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Neeraj Jain

Publications and source records attributed to Neeraj Jain.

At least 19 recordsLinked to original sources

Cortical and thalamic connections of the representations of the teeth and tongue in somatosensory cortex of new world monkeys.

Connections of representations of the teeth and tongue in primary somatosensory cortex (area 3b) and adjoining cortex were revealed in owl, squirrel, and marmoset monkeys with injections of fluorescent tracers. Injection sites were identified by microelectrode recordings from neurons responsive to touch on the teeth or tongue. Patterns of cortical label were related to myeloarchitecture in sections cut parallel to the surface of flattened cortex, and to coronal sections of the thalamus processed for cytochrome oxidase (CO). Cortical sections revealed a caudorostral series of myelin dense ovals (O1-O4) in area 3b that represent the periodontal receptors of the contralateral teeth, the contralateral tongue, the ipsilateral teeth, and the ipsilateral tongue. The ventroposterior medial subnucleus, VPM, and the ventroposterior medial parvicellular nucleus for taste, VPMpc, were identified in the thalamic sections. Injections placed in the O1 oval representing teeth labeled neurons in VPM, while injections in O2 representing the tongue labeled neurons in both VPMpc and VPM. These injections also labeled adjacent part of areas 3a and 1, and locations in the lateral sulcus and frontal lobe. Callosally, connections of the ovals were most dense with corresponding ovals. Injections in the area 1 representation of the tongue labeled neurons in VPMpc and VPM, and ipsilateral area 3b ovals, area 3a, opercular cortex, and cortex in the lateral sulcus. Contralaterally, labeled neurons were mostly in area 1. The results implicate portions of areas 3b, 3a, and 1 in the processing of tactile information from the teeth and tongue, and possibly taste information from the tongue.

Animals↗

Biosorption of copper(II) from aqueous solutions by Spirogyra species.

Batch studies were conducted to investigate the kinetics and isotherms of Cu(II) biosorption on the biomass of green alga Spirogyra species. It is observed that the biosorption capacity of the biomass strongly depends on pH and algal dose. The maximum biosorption capacity of 133.3 mg Cu(II)/g of dry weight of biomass was observed at an optimum pH of 5 in 120 min with an algal dose of 20 g/L. Desorption studies were conducted with 133.3 mg/g of Cu(II) loaded biomass using different desorption agents including HCl, EDTA, H2SO4, NaCl, and H2O. The maximum desorption of 95.3% was obtained with HCl in 15 min. The results indicate that with the advantages of high metal biosorption capacity and satisfactory recovery of Cu(II), Spirogyra can be used as an efficient and economic biosorbent material for the removal and recovery of toxic heavy metals from polluted water.

Adsorption↗

Adsorption of As(III) from aqueous solutions by iron oxide-coated sand.

Arsenic is a toxic element and may be found in natural waters as well as in industrial waters. Leaching of arsenic from industrial wastewater into groundwater may cause significant contamination, which requires proper treatment before its use as drinking water. The present study describes removal of arsenic(III) on iron oxide-coated sand in batch studies conducted as a function of pH, time, initial arsenic concentration, and adsorbent dosage. The results were compared with those for uncoated sand. The adsorption data fitted well in the Langmuir model at different initial concentration of As(III) at 20 g/l fixed adsorbent dose. Maximum adsorption of As(III) for coated sand is found to be much higher (28.57 microg/g) than that for uncoated sand (5.63 microg/g) at pH 7.5 in 2 h. The maximum As(III) removal efficiency achieved is 99% for coated sand at an adsorbent dose of 20 g/l with initial As(III) concentration of 100 microg/l in batch studies. Column studies have also been carried out with 400 microg/l arsenic (pH 7.5) by varying the contact time, filtration rate, and bed depth. Results of column studies demonstrated that at a filtration rate of 4 ml/min the maximum removal of As(III) observed was 94% for coated sand in a contact time of 2 h. The results observed in batch and column studies indicate that iron oxide-coated sand is a suitable adsorbent for reducing As(III) concentration to the limit (50 microg/l) recommended by Indian Standards for Drinking Water.

