Tumour cell membrane laminin expression is associated with basal-like phenotype and poor survival in Nigerian breast cancer.

INTRODUCTION: Laminin is a glycoprotein with diverse functions in carcinogenesis including cell proliferation, invasion, metastases and epithelial-mesenchymal transition (EMT). In breast cancer (BC) laminin expression is speculated to be associated with unfavourable clinicopathological and molecular characteristics. We hypothesize that laminin expression would contributed to the aggressive nature of basal like and triple negative BC phenotype observed in Black women. METHODS: The expression of laminin was determined in a well-characterised Nigerian cohort of 255 BC using tissue microarray and immunohistochemistry. Laminin expression was compared with clinical, pathological and survival characteristics. RESULTS: Laminin was expressed in 146 (57.3%) cases and significantly correlated with younger age at diagnosis (p=0.005), premenopausal status (p=0.003), expression of EGFR (p=0.002), ID4 and MTA1, basal cytokeratin 5/6, p53, and triple negative tumours (all p<0.001). In addition, there was an inverse association of laminin expression with E-cadherin (p=0.03), ER and PgR (all p<0.001) and a trend with BRCA1 (p=0.05). Univariate survival analysis showed tumours positive for laminin had significantly poorer breast cancer specific survival (BCSS, p=0.009) and disease free interval (p=0.03), but not associated in Cox multivariate analysis. CONCLUSION: This study demonstrates that laminin expression may have important roles in the aggressive nature observed in the basal-like and triple negative molecular subtype of Nigerian BC women.

Effect of Methamidophos on cerebellar neuronal cells.

Methamidophos is a toxic organophosphorus compound that inhibits acetlycholinesterase activity, and induces neurotoxicity. It is a synthetic chemical commonly used as pesticides to limit pest damages to cultivated plants. Currently, there is serious public health concern over its safety and use due to its global nature, persistence and bioaccumulations. We have previously reported that methamidophos suppressed thyroid hormone receptor (TR)-mediated transcription, but did not dissociate the interaction between TR and its response element (thyroid hormone response element; TRE), neither did it interact with nuclear cofactors. In the present study, we investigated the effects of methamidophos on cerebellar neuronal cells. Using primary cerebellar culture from new born rats, We observed that Purkinje cell dendrite arborization were greatly impaired in the absence of thyroid hormone (TH), However, low dose methamidophos 10-6 M did not significantly impair dendrite arborization of cerebellar Purkinje cells in the presence of thyroid hormone (TH). However, using granule cell reaggregate culture, we observed that low dose methamidophos 10-6 M remarkably suppressed granule cell neurite extension in the presence of TH. Taken together, our study shows that low dose methamidophos may negatively impact TH-mediated cerebellar neuronal cell development and function, and consequently could interfere with TH-regulated neuronal events.

Hypertension, and blood pressure response to graded exercise in young obese and non-athletic Nigerian university students.

Hypertension, and the effect of graded exercise on blood pressure (BP), in 60 obese non-athletic young medical students (40 females and 20 males) with body mass index (BMI) greater than 30 were studied. The subjects were in the age range of 18-22 years with mean age of 20.30 +/-1.32 years. Twenty percent of the males and 7 percent of the females were found to be hypertensives [P < 0.05] and the severity of the hypertension significantly [P < 0.05] increased linearly with increase in BMI (r =0.6). Our study reveals a positive direct correlation between obesity and socioeconomic status and BP. Marked increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), time of return (RT) were observed in the obese individuals compared to control at all levels of graded exercise with the highest rises seen during severe exercise. Among the obese subjects, the increases in BP were more in the males than females, but time of return was higher in females than males. This study further confirms that obese young individuals are prone to early onset of hypertension and thus other cardiovascular diseases and less tolerant to physical exercises. Our results add to the evidence that hypertension is common among obese young adults.

Prevalence of byssinosis and other respiratory problems among textile mill workers in Asaba, Nigeria.

OBJECTIVES: This study was conducted to determine the distribution and severity of byssinosis and other respiratory problems in the different operation sections in a textile mill industry in Asaba. PATIENTS AND METHODS: This is a cross-sectional and analytic study in which workers directly exposed to cotton dust are compared with those not directly exposed to cotton dust at one point in time. RESULTS: A total of 735 workers were interviewed and 437 workers had respiratory examinations carried out on them. Byssinosis was diagnosed in 8 out of 405 workers (prevalence of 1.98%) who were not directly exposed to cotton dust, and 21 out of 330 workers (prevalence of 6.36%) who were directly exposed to cotton dust. The difference was found to be statistically significant (chi2 =9.25; df=1; 0.01

Influence of smoking on respiratory symptoms and lung function indices in sawmill workers in Benin City, Nigeria.

