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Biomedical subjects

F Patel

Publications and source records attributed to F Patel.

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↗
PubMed2001

Lymphoproliferative responses in cord blood and at one year: no evidence for the effect of in utero exposure to dust mite allergens.

BACKGROUND: Maternal allergen exposure beyond the 22nd week of pregnancy may be important in foetal T cell priming. Allergen-specific cord blood mononuclear cell (CBMC) immunoproliferative responses without corresponding bacterial antigen responses (tetanus toxoid), have been suggested as evidence of in utero sensitization. OBJECTIVES: To investigate the relationship between lymphoproliferative responses at birth and at 1 year with maternal and 1-year infants house dust mite allergen exposure. METHODS: Home visits and dust sampling were performed by the 20th week of pregnancy, immediately after birth, and then at 1 years of age. Der p 1 was assayed using a two-site immunometric ELISA. CBMC immunoproliferative responses (AIM V serum-free medium; 1 x 105 cells/well) were measured for 225 neonates (171 had a high risk of atopy (HR)--both parents skin test positive; 59 had a low risk of atopy (LR) - both parents skin test negative, no history of atopy) by 3H-Thymidine (1microCi/well) incorporation after stimulation in primary culture with phytohaemagglutinin (PHA) (1 microg/mL), house dust mite [HDM] extract (30 microg/mL), immunopurified Der p 1 (30 microg/mL), Tetanus toxoid (TT) (aluma free, 30 Lf/mL) or vehicle. Blood was collected from 144 infants at the age of 1 years and stimulated proliferative responses were assessed using the same procedure. RESULTS: PHA-stimulated lymphoproliferative response was significantly lower in HR compared to LR neonates (mean difference 38%, 95% CI 15%-54%; P = 0.003); significantly lower proportion of positive CBMC responses to HDM occurred in LR than in HR neonates (30.4% vs. 46.6%; P = 0.034). There was no relationship between Der p 1 levels in maternal bed and CBMC immunoproliferative responses, despite the 21 000-fold range of maternal Der p 1 exposure. No significant differences in magnitude, or in proportion of positive responses to any stimulant were observed between the neonates at low, medium or high tertile of allergen exposure. Immunoproliferative responses at birth were not predictive of 1-year PBMC responses. There was no relationship between maternal allergen exposure in pregnancy and 1-year PBMC proliferative responses. However, the proportion of positive proliferative responses at 1 years significantly increased with increasing infant Der p 1 exposure at 1 years. CONCLUSION: These results indicate that the magnitude of immunoproliferative responses are unrelated to maternal mite allergen exposure and cannot be used as evidence for in utero sensitization to inhalant allergens. The immunoproliferative responses at 1 year seem to shift away from the genetically influenced responses at birth towards responses to specific stimulants which correlate with environmental exposure to those specific stimulants. These data support the concept of sensitization to inhalant allergens occurring in early life, but not in utero.

Allergens↗
PubMed2001

Understanding preterm labor.

Increased uterine contractility at term and preterm results from activation and then stimulation of the myometrium. Activation can be provoked by mechanical stretch of the uterus and by an endocrine pathway resulting from increased activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis. In fetal sheep, increased cortisol output during pregnancy regulates prostaglandin H synthase type 2 (PGHS2) expression in the placenta in an estrogen-independent manner, resulting in increased levels of PGE2 in the fetal circulation. Later increases in maternal uterine expresssion of PGHS2 require elevations of estrogen and lead to increased concentrations of PGF2alpha in the maternal circulation. Thus, regulation of PGHS2 at term is differentially controlled in fetal (trophoblast) and maternal (uterine epithelium) tissue. This difference may reflect expression of the glucocorticoid receptor (GR), but not estrogen receptor (ER), in placental trophoblast cells. In women, cortisol also contributes to increased PG production in fetal tissues through upregulation of PGHS2 (amnion and chorion) and downregulation of 15-OH PG dehydrogenase (chorion trophoblasts). The effect of cortisol on chorion expression of PGDH reverses a tonic stimulatory effect of progesterone, potentially through a paracrine or autocrine action. We have interpreted this interaction as a reflection of "progesterone withdrawal" in the primate, in relation to birth. Other agents, such as proinflammatory cytokines, similarly upregulate PGHS2 and decrease expression of PGDH, indicating the presence of several mechanisms by which labor at term or preterm may be initiated. These different mechanisms need to be considered in the development of strategies for the detection and management of the patient in preterm labor.