Journal Article↗

p53 gene mutation and human papillomavirus (HPV) infection in esophageal carcinoma from three different endemic geographic regions of India.

Infection of high-risk human papillomaviruses (HPVs), particularly the HPV types 16 and 18 and mutation or aberrant expression of the p53 tumour suppressor gene, has strongly been implicated in human esophageal carcinoma, which shows a great variation in geographic distribution. Neither the reason(s) for such a variation nor the etiopathogenesis of the disease is clearly understood. The present study has been carried out to determine prevalence of high-risk HPV types 16 and 18 and the p53 gene mutation in patients from three distinctly different endemic geographic regions of India, viz. Kashmir, Dibrugarh, and New Delhi where esophageal cancer is most prevalent. The people from each of these regions differ considerably in their food, drinking, smoking and chewing habits (tobacco and betel nut) and ethnic background. While PCR was employed to detect high-risk HPV types 16 and 18 DNA sequences, PCR-SSCP and direct nucleotide sequencing was used for analysis of p53 mutation. Out of a total of 101 biopsy specimens of carcinoma esophagus analysed, the frequency of HPV was found to be the highest 14/32 (44%) in Dibrugarh followed by 33% (11/33) in Kashmir, but, interestingly, no high-risk HPV could be detected in New Delhi patients who showed the highest frequency (30.6%) of p53 mutation as against only 12.5% in Dibrugarh and 6.1% in Kashmir. The difference in the frequency of p53 mutation between the three regions was statistically highly significant (0.018). Out of a total of 21 nucleotide alterations observed, 12 missense, five frameshift and four were silent changes. The p53 exon 7 appears to be the 'hot-spot' for esophageal cancer as it alone was responsible for more than 76% (13/17) of mutations and more than 95% (20/21) of the patients with p53 mutation were smokers. The results demonstrate differential distribution of HPV infection and p53 mutation in esophageal cancer from different geographic regions of India and this could be due to variation in diet, drinking, and tobacco habit, including ethnic, socio-cultural and genetic variation.

Adult↗

Assessment of possible tuberculous lymphadenopathy by PCR compared to non-molecular methods.

Tuberculosis is a major public health problem in India and other developing countries and has formed a lethal partnership with AIDS. It often presents a diagnostic challenge especially when clinical presentation is suggestive but bacteriological proof is lacking. The objective of this study was to compare the various diagnostic techniques in clinically suspected cases of tubercular lymph nodes and to find a suitable, cost-effective but sensitive and specific method for diagnosis. A total of 100 cases were recruited for the study. Fine needle aspiration cytology was done in all cases and the smears prepared were processed for Giemsa, Ziehl-Neelsen's, Kinyoun and Papanicolaou stains. Parts of the aspirated materials were assessed by fluorescent staining, culture and PCR. Seventy-four percent of aspirates were positive by fluorescent stain while only 22% were positive by culture. PCR could be performed in 55 cases, out of which 22 (40%) were positive. When compared to culture, the sensitivity and specificity of PCR were found to be 89.5% and 86.1%, respectively. Fluorescent stain was found to be the most sensitive (81.8%) of the conventional methods but showed poor specificity (28.2%). Interestingly, PCR detected 80% of smear-negative but culture-positive cases.

Adolescent↗

Infection of human papillomavirus type 18 and p53 codon 72 polymorphism in lung cancer patients from India.