The study was done to assess the influence of smoking on respiratory symptoms and respiratory function in sawmill workers in Benin City. 150 sawmill workers who were all males and aged between 18 and 50 years, and had been in continuous employment in sawmill factories for a minimum of one year were studied. They were selected by a two-stage random sampling process from sawmills in Benin City. These were compared to 150 age and sex matched controls in order to determine the effect of sawdust exposure on the respiratory system. Questionnaire was used to elicit morbidity patterns and anthropometric measurements were also made. Respiratory rates, Peak Expiratory Flow Rates and Blood Pressures were measured in both groups. Respiratory symptoms were more common among sawmill workers compared to the controls. Smoking by some of these workers further aggravated their respiratory symptoms. Although blood pressure was similar in both groups, Respiratory rates were higher and Peak Flow Rates were lower in the sawmill workers compared to the controls (20.83 +/- 2.02 cycles/minute and 516.72 +/- 38.48 L/minute for the sawmill workers; 15.45 +/- 1.23 cycles/minute and 575.37 +/- 27.34 L/minute for the controls, respectively). Less than 5% of the sawmill workers wore protective devices/clothing, and health and safety standards were neither practiced nor enforced. The findings suggest that respiratory symptoms especially sputum production and chest pain are common in sawmill workers. Respiratory function is compromised in these workers.

Variations of peak expiratory flow rate with anthropometric determinants in a population of healthy adult nigerians.

Peak expiratory flow rate (PEFR) was measured in 300 healthy adult male and female staff and students of the University of Benin, Benin City, and the College of Education, Ekiadolor, near Benin. The variations of Peak Expiratory Flow Rate with respect to height (ht), weight (wt) and chest circumference (cc) were determined in these subjects. PEFR values fell within the middle to the lower limits of the range for the general male and female populations. There was a linear increase in PEFR with respect to the three anthropometric variables (ht, wt and cc) only in the young adult males, whereas in the older adult males and females, PEFR fluctuated considerably with the variables. PEFR correlates more with height, weight and chest circumference in young adults than in older adults. Respiratory function indices collected from healthy young adults may be more reliable and predictable than those from older adults.

Cerebral blood flow velocity during and after sustained isometric skeletal muscle contractions in man.

1. Twenty-seven young subjects used their right hand to perform sustained, isometric contractions at 40% of maximum for 2 min while lying supine. 2. During the last 30 s of exercise, mean arterial blood pressure increased by 38 +/- 4 mmHg (mean +/- S.E.M.) and heart rate by 27 +/- 2 beats/min. 3. Nineteen of the subjects respired eucapnically during exercise, increasing ventilation by 4.1 +/- 0.5 litres/min. Eight subjects hyperventilated (7.1-19.6 litres/min) and decreased end-tidal PCO2 by 8.2 to 15.1 mmHg during the last minute of exercise. 4. In the eucapnic subjects mean flow velocity in the right (i.e. contralateral to the activated cortex) middle cerebral artery increased by 11.4 +/- 1.0 cm/s, a change of 17%, during the contraction. This represents an increase in volume flow to the territory of this vessel, but an increase in global flow to the brain cannot be inferred. 5. In the eight subjects who hyperventilated during exercise, there was no rise of flow velocity in the middle cerebral artery, and in some subjects there was a fall during the first 2 min of recovery. These findings suggest that if subjects hyperventilate during handgrip exercise there could be a fall in volume flow to many regions of the brain during and after the exercise.

Changes in blood pressure and serum cholesterol following exercise training in Nigerian hypertensive subjects.

