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Biomedical subjects

Inderjeet Kaur

Publications and source records attributed to Inderjeet Kaur.

At least 19 recordsLinked to original sources

Long noncoding RNAs and diabetic retinopathy: Current understanding, future directions and challenges.

Diabetic retinopathy remains as the leading cause of preventable blindness in working-aged people. The pathophysiology of this sight-threatening disease is complex and involves intricate interactions among metabolic, hemodynamic and epigenetic pathways, leading to molecular, structural, functional and genomic abnormalities in retinal vascular and nonvascular cells. Diabetes also results in differential expressions of several noncoding RNAs, including micro RNAs (miRNAs) and long noncoding RNAs (LncRNAs). Compared to about 2000 miRNA identified in human genome thus far, more than 30,000 LncRNA transcripts have been already identified, but the function and mechanism of action of most of the LncRNAs is still not fully characterized, and there remains a possibility that some LncRNAs could have diverse functions under different contexts. LncRNAs are mainly noncoding, but they have many regulatory functions, and regulate gene expression by interacting with DNA, RNA and protein. Aberrant expressions of several LncRNAs including MALAT1, MEG3, HOTAIR, MIAT1 and H19, is associated with metabolic abnormalities implicated in the pathogenesis of diabetic retinopathy. LncRNAs are also released into circulation and show high organ and cell specificity, and greater disease-associated differences compared to disease-associated mRNAs. Furthermore, LncRNAs maintain stable expression in the plasma and can be isolated from total RNA present in biological samples including blood, which makes them promising and reliable candidates for diagnostic or prognostic markers and therapeutic targets for various diseases. With continued improvement in innovative RNA modifications and delivery modalities, use of LncRNAs as possible biomarkers, and of LncRNA-based therapeutics, for diabetic retinopathy appears promising.

Biomarkers↗

Globally, CYP1B1 mutations in primary congenital glaucoma are strongly structured by geographic and haplotype backgrounds.

PURPOSE: To obtain a global perspective on the distribution and evolution of CYP1B1 mutations in primary congenital glaucoma (PCG) worldwide. METHODS: Five intragenic single-nucleotide polymorphisms in CYP1B1-R48G, A119S, V432L, D449D, and N453S-were used to generate haplotype data from 138 Indian patients with PCG and 132 ethnically matched normal controls, which were then analyzed in conjunction with data from other populations. Maximum-likelihood estimates of haplotype frequencies were estimated from the genotype data. Subsets of patients and normal control subjects were also genotyped with respect to eight short tandem repeat (STR) markers around the CYP1B1 locus (D2S305, D2S165, D2S367, D2S2259, D2S391, D2S3337, D2S23678, and D2S286), to gain evolutionary insights. RESULTS: Common mutations in CYP1B1 that are causal of PCG occurred on a uniform haplotype background among Indian patients, which is completely distinct from the modal haplotype background found among unaffected control subjects. Comparison of these data with data from other global regions reveals strong clustering of CYP1B1 mutations by geographic and haplotype backgrounds. The two distinct modal haplotypes found among Indian patients with PCG and control subjects are both ancient with ages of similar magnitudes, as indicated by large variances in the number of repeats at eight STR loci. Together with data from chimpanzee and normal control subjects from India and other global regions, it was possible to make a parsimonious reconstruction of the evolution of these haplotypes. CONCLUSIONS: The strong association of specific haplotypes with some predominant CYP1B1 mutations underlying PCG and the observed geographical clustering, probably due to founder effects, may be useful for predictive testing.

Africa↗

Analysis of CFH, TLR4, and APOE polymorphism in India suggests the Tyr402His variant of CFH to be a global marker for age-related macular degeneration.

