Search PubMed⌕ Search

Biomedical subjects

A A Hakim

Publications and source records attributed to A A Hakim.

At least 19 recordsLinked to original sources
PubMed1999

Effects of walking on coronary heart disease in elderly men: the Honolulu Heart Program.

BACKGROUND: Effects of walking on the risk of coronary heart disease morbidity and mortality have not been identified in the elderly. The purpose of this study was to determine whether walking is associated with a reduced risk of coronary heart disease in a sample of elderly men. METHODS AND RESULTS: For this study, distance walked (mile/d) was examined at a baseline examination that occurred from 1991 to 1993 in the Honolulu Heart Program. Incident coronary heart disease from all causes was observed over a 2- to 4-year follow-up period. Subjects followed up were 2678 physically capable elderly men aged 71 to 93 years. During the course of follow-up, 109 men developed coronary heart disease. Men who walked <0.25 mile/d had a 2-fold increased risk of coronary heart disease versus those who walked >1. 5 mile/d (5.1% versus 2.5%; P<0.01). Men who walked 0.25 to 1.5 mile/d were also at a significantly higher risk of coronary heart disease than men who walked longer distances (4.5% versus 2.5%; P<0. 05). Adjustment for age and other risk factors failed to alter these findings. CONCLUSIONS: Findings from the Honolulu Heart Program, which targeted physically capable elderly men, suggest that the risk of coronary heart disease is reduced with increases in distance walked. Combined with evidence that suggests that an active lifestyle reduces the risk of cardiovascular disease in younger and more diverse groups, this suggests that important health benefits could be derived by encouraging the elderly to walk.

Aged↗
PubMed1999

Screening for coronary heart disease in elderly men based on current and past cholesterol levels.

Efficient use of cholesterol measurements to screen for coronary heart disease in the elderly is not well defined. The purpose of this report is to examine such screening based on national guidelines in a sample of older men. Since relations between cholesterol and coronary heart disease are better established in those who are younger, screening in the elderly will also consider levels of cholesterol that existed earlier in life. Data are from a prospective study of 1,170 men enrolled in the Honolulu Heart Program who were followed over a 12-year period for coronary heart disease. Follow-up began from 1980 to 1982, when cholesterol levels were determined in men who were aged 61 to 81 years. Past cholesterol levels were measured 10 years earlier (1970-1972). During the course of follow-up, coronary heart disease developed in 117 of the men. Risk of disease rose significantly (P = 0.003) with increases in past cholesterol levels (1970-1972) but not with more recent levels (1980-1982). For men with current cholesterol levels that were desirable (<5.2 mmol/L [200 mg/dl], as defined by guidelines from the National Cholesterol Education Program), disease incidence continued to rise with increasing past cholesterol levels (P<0.001). Accounting for high-density lipoprotein cholesterol and other screening factors did little to alter these findings. We conclude that desirable cholesterol levels in the elderly may not be a marker of a healthy risk profile if past cholesterol levels were high. Screening for coronary heart disease in the elderly could be improved by considering past cholesterol levels, rather than just a single measurement in later life.

Aged↗
PubMed1998

Changes in total and high-density lipoprotein cholesterol over 10- and 20-year periods (the Honolulu Heart Program).

Limited data are available on patterns of change in lipids and lipoproteins as persons age. The purpose of this report is to describe the 10-year change in total and high-density lipoprotein (HDL) cholesterol according to suspected determinants in 898 Japanese-American men enrolled in the Honolulu Heart Program. Data are based on examinations that occurred from 1970 to 1972 and at repeat examinations received 10 and 20 years later. At the last examination, men were aged 71 to 93 years. Mean reductions in total cholesterol in the second 10 years of follow-up (24 mg/dl) were more than double the reductions observed in the first 10 years (9 mg/dl). Levels of total cholesterol declined and levels of HDL cholesterol increased regardless of beginning levels of systolic blood pressure, body mass index, physical activity, cigarette smoking status, or the use of treatment for hypertension or elevated total cholesterol. Men with prevalent coronary heart disease experienced greater reductions (p <0.05) in total cholesterol during the second 10 years of follow-up (32 mg/dl) versus men without coronary heart disease (22 mg/dl). Adjustment for baseline covariates failed to alter these findings appreciably. We conclude that alterations in total and HDL cholesterol with advancing age may be expected to occur regardless of risk factor status, disease prevalence, or pharmacologic intervention. In the presence of such effects, evaluation of treatment programs to alter levels of total and HDL cholesterol in older persons should consider the possibility that even in the absence of intervention, changes could also occur due to aging alone.