Corticotropin-Releasing Hormone↗
PubMed2001

Anticonvulsant effects of gamma surgery in a model of chronic spontaneous limbic epilepsy in rats.

OBJECT: The management of intractable epilepsy remains a challenge, despite advances in its surgical and nonsurgical treatment. The identification of low-risk, low-cost therapeutic strategies that lead to improved outcome is therefore an important ongoing goal of basic and clinical research. Single-dose focal ionizing beam radiation delivered at necrosis-inducing and subnecrotic levels was investigated for its effects on seizure activity by using an established model of chronic recurrent spontaneous limbic seizures in rats. METHODS: A single 90-minute period of repetitive electrical stimulation (inducing stimulus) of the hippocampus in rats elicited a single episode of status epilepticus, followed by a 2- to 4-week seizure-free period. Spontaneous recurrent seizures developed subsequently and persisted for the duration of monitoring (2-10 months). Simultaneous computerized electroencephalography and video recording were used to monitor the animals. After the establishment of spontaneous recurrent seizures, bilateral radiation centered in the ventral hippocampal formation was administered with the Leksell gamma knife, aided by a stereotactic device custom made for small animals. A center dose of 10, 20, or 40 Gy was administered using a 4-mm collimator. Control animals were subjected to the same seizure-inducing stimulus but underwent a sham treatment instead of gamma irradiation. In a second experiment, the authors examined the effects of gamma irradiation on the proclivity of hippocampal neurons to display epileptiform discharges. Naive animals were irradiated with a single 40-Gy dose, as already described. Slices of the hippocampus were prepared from animals killed between 1 and 178 days postirradiation. Sensitivity to penicillin-induced epileptiform spiking was examined in vitro in slices prepared from control and irradiated rat brains. CONCLUSIONS: In the first experiment, single doses of 20 or 40 Gy (but not 10 Gy) reduced substantially, and in some cases eliminated, behaviorally and electrographically recognized seizures. Significant reductions in both the frequency and duration of spontaneous seizures were observed during a follow-up period of up to 10 months postradiation. Histological examination of the targeted region did not reveal signs of necrosis. These findings indicate that single-dose focal ionizing beam irradiation at subnecrotic dosages reduces or eliminates repetitive spontaneous seizures in a rat model of temporal lobe epilepsy. In the second experiment, synaptically driven neuronal firing was shown to be intact in hippocampal neurons subjected to 40-Gy doses. However, the susceptibility to penicillin-induced epileptiform activity was reduced in the brain slices of animals receiving 40-Gy doses, compared with those from control rats that were not irradiated. The results provide rational support for the utility of subnecrotic gamma irradiation as a therapeutic strategy for treating epilepsy. These findings also provide evidence that a functional increase in the seizure threshold of hippocampal neurons contributes to the anticonvulsant influence of subnecrotic gamma irradiation.

Animals↗
PubMed1999

Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension.

