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Biomedical subjects

A Ghaffar

Publications and source records attributed to A Ghaffar.

At least 37 records · Page 2Linked to original sources
PubMed2000

Exercise and tumor development in a mouse predisposed to multiple intestinal adenomas.

UNLABELLED: Epidemiological evidence suggests that physical activity may be protective against the development of colon cancer. Potential mechanisms remain largely unexplored due to the paucity of appropriate experimental models. PURPOSE: The purpose of this study was to examine the effect of exercise training on polyp development in an induced mutant mouse strain predisposed to multiple intestinal neoplasia (Min mouse). METHODS: Three-week-old male and female heterozygotes were randomly assigned to control (CON; 10 males, 6 females) or exercise (EX; 11 males, 11 females) groups. In the first week, EX mice were acclimated to treadmill running at 10-18 m x min(-1) for 15-60 min x d(-1). From 4-10 wk of age, mice ran at 18-21 m x min(-1) for 60 min. CON mice sat in Plexiglas lanes suspended above the treadmill for the same time periods. At 10 wk of age, the mice were sacrificed and the intestines removed, opened, and counted for polyps. RESULTS: Skeletal muscle oxidative capacity increased with training as shown by a 64% increase in citrate synthase activity in the gastrocnemius/soleus muscle of EX compared with CON (P = 0.009). There were no significant effects of exercise in the males and females combined on small intestine, colon, or total intestinal polyps (P > 0.05). When analyzed separately, however, there were fewer colon and total polyps in the EX than in the CON males, although the difference was not statistically significant (P = 0.06). CONCLUSIONS: These results suggest that seven weeks of exercise training do not affect the development of intestinal polyps in the Min mouse. Further studies are required to determine if a true sex difference exists or if variations on the current training protocol may affect tumor outcomes.

Adenoma↗
PubMed2000

Motor vehicle crashes in Pakistan: the emerging epidemic.

SETTING: Motor vehicle injuries are increasingly being recognized as a growing public health issue in the developing world. Pakistan is a developing country in South Asia where motor vehicle use has increased since independence in 1947. OBJECTIVE: This paper explores the magnitude and impact of injuries from motor vehicle crashes in Pakistan. METHODS: An exhaustive review of published and gray literature, together with a detailed analysis of government data from 1956. RESULTS: The data indicate a persistent increase in the numbers of motor vehicle crashes, injuries, and fatalities. Changes in the reporting of rates are important to note in evaluating the data. Commercial vehicles contribute disproportionately to these motor vehicle injuries. CONCLUSIONS: There is a need to further the recognition of injuries as a public health issue in this country. Specific exploration of the epidemiological data; intersectoral collaboration between health, law, police and transport; and the development of appropriate information systems, will contribute to an appropriate response by Pakistan.

Accidents, Traffic↗
PubMed1999

Injuries in Pakistan: directions for future health policy.

Injuries result in major financial and productivity losses to nations while inflicting tremendous personal burden on the injured and their families. Two-thirds of the global deaths from injuries occur in the developing world, consuming substantial health sector resources. Pakistan is a developing country with a population of 136 million and no reported estimate of the national impact of injuries. This study presents a profile of injuries in Pakistan, estimates the impact on the country and recommends strategies to further delineate this important public health problem. A methodical review of published, unpublished and government literature was undertaken and data collected for all types of injuries principally over the 1982-1994 period. Motor vehicle injuries, homicides, assaults, work-related injuries, poisonings and risk factors have been included. Selected epidemiological estimates have been generated and the WHO motorization index has been used to assess road-side accident risk. The lack of reliable data and under-reporting of work-related injuries is revealing. The rising time trend in all injuries, the significant loss of life from injuries and the age of those injured have a critical impact on the national economy and health system. Data on injuries in Pakistan are primarily recorded by police authorities and used for legal purposes. Pakistan must institute an information system to evaluate the true impact of injuries and develop national safety standards. Implementation of such standards is especially important for road traffic safety and occupational health in industrial units within the country.

Accidents, Traffic↗
PubMed1998

The role of stress hormones in exercise-induced suppression of alveolar macrophage antiviral function.