Aged↗
PubMed1998

Effects of walking on mortality among nonsmoking retired men.

BACKGROUND: The potential benefit of low-intensity activity in terms of longevity among older men has not been clearly documented. We examined the association between walking and mortality in a cohort of retired men who were nonsmokers and physically capable of participating in low-intensity activities on a daily basis. METHODS: We studied 707 nonsmoking retired men, 61 to 81 years of age, who were enrolled in the Honolulu Heart Program. The distance walked (miles per day) was recorded at a base-line examination, which took place between 1980 and 1982. Data on overall mortality (from any cause) were collected over a 12-year period of follow-up. RESULTS: During the follow-up period, there were 208 deaths. After adjustment for age, the mortality rate among the men who walked less than 1 mile (1.6 km) per day was nearly twice that among those who walked more than 2 miles (3.2 km) per day (40.5 percent vs. 23.8 percent, P=0.001). The cumulative incidence of death after 12 years for the most active walkers was reached in less than 7 years among the men who were least active. The distance walked remained inversely related to mortality after adjustment for overall measures of activity and other risk factors (P=0.01). CONCLUSIONS: Our findings in older physically capable men indicate that regular walking is associated with a lower overall mortality rate. Encouraging elderly people to walk may benefit their health.

Aged↗
PubMed1998

Coffee consumption in hypertensive men in older middle-age and the risk of stroke: the Honolulu Heart Program.

OBJECTIVE: To examine the association between coffee consumption and the development of stroke in men at high risk for cardiovascular disease. METHODS: Coffee intake was observed from 1965 to 1968 in a cohort of men enrolled in the Honolulu Heart Program with follow-up for incident stroke over a 25-year period. Subjects were 499 hypertensive men (having systolic or diastolic blood pressures at or above 140 and 90 mm Hg, respectively) in older middle-age (55 to 68 years) when follow-up began. Past and current cigarette smokers were excluded from follow-up. RESULTS: In the course of follow-up, 76 men developed a stroke. After age-adjustment, risk of thromboembolic stroke increased significantly with increases in coffee consumption (P = 0.002). No relationships were observed with hemorrhagic stroke. When adjusted for other factors, the risk of thromboembolic stroke was more than doubled for men who consumed three cups of coffee per day as compared to nondrinkers of coffee (RR = 2.1; 95% CI = 1.2-3.7). CONCLUSIONS: Although in need of further confirmation, consumption of coffee appears to be positively associated with an increased risk of thromboembolic stroke in hypertensive men in older middle-age. Findings suggest that it may be prudent to advise older middle-aged men with hypertension who consume large amounts of coffee to consider reducing their coffee intake.

Aged↗
PubMed1997

Cross-sectional and longitudinal changes in total and high-density-lipoprotein cholesterol levels over a 20-year period in elderly men: the Honolulu Heart Program.

