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Biomedical subjects

R Rai

Publications and source records attributed to R Rai.

At least 19 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed2006

A meta-analysis on the influence of inflammatory bowel disease on pregnancy.

BACKGROUND: Inflammatory bowel disease (IBD) has a typical onset during the peak reproductive years. Evidence of the risk of adverse pregnancy outcomes in IBD is important for the management of pregnancy to assist in its management. AIM: To provide a clear assessment of risk of adverse outcomes during pregnancy in women with IBD. DESIGN: The Medline literature was searched to identify studies reporting outcomes of pregnancy in patients with IBD. Random-effect meta-analysis was used to compare outcomes between women with IBD and normal controls. PATIENTS AND SETTING: A total of 3907 patients with IBD (Crohn's disease 1952 (63%), ulcerative colitis 1113 (36%)) and 320 531 controls were reported in 12 studies that satisfied the inclusion criteria. RESULTS: For women with IBD, there was a 1.87-fold increase in incidence of prematurity (<37 weeks gestation; 95% CI 1.52 to 2.31; p<0.001) compared with controls. The incidence of low birth weight (<2500 g) was over twice that of normal controls (95% CI 1.38 to 3.19; p<0.001). Women with IBD were 1.5 times more likely to undergo caesarean section (95% CI 1.26 to 1.79; p<0.001), and the risk of congenital abnormalities was found to be 2.37-fold increased (95% CI 1.47 to 3.82; p<0.001). CONCLUSION: The study has shown a higher incidence of adverse pregnancy outcomes in patients with IBD. Further studies are required to clarify which women are at higher risk, as this was not determined in the present study. This has an effect on the management of patients with IBD during pregnancy, who should be treated as a potentially high-risk group.

Birth Weight↗
PubMed2006

Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review.

BACKGROUND: Histopathological examination of products of conception from miscarriages is part of routine clinical practice. The extent of additional clinically relevant information provided by this investigation in the setting of recurrent spontaneous abortion remains uncertain. METHODS: Review of the literature was performed to identify studies reporting on findings of histological examination of routinely obtained products of conception in the setting of recurrent spontaneous abortion. The initial search identified 312 potential references, but 300 were excluded on further examination due to lack of data on specific histopathological findings in routine products of conception specimens from patients with recurrent spontaneous abortion. The 12 included studies indicated that such examination may identify hydatidiform moles, villous dysmorphic features suggesting fetal aneuploidy, chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition and impaired trophoblast invasion. However, in most cases, morphological assessment cannot reliably determine the cause of the miscarriage or distinguish recurrent from sporadic miscarriage. Studies reporting on the use of additional immunohistochemical methods do not currently provide additional clinically useful diagnostic or prognostic information. CONCLUSION: Routine histological examination of products of conception in the setting of recurrent spontaneous abortion can provide important clinical information in a minority of cases.

Abortion, Habitual↗
PubMed2006

Genetic thrombophilic mutations among couples with recurrent miscarriage.

BACKGROUND: Some cases of recurrent first trimester miscarriage (RM)-the loss of three or more consecutive pregnancies at <12 weeks' gestation-have a thrombotic aetiology. METHODS: We determined (i) the prevalence of three thrombophilic mutations [factor V Leiden (FVL), prothrombin G20210A (PTG) and methylenetetrahydrofolate reductase (MTHFR) C677T] amongst 357 Caucasian couples with RM and 68 parous Caucasian couples with no history of miscarriage and (ii) the prospective outcome of untreated pregnancies amongst couples with RM in which either partner carried a thrombophilic mutation. RESULTS: The allele frequencies of FVL (2%), PTG (2%) and MTHFR C677T (31%) were similar between cases and controls. The prevalence of multiple thrombophilic mutations (greater than one mutation) was also similar between cases and controls. Amongst couples in whom either partner carried greater than one thrombophilic allele, the relative risk of miscarriage in a future untreated pregnancy was 1.9 (95% confidence interval, 1.3-2.8) compared with those couples who carried no thrombophilic mutation. CONCLUSION: The prevalence of thrombophilic mutations is similar in couples with RM and parous controls. In couples with RM, multiple genetic thrombophilic mutations in either partner significantly increases the risk of miscarriage in a subsequent pregnancy.