We hypothesized that a previously observed exercise-induced suppression of alveolar macrophage antiviral resistance results from increases in corticosterone and/or epinephrine. Mice (CD-1) were run to fatigue on a treadmill (exercise), or placed in Plexiglas lanes above the treadmill (control). The role of corticosterone was assessed by further dividing mice into groups receiving one of the following treatments; sham surgery, adrenalectomy, or adrenalectomy plus corticosterone replacement. Macrophage antiviral function was suppressed in the exercised mice compared to the control mice. However, macrophage antiviral function was not suppressed in the exercised mice that underwent adrenalectomy or adrenalectomy plus corticosterone replacement. We tested whether another adrenal factor (epinephrine) may be involved by dividing mice into exercise and control groups treated with either saline or propranolol. Macrophage antiviral function was again suppressed in the saline-treated exercised mice compared to saline-treated control mice, but no differences were found between the exercised mice receiving propranolol, control mice receiving propranolol, or saline-treated control mice. Isoproterenol, when added to alveolar macrophages in culture, also suppressed antiviral resistance. These findings suggest that decreased macrophage antiviral function following exercise may be due to increased release of adrenal catecholamines.

Adrenal Insufficiency↗
PubMed1998

Immune system activation and fatigue during treadmill running: role of interferon.

UNLABELLED: Extreme fatigue often accompanies infection and other diseases, but the causal mechanisms are unknown. Recent research has focused on various cytokines as potential immune system mediators of fatigue during illness. Interferon-alpha/beta (IFN-alpha/beta) has attracted the most interest in this regard. PURPOSE: The purpose of this research was to study the effect of IFN-alpha/beta on fatigue during treadmill running in mice. METHODS: Mice (male CD-1) were acclimated to treadmill running for 4 d before experimental sessions. In experiment 1 (EXP 1), mice were injected with either polyI:C (pI:C) (5 mg.kg-1 body weight) or saline (CON) 12 or 24 h before the exercise session. These sessions consisted of treadmill running to fatigue (approximately 3 h, 19-24 m.min-1, 5% grade, no shock). In experiment 2 (EXP 2), mice were injected 24 h before exercise with normal rabbit serum (CON), pI:C, or pI:C + anti-IFN-alpha/beta antibody (pI:C + Ab). RESULTS: The results of EXP 1 showed that the plasma IFN-alpha/beta titer was much higher at 24 h than at 12 h after pI:C injection (P < 0.001) and that run time to fatigue was significantly reduced only when the exercise occurred 24 h after injection (P < 0.05). In EXP 2, administration of the anti-IFN-alpha/beta antibody attenuated both the pI:C-induced increase in plasma IFN-alpha/beta (P < 0.001) and the decrease in run time to fatigue (r = -0.81, P < 0.001). CONCLUSIONS: These results suggest that immune system activation by pI:C was associated with early fatigue during prolonged treadmill exercise and that this effect may, at least partially, result from increased IFN-alpha/beta.

Animals↗
PubMed1998

Exercise effects on IFN-beta expression and viral replication in lung macrophages after HSV-1 infection.

Mice exercised to fatigue and exposed to herpes simplex virus type 1 (HSV-1) exhibit greater mortality than control mice. In this study, we examined lung macrophage resistance to HSV-1 after exercise in terms of both viral replication and interferon (IFN)-beta production. We utilized the reverse transcriptase-rapid polymerase chain reaction to measure the IFN-beta mRNA content in alveolar macrophages. IFN release was measured with a bioassay, and viral replication within the macrophage was assessed by plaque titration. Exercised (Ex) mice ran on a treadmill until fatigue while control (Con) mice remained in lanes above the treadmill. After exercise, alveolar macrophages were removed and incubated with HSV-1. Alveolar macrophage IFN-beta mRNA was greater in Ex than in Con mice. Culture supernatant from infected macrophages showed a higher degree of IFN release and a higher number of infectious viral particles in Ex vs. Con mice. It is likely that the increase in IFN-beta mRNA occurs in response to a higher degree of viral replication. These results suggest that macrophages from Ex mice are less resistant to infection with HSV-1.

Animals↗
PubMed1998

Exercise effects on lung tumor metastases and in vitro alveolar macrophage antitumor cytotoxicity.

This study examined the effects of moderate and prolonged exercise on 1) lung tumor metastases and 2) alveolar macrophage antitumor response in vitro. C57B1/6 mice were assigned to either Ex-30 (30-min run), Ex-F (run to fatigue), Ex-F-24 h (run to fatigue 24 h before tumor injection), or Con (rested in lanes above the treadmill). Mice received intravenous injections of syngeneic B16 melanoma cells 30 min postexercise. Lungs were removed 7 or 10 days later, and tumor foci were counted. Ex-F had fewer tumors than either Ex-30 or Con, whereas Ex-F-24 h also showed a strong trend toward fewer tumors. The initial localization of tumor cells in the lungs after injection was not different among groups. For the in vitro experiment, mice were killed immediately after exercise or 8 h later. Alveolar macrophages were removed and cultured in vitro with B16 melanoma cells. The growth of the tumors cultured with macrophages from Ex-F was lower than Con after exercise and, to a lesser extent, 8 h later. In Ex-30, this effect was only found immediately after exercise. The data suggest that prolonged exercise has a protective effect on lung tumor metastases and enhances alveolar macrophage antitumor cytotoxicity.