PURPOSE: The purpose of this report is to describe levels of total cholesterol and high-density-lipoprotein cholesterol (HDL-C) in a group of elderly men and to compare these levels to those that were observed 20 years earlier. METHODS: From 1965-1968, the Honolulu Heart Program began following 8006 men of Japanese ancestry living on the island of Oahu, Hawaii, in a prospective study of coronary heart disease and stroke. This report presents data for 971 men who participated in a separate fasting study of lipids and lipoproteins that first occurred from 1970-1972 and in those who received repeat examinations 10 and 20 years later. Men were aged 71-93 years at the last examination. RESULTS: Over the 20-year period, total cholesterol declined by 1.6-1.8 mg/dL per year (P < 0.001), from average baseline values of 219-222 mg/dL. Levels of HDL-C rose 0.2-0.3 mg/dL per year (P < 0.001), from average baseline values of 44-46 mg/dL. After adjustment for baseline cholesterol levels, men with prevalent coronary heart disease at the end of the 20-year follow-up experienced significantly greater reductions in total cholesterol levels than men without disease (P < 0.001). Men who developed coronary heart disease within the first 10 years of follow-up had the greatest yearly decline in total cholesterol (1.9 mg/dL), followed by men who developed heart disease later (1.8 mg/dL) and men who remained disease free (1.5 mg/dL). Differences between men with recent and earlier disease were not statistically significant, although men without coronary disease experienced a significantly smaller decrease in total cholesterol than either of these groups (P < 0.05). CONCLUSIONS: Changes in total cholesterol and HDL-C levels with advancing age may be part of a natural aging process. Some changes, however, such as large reductions in total cholesterol, may signal occult disease or declines in overall health. Selective survival may contribute to these findings since improvements in lipid and lipoprotein levels that are beneficial in younger ages were common in this long-lived cohort of men.

Aged↗
PubMed1994

Endocrine abnormalities in patients with amyloidosis.

This study was conducted to examine systematically the endocrine function in 10 patients diagnosed to have renal amyloidosis. Basal and dynamic endocrine tests (GnRh, TRH, and ACTH stimulation tests as well as modified glucose tolerance test) were performed in all patients. Eight patients had advanced renal disease (creatinine clearance < 10 mL/min). Hypofunction of the thyroid gland was present in 5 out of those 8 patients, and thyroid biopsy confirmed amyloid deposition. Of those 5 patients, pituitary and adrenal defects were present in 2. In conclusion, endocrine abnormalities were evident at a later stage of renal amyloidosis. Hypothyroidism was present in all patients who manifested endocrine defects and should be considered as an early sign of endocrine involvement with the disease.

Adrenal Glands↗
PubMed1989

Prognostic significance of mRNA-encoding estrogen receptor and epithelial growth factor receptor in breast carcinoma progression into lymph nodes: 1. Estrogen receptor encoding mRNA.

The main objective of this study was to differentiate between lymph nodes infiltrated by estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast carcinoma. Lymph nodes were obtained from 40 postmenopausal cancer patients, 10 from each disease stage. Six patients from each group had estrogen receptor-positive (BCaER+) and four estrogen receptor-negative (BCaER-) tumors. Both tumor-containing (T) and uninvolved (N) lymph nodes from the same patient were examined by the following parameters: magnitude of lymph node nucleic acid hybridization with cDNA probes from breast cancer MCF-7ER+ and MCF-7ER- cells; and binding capacity of 3H-estradiol, 125I-EGF, and 125I-PDGF binding and protein kinase C activities of the lymph nodes. Concomitant with the appearance of transformed cells, several events occur: Tumor cells induce stimulation of mononuclear cells and macrophages and evoke T- and B-cell proliferation, leading to the synthesis of tumor cell membrane-associated antibodies. In estrogen receptor-positive (ER+) breast carcinoma, estrogens and host hormonal modulatory mechanisms stimulate production and release of epithelial growth (EGF) and platelet-derived growth factors (PDGF). These factors are characterized by protein kinase C activities. There is infiltration of tumor cells into the lymph node and infiltration of leukocytes into the tumor site. In the lymph node, tumor progression depends on tumor cell proliferation rate and metastatic aggressiveness. The experiments described in this study document the changes that occur in lymph nodes, with differences between nodes infiltrated with BCaER+ and BCaER- breast carcinomas. Hybridization of 32P-cDNA from MCF-7ER+ cells with cellular RNA from BCaER+ involved (T) lymph nodes is greater than with cellular RNA from uninvolved (N) lymph nodes. The magnitude of hybridization correlated (P less than 0.005) with the disease stage.

Breast Neoplasms↗
PubMed1988

Peripheral blood lymphocytes from patients with cancer lack interleukin-2 receptors.