The effect of exercise training on blood pressure (BP) and serum cholesterol level was studied in hypertensive Nigerians. Fifty-eight subjects aged 30-65 years completed the study. They exercised on a cycle ergometer at 70% maximum O2 consumption. The frequency of exercise increased from 1 x 30 min/week for 16 weeks to 3 x 30 min/week for 16 weeks. Overall, there was a significant decrease in systolic (S) BP from 161 mm Hg at the onset, to 148 mm Hg at the end of exercise training (P < 0.01). Also there was a significant decrease in diastolic (D) BP from 100 mm Hg to 95 mm Hg (P < 0.05). The younger hypertensives (30-50 years) had a better response than the older hypertensives (51-65 years). There was a slight decrease in total cholesterol and low density lipoprotein levels, but high density lipoprotein level increased from an onset value of 0.94 mmol/l to 1.38 mmol/l at the end of exercise training (P < 0.05). Thus exercise training decreased BP and increased high density lipoprotein in hypertensive Nigerians.

Enhanced sensitivity to salt-induced high blood pressure in diabetes mellitus.

Salt-induced high blood pressure in diabetic rats was compared with that in non-diabetic (control) rats. Before the rats had eaten the high-salt diet, the diabetic group exhibited significantly greater pressor response to noradrenaline (100 ng/100 g body weight) than the controls (P < 0.05). When the rats were given a high-salt diet, a significant increase in blood pressure was recorded 4 weeks earlier in the diabetic than in the control group (P < 0.05); this increase occurred after 2 weeks in the diabetic group, but after 6 weeks of high-salt diet in the controls. The enhanced state of vascular reactivity in the diabetic rats was probably responsible for their enhanced sensitivity to salt-induced high blood pressure.

Duration-dependent attenuation of acetylcholine--but not histamine--induced relaxation of the aorta in diabetes mellitus.

1. The relaxations of aortic preparations from 1, 4 and 12 week diabetic rats to acetylcholine and histamine were studied. 2. The relaxation to acetylcholine but not to histamine was significantly attenuated in the 4th and 12th weeks of the disease. In addition, the tissues became less sensitive to acetylcholine but not to histamine with increasing duration of the disease. 3. The results show that there is differential alteration in the responsiveness of the aorta from diabetic rats to both agents.

Ventilatory function of workers at Okpella cement factory in Nigeria.

Simple ventilatory function tests were done in 447 cement factory workers. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were higher in males than females and correlated well with age and height. FEV1 was smaller in workers who were in closer contact with cement dust. The three measured indices of ventilatory function decreased with years of service and the fall was neither accounted for by age nor height. Eleven chronic bronchitics were found, but these were heavy smokers. Overall, the lung volumes obtained were within the normal range for Nigerians. However, the nature of job done in the cement factory, and duration of service may well be important in the aetiology of "cement factory lung disease".

Ventilatory responses to inhaled carbon dioxide at rest and during exercise in man.

1. Rapid steady-state CO2 responses were determined in six normal subjects at rest and five subjects at four different work loads up to 125 W, by injecting pure CO2 at constant flow into a small mixing chamber in the inspiratory limb of a breathing circuit. 2. The time course of the response of ventilation (V) and mean alveolar PCO2 (PACO2) was checked in separate experiments, where the flow rate of injected CO2 was changed abruptly and the effects were followed for 10 min. 3. V and PACO2 were measured every breath, and the results ensemble-averaged for each subject (two or three runs per subject) and then for the groups as a whole, in 30 s or 60 s time bins. 4. PACO2 during exercise was estimated by graphical reconstruction from the sloping alveolar plateau, and separately by the empirical equation of Jones, Robertson & Kane [1]. At rest, PACO2 was assumed equal to end-tidal PCO2 (PetCO2). 5. With the constant inflow technique, 4 min was required to reach steady-state V and PACO2 during exercise, and 6 min at rest. 6. At rest, with 4 min steps (doubtful steady state) the averaged CO2 response was concave up. With 6 min steps the response was almost linear. In neither case was the deviation from linearity statistically significant. 7. During exercise, the averaged CO2 responses were essentially isocapnic at work loads greater than 75 W with either method of deriving PACO2.

Immediate ventilatory response to sudden changes in venous return in humans.

We changed venous return transiently by postural manoeuvres, and by lower body positive pressure, to see what happened simultaneously to ventilation. Cardiac output was measured by a Doppler technique. In seven subjects, after inflation of a pressure suit to 80 and 40 mmHg at 30 deg head-up tilt, both cardiac output and ventilation increased. Ventilation increased rapidly to a peak in the first 5 s, cardiac output more slowly to a steady state in about 20 s, at 80 mmHg inflation. After inflation to 80 mmHg in six subjects at 12.5 deg head-up and 30 deg head-down tilt, cardiac output did not change in the first, and fell in the second case. There were no significant changes in ventilation. On release of pressure there were transient increases in both cardiac output and ventilation, with ventilation lagging behind cardiac output, in contrast to (2) above. In five subjects, elevation of the legs at 30 deg head-up tilt caused a rise in both cardiac output and ventilation, but in two subjects neither occurred. In all seven subjects there was a transient increase in cardiac output and ventilation when the legs were lowered. Ventilation and cardiac output changes were approximately in phase. We were therefore unable to dissociate entirely increasing cardiac output from increasing ventilation. The relation between them was certainly not a simple proportional one.

Ventilatory sensitivity to inhaled carbon dioxide around the control point during exercise.

Rapid steady-state CO2 responses were determined in five normal adults at rest and at up to six levels of exercise by injecting pure CO2 at a constant flow into the inspiratory limb of a breathing circuit. Ventilation (V) was measured with a dry gas meter and PCO2 at the mouth was recorded by a mass spectrometer. Mean alveolar PCO2 (PACO2) was taken as equal to end-tidal PCO2 at rest, and during exercise was derived graphically from the sloping alveolar plateaus. The accuracy of the latter method was checked in separate experiments against arterial PCO2 (PaCO2). The mean results showed a linear relationship between change in PACO2 and change in V for work loads ranging from rest to 75 W (r = 0.94-0.98). Above 75 W the response became concave down with an initial essentially isocapnic phase. This suggests that during exercise there is a large increase in CO2 sensitivity about the control point.

Ventilation and cardiac output during the onset of exercise, and during voluntary hyperventilation, in humans.

Three normal subjects performed rest--exercise transitions on a cycle ergometer, from rest to unloaded pedalling (0 W), 50, 100 and 150 W. Each experiment was performed in triplicate, with randomized work load order, in two sessions. Ventilation was obtained breath-to-breath by integration of a pneumotachygraph signal, and cardiac output beat-to-beat by a new development of the Doppler technique. Results were bin-averaged in 4 s bins over the first 20 s, and compared to resting values. Both ventilation and cardiac output increased significantly in the first 2 s. This initial rise in ventilation was due entirely to an increase in rate, the subsequent rise mainly to increase in tidal volume. Cardiac output increased predominantly through change in rate with smaller increases in stroke volume. A striking feature was a tendency for ventilation and cardiac output responses to be biphasic with an initial rise followed by a slight fall at the 14 s mark, and a subsequent rise, at all work loads. Overall correlation between ventilation and cardiac output was therefore high (r = 0.92). Six normal subjects hyperventilated for 45 s voluntarily, (a) at rate 24/min and normal tidal volume; (b) at normal rate and tidal volume of 1.5 l; (c) at rate 24/min and tidal volume of 1.5 l. Cardiac output, averaged over 10-45 s, rose by 0.4, 0.5, and 1.0 l min-1 respectively, with falls in end-tidal PCO2 of 4, 6, and 8 mmHg. Six normal subjects hyperventilated for 60 s with rate 24/min and tidal volume of 1.4 l, and end-tidal PCO2 maintained at 38 +/-2 mm Hg. Cardiac output, averaged from 10-60 s, rose by 1.0 l min-1. With increased rate and tidal volume, whether isocapnic or hypocapnic, cardiac output responses showed an overshoot with a peak value at about 30 s. The hypothesis of 'cardiodynamic hyperpnoea' considers a possible effect of increasing cardiac output on ventilation. The effects of ventilation on cardiac output must also be considered. We propose an extended hypothesis involving stable positive feed-back.

Validation of a Doppler technique for beat-to-beat measurement of cardiac output.

We have measured aortic flow in the ascending aorta in man with a Bach-Simpson BVM 202 blood velocity meter, and aortic root diameter by M-mode echocardiography, and thus derived beat-to-beat cardiac output (Q). We tested the technique in 21 patients (53 comparisons) with various cardiovascular problems against a thermodilution method, and in four normal subjects at rest and two levels of exercise (50 and 100 W) against a nitrous oxide rebreathing method. We obtained excellent overall correlation in a range of 0.5-10 litres/min (r = 0.98, n = 77, sy,x = 0.48 litre/min), the formula for the least squares regression being: (Q Doppler) = 0.95 (Q Thermodilution/N2O) + 0.11 litre/min. The Doppler signal is sufficiently noise-free to obtain maximum acceleration of flow from the first derivative of velocity.