The influence of INK4 proteins on growth and self-renewal kinetics of hematopoietic progenitor cells

This study investigated the influence of expression of proteins of the INK4 family, particularly p16, on the growth and self-renewal kinetics of hematopoietic cells. First, retrovirus-mediated gene transfer (RMGT) was used to restore p16(INK4a) expression in the p16(INK4a)-deficient lymphoid and myeloid cell lines BV173 and K562, and it was confirmed that this inhibited their growth. Second, to sequester p16(INK4a) and related INK4 proteins, cyclin-dependent kinase 4 (CDK4) was retrovirally transduced into normal human CD34(+) bone marrow cells and then cultured in myeloid colony-forming cell (CFC) assays. The growth of CDK4-transduced colonies was more rapid; the cell-doubling time was reduced; and, upon replating, the colonies produced greater yields of secondary colonies than mock-untransduced controls. Third, colony formation was compared by marrow cells from p16(INK4a-/-) mice and wild-type mice. The results from p16(INK4a-/-) marrow were similar to those from CDK4-transduced human CFCs, in terms of growth rate and replating ability, and were partially reversed by RMGT of p16(INK4a). Lines of immature granulocytic cells were raised from 15 individual colonies grown from the marrow of p16(INK4a-/-) mice. These had a high colony-forming ability (15%) and replating efficiency (96.7%). The p16(INK4a-/-) cell lines readily became growth factor-independent upon cytokine deprivation. Taken together, these results demonstrate that loss of INK4 proteins, in particular p16(INK4a), increases the growth rate of myeloid colonies in vitro and, more importantly, confers an increased ability for clonal expansion on hematopoietic progenitor cells.     

Incidence of Urolithiasis in Northeast Thailand

Background :
Urolithiasis is a major health problem in the northeast part of Thailand. In this study, we examined the prevalence of renal stone disease and differences of urinary components between stone formers and healthy control subjects in northeastern rural areas of Thailand.
Methods :
We selected 3 villages in the rural areas of Khon Kaen province in northeast Thailand. Three hundred and sixty-seven persons were asked questions relating to urolithiasis and were examined by abdominal ultrasound (US). We collected a spot urine sample from stone formers and healthy control subjects from each village.
Results :
Abnormal findings by US were detected in 39 individuals (10.6%), and included 31 individuals with renal calculi (8.4%), 16 with hydronephrosis (4.4%), and 1 individual with a renal cyst (0.3%). This yielded a disease rate of urinary stones in this study of 16.9%. The male/female ratio was 2/1 and the average age of the individuals examined was 40.3 + 13.9 years. However, there was no significant difference between the urinary parameters of stone formers and the healthy control subjects. Conclusion: There was a high incidence of renal stone disease in the northeast part of Thailand, but the tendency for hypocitraturia was only found in stone formers.     

Survival and prognostic factors of different sites of head and neck cancer: an analysis from Thailand

Background: Head and neck cancers are prevalent in Thailand, in particular in the southern region of the country. However, survival with a large data set has not been reported. The purpose of the present study was to evaluate the survival figures and the prognostic factors in a cohort of patients treated in a university hospital located in the south of Thailand. Patients and Methods: Consecutive new cases of primary carcinoma of the oral cavity, oropharyx, hypopharynx and larynx, treated at Songklanagarind Hospital during 2002 to 2004, were analyzed. The 5-year overall survival rates were obtained by the Kaplan-Meier method. Prognostic factors were identified through multivariate Cox regression analysis. Results: A total 1,186 cases were analyzed. Two-thirds (66.6%) of the cases were at advanced stage (stage III & IV) at presentation. The five-year overall survivals for the whole cohort, oral cavity, oropharynx, hypopharynx and larynx were 24.1%, 25.91%, 19.2%, 13.4%, 38.0% respectively. Stage and treatment type were strong prognostic factors for all sites. An age ≥ 80 years was associated with poor survival in oral cavity and larynx cancer. Conclusions: The results revealed remarkably poor outcomes of the patients in the series, indicating a strong need to increase the proportion of early stage presentations and maximize the treatment efficacy to improving outcomes. Very old patients are of particular concern for treatment care of oral cavity and larynx cancer.     

Uricosuric effect of Roselle (Hibiscus sabdariffa) in normal and renal-stone former subjects