STUDY OBJECTIVES: Infection with specific high-risk HPV types 16 and 18 and polymorphism of p53 codon 72 has been strongly associated with the genesis of various neoplasms in humans, but such study in lung cancer is limited and the results are controversial. In India, the role of these two factors has been strongly implicated in cervical and other cancers, but the occurrence of HPV or p53 codon 72 polymorphism has not been examined in lung cancer, which is the most common cause of cancer-related death in India. DESIGN AND PATIENTS: A total of 40 tumor biopsy specimens from advanced lung cancer patients and blood samples from 40 matching control subjects were obtained for the analysis of high-risk HPV types 16 and 18 infection and p53 codon 72 polymorphism by polymerase chain reaction. RESULTS: Only HPV type 18 was detected in 5% (2 of 40 lung cancer patients), but no other HPV could be detected. A significantly increased frequency of Arg/Arg homozygotes was observed in patients with advanced lung cancer when compared to that of control subjects (p = 0.004; odds ratio, 5.13; 95% confidence interval, 1.59 to 17.26). However, no significant correlation could be made between p53 polymorphism and different clinical stages, except for advanced stage IV patients, who showed a higher proportion of Arg/Pro heterozygous genotype. CONCLUSIONS: HPV detected in a small proportion of lung cancer patients in India demonstrated an exclusive prevalence of HPV type 18, and there was a significantly higher frequency of p53 Arg/Arg genotype when compared to that of control subjects. Observation of a shorter duration of symptoms (< or = 4 months) in as many as 78% (seven of nine stage IV patients) with Arg/Pro genotype may be an indication that lung cancer patients with the heterozygous p53 genotype are more susceptible to early progression.

Aged↗

Bilateral effects of spinal overhemisections on the development of the somatosensory system in rats.

Connections of the forepaw regions of somatosensory cortex (S1) were determined in rats reared to maturity after spinal cord overhemisections at cervical level C3 on postnatal day 3. Overhemisections cut all ascending and descending pathways and intervening gray on one side of the spinal cord and the pathways of the dorsal funiculus contralaterally. Bilateral lesions of the dorsal columns reduced the size of the brainstem nuclei by 41%, and the ventroposterior lateral subnucleus (VPL) of the thalamus by 20%. Bilateral lesions also prevented the emergence of the normal cytochrome oxidase barrel pattern in forepaw and hindpaw regions of S1. Injections of wheat germ agglutinin conjugated to horseradish peroxidase were placed in the forepaw region of granular S1 and surrounding dysgranular S1 contralateral to the hemisection. The VPL nucleus was densely labeled, whereas the adjoining ventroposterior medial subnucleus, VPM, representing the head, was unlabeled. Thus, there was no evidence of abnormal connections of VPM to forepaw cortex. Foci of transported label in the ipsilateral hemisphere appeared to be in normal locations and of normal extents, but connections in the opposite hemisphere were broadly and nearly uniformly distributed in sensorimotor cortex in a pattern similar to that in postnatal rats. Rats with incomplete lesions that spared the dorsal column pathway on the left side but not the right demonstrated surprisingly normal distributions of callosal connections in the nondeprived right hemisphere, even though the injected left hemisphere was deprived. Thus, the development of the normal pattern of callosal connections depends on dorsal column input and not on normal interhemsipheric interactions.

Afferent Pathways↗

Two new novel point mutations localized upstream and downstream of the HMG box region of the SRY gene in three Indian 46,XY females with sex reversal and gonadal tumour formation.

The Y chromosome-specific gene SRY is one of the key genes involved in human sex determination. The SRY gene encodes a testis-specific transcription factor that plays a key role in sexual differentiation and development in males and is located on the distal region of the short arm of the Y chromosome. Mutations in SRY gene result in XY sex reversal and pure gonadal dysgenesis. SRY expression initiates a network of gene activity that transforms the undifferentiated gonad, genital ridge into testis. Mutations in the SRY gene have been considered to account for only 10-15% of 46,XY gonadal dysgenesis cases, whereas the majority of the remaining cases may have mutation(s) in the SRY regulatory elements or other genes involved in the sex differentiation pathway. Patients both with gonadal dysgenesis and Y-chromosome presence are at high risk of developing gonadoblastoma. Using PCR, single strand conformational polymorphism (SSCP) and automated DNA sequencing, we analysed the mutations in the SRY gene in three 46,XY sex reversal patients. Two patients demonstrated nucleotide substitution (A-->G) within the open reading frame just outside and upstream of the conserved DNA-binding motif called the high-mobility group (HMG) box, replacing glutamine at codon 57 with arginine. Altered SSCP patterns were also observed in these patients. Histological examination of gonads in patient 1 revealed the formation of gonadoblastoma. Patient 3 demonstrated A-->T substitution which replaces serine at codon 143 with cysteine, just outside but downstream of the HMG box. Results suggest the involvement of SRY gene in sex reversal which further supports the relationship between SRY alterations, gonadal dysgenesis and/or primary infertility.