PURPOSE: To screen polymorphisms in complement factor-H (CFH), toll-like receptor 4 (TLR4), and APOE genes as potential risk factors for age-related macular degeneration (AMD) in Indian patients. METHODS: One hundred patients with AMD and 120 normal control subjects were screened for the polymorphisms by restriction digestion and resequencing. Five intragenic SNPs in CFH were screened to generate haplotype data in cases and controls. The data were analyzed in conjunction with data from other populations based on genotype and haplotype frequencies, and odds ratios were computed to estimate the risk of AMD in the different genotypes. RESULTS: Significant association was noted with the CFH variant (Tyr402His) among AMD cases (P = 1.19 x 10(-7)). Individuals homozygous for the mutant genotype CC had a significantly higher risk (P < 0.0001) of AMD (OR = 11.52; 95% CI 5.05-26.28) than those carrying a single copy of the C allele (OR = 1.51; 95% CI 0.82-2.80), after adjusting for age, gender, and diabetes. Linkage disequilibrium and haplotype analysis at the CFH locus indicated the C-G-T-C-A-G to be a risk haplotype (P = 0.0003). No significant differences were observed in the genotype frequencies of APOE polymorphisms among patients and control subjects (P = 0.76). The carriers of epsilon4 allele had a reduced risk (P = 0.03) of AMD (OR = 0.42, 95% CI 0.19-0.91). TLR4 did not exhibit any association with AMD. CONCLUSIONS: The CFH polymorphism Tyr402His appears indicative of AMD pathogenesis. Diabetes, age, and gender in the presence of the homozygous "CC" genotype in CFH carry an increased risk of AMD. Hence this polymorphism could be used as a potential marker for predictive testing across continents.

Aged↗

Lichen scrofulosorum in a patient with lepromatous leprosy after BCG immunotherapy.

Lichen scrofulosorum is a rare form of tuberculid seen in children and young adults. The cutaneous lesions are typically symptomless papular eruptions, associated with a strong Mantoux reaction, tuberculosis of lymph nodes and/or other organs or rarely following BCG vaccination. We describe an unusual case of occurrence of lichen scrofulosorum following BCG immunotherapy in a patient with lepromatous leprosy.

Adult↗

Study of apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions.

In leprosy on treatment, one factor contributing to the healing of skin lesions with minimal fibrosis may be apoptosis of inflammatory cells, even though apoptosis is sparse in leprosy as compared to tuberculosis. The degree of apoptosis in skin lesions of leprosy was studied by histopathologic examination (HPE) and by DNA fragmentation and electrophoresis. The effect of various parameters on apoptosis was noted in untreated disease, during treatment at 3 and 6 months, and in lepra reactions in different parts of the spectrum of leprosy. Of the 31 patients, 13 had paucibacillary (PB) and 18 multibacillary (MB) disease. Twenty one patients were in reaction: 16 had type 1 reaction and 5 had type 2 reaction. The controls included patients with non-granulomatous skin diseases; there were no normal controls, and no separate controls for cases with reaction. Apoptosis occurred more frequently in patients with leprosy as compared to the controls. In both PB & MB lesions, apoptosis was observed to increase progressively with treatment at 3 and 6 months, and was more prominent in the MB cases at 6 months of treatment. When lesions in either type 1 or type 2 reaction were compared to lesions not in reaction, a significant increase in apoptosis (p = 0.014) was found only in lesions with type 2 reaction and those which were at 6 months of treatment. The type of treatment regimen, or oral steroids given for reactions, did not significantly alter the degree of apoptosis. Our observations indicate that increased apoptosis is present in leprosy lesions and that in leprosy it progressively increases with anti-leprosy treatment up to 6 months. If the process of apoptosis in skin lesions is followed up for a longer period of time, the degree of apoptosis may be expected to decline. The study of apoptosis may help to understand the mechanism of clearance of bacilli and resolution of granulomas in leprosy patients.

Adolescent↗

Comparative evaluation of immunotherapeutic efficacy of BCG and mw vaccines in patients of borderline lepromatous and lepromatous leprosy.