Animals↗
PubMed1997

Effects of exercise intensity on natural killer cell activity in women.

Exercise effects on natural killer cell (NK) activity in men appear to be intensity dependent, but there is very little data in women. We tested the effect of high versus moderate-intensity exercise relative to non-exercising controls on NK cytolytic activity (NK activity) in women using oral contraceptives. Subjects (n = 8) participated in 3 treatments consisting of 25 min of cycle ergometer exercise at 80% (HI-INT) and 40% (MOD-INT) VO2max, and a 25 min control (CON) session in which the subject remained seated on the cycle ergometer, but did not exercise. Blood was obtained prior to exercise, immediately after, and at 90 min and 3 h after exercise. During CON, NK activity gradually increased and cortisol gradually decreased during the approximately 3.5 h experimental period. Relative to CON, HI-INT increased NK activity, %CD56+ (NK) cells, and plasma norepinephrine immediately post exercise (p < or = 0.05). There was also a trend for decreased NK activity at 90 min (p = 0.075). No differences among treatment groups were found by 3 h post exercise. In MOD-INT, there were no differences from CON in any variable at any time. These data suggest that the typical NK response to intensive exercise in men, which consists of a brief increase followed by a more prolonged suppression, also occurs in women using oral contraceptives. However, it is important to use time-matched control measurements in determining this response.

Adult↗
PubMed1997

Exercise, alveolar macrophage function, and susceptibility to respiratory infection.

The effects of exercise on susceptibility to respiratory infection were determined by using a murine model of intranasal challenge with herpes simplex type 1 virus (HSV-1). Two doses of treadmill exercise were assessed: moderate short-term (30 min) exercise and prolonged strenuous exercise to voluntary fatigue (2.5-3.5 h). Morbidity and mortality among exercised and control mice were compared after intranasal challenge with HSV-1. We also assessed the ability of alveolar macrophages to restrict HSV-1 viral replication (intrinsic resistance) among exercise and control groups of mice at several time points postexercise. Exercise to fatigue followed by exposure to viral infection resulted in greater morbidity and mortality than either no exercise or short-term moderate exercise. In addition, antiviral resistance of macrophages obtained from the lungs of both exercised groups was suppressed, albeit for a longer duration in the fatigued group. These data are particularly important in that they identify an exercise-induced decrease in antiviral resistance of a specific component of the immune system within the lungs, in conjunction with increased susceptibility to respiratory infection in vivo. The specific mechanism of decreased antiviral resistance of alveolar macrophages and its role in respiratory infection after exercise remains to be determined.

Administration, Intranasal↗
PubMed1996

Lipopolysaccharide-induced suppression of phagocytosis: effects on the phagocytic machinery.

We have shown previously that Lipopolysaccharide (LPS) can suppress macrophage phagocytosis and that suppression was not mediated by the induction of cytokines (1). In this study we investigated the mechanisms by which LPS may be suppressing phagocytosis in thioglycolate-elicited murine peritoneal macrophages, by evaluating the effect of LPS on various components of the phagocytic machinery. LPS mediated suppression in vitro was not due to reduced Fc gamma receptor gene expression. LPS-treatment did result in a slight reduction in the number of Fc gamma RI receptors but this reduction could not account for the degree of suppression seen following LPS treatment. LPS treatment altered the distribution of microfilaments and microtubules and Møs with such alterations had reduced phagocytic activity, suggesting that LPS may be suppressing phagocytosis via its effects on the cytoskeletal network. LPS administration in vivo also resulted in reduced phagocytic activity.

Animals↗
PubMed1994

Effects of exercise on macrophage activation for antitumor cytotoxicity.