Abortion, Habitual↗
PubMed2005

Study of apoptosis and heat shock protein (HSP) expression in hepatocytes following radiofrequency ablation (RFA).

BACKGROUND: Radiofrequency ablation (RFA) of the liver produces necrosis of the hepatocytes. Histological examination shows a sharp demarcation between ablated and normal liver tissue. This experiment was carried out to study the cellular injury produced by RFA in area surrounding the ablated tissue and effect of reperfusion on this zone. MATERIAL AND METHODS: Five pigs underwent RFA of liver parenchyma. Four pigs were sacrificed 30 min after RFA and one pig was sacrificed 5 days later. Ablated lesions including surrounding liver parenchyma was examined for apoptosis and HSP 70 expression. RESULTS: There was a zone of transition surrounding the necrotic ablated area that showed apoptosis as well as increased HSP 70 expression. This was more prevalent in the pig that was sacrificed 5 days later. CONCLUSION: RFA produces sub lethal injury in the zone of transition causing apoptosis and increase in HSP 70 expression. Increased HSP expression enhances immunogenicity of these cells that can have therapeutic implications for the treatment of liver.

Animals↗
PubMed2005

Creation of porcine liver tumor using human hepatoma cell lines: experimental study.

BACKGROUND: Pig is an ideal animal to study the efficacy of surgical and ablative treatment options available for the treatment of liver tumors. But there is no liver tumor model available in pig. This experiment was carried out to create liver tumors in the pig using immunosuppression and portal tolerance. MATERIAL AND METHODS: Two mini pigs (specific pathogen free) were immunosupressed using cyclosporine, azathioprine and prednisolone immunotherapy. Human hepatoma cell line (HepG2) was delivered into the liver through portal vein injection. Engraftment of the tumor cell was monitored using regular measurement of serum alfa- fetoprotein level (AFP). Pigs were sacrificed at the end of six weeks to confirm any evidence of tumor in the liver. RESULT: Although there was rise in serum AFP level in the first week, tumor cells did not engraft in the liver and there was no evidence of liver tumor at the end of experiment. CONCLUSION: Effect of immunosuppression and portal tolerance does not prevent rejection of human hepatoma cells by porcine immune system.

Animals↗
PubMed2004

Medical arthroscopy--emerging era of rheumatological intervention.

OBJECTIVE: To evaluate the safety and diagnostic value of arthroscopy performed by a rheumatologist. METHODS: Decisions for performing arthroscopy were taken when detailed clinical history-and relevant rheumatological investigations failed to arrive at a definite diagnosis. Arthroscopies were performed under local anesthesia as a daycare procedure. Synovial biopsies taken during procedures were subjected to histopathological examination (HPE). RESULTS: Of the 50 patients enrolled, 39 were males while 11 were females with mean age of 35.5 years. In lower limb oligoarthritis group of patients, three had macroscopic picture of crystal arthropathy, rest of the 29 patients revealed gross picture indicative of non-specific synovitis. While in polyarticular group of eight patients, three had macroscopic picture suggestive of crystal arthropathy (probably polyarticlar gout) while five were indicative of rheumatoid arthritis. In monoarticular disease pattern (n= 10) macroscopic picture findings were as follows- crystal arthropathy-two, tubercular-three, synovial chondromatosis-one and non-specific synovitis-two. HPE of synovium did not correlate in many cases. CONCLUSION: Arthroscopy using a 4 mm scope under local anesthesia in the hands of rheumatologists is a safe daycare procedure. In few cases arthroscopy helped in arriving at a final diagnosis but many patients remained undiagnosed. Both the rheumatologists and the pathologists require further experience in this field.

Adult↗
PubMed2004

Assessment of adrenocortical function in the critically ill.

