Young sedentary adult males of Malay, Indian, and Chinese origin who had established continuous residence in tropical Malaysia and presumed to be naturally acclimatized to heat, were studied to evaluate their physiological responses to a standard heat stress test. The Malay and Indian races have evolved in hot and humid geographical zones, whereas the Chinese originated from a temperate area. Subjects exercised at 50% VO2max alternating 18 minutes walking and 2 min rest during a 2-h exposure to an ambient of 34.9 degrees C dry bulb and 32.1 degrees C wet bulb. Heart rates, core and skin temperatures, sweat rates, and oxygen uptakes were measured during the heat exposure. The subjects of Malay origin exhibited the least circulatory stress of the three ethnic groups. The data obtained on these long-term residents of a hot-wet climate and who were considered acclimatized to this environment were compared to experimental data obtained by other investigators and other ethnic groups.
Cardiorespiratory adjustments to maximal treadmill exercise were studied in young untrained Malaysia men representative of the three major ethnic groups in Malaysia and Singapore. Maximal values for oxygen uptake and cardiac performance were essentially similar In the three groups and were comparable to those reported for other populations.
The investigation examined the possibility that observance of Ramadan by Moslems in Malaysia is associated with modification of circulatory parameters. Cardiovascular reactivity was investigated employing the cold hand immersion test as the stressor stimulus. Resultant data showed increased blood pressures and vascular resistance during Ramadan in the absence of cold stimulus while the magnitude of the maximal cardiac and vascular response to the applied stressor which served as indicators of reactivity was not affected by the Ramadan situation.
1. Anthropometric variables, resting heart rate and respiratory gas exchange were measured in twelve male and nine female Asiatic adult Moslems during the month of Ramadan, the week before and the month after Ramadan. 2. Energy intakes were estimated from dietary recall during fasting and non-fasting conditions. 3. Both male and female subjects experienced a decrease in body mass with the reduction in energy intake during fasting. Males experienced a greater reduction than females in resting heart rate; females lost more body-weight and subcutaneous fat than males. 4. Urine output and fluid intake were measured in twelve male subjects for 1 d during each week of fasting and 1 d during the pre-fasting control period. Among the subjects examined, the Ramadan regimen did not result in changes in the pattern of fluid exchange.
The effect of alteration of eating pattern during Ramadan on body mass index (BMI), serum fructosamine: total protein ratio (F/TP), and glucose level in 18 healthy male Asiatic Moslems were studied. The results showed a significant decrease (p less than 0.025) in F/TP at the second week of Ramadan in 11 subjects who experienced continuous decrease in BMI throughout Ramadan. The remaining 7 subjects showed no significant changes in BMI and F/TP. No evidence of hypoglycaemia was observed in the subjects during the study. Serum fructosamine: total protein ratio in subjects with altered eating pattern preferably should be interpreted along with the change in body mass index.
Urine analysis was conducted on male Muslims before, during and after Ramadan. Various changes in urine volume, osmolality, total solute, sodium, potassium, titratable acidity and urea in response to altered feeding and activity regimens were found. There were no detectable levels of ketones, protein, glucose, urobilinogen and haemoglobin. It was concluded that the body adapted to fasting during Ramadan and that there were no adverse effects on renal function.
Pulmonary function parameters were examined in a Malay Muslim population during normal activity and Ramadan fasting conditions. The validity of employing various lung function prediction formulae for the subjects was also assessed. Present findings indicate that the water deprivation regime and resultant dehydration during Ramadan did not cause significant changes in ventilatory functions. Although pulmonary prediction formulae based on Caucasian and African populations were inapplicable to the subjects examined, the equations derived from the neighbouring populations in Singapore could be employed.
The interaction of lymphoma cells with their microenvironment has an important role in disease pathogenesis and is being actively pursued therapeutically using immunomodulatory drugs, including immune checkpoint inhibitors. Diffuse large B-cell lymphoma (DLBCL) is an aggressive high-grade disease that remains incurable in ~40% of patients treated with R-CHOP immunochemotherapy. The FOXP1 transcription factor is abundantly expressed in such high-risk DLBCL and we recently identified its regulation of immune response signatures, in particular, its suppression of the cell surface expression of major histocompatibility class II (MHC-II), which has a critical role in antigen presentation to T cells. Using CRISPR/Cas9 genome editing we have depleted Foxp1 expression in the aggressive murine A20 lymphoma cell line. When grown in BALB/c mice, this cell line provides a high-fidelity immunocompetent disseminated lymphoma model that displays many characteristics of human DLBCL. Transient Foxp1-depletion using siRNA, and stable depletion using CRISPR (generated by independently targeting Foxp1 exon six or seven) upregulated cell surface I-Ab (MHC-II) expression without impairing cell viability in vitro. RNA sequencing of Foxp1-depleted A20 clones identified commonly deregulated genes, such as the B-cell marker Cd19, and hallmark DLBCL signatures such as MYC-targets and oxidative phosphorylation. Immunocompetent animals bearing Foxp1-depleted A20 lymphomas showed significantly-improved survival, and 20% did not develop tumors; consistent with modulating immune surveillance, this was not observed in immunodeficient NOD SCIDγ mice. The A20 Foxp1 CRISPR model will help to further characterize the contribution of Foxp1 to lymphoma immune evasion and the potential for Foxp1 targeting to synergize with other immunotherapies.
FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL.
A settlement of Temiars, an aboriginal tribe residing in the north-eastern jungles of the Malay Peninsula, was selected for a study of their cardiorespiratory fitness. A step-test was used to elicit the Vo2max, V E max and HR max in a group of 19 boys aged 12 to 18 years and 6 men aged 19 - 40 years. The mean VO2max of the boys was found to be 45.9 +/- 6.9 ml-kg-1-min-1 compared with 45.6 +/- 5.4 ml-kg-1-min-1 for the men. The mean V E max, HR max and blood lactate levels were found to be 65.5 +/- 11.31/min and 69.2 +/- 23.71/min; 194 +/- 8 beats/min and 186 +/- 10 beats/min; and 79.8 +/- 13.4 mg% and 97.7 +/- 33.4 mg% respectively. These results are comparable to those obtained in urban populations as well as those found in other primitive communities. Telemetric monitoring of the routine daily physical activity of the men revealed that these jungle dwellers rarely tax their oxygen transport systems in their daily living and their cardiorespiratory functions were similar to communities who do not specifically train for physical fitness.