Recent evidence suggests that exercise affects macrophage functions and that amount of exercise may be important. We determined effects of moderate (MOD) and exhaustive treadmill running (EXH) on 1) ability of macrophages to become activated for antitumor cytotoxicity after injection of heat-inactivated Propionibacterium acnes in vivo, 2) macrophage responsiveness to activating agents lipopolysaccharide and interferon-gamma, and 3) role of glucocorticoids and various macrophage metabolic products in modulating cytotoxicity in exercised animals. Male C3H/HeN mice were randomly assigned to MOD (18 m/min, 5% grade, 30 min/day) or EXH (18-35 m/min, 5%, 2-4 h) on a motor-driven treadmill. Control animals were kept in simulated treadmill lanes located directly over the runners. In general, both MOD and EXH increased cytotoxicity (42 and 22%, respectively, across all experiments; P < 0.05). Enhanced cytotoxicity was not due to altered macrophage adherence, tumor necrosis factor-alpha, interleukin-1 beta, or reactive oxygen species. Reactive nitrogen species were responsible for enhanced toxicity in EXH only. Macrophage cytotoxicity was further increased by lipopolysaccharide and interferon-gamma to a similar maximal level that was the same in all groups. Plasma corticosterone was elevated two- and fourfold in MOD and EXH, respectively, but there was no correlation between plasma corticosterone and macrophage cytotoxicity when compared across all groups even though cells were sensitive to steroid-mediated suppression in vitro. However, consistent with a corticosterone effect, EXH reduced the number of peritoneal macrophages elicited during P. acnes inflammation and abolished the typical exercise-induced increase in cytotoxicity of activated macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of exercise on the immune response to cancer.

This study examined the effects of two doses of exercise on tumor incidence and progression, and the number and activity of intratumoral phagocytic cells (80% macrophages [M phi's]). Male mice were randomly assigned to control (CON), moderate (MOD) or exhaustive (EXH) treadmill running. Mice were inoculated subcutaneously with 2.5 x 10(5) mammary adenocarcinoma cells after 3 d of running (3 h after the last run at a point when enhancement in M phi cytotoxicity is observed). This tumor was chosen due to its susceptibility to M phi inhibition in vitro and in vivo. Mice continued daily running for 14 d. Food intakes were higher during the last 3 d in MOD and EXH, but body weights were no different. Flow cytometer analysis of tumor masses revealed that MOD had greater numbers of phagocytic cells (vs EXH) with slightly higher phagocytic activities (vs CON and EXH) (P < 0.05). However, no group differences in tumor appearance were seen except on day 7 when CON had less observable tumors than MOD and EXH (P < 0.05). Tumor size was also not different between groups at any point. These results indicate that moderate exercise can increase the phagocytic capacity of intratumoral phagocytic cells, but these changes had no apparent effect on tumor incidence or progression in this study.

Adenocarcinoma↗
PubMed1993

Lipopolysaccharide-induced suppression of erythrocyte binding and phagocytosis via Fc gamma RI, Fc gamma RII, Fc gamma RIII, and CR3 receptors in murine macrophages.

In this study we have investigated the ability of lipopolysaccharide (LPS) to suppress binding and phagocytosis of erythrocytes via various receptors on mouse macrophages. Thioglycollate-elicited peritoneal macrophages were treated in vitro with LPS and the ability to bind and phagocytose radiolabeled sheep red blood cells was determined. We show that LPS can directly suppress phagocytosis of immunoglobulin G-opsonized and nonopsonized sheep red blood cells (SRBCs) by inflammatory macrophages. Suppression was dose dependent and was observed after 4 h of exposure. This effect lasted for at least 24 h following the removal of LPS. LPS suppressed the binding, rate, and absolute level of phagocytosis via Fc receptors. Phagocytosis via all Fc receptors (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) was suppressed by LPS. Furthermore, suppression was not limited to Fc receptor-mediated phagocytosis because binding and uptake of C3bi-opsonized SRBCs to CR3 receptors was also decreased following LPS treatment. LPS did not exert its effects via the production of interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha, or interferon alpha/beta, because antibodies to these cytokines did not abrogate the effect. The ability of LPS to suppress binding and phagocytosis of microorganisms may contribute to the toxic effects of LPS during gram-negative sepsis by preventing or delaying elimination of bacteria by host macrophages.

Animals↗
PubMed1993

Poly I:C-induced antiviral and cytotoxic activities are mediated by different mechanisms.

Macrophages play an important role in host defenses against tumors and virus infections by killing tumor or virus infected cells (extrinsic cytotoxicity) and by limiting virus replication within themselves (intrinsic antiviral activity). Since common macrophage products may be involved in both extrinsic cytotoxicity and intrinsic antiviral activity, we decided to investigate the mechanisms by which Poly I:C-activated macrophages resist infection with HSV-1 and inhibit the growth of tumor cells. The ability of macrophages to resist infection with HSV-1 or to inhibit growth of tumor cells was assessed following treatment with Poly I:C in the presence of antibodies to various cytokines or in the presence of inhibitors/scavengers of toxic macrophage products. Only antibodies to IFN-beta were able to abrogate the protective effects of Poly I:C in macrophages infected with HSV-1, suggesting that the antiviral activity induced by this immunomodulator was mediated by the production of IFN-beta, which acted in an autocrine manner. In contrast, anti-TNF-alpha, anti-IFN-alpha/beta anti-IFN-beta antibodies and inhibitors of nitric oxide and C1q production were all able to partially abrogate Poly I:C-induced cytostatic activity, suggesting that multiple mechanisms are involved in macrophage cytostasis. Our results indicate the Poly I:C-induced intrinsic antiviral and extrinsic cytotoxic activities are mediated by different mechanisms.

