this population, although among women with exposure to both OC and HRT there was a suggested increase in risk (RR = 1.42; CI = 0.71-2.85).

Aged↗
PubMed1989

Cohort study of diet, lifestyle, and prostate cancer in Adventist men.

Dietary and lifestyle characteristics were evaluated in relation to subsequent prostatic cancer risk in a cohort of approximately 14,000 Seventh-day Adventist men who completed a detailed lifestyle questionnaire in 1976 and who were monitored for cancer incidence until the end of 1982. During the 6-year follow-up period, 180 histologically confirmed prostatic cancers were detected among some 78,000 man-years of follow-up. Increasing educational attainment was associated with significantly decreased risk of prostate cancer in this study; age at first marriage was also inversely associated with risk, although this was not significant. There was no relationship between body mass index (as measured by Quetelet's Index) and risk. A history of prostate "trouble" was associated with a 60% increase in risk which was highly significant. Although there were suggestive relationships between increasing animal product consumption and increased risk, these results did not persist after accounting for the influence of fruit and vegetable consumption. Nor was exposure to the vegetarian lifestyle during the childhood years associated with alterations in subsequent risk. However, increasing consumption of beans, lentils and peas, tomatoes, raisin, dates, and other dried fruit were all associated with significantly decreased prostate cancer risk.

Adult↗
PubMed1989

Risk factors for tumors of the brain and cranial meninges in Seventh-Day Adventists.

We studied the occurrence of tumors of the brain and cranial meninges in a cohort of 34,000 California Seventh-Day Adventists who completed a detailed life-style questionnaire in 1976 and who were followed for cancer incidence until the end of 1982. During the period of follow-up, 31 tumors were diagnosed in the cohort (21 gliomas, 10 meningiomas). Increased risk for glioma was associated with rural residence, history of a positive tuberculosis skin test and consumption of pork products; increased meningioma risk was associated with a positive reaction to a tuberculosis skin test, previous stroke, use of tranquillizers and a vegetarian life-style in childhood.

Adult↗
PubMed1989

Is early natural menopause a biologic marker of health and aging?

The relation between age at natural menopause and all-cause mortality was investigated in a sample of 5,287 White women, ages 55 to 100 years, naturally-postmenopausal, Seventh-day Adventists who had completed mailed questionnaires in 1976. The age-adjusted odds ratio of death during 1976-82 in women with natural menopause before age 40 was 1.95 (95% confidence interval = 1.24, 3.07), compared to the reference group of women reporting natural menopause at ages 50 to 54. Corresponding odds ratios of death were 1.39 (95% CI = 1.06, 1.81) for natural menopause at ages 40 to 44, and 1.03 (95% CI = 0.84, 1.25) for natural menopause at ages 45 to 49. Among 3,166 White, 55- to 100-year-old, surgically-postmenopausal, Adventist women, there was no relation between age at surgical menopause and mortality. Logistic regression analyses indicated that findings from this study were apparently not due to confounding by smoking, over- or underweight, reproductive history, or replacement estrogen use.

Adult↗