When tumor cells develop in healthy adults, they activate the cellular immune system--natural killer (NK) cells, antigen-specific cytotoxic lymphocytes (CTL), and the synthesis of antigen specific cytotoxic antibodies. These are aimed at killing the intruding cells. However, in cancer patients the tumor continues to grow. As tumor cells proliferate, they were shown to release factors that mediate the inactivation of the host immune defense systems. The study documented in this article examined peripheral blood lymphocytes, mononuclear cells (MNC), NK cells, T-helper cells (THC). This study confirmed the interaction of the released inhibitor factors with these mononuclear cells. NULL cells from healthy adults responding to interleukin-2 (IL-2) and NILL cells from patients with metastatic breast carcinoma nonresponsive to IL-2 were also isolated by the standard antibodies-pinning technique. The cells were obtained from age-matched subjects: ten healthy adults; ten patients each from Stage I, II, III, and IV metastatic breast carcinoma (BCa-I, BCa-II, BCa-III, and BCa-IV or MBCa); and ten patients with benign breast disease (BBD). The responsiveness of these THC, PBMNC, NK, NULL, and NILL cells in vitro to graded levels of phytohemagglutinin (PHA), Concanavalin A (Con A), and recombinant interleukin-2 (rIL-2) was examined. Responsiveness was monitored by 3H-thymidine (3H-TdR) uptake, production and release of IL-2, interleukin-2 receptor (IL-2R), and cytotoxic activities against K-562 cells and breast carcinoma short-term cell lines. A lack of functional IL-2R in peripheral blood lymphocytes from patients with metastatic breast carcinoma was confirmed by nonsignificant anti-Tac antibody binding. An elevation in the expression of cell surface antigen GP-120 has been observed to be associated with the activation in vitro of T-cells from healthy adults and from patients with benign breast disease, but not of T-cells from patients with breast carcinoma. Biochemical studies of the GP-120 using high performance liquid chromatography combined with nitrocellulose blotting confirmed that the glycoprotein was resistant to trypsin and chymotrypsin, but susceptible to pronase. It contained sialic acid and lactosaminoglycan as O-linked sugars. It could be labeled with pariodate/NaB(3H4) and is recognized by MAbT-305 monoclonal antibodies. It contained sialic acid linked (2---3) to galactose.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Peripheral blood lymphocytes from patients with cancer lack interleukin-2 (IL-2) receptor expression: isolation of mRNA encoding IL-2R.

In healthy adults, tumor cells stimulate the cellular immune defense mechanisms: natural killer (NK), antigen-specific cytotoxic lymphocytes (CTL), and synthesis of antigen-specific cytotoxic antibodies, all aimed at the destruction of the intruding tumor cells. The experiments described in this study examined responsiveness of peripheral blood lymphocyte mononuclear (MNC) cells, natural killer (NK) cells, T-helper (THC) cells, and NILL (cells obtained from patients with advanced breast cancer) cells from 10 of each age-matched subjects from 10 healthy adults and patients, 10 with benign breast diseases (BBD), and 10 from patients from each of the breast carcinoma pathological stage BCa PS I, BCa PS II, BCa PS III, and BCa PS IV. Cellular responsiveness to graded levels of phytohemagglutinin (PHA), concanavalin A (Con A), and recombinant interleukin-2(r IL-2) was monitored by 3H-thymidine (3H-TdRO) uptake, production, and release of interleukin-2 (IL-2) and interleukin-2 receptor (IL-2R) and cytotoxic activities against K-562 and breast carcinoma (BCa) short-term cell lines. Suppressed cellular responsiveness is caused by the lack of functional IL-2R in peripheral blood lymphocytes with metastatic breast carcinoma (MBCa). This is confirmed by suppression of the anti-Tac antibodies binding and lack of cellular mRNA encoding IL-2R.

Adult↗
PubMed1988

A mechanism by which human breast carcinoma cells escape the host immune system.