BACKGROUND: Even after 12 months of multi-drug therapy (M.D.T.) multibacillary (MB) therapy patients with high bacterial index (B.I.) continue to harbor dead bacilli and viable persisters, which lead to immunological complications such as recurrent reactions and late relapses, respectively. To achieve faster killing of viable bacilli and clearance of dead bacilli, various immunotherapeutic agents (vaccines and cytokines) are being evaluated as an adjunct to M.D.T. Aims and objectives. To evaluate the role of BCG and Mw vaccines in the immunotherapy of leprosy. MATERIALS AND METHODS: Sixty untreated leprosy patients with a BI = 2 were randomly allocated to three treatment groups of twenty patients each. Group A patients received World Health Organization (W.H.O.) (12 months M.D.T.-MBR) and BCG intradermally (105 live bacilli/per dose). Group B patients were administered 12 months M.D.T.-MBR and Mycobacterium w (1 x 108) killed bacilli as first dose and 0.5 x 108 /dose in subsequent doses. Group C received 12 months M.D.T. MBR with 0.1 ml of normal saline as placebo. All the groups received 4 doses of vaccine or normal saline repeated at three monthly intervals. The patients were periodically monitored by clinical (Ramu's score), bacteriological (slit skin smear), and histopathological (skin biopsy) parameters, six monthly during and one year after completion of M.D.T. RESULTS: The mean reduction in clinical scores in BCG and Mw groups was significantly more when compared to controls. At 12 and 24 months, the patients in BCG group had significantly greater reduction in Ramu's score as compared to those in the Mw group. BI declined by 2.40 units/year in patients receiving BCG, 2.05 units/year in the Mw group and 0.85 units/year in the control group. Although the incidence of type 1 reactions was apparently more in the BCG and Mw vaccinated groups, the incidence of type 2 reactions, neuritis and development of new deformities was less as compared to the controls. CONCLUSIONS: In our study, BCG exhibited slightly better and faster effect on bacteriological clearance and clinical improvement as compared to Mw vaccine in borderline lepromatous (BL)/ polar lepromatous (LL) patients with a high initial B.I., however, their effect on histopathological (decrease in GF) improvement was comparable. Both the vaccines were well tolerated. Immunotherapy can be a useful adjunct to the shortened (12 months) M.D.T. MB regimen to decrease the risk of reactions and relapses in highly bacilliferous BL/LL patients.

Adolescent↗

Topical 0.25% methotrexate gel in a hydrogel base for palmoplantar psoriasis.

Palmoplantar psoriasis (PPP) is a chronic, disfiguring condition, and its management is difficult. The systemic side effects of methotrexate can be avoided if it is effective topically. We studied the efficacy and safety of a recently marketed topical methotrexate (0.25%) preparation in a hydrogel base in patients with palmoplantar lesions. A total of 14 adult patients diagnosed clinically as plaque type of palmoplantar psoriasis (>30% of the palm and/or sole areas involved) were included in the study. Topical methotrexate 0.25% in a hydroxygel base was applied twice daily to the lesions for twelve weeks. The lesions were assessed for degree of erythema, scaling, induration and fissuring (ESIF) and were scored on a severity score of 0-3 (0--clear, 1--mild, 2--moderate, 3--severe) every two weeks. The most severe condition was given 12 points; 0 denoted no disease. The response at the end of the study was graded as minimal if there was up to 25% reduction in the EISF score, mild as 26-50% reduction, moderate improvement as 51-75% reduction in score, and marked improvement as >75% reduction in score. The average age of the 11 male and female patients was 41.5 years (18-57 years) with the duration of the disease varying from 2 months to 15 years. Ten patients had both palmar and plantar lesions; two each had only palmar lesions or plantar lesions. The ESI score at baseline was 5.8 +/- 0.9 for the palms and 6.8 +/- 0.5 for the soles. The scores at the end of the study were 3.5 +/- 0.7 for palms and 4.8 +/- 0.2 for the soles. The average time taken for improvement was at least six weeks. None of the patients had complete clearance of lesions. The drug was well tolerated by all patients. Methotrexate 0.25% in a hydrophilic gel is well tolerated but is not very effective in controlling the lesions of psoriasis on the palms and soles. A higher concentration in a different base with better penetration could possibly provide better results.

Administration, Topical↗

Epidemiology of childhood psoriasis: a study of 419 patients from northern India.