AIM OF THE STUDY: The Roselle (Hibiscus sabdariffa) was investigated for its uricosuric effect. MATERIALS AND METHODS: A human model with nine subjects with no history of renal stones (non-renal stone, NS) and nine with a history of renal stones (RS) was used in this study. A cup of tea made from 1.5 g of dry Roselle calyces was provided to subjects twice daily (morning and evening) for 15 days. A clotted blood and two consecutive 24-h urine samples were collected from each subject three times: (1) at baseline (control); (2) on days 14 and 15 during the tea drinking period; and (3) 15 days after the tea drinking was stopped (washout). Serum and 24-h urinary samples were analyzed for uric acid and other chemical compositions related to urinary stone risk factors. RESULTS: All analyzed serum parameters were within normal ranges and similar; between the two groups of subjects and among the three periods. Vis-à-vis the urinary parameters, most of the baseline values for both groups were similar. After taking the tea, the trend was an increase in oxalate and citrate in both groups and uric acid excretion and clearance in the NS group. In the RS group, both uric acid excretion and clearance were significantly increased (p<0.01). When the fractional excretion of uric acid (FEUa) was calculated, the values were clearly increased in both the NS and SF groups after the intake of tea and returned to baseline values in the washout period. These changes were more clearly observed when the data for each subject was presented individually. CONCLUSIONS: Our data demonstrate a uricosuric effect of Roselle calyces. Since the various chemical constituents in Roselle calyces have been identified, the one(s) exerting this uricosuric effect need to be identified.     

Hypoalbuminemia is a predictor of delayed postoperative bowel function and poor surgical outcomes in right-sided colon cancer patients

PURPOSE: To determine the relationship between preoperative serum albumin and postoperative bowel function as well as surgical outcomes in right-sided colon cancer patients. METHODS: This retrospective study in a university hospital included 84 patients who underwent elective right hemicolectomy for adenocarcinoma of the right-sided colon between January 2004 and December 2005. The patients had a preoperative serum albumin assessment. Serum albumin less than 3.5 g/dL was regarded as hypoalbuminemia. Postoperative outcomes were classified into mortality, morbidity (infectious and noninfectious complications), time to first bowel movement, time to resume normal diet, and hospital stay. RESULTS: Forty males (48%) and forty-four females (52%) with a mean age of 64 (range, 27-89) years were included. Forty-eight patients (57%) had hypoalbuminemia. No 30-day postoperative mortality occurred. All 14 postoperative complications occurred in hypoalbuminemic cases. Therefore, 29% of the hypoalbuminemics had complications whereas none occurred in nonhypoalbuminemics (p=0.001). In univariate analysis, hypoalbuminemia and postoperative complications were the risk factors for delayed postoperative recovery of bowel function and prolonged length of hospital stay. In multivariate analysis, hypoalbuminemia was the significant risk factor for postoperative complications (p<0.001) and delayed time to first bowel movement (p=0.018) whereas postoperative complications were the significant risk factor for delayed time to resume normal diet (p<0.001) and prolonged hospital stay (p<0.001). CONCLUSION: Hypoalbuminemia is a potential predictor of delayed recovery of bowel function postoperatively and significantly associated with postoperative complications in right-sided colon cancer patients undergone right hemicolectomy.     

Urinary citrate excretion in patients with renal stone: roles of leucocyte ATP citrate lyase activity and potassium salts therapy

BACKGROUND: Hypocitraturia is a major metabolic abnormality in rural Northeast Thais with renal stones. These people also have low serum and urinary potassium and consume a high carbohydrate and low fat diet, which together might influence the intracellular metabolism and urinary excretion of citrate. METHODS: In Study A, we measured plasma and urinary chemistries and assayed leucocyte ATP citrate lyase (ACL) activity in 30 normal urban control subjects (Group A1) and 30 rural renal stone patients (Group A2) in Northeast Thailand. Some of the subjects from both groups were also used to evaluate the intake of carbohydrate, protein and fat. In Study B, we examined the effects of potassium salts therapy with another group of 30 rural renal stone patients: Group B1 (n = 15) treated with potassium chloride and Group B2 (n = 15) with potassium-sodium citrate (with an aim to achieve 42 mEq potassium, 21 mEq sodium and 62 mEq citrate per day for 1 month). RESULTS: In Study A, the leucocyte ACL activity of Group A1 was much lower than that of Group A2 (3.2 +/- 0.7 vs. 9.3 +/- 3.8 micromol acetylhydroxamate/mg protein/30 min, p < 0.0001). The plasma potassium, urinary excretions of potassium and citrate in Group A1 were higher than in Group A2. When data of the two groups were combined, urinary citrate excretion was inversely correlated with leucocyte ACL activity (r = 0.6783, p < 0.001). While the dietary protein intake did not differ between Groups A1 and A2, the carbohydrate intake by Group A1 was significantly lower (65.2 +/- 7.9% vs. 83.1 +/- 2.9%, p < 0.01) and fat higher (21.0 +/- 6.4% vs. 6.2 +/- 4.1%, p < 0.002) than Group A2. After treatment with potassium chloride (Group B1), only the potassium was increased (p < 0.001), while those treated with potassium-sodium citrate (Group B2) experienced a significant increase in urinary pH (p < 0.002), potassium (p < 0.001) and citrate (p < 0.001), and a decrease in leucocyte ACL activity (p < 0.001). CONCLUSIONS: Compared to normal subjects, renal stone patients have low urinary citrate excretion with high leucocyte ACL activity. In Northeast Thailand, low potassium status and a high carbohydrate and low fat diet may cause the increased ACL activity. However, hypokaliuria, hypocitraturia and high leucocyte ACL activity can be corrected by potassium-sodium citrate salt therapy.