Serum Lysozyme Pattern and Hematological Changes in the Host During Growth of a Transplantable Murine Lymphoma

The serum lysozyme concentrations were determined in the host mice bearing a transplantable ascitic lymphoma during growth of the tumour. Simultaneously, the hematological changes were also recorded. These ob-servations were made at weekly intervals till the animals survived and were made at weekly intervals till the animals survived and were compared with their normal counterparts. It has been shown that there is a progressive increase in the concentration of lysozyme along with the growth of the tumour cells within the peritoneal cavity which reaches a peak on the third week following transplantation of tumour cells and then falls off. The con-centration of the enzyme, however, never reaches the normal values ob-served. This shows a parallelism with the growth pattern of the tumour in general. Total and differential counts of white blood cells revealed a marked rise in the total leukocyte counts and a reversal of the lymphoid-myeloid ratio during the growth of the tumour in the host

The Multiple Causes of Obesity

Obesity is known to cause physical and metabolic diseases. It is often assumed by people (including the healthcare workers) that the person with obesity lacks self-control in matters of diet and physical exercise, and is therefore responsible for his or her weight. Persons with obesity have to face sarcasm, barbs, and discrimination due to their condition. They often have difficulty in getting jobs or have to accept lower than standard pay for their work. Although weight gain requires calorie intake in excess of calorie expenditure, it is sometimes not easy for the person to restrict calories due to the underlying causes of obesity. The body resists losing weight, and attempts to hoard calories by reducing the metabolic rate. In this chapter we have explained and classified the causes of obesity into endogenous and exogenous. The endogenous causes include genetic and epigenetic causes, maternal factors, and hormonal causes, while exogenous causes include obesogenic environment, lifestyle, and weight-gain promoting medicines. It must be realized that losing weight and keeping it off is not easy for a person with obesity

Association of Intracellular TH1-TH2 Balance in CD4+ T-cells and MIP-1α in CD8+ T-cells with Disease Severity in Adults with Dengue

Background: We tested the hypothesis that dengue haemorrhagic fever (DHF) is associated with a TH1-skewed immune response as opposed to dengue fever (DF). Methods: We estimated intracellular (in T-cells) and serum levels of designate TH1/TH2 cytokines [interferon-γ (IFN-γ), interleukin-4 (IL-4), and tumor necrosis factor-α] and macrophage inflammatory protein-1α (MIP-1α) at admission, 48 h, and day 5 in 20 adults with dengue (DF=10, DHF=10) and 10 dengue-naive healthy controls. Results: At admission, intracellular IFN-γ/IL-4 ratio in CD4+ T-cells and proportion of MIP-1a-positive CD8+ T-cells were significantly higher in patients with DHF [7.21 (5.36 ~ 10.81) vs. 3.04 (1.75 ~ 4.02); p=0.011 and 6.2% (3.2 ~ 8.2%) vs. 2.4% (2.0 ~ 3.6%); p=0.023]. The latter showed a significant positive correlation with IFN-γ/IL-4 ratio in CD4+ T-cells (Spearman's rho=0.64; p=0.003), percentage-change in haematocrit (rho=0.47; p=0.048), and serum alanine aminotransferase level (rho=0.61; p=0.009). Conclusion: We conclude that DHF is associated with a TH1-skewed immune response. Further, MIP-1α in CD8+ T-cells is an important immunologic correlate of disease severity in dengue

Regulatory T Cells Suppress T Cell Activation at the Pathologic Site of Human Visceral Leishmaniasis

Suppression of T cell response is thought to be involved in the pathogenesis of visceral leishmaniasis (VL). Regulatory T cell (Treg) mediated immune-suppression is reported in animal models of Leishmania infection. However, their precise role among human patients still requires pathologic validation. The present study is aimed at understanding the frequency dynamics and function of Treg cells in the blood and bone marrow (BM) of VL patients. The study included 42 parasitologically confirmed patients, 17 healthy contact and 9 normal bone marrow specimens (NBM). We show i) the selective accumulation of Treg cells at one of the disease inflicted site(s), the BM, ii) their in vitro expansion in response to LD antigen and iii) persistence after successful chemotherapy. Results indicate that the Treg cells isolated from BM produces IL-10 and may inhibit T cell activation in IL-10 dependent manner. Moreover, we observed significantly higher levels of IL-10 among drug unresponsive patients, suggesting their critical role in suppression of immunity among VL patients. Our results suggest that IL-10 plays an important role in suppression of host immunity in human VL and possibly determines the efficacy of chemotherapy

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec