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Biomedical subjects

S Shroff

Publications and source records attributed to S Shroff.

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

Sulfatide is essential for the maintenance of CNS myelin and axon structure.

Galactocerebroside (GalC) and sulfatide are abundant myelin lipids. In mice incapable of synthesizing these lipids, myelin is thin and regionally unstable and exhibits several subtle structural abnormalities. Although galactolipid-null mice have been beneficial in the analysis of galactolipid function, it has not been possible to differentiate between the functions of GalC and sulfatide with these mice alone. In the present work, we have analyzed a murine model that forms normal levels of GalC but is incapable of synthesizing sulfatide. By comparing a plethora of morphological features between the galactolipid-null and the sulfatide-null mice, we have begun to differentiate between the specific functions of these closely related lipids. The most striking difference between these two mutants is the reduction of myelin developmental abnormalities (e.g., redundant and uncompacted myelin sheaths) in young adult sulfatide-null mice as compared with the galactolipid-null animals. Although sulfatide appears to play a limited role in myelin development, this lipid is essential for myelin maintenance, as the prevalence of redundant, uncompacted, and degenerating myelin sheaths as well as deteriorating nodal/paranodal structure is increased significantly in aged sulfatide-null mice as compared with littermate wildtype mice. Finally, we show that the role played by sulfatide in CNS maintenance is not limited to the myelin sheath, as axonal caliber and circularity are normal in young adult mutant mice but are significantly altered in aged sulfatide-null animals.

Aging↗
PubMed2006

Renal abscess.

This study analyses the pre-disposing factors, diagnostic modalities, therapeutic options and prognostic factors involved in 7 subjects with renal abscess. Most often they presented with high fever and flank pain. USG and CT were used to establish the diagnosis. Urine culture yielded organisms in five cases and hence empirical antibiotic therapy for Gram-negative organism was offered. Complicated abscess in our series carried high mortality especially in immuno suppressed and cachectic patients.

Abscess↗
PubMed2003

Bilateral renal papillary necrosis due to Candida infection in a diabetic patient presenting as anuria.

A 38 years insulin-dependent diabetic male, with nephropathy on antituberculous treatment presented with painless frank hematuria followed by anuria for a day which was associated with fever. Ultrasonogram of the abdomen showed bilateral hydroureteronephrosis. Necrotic papillae were retrieved after ureteroscopy which on histopathological examination and culture showed Candida albicans. This was successfully treated with fluconazole and ureteroscopic removal of necrotic papillae.

Adult↗
PubMed2001

Pathological analysis of local delivery of paclitaxel via a polymer-coated stent.

BACKGROUND: Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored. METHODS AND RESULTS: Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 microgram of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean neointimal thickness at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents containing 42.0 and 20.2 microgram of paclitaxel per stent, respectively, versus CSG-coated stents without paclitaxel. However, histological findings suggested incomplete healing in the higher-dose (42.0 and 20.2 microgram) paclitaxel-containing stents consisting of persistent intimal fibrin deposition, intraintimal hemorrhage, and increased intimal and adventitial inflammation. Stents coated with CSG alone (without paclitaxel) had similar neointimal growth as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 microgram of paclitaxel CONCLUSIONS: CSG coating appears to be a promising medium for localized drug delivery. Paclitaxel polymer-coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointimal suppression was not maintained at 90 days.

Angiogenesis Inhibitors↗
PubMed2001

Late arterial responses (6 and 12 months) after (32)P beta-emitting stent placement: sustained intimal suppression with incomplete healing.

BACKGROUND: Three-month studies of stent-delivered brachytherapy in the rabbit model show reduced neointimal growth. However, intimal healing is delayed, raising the possibility that intimal inhibition is merely delayed rather than prevented. The purpose of this study was to explore the long-term histological changes after placement of beta-emitting radioactive stents in normal rabbit iliac arteries. METHODS AND RESULTS: Three-millimeter beta-emitting (32)P stents (6, 24, and 48 microCi) were placed in normal rabbit iliac arteries with nonradioactive stents as controls. Animals were euthanatized at 6 and 12 months, and histological assessment, morphometry, and analysis of endothelialization were performed. Morphometric measurements demonstrated a >50% reduction in intimal growth and percent lumen stenosis within 24- and 48-microCi stents versus control nonradioactive stents at both 6 and 12 months. However, the 24- and 48-microCi stents also showed delayed healing of the intimal surface, characterized by persistent fibrin thrombus with nonconfluent areas of matrix, incomplete endothelialization, and increased intimal cellular proliferation. Stent edge stenosis was present at 12 months in the 24- and 48-microCi stent groups, characterized by both intimal thickening and negative arterial remodeling. CONCLUSIONS: Inhibition of intimal growth is maintained 6 and 12 months after (32)P beta-emitting stent placement. However, delayed arterial healing, incomplete endothelialization, and edge effects are present.

Animals↗
PubMed2000

Neointimal responses 3 months after (32)P beta-emitting stent placement.