Rectal bleeding due to radiation proctosigmoiditis is often difficult to manage. We had earlier shown the efficacy of short-term therapy with topical sucralfate in controlling bleeding in the radiation proctosigmoiditis. We now report our long-term results with this form of therapy. The study comprised 26 patients with radiation proctosigmoiditis. Sigmoidoscopically, 9 (34.6%) patients had severe changes, 15 (57.69%) had moderate, and 2 (7.69%) had mild changes. Severity of bleeding was graded as severe (> 15 episodes per week), moderate (8-14 episodes per week), mild (2-7 episodes per week), negligible (< or = 1 episode per week), or nil (no bleeding). Ten patients had moderate rectal bleeding, while 16 had severe bleeding. All patients were treated with 20 ml of 10% rectal sucralfate suspension enemas twice a day until bleeding per rectum ceased or failure of therapy was acknowledged. Response to therapy was considered good whenever the severity of bleeding showed improvement by a change of two grades. Rectally administered sucralfate achieved good response in 20 (76.9%) patients at 4 weeks, 22 (84.6%) patients at 8 weeks, and 24 (92.3%) patients at 16 weeks. This change was significant by Wilcoxon matched-pairs signed-ranks test. Two patients required surgery due to poor response. Over a median follow-up of 45.5 months (range 5-73 months) after cessation of bleeding, 17 (70.8%) patients had no further bleeding while 7 (22.2%) had recurrence of bleeding. All recurrences responded to short-term reinstitution of therapy. No treatment-related complications were observed. Ten patients had other associated late toxicity due to pelvic irradiation in the form of asymptomatic rectal stricture (N = 3), rectovaginal fistula (N = 1), intestinal stricture (N = 1), vaginal stenosis (N = 1), and hematuria (N = 6). Three patients had progression of the primary disease in the form of pelvic recurrence (N = 2) and hepatic metastases (N = 1). We conclude that topical sucralfate induces a lasting remission in a majority of patients with moderate to severe rectal bleeding due to radiation proctosigmoiditis.

Administration, Topical↗
PubMed1998

Influence of plasma phytanic acid levels in Refsum's disease on the behaviour of the erythrocyte membrane sodium-lithium countertransporter.

BACKGROUND: Abnormal behaviour of the erythrocyte membrane sodium-lithium countertransporter (SLC) is associated with plasma triglyceride concentrations. Refsum's disease is characterized by progressive neurological dysfunction and accumulation of phytanic acid, an isoprenoid fatty acid, in fat-containing tissues. METHODS: This study explored the effects of plasma phytanic acid on SLC kinetics in nine Caucasian patients with Refsum's disease and in age- and sex-matched Caucasian control subjects. RESULTS: A dose-dependent association was seen between countertransporter maximal velocity and phytanic acid content of low-density lipoprotein (LDL)-cholesterol (r = -0.61, r = -0.65 respectively; P = 0.05, P = 0.04) and high-density lipoprotein (HDL)-cholesterol (r = -0.81, -0.82 respectively; P = 0.005, P = 0.003). No significant association was seen with the sodium affinity of the transporter (r = -0.44, P = 0.20, for LDL; and -0.43, P = 0.21, for high-density lipoprotein). CONCLUSION: These findings suggest that phytanic acid may alter the behaviour of the sodium-lithium countertransporter.

Antiporters↗
PubMed1998

Seafood-induced fatal anaphylaxis.

Two cases of fatal anaphylaxis caused by seafood allergy are reported. The first serves as a reminder of the importance of obtaining a full medical history and details of the circumstances of death, and of the need to be aware of forensic post-mortem artefacts. Observations on the immunological mechanisms of type 1 or immediate hypersensitivity seen in the second case, and a discussion of preventive measures, offer subjects for medicolegal deliberation.

Adult↗
PubMed1998

Prognostic significance of DNA ploidy and S-phase fraction in malignant serous cystadenocarcinoma of the ovary.

OBJECTIVE: To determine the prognostic value of DNA ploidy and S-phase fraction in malignant serous cystadenocarcinoma of the ovary. STUDY DESIGN: Flow cytometric analysis of nuclear DNA content was performed on paraffin-embedded tissues of 31 serous cystadenocarcinomas of the ovary. DNA ploidy, DNA index and S-phase fraction were determined without knowing the final outcome in the patients. RESULTS: Histograms in 14 (46%) cases were aneuploid, whereas 17 (54%) were diploid. Aneuploidy was more frequent at the advanced stages of the disease as well as in the poorly differentiated histologic types. However, ploidy had a prognostic influence: both the disease-free survival and overall survival were better in diploid than aneuploid tumors at early and advanced stages. S-phase fraction (SPF) could be correctly assessed in 19 cases (62%) and was > 15% in 21% (4 cases). The survival of those patients, however, was not significantly different from that of those with SPF < 15%. CONCLUSION: If used as an adjunct, DNA ploidy is of value in predicting tumor behavior, response to chemotherapy and disease recurrence.