Animals↗
PubMed1993

Exercise increases inflammatory macrophage antitumor cytotoxicity.

This study determined the effects of exercise on the ability of inflammatory macrophages to inhibit tumor cell growth in vitro (macrophage cytotoxicity). Thioglycollate injection (1 ml ip) was used as an inflammatory challenge and to partially activate macrophages for cytotoxicity. Inbred male C3H/HeN mice (n = 180) exercised moderately (MOD, 18 m/min, 30 min/day, 5% grade) or to exhaustion (EXH, 18-35 m/min, 2-4 h, 5% grade) on a motor-driven treadmill for 3 consecutive days after injection. Control (CON) mice were kept in stimulated treadmill lanes directly over the runners. Mice were killed immediately or 3 or 8 h postexercise. Macrophages from both MOD and EXH exercise groups manifested significantly (P < 0.05) enhanced (approximately 50%) cytotoxicity compared with those from CON group at all time points postexercise. This potentially beneficial exercise effect was not related to macrophage production of interleukin-1 beta, reactive nitrogen or oxygen intermediates, or number of macrophages in the assay but may have been manifested, in part, by tumor necrosis factor-alpha. Plasma corticosterone was significantly elevated immediately postexercise in MOD and EXH compared with CON mice; however, no evidence existed for an immuno-suppressive effect of corticosterone on macrophage cytotoxicity, perhaps because of insensitivity of inflammatory macrophages to glucocorticoid suppression seen in vitro. These data only partially support the "inverted U hypothesis," which states that moderate exercise may enhance, whereas very heavy exercise or a lack of exercise may attenuate, the immune response. Further study is needed to determine the physiological significance of these findings and the effects of exercise on macrophage subsets sensitive to glucocorticoid suppression (i.e., fully activated macrophages).

Animals↗
PubMed1992

Localization of metallothionein in the brain of rat and mouse.

Metallothionein (MT) is a low molecular mass protein inducible by heavy metals such as cadmium (Cd), zinc, and copper, and having high affinity for these metals. In the present study, we investigated the immunohistological localization of MT in the brains of rats and mice. In adult rat brain, almost no MT immunostaining was observed, whereas in adult mouse brain strong MT immunostaining was found in the ependymal cells, some glial cells, arachnoid, and pia mater. No immunostaining was detected in neurons and endothelial cells. In younger rats (1-3 weeks old), strong MT immunostaining was observed in ependymal cells, choroid plexus epithelium, arachnoid, and pia mater. The overall MT concentration in adult mouse brain appeared higher than that of the brains of young and adult rats. When adult rats were administered Cd, MT was induced not only in some glial cells, ependymal cells, arachnoid, and pia mater but also in endothelial cells. Although Cd treatment resulted in an increase in the MT immunostaining in the specific cells described above, the MT induction was not great enough to significantly affect the overall MT level in the brain. The present result suggest a possible link of MT with cell growth of choroid plexus epithelium and ependymal cells, as well as a detoxifying role of MT in the blood-brain barrier and the cerebrospinal fluid-brain barrier.

Aging↗
PubMed1991

Poly I:C-induced anti-herpes simplex virus type 1 activity in inflammatory macrophages is mediated by induction of interferon-beta.

We examined the mechanism by which Polyriboinosinic:Polyribocytidylic acid (Poly I:C) augments resistance of thioglycolate-elicited inflammatory macrophages to infection with herpes simplex virus type 1 (HSV-1). We show that Poly I:C-induced antiviral activity is completely abrogated by antibodies to interferon-beta (IFN-beta) whereas antibodies to other interferons or to other cytokines have no effect. Furthermore, treatment of inflammatory macrophages with exogenous IFN renders them resistant to HSV-1, whereas treatment with other cytokines does not. In addition, we demonstrate that supernatants from macrophages treated with Poly I:C contain IFN-beta but not IFN-alpha. Taken together these data indicate that the antiviral effects of Poly I:C in inflammatory macrophages are mediated solely by IFN-beta, which acts in an autocrine manner to induce resistance to HSV-1.

Animals↗