OBJECTIVE: To review current concepts in the diagnosis of adrenocortical disease in the critically ill patient. DATA SOURCES: A review of articles reported on adrenocortical insufficiency in the acutely ill patient. SUMMARY OF REVIEW: The contribution of adrenal insufficiency to the morbidity of critically ill patients is currently under renewed scrutiny. The debate continues about the role of steroids in sepsis and essentially the question remains unanswered. Central to this debate is the issue of whether adrenal insufficiency is common in the critically ill patient. What is incontrovertible is that adrenocortical function is essential for host survival during critical illness, but what constitutes adrenocortical insufficiency in critically ill patients is not clear. Absolute adrenocortical insufficiency (diagnosed by very low plasma cortisol concentrations) is uncommon in the intensive care population. The diagnosis of relative adrenocortical insufficiency (elevated basal plasma cortisol with a subnormal increase in plasma concentrations following an ACTH stimulus) continues to generate debate. The controversy surrounding the role of steroids in sepsis and the confusion over the criteria for diagnosing adrenal insufficiency in the critically ill are reviewed. CONCLUSIONS: We suggest that the following caveats be borne in mind when diagnosing adrenal insufficiency in the critically ill patient. Firstly, the gold standard for the diagnosis has not been established. Secondly, caution must be exercised when interpreting a single plasma cortisol value. In the event of a single result indicating adrenal hypofunction, we suggest repeating the measurements after a 6 to 12 hour interval. The clinician must also be aware of variations in cortisol concentrations induced by the assay. Thirdly, the clinician must be aware of the potential limitations of the conventional high dose corticotrophin test. We also suggest that plasma free cortisol is more relevant than total plasma cortisol in the assessment of adrenal function in critical illness and that the low dose corticotrophin test is more sensitive than the conventional high dose test. These areas should be the subject of further investigations.

Journal Article↗
PubMed2003

Thromboelastography, whole-blood haemostasis and recurrent miscarriage.

BACKGROUND: Some cases of recurrent miscarriage have a thrombotic basis. Thromboelastography is a rapid, reproducible test of whole-blood haemostasis. METHODS: Thromboelastography was performed in 494 consecutive, non-pregnant women (median age 35 years; range 21-48) with a history of miscarriages at <12 weeks gestation (median 4; range 3-12) and 55 parous women (median age 33 years; range 20-41) with no history of pregnancy loss. The prospective outcome of untreated pregnancies amongst 108 women with recurrent miscarriage was studied. RESULTS: The maximum clot amplitude (MA) (median 66.0 mm; range 48.0-76.0) was significantly higher and the rate of clot lysis (LY30) (median 2.5%; range 0.5-7.8) significantly lower amongst women with recurrent miscarriage compared with controls (MA 61.5 mm; range 50.0-67.0; P = 0.01; LY30 4.9%; range 2.9-9.7; P = 0.01). The pre-pregnancy MA was significantly higher amongst women who subsequently miscarried (median 66.0 mm; range 54.0-73.0) compared with those whose had a live birth (median 61.7 mm; 48.0-71.5; P < 0.01). A pre-pregnancy MA >or=64 mm has a sensitivity of 68% and specificity of 82% to predict miscarriage. CONCLUSIONS: Thromboelastography identifies a subgroup of women with recurrent miscarriage to be in a prothrombotic state outside of pregnancy. Women in such a state are at increased risk of miscarriage in future untreated pregnancies.

Abortion, Habitual↗
PubMed2002

Pinopode expression during human implantation.

Implantation failure is considered the major impediment to successful in vitro fertilization pregnancy rate. Despite recent advances in reproductive medicine, the role played by uterine receptivity in contributing to human infertility remains unclear. Several clinical studies suggest the importance of blastocyst implantation in a narrow window of uterine receptivity, between 6 and 8 days after ovulation. This brief and precise period, called "implantation or nidation window", lasts less than 48 h and coincides with the formation of large and smooth projections, called "pinopodes", on the apical membranes of the endometrial epithelial cells. Pinopode expression appears to advance or retard depending on the hormonal treatments and an individual's particular response. This displacement can be followed through endometrial biopsy and scanning electron microscopy (SEM). Therefore, pinopode expression could be considered a useful biological marker to assess endometrial receptivity and to locate the implantation window.

Embryo Implantation↗