Adult↗
PubMed1997

HIV serophobia in the mortuary: an algorithm system for handling high-risk forensic cases.

A serophobia of the human immunodeficiency virus type 1 (HIV-1) is very noticeable in mortuaries handling high-risk cases. The morbid anxiety about occupationally acquired HIV infection in the forensic practice has made mortuary workers unduly overcautious. Despite the availability of codes of practice and informed principles of health and safety, there is considerable anxiety that an HIV carrier with no identifiable risk factors may be overlooked or a seronegative body may be inadvertently assumed to be uninfected. In contrast, a false sense of safety can pose a health hazard and has public health implications. An algorithm system is outlined for selective handling of unsuspected or unrecognized high-risk cases. It is necessary that guidelines are reasonably simple and incorporate statutory health and safety regulations and local safe working practice in the mortuary. Although it is not a legal obligation, approval by the coroners should facilitate consistent implementation of a protocol. A common experience in public and NHS hospital mortuaries in the London coroners' jurisdictions is characterized.

Attitude of Health Personnel↗
PubMed1997

Results of treatment in endometrial carcinoma: ten years experience.

From 1980 to 1989, 145 patients of histologically proven adenocarcinoma of the endometrium were seen and treated at the Department of Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, Majority of the patients (84/145) presented with FIGO stage I disease. Relationship of myometrial invasion to grade was highly significant (p < 0.001). One hundred and seven patients were treated by surgery in combination with pre-operative or post-operative radiotherapy. The importance of various prognostic factors was assessed and grade of the tumour had statistically highly significant effect on survival (p < 0.005). Postoperative radiotherapy is recommended in patients with poor prognostic factors.

Combined Modality Therapy↗
PubMed1996

A high fatal postmortem blood concentration of cocaine in a drug courier.

A fatality in a teenage drug courier who swallowed multiple packages of a controlled drug for concealment in the gastrointestinal tract is described. There were a couple of burst-open short cylindrical packages of cocaine and several with damaged external latex wrapping. A hazardous breakage or leakage has been considered unlikely with similar type of cocaine packages otherwise. The deceased succumbed to a remarkably high fatal postmortem blood cocaine concentration of 104 mg/l, having curiously survived the usual lethal range for cocaine toxicity. The phenomenon of postmortem release and redistribution of drugs and spontaneous biodegradation of cocaine which may confound the postmortem toxicology is briefly discussed. There is a comparable forensic problem in estimating the time of drug ingestion from the rate of gastric emptying or transit in the gut as a crude guide to deduce the time of death.

Adolescent↗
PubMed1996

Traumatic baso-brainstem subarachnoid haemorrhage.

Traumatic basal subarachnoid haemorrhage is an uncommon disorder that is well described in the forensic literature. The aetiology traditionally has been a relatively minor blunt trauma which is sustained typically at the level of the base of head and injures the arterial system to the brain. The site of trauma may be occult and not always demonstrable. In the case discussed, an acute baso-brainstem subarachnoid haemorrhage was caused by a severed extracranial vertebral artery due to a stabwound injury to the upper neck. A gravitational factor and alcohol intoxication, which might contribute to the basal intracranial haematoma, is given a novel thought.

Adult↗
PubMed1995

Ancillary autopsy--forensic histopathology and toxicology.

Under the Coroners Act 1988 and the Coroners Rules 1984, the removal of parts or contents of the body which does not bear directly upon the cause of death is restricted. However, it may not be possible in every forensic necropsy to foretell whether the post-mortem removal of body tissue will fulfil a statutory proviso. To emphasize this medico-legal predicament, some examples in which ancillary histopathological examination or toxicological analysis assisted in ascertaining an accurate cause and manner of death are presented as short cases.

Adult↗
PubMed1995

Artefact in forensic medicine: pseudo-rodent activity.

Postmortem rodent activity is a potential source of confounding marks for forensic pathologists when unmasking criminal activity. It might also be that something innocent could be masquerading an "end result" of rodent disturbance. A chronic skin lesion which proved to be a "pseudo-rodent" artefact is briefly communicated and supplements an earlier published article on artefact in forensic medicine.

Aged↗