Adult↗

Novel germline mutations in breast cancer susceptibility genes BRCA1, BRCA2 and p53 gene in breast cancer patients from India.

Mutations in breast cancer susceptibility genes, BRCA1 and BRCA2 account for more than 80% of hereditary breast and ovarian cancers. p53 tumor suppressor gene that controls cellular growth and differentiation is also known to be mutated in more than 50% of human cancers including breast cancer. We have carried out a study on BRCA1 and BRCA2 along with p53 gene mutations in both sporadic as well as familial breast cancer patients from India where breast cancer is fast emerging as a major cancer among premenopausal urban women. We examined 124 untreated primary breast cancer patients comprising 100 sporadic and 24 familial cases including 56 age-matched healthy controls for the presence of BRCA1, BRCA2 and the p53 gene mutations using PCR-SSCP and direct nucleotide sequencing. Certain frequently mutated exons such as 2, 5, 11, 13 and 20 of BRCA1, exons 2, 9, 11 (for 6174delT), 18 and 20 of BRCA2 and 4-9 exons of p53 gene were analyzed in sporadic breast cancer while all 22 coding exons of BRCA1 including its flanking intronic regions along with above mentioned exons of BRCA2 and p53 gene were analyzed in familial breast cancer patients. We identified six patients (25%) with BRCA1 mutation of which three were found to be of novel type one in exon 16 (4956insG) and two in exon 7 (Lys110Thr) (Ser114Pro) out of 24 familial breast cancer patients studied from two different geographic regions/populations of India. Two sisters from a single family (12.5%) out of eight families from Goa with Portuguese colonial origin showed presence of founder Ashkenazi Jewish BRCA1 mutation (185delAG) along with (IVS7 561-34T>C; IVS18 5271 + 66G > A). While from New Delhi, four (25%) of 16 breast cancer families showed BRCA1 mutations; a frame shift protein truncating (4956insG), a transition nonsense (Gln1395Stop) and two amino acid substitutions (Lys110Thr) and (Ser114Pro). Only one (4%) p53 mutation (Val97Ile) in its exon 4 along with BRCA1 mutation (4956insG) could be detected. No major sequence variation in BRCA2 gene was observed except for G203A at 5' UTR of exon 2, a common population polymorphism in two Goan patients who also showed silent nucleotide change for amino acid serine at codon 1436 of BRCA1 gene. None of the 100 sporadic breast cancer patients revealed any protein truncating or deleterious BRCA1 or BRCA2 gene mutation. Interestingly, three (3%) p53 mutations in its exon 5 were detected in sporadic breast cancer patients. Although three novel BRCA1 mutations including a founder Ashkenazi Jewish BRCA1 mutation were recorded in Indian women with familial breast cancer, the overall prevalence of BRCA gene mutations in Indian women with a family history of breast cancer appears to be low.

Adult↗

The visual pulvinar in tree shrews I. Multiple subdivisions revealed through acetylcholinesterase and Cat-301 chemoarchitecture.