BACKGROUND: We undertook this study in order to determine the pattern and prevalence of childhood psoriasis in northern India and to highlight the differences and similarities with previous studies. MATERIALS AND METHODS: In this retrospective epidemiologic study, the data from 419 children (less than 14 years of age) with psoriasis registered at the Psoriasis Clinic between January 1990 and December 2002 were included. RESULTS: The 419 children registered at the Psoriasis Clinic constituted 0.3% of the dermatology outpatients and 12.5% of the total psoriasis patients seen over a period of 13 years in the department. There were 219 (52.2%) boys and 200 (47.7%) girls, with a male to female ratio of 1.09 : 1. The age of onset ranged from 4 days to 14 years. The mean age of onset was 8.1 +/- 2.1 years in boys and 9.3 +/- 2.3 years in girls. The peak age of onset in boys was in the 6-10-year age group, whereas the majority of girls showed an onset of psoriasis between the ages of 10 and 14 years. A positive family history was present in only 19 (4.5%) patients. The extensors of the legs were the most common initial site affected [105 (25%) cases], followed by the scalp [87 (20.7%)]. Classical plaque psoriasis was the most frequent clinical presentation [254 (60.6%) patients], followed by plantar psoriasis [54 (12.8%)]. Nail involvement was observed in 130 (31%) cases. All types of nail changes described in psoriasis were seen in these patients. Pitting was the most common nail change, followed by ridging and discoloration. Five children (1.1%) (three girls and two boys) had psoriatic arthropathy. Precipitating factors that brought about the onset of the disease or were associated with exacerbation could be recalled in only 28 (6.6%) patients. Koebnerization was observed in 27.9% of patients. Pruritus was the most frequent symptom, reported by 365 (87.1%) children. Twenty-seven (6.4%) children had other concurrent mucocutaneous diseases (vitiligo, pityriasis alba, alopecia areata, ichthyosis vulgaris, halo nevus, aphthous stomatitis, urticaria, pityriasis versicolor, nummular eczema, salmon patch, and verrucous epidermal nevus). Eighteen children had systemic disorders, including seizures, bronchial asthma, mitral regurgitation, scleroderma, Down's syndrome, high arched palate, cholelithiasis, anterior mongoloid slant, and prognathism; however, these conditions were possibly chance findings only and no correlation with the age of onset or severity of the disease was found. CONCLUSIONS: Our findings differ from those of previous studies in showing a delayed onset, equal sex distribution, less frequent facial involvement, uncommon guttate lesions, more frequent involvement of the soles, and a less frequent history of familial occurrence.

Adolescent↗

Pure neuritic leprosy in India: an appraisal.

BACKGROUND: Pure neuritic leprosy (PNL) constitutes a significant proportion of all cases in India, however, this form of disease has not been fully recognized and investigated and there is little information in the existing literature. OBJECTIVE: To study the epidemiological characteristics of PNL in India. MATERIALS AND METHODS: A retrospective analysis of leprosy clinic records for the period 1993 to 2003 was undertaken. Detailed demographic profiles and clinical findings were noted from the predesigned clinic proforma. A slit-skin smear for acid-fast baclli (AFB) was done in all cases from the area of sensory loss. A skin biopsy was done from the area of sensory impairment to study histopathological changes. Further investigations such as nerve conduction velocity studies (NCV), fine needle aspiration cytology (FNAC), or nerve biopsy (superficial nerve twigs) were done if indicated in patients whenever there was difficulty in clinical diagnosis. RESULTS: Of the total 1542 leprosy patients seen over this period, 65 (4.2%) had PNL. Males were more commonly affected than females (2.6:1.). The majority of patients 40/65(61.5%) were aged between 15 and 35 yrs. Predominant presenting symptoms were paresthesia, pain, sensory/motor deficit, and trophic changes. A majority of the patients 39/65 (60.0%) presented with involvement of 2 or more nerves in the same extremity. Mononeuritis was seen in 26 (40%) patients. The nerves most often involved were the right ulnar nerve in the upper extremity, and the right common peroneal nerve in the lower limb. In general, the nerves of the upper extremity were more commonly involved than in the lower limbs (67 vs. 55). Motor deformities such as claw hand and foot drop were present in 13/75 (20%) and 7/65 (10.8%) patients, respectively. Slit-skin smears were negative in all patients, and skin histopathology from the area of sensory loss revealed non-specific inflammation in the dermis in a majority of patients, with perineural inflammation in a few. All patients were treated with multi-drug therapy (MDT); patients with >/=2 peripheral nerve trunk involvements were treated with WHO MDT MB regimen, while others were administered WHO MDT PB regimen. Follow-up for up to 2 yrs was available in only 32/65 (49.2%) patients, none of whom developed any skin lesions during this period. CONCLUSION: PNL is a distinct subset of disease frequently seen in India. There is need to pay more attention to this form of leprosy and diagnose and treat patients earlier to prevent deformities and sequelae of nerve damage.

Adolescent↗