The experiments described in this study examined cell membrane oligosaccharides, malignancy-related cell phenotypes and tumor cell susceptibility to the killing effect of human cytotoxic cells. Short term breast carcinoma (BCa) cell lines were prepared from biopsies obtained from patients at each of the pathological Stages I, II, III and from patients with disseminated liver metastasis. Five patients at each stage donated the tissue. To obtain large enough quantities, the cells were cultured as monolayers for a brief period, then transferred to roller bottles using serum-free hormone defined medium. Natural killer (NK) cells, lymphokine (IL-2)-activated killer (LAK), tumor-infiltrating lymphocytes (TIL) and peripheral cytotoxic lymphocytes (CTL) from patients with BCa at PS I were used as the effector cells. Susceptibility of the tumor cells to the killing effects of the effector cells was monitored by the well established 4 h 51Cr-release assay technique. Growth factor expression, oncogenicity in athymic female mice and colonigenicity in soft agar were used as parameters to monitor breast carcinoma cell malignancy phenotypes. The cell membrane oligosaccharides were determined from the carbohydrate elution profiles from BioGel P-6 columns. The results indicate a correlation between progression of malignancy from PS I to the metastatic stage PS IV, and the magnitude of malignancy phenotypes, resistance to the host killer cells and oligosaccharide profile shift to a higher molecular size with increased sialylation and fucosylation of the carbohydrate moieties.

Animals↗
PubMed1988

Correlation between colon cell oligosaccharides progressive alteration, cellular colonigenicity in soft agar and metastatic ability.

Earlier studies showed that the extracellular matrix and the conditioned medium from colon carcinoma support and catalyze the conversion of normal epithelial to colon carcinoma cells (14, 16). Since the cause of this apparent change in malignant potential is completely unknown, the following experiments examined molecular changes accompanying and mediating the transition. Colon epithelial cell cultures were initiated from normal colon biopsies. The cell cultures were carried on in standard medium on fibronectin-coated plates, and in conditioned medium on extracellular matrix from confirmed colon carcinoma. At time intervals, during 12 months period, aliquots were harvested, transferred into roller bottles to obtain enough cells to isolate cellular Poly(A)+-enriched RNA, cell membrane oligosaccharides and to determine cellular growth characteristics. During the 12 months in vitro culture, normal colon epithelial (NCE) cells grown on fibronectin in the standard growth medium maintained their initial characteristics. Whereas, NCE cells grown on the extracellular matrix and in colon carcinoma conditioned medium, progressively acquired the ability to form colonies in soft agar, to form tumors when implanted subcutaneously and to metastasize into the liver when administered intravenously into athymic mice. Poly(A)+-enriched RNA from NCE cells grown on fibronectin and in standard culture medium, did not, whereas the RNA from NCE cells grown on the extracellular matrix and in the colon carcinoma conditioned medium hybridized with 32P-cDNA from colon carcinoma. There were significant changes in the composition and profile of the oligosaccharides from membranes of NCE cells grown on the extracellular matrix. There was significant correlation (P less than 0.001) between the last characteristics.

Agar↗
PubMed1987

Ulcerative colitis and familial polyposis oncologic transformation to colon carcinoma: changes in carcinoembryonic antigen release.

During cell proliferation, several "factors" are released into the microenvironment, or culture medium. The experiments described sought and examined agents that may cause or support malignant cell transformation. The response of colon cells from patients with ulcerative colitis (UC), familial polyposis coli (FPC) and colon carcinoma (CCC) to these agents was monitored by carcinoembryonic antigens (CEA) released into the medium during cell proliferation in a serum-free hormone-defined (SFHDM) medium, oncogenicity in athymic mice and colonigenicity, i.e. the ability of the cells to form colonies in soft agar. When cultured on the extracellular matrix (EM), i.e. footprints from colon carcinoma cells (short term or established cell lines), and in SFDHM, colon cells from patients with UC and FPC showed significant (P = 0.001) increases in all the three parameters. Analyses indicated that EM from cultures of [35S]methionine-labelled normal epithelial colon cells (NCE) differed from those left by UCC, FPC and CCC cell cultures. EM from NCE cell cultures did not contain [35S]methionine-labelled glycoproteins resistant to collagenase action which were not fragments of fibronectin, and which were present in EM from CCC cells. It is concluded that the extracellular matrix from malignant colon cells contains agents that support colon cell oncogenic transformation.

Adenomatous Polyposis Coli↗