Tree shrews are highly visual mammals closely related to primates. They have a large visual pulvinar complex, but its organization and relation to visual cortex is only partly known. We processed brain sections through the pulvinar with seven different procedures in an effort to reveal histologically distinct compartments. The results revealed three major subdivisions. A dorsal subdivision, Pd, stains darkly for acetylcholinesterase (AChE) and occupies the dorsoposterior one-third of the pulvinar complex. A ventral subdivision, Pv, stains darkly when processed with the Cat-301 antibody and occupies the ventroanterior fifth of the pulvinar complex along the brachium of the superior colliculus. Unexpectedly, part of Pv is ventral to the brachium. A large central subdivision, Pc, stains moderately dark for AChE and cytochrome oxidase (CO), and very light for Cat-301. Pc includes about half of the pulvinar complex, with parts on both sides of the brachium of the superior colliculus. These architectonic results demonstrate that the pulvinar complex of tree shrews is larger and has more subdivisions than previously described. The complex resembles the pulvinar of primates by having a portion ventral to the brachium and by having histochemically distinct nuclei; the number of nuclei is less than in primates, however.

Acetylcholinesterase↗

The visual pulvinar in tree shrews II. Projections of four nuclei to areas of visual cortex.

Patterns of thalamocortical connections were related to architectonically defined subdivisions of the pulvinar complex and the dorsolateral geniculate nucleus (LGN) in tree shrews (Tupaia belangeri). Tree shrews are of special interest because they are considered close relatives of primates, and they have a highly developed visual system. Several distinguishable tracers were injected within and across cortical visual areas in individual tree shrews in order to reveal retinotopic patterns and cortical targets of subdivisions of the pulvinar. The results indicate that each of the three architectonic regions of the pulvinar has a distinctive pattern of cortical connections and that one of these divisions is further divided into two regions with different patterns of connections. Two of the pulvinar nuclei have similar retinotopic patterns of projections to caudal visual cortex. The large central nucleus of the pulvinar (Pc) projects to the first and second visual areas, V1 and V2, and an adjoining temporal dorsal area (TD) in retinotopic patterns indicating that the upper visual quadrant is represented dorsal to the lower quadrant in Pc. The smaller ventral nucleus (Pv) which stains darkly for the Cat-301 antigen, projects to these same cortical areas, with a retinotopic pattern. Pv also projects to a temporal anterior area, TA. The dorsal nucleus (Pd), which densely expresses AChE, projects to posterior and ventral areas of temporal extrastriate cortex, areas TP and TPI. A posterior nucleus, Pp, projects to anterior areas TAL and TI, of the temporal lobe, as well as TPI. Injections in different cortical areas as much as 6 mm apart labeled overlapping zones in Pp and double-labeled some cells. These results indicate that the visual pulvinar of tree shrews contains at least four functionally distinct subdivisions, or nuclei. In addition, the cortical injections revealed that the LGN projects topographically and densely to V1 and that a significant number of LGN neurons project to V2 and TD.

Acetylcholinesterase↗

Patterned activity via spinal dorsal quadrant inputs is necessary for the formation of organized somatosensory maps.

The normal development of the somatosensory system requires intact sensory inputs from the periphery during a critical window of time early in development. Here we determined how the removal of only part of the ascending spinal inputs early in development affects the anatomical and neurophysiological development of the somatosensory system. We performed spinal overhemisections in rat pups at C3/C4 levels on the third day after birth. This procedure hemisects the spinal cord on one side and transects the dorsal funiculus on the other side. When the rats were 6-8 months old, the responsiveness and somatotopy of the primary somatosensory cortex (S1) contralateral to the hemisection were determined using standard multiunit mapping techniques. Sections of the flattened cortex were processed for cytochrome oxidase activity, Nissl substance, or myelin. We found that histologically apparent modules that are normally present in the regions of the forepaw and the hindpaw representations were absent, whereas the lateral barrel field representing the face was completely normal. The neurons in the forepaw regions of S1 either did not respond to the stimulation of the skin of any region of the body or responded to the stimulation of the upper arm afferents that enter the spinal cord rostral to the site of the lesion. The results show that a lack of normal sensory inputs via ascending pathways in the dorsal spinal cord during early development results in massive anatomical and neurophysiological abnormalities in the cortex. Intact crossed spinothalamic pathways are unable to support the normal development of the forepaw barrels.