PURPOSE: Studies have shown a potential benefit of brachytherapy in preventing restenosis. However, the effects of intravascular radiation on arterial healing have not been well-established. The purpose of this study was to explore the histologic changes following placement of beta-emitting radioactive stents in arteries focusing on intimal responses and endothelialization. METHODS AND MATERIALS: 3.0-mm beta-emitting (32)P stents (6-microCi and 24-microCi) were placed in rabbit iliac arteries with nonradioactive stents serving as controls. Animals were euthanized at 3 months and histologic assessment, morphometry, and analysis of endothelialization were performed. RESULTS: The lumen areas of 24-microCi stents (4.24 +/- 0.22 mm(2), p < 0.0007) and 6-microCi stents (4.23 +/- 0.49 mm(2), p < 0.01) were larger than control stents (3.64 +/- 0.44 mm(2)). The mean lumen percent stenosis was 11. 4 +/- 3.0% in the 24-microCi stents (p < 0.007 vs. 6-microCi stents and p < 0.0001 vs. control stents), 18.7 +/- 6.4% in the 6-microCi stents (p < 0.02 vs. control stents), and 25.0 +/- 4.9% in control stents. Neointimal area was least in the 24-microCi stent (54.2% smaller than controls and 42.7% smaller than 6-microCi); the neointimal area of the 6-microCi stents was 20.0% less than controls. The control stent neointima consisted of smooth muscle cells in a proteoglycan and collagen matrix. In contrast, the intima of radioactive stents showed persistent fibrin thrombus with nonconfluent areas of matrix. Actin-positive intimal cell density was reduced with radioactive stenting, but intimal cell proliferation was increased. Evans blue staining, an indicator of increased endothelial permeability, was present on 86 +/- 9% of the stented segment of 6-microCi stents vs. 10 +/- 11% in controls (p < 0.0001). Scanning electron microscopy demonstrated endothelialization of 97 +/- 8% of the intimal surface of control stents; in contrast, the midportion of the 6-microCi stents remained nonendothelialized, and only 33 +/- 15% (p < 0.0001) of the entire stent surface was endothelialized. CONCLUSIONS: (32)P beta-emitting stents reduce neointimal growth, but healing is incomplete with poor endothelialization at 3 months. Longer-term studies with complete arterial healing are needed to determine whether there is sustained neointimal inhibition by stent-delivered brachytherapy.

Animals↗
PubMed1999

Modified technique of suction blistering for epidermal grafting in vitiligo.

BACKGROUND: Suction blister epidermal grafting is a useful modality of treatment of resistant and stable vitiligo; however, it requires expensive and heavy suction apparatus. This study is an attempt to develop a cheap and small apparatus which can be assembled in the physician's own office. PATIENTS AND METHODS: The method was tried in 22 vitiligo/leukoderma patients. The apparatus consisted of a cylindrical funnel connected with a three-way tap, and suction was given by a 50-mL syringe. The pressure inside the suction cup was retained by changing the position of lock of the three-way tap. The pressure was measured by connecting the three-way tap to a vacuum gauge. The apparatus remained adhered to the donor area because of negative pressure. The blister was formed in about 1.5 h. The roof of the blister was grafted onto the dermabraded recipient site. RESULTS: The pigmentation was complete in 20 out of 22 patients. There were no complications. CONCLUSIONS: The technique is inexpensive and easy and obviates the need of cumbersome and heavy equipment.

Adolescent↗
PubMed1999

Reproductive and sexual health and safe motherhood in the developing world.

The aim of this paper is to discuss the main hurdles and possible solutions concerning reproductive and sexual health and safe motherhood in the developing countries. In response to the changing global situation, a broader new concept of reproductive health has emerged. The Programme of Action of The International Conference on Population and Development (ICPD) emphasizes and highlights various aspects of reproductive health. No population in the world has met the goals of the ICPD. The problems are particularly acute in developing countries: between 20 and 40% of births are unwanted or wrongly timed, posing hardships for families and jeopardizing the health of a million women and children. An estimated 50 million induced abortions are performed each year, with some 20 million of these performed under unsafe conditions or by untrained providers. Almost 600,000 women die every year due to pregnancy-related causes, 99% of them in developing countries. Approximately 7.6 million infant deaths occur during the perinatal period each year. There are more than 333 million new cases of curable sexually transmitted diseases world-wide each year. Nearly 22 million people are estimated to be infected with the human immunodeficiency virus, of whom 14 million are in sub-Saharan Africa, with rapidly increasing numbers of infected persons in South and South-East Asia. When compared to the developed world, these figures are staggering because of barriers operating at different levels and preventing women from receiving care that is timely and of good quality. United efforts of obstetricians, pediatricians, sociologists, and different governmental and non-governmental organizations are required to achieve our targets.

Adolescent↗
PubMed1998

Renal aspergillosis giving rise to obstructive uropathy and recurrent anuric renal failure.

A sixty-year-old previously healthy male patient presented with anuric renal failure of sudden onset. He was detected to have Aspergillus fumigatus fungal balls in the renal pelvis, ureters and bladder which were removed and his renal function improved. He was treated with itraconazole and sent home. Three weeks later he again presented with anuria and renal failure. He had recurrence of the obstruction with the same fungus. The fungal ball was removed, a double 'J' stenting was performed and he was treated with amphotericin B and itraconazole. Hence we report a previously healthy patient with no evidence of immunosuppression presenting an obstructive anuric renal failure due to isolated renal aspergillosis.

Acute Kidney Injury↗