Afferent Pathways↗

Polymorphism of the p53 codon 72 Arg/Pro and the risk of HPV type 16/18-associated cervical and oral cancer in India.

Infection of high risk human papillomaviruses (HPVs) specifically the types 16 and 18 has been strongly implicated in the development of cervical cancer. The E6 oncoproteins of these high risk HPVs are known to bind and induce degradation of p53 tumour suppressor protein through the ubiquitin pathways. This degradation is controlled by a common polymorphism of the p53 gene encoding either a proline or an arginine at its codon 72 in exon 4. Recently, it has been demonstrated that the presence of homozygous arginine at codon 72 renders p53 about seven times more susceptible to E6-mediated proteolytic degradation as well as to cervical cancer than those with proline homozygotes or proline/arginine heterozygotes. In India, prevalence of HPV as well as cancers of the uterine cervix and the oral cavity are highest in the world. We have examined this allele-specific predisposition in cervical and oral cancer which is associated with HPV as well as in a non-HPV-linked cancer of the breast. We have carried out investigation in women comprising whole spectrum of cervical lesions with 128 HPV 16/18 positive and 35 HPV negative invasive cervical carcinomas and 34 cases of HPV (16/18) positive and 16 HPV negative cervical dysplasias (mild, moderate and severe) and 104 age-group-matched healthy women as controls. Additionally, we have analysed p53Arg-Pro polymorphism in 13 high risk HPV positive and 31 HPV negative oral cancers along with 20 normal controls and 77 breast cancers with 41 age-matched healthy controls. We observed more than two fold higher risk for homozygous arginine (chi2 = 6.3, df = 2, p = 0.04; OR = 2.3; 95% CI: 1.08-5.16) for HPV 16/18-positive cervical carcinomas when comparison was made only between HPV positive cervical cancers and normal controls but most interestingly, no significant association either in the frequency of homozygous arginine or proline alleles or their heterozygotes could be observed when all the three groups i.e. HPV-positive, HPV-negative cervical cancers and controls were considered simultaneously. No difference was also observed for either arginine or proline polymorphism between women with precancerous lesions of the uterine cervix carrying HPV 16/18 infection and controls. Similarly, increased risk of oral or breast cancer could not be correlated with the polymorphism of arginine/proline allele. Thus the interaction between HPV oncoproteins and the p53 gene polymorphism specifically, homozygous arginine at codon 72 appears to play no role in the development of either cervical or oral cancer and also it can not serve as a biomarker for early identification of cervical, oral or breast cancer.

Adult↗

Few intrinsic connections cross the hand-face border of area 3b of New World monkeys.

After long-standing loss of afferents from the hand, the hand representation in area 3b of the somatosensory cortex of monkeys becomes responsive to touch on the face. Because the reactivation of deprived hand cortex by the face inputs could depend on axonal connections across the hand-face border, we determined the extent of such connections in New World marmosets, owl monkeys, and squirrel monkeys. Small injections of anatomic tracers were placed in the hand or the face representations after these representations were identified by microelectrode recordings. The positions of retrogradely labeled neurons were plotted in processed brain sections cut parallel to the brain surface, and their locations were related to anatomic isomorphs of the hand and face representations revealed in adjacent brain sections stained for myelin. In these sections, the hand-face border was clearly visualized as a myelin-poor septum. The intrinsic connections of area 3b labeled by injections in either the hand or face representations were almost completely confined to their respective representation, and very few neurons projected across the border. In addition, neurons in the somatosensory thalamus labeled by injections in either face or hand representations were confined to either VPM, representing the face, or the hand subnucleus of VPL. Thus the reactivation of hand cortex by face stimulation does not depend on a previously existing network of intrinsic cortical connections across the hand-face border, or mismatched thalamocortical projections.

Afferent Pathways↗