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Papers by Harinder Sandhu
Journal of Oral Pathology & Medicine, 1991
HIV-related oral candidiasis was investigated in 71 HIV-seropositive patients who received interv... more HIV-related oral candidiasis was investigated in 71 HIV-seropositive patients who received interviews, oral examinations and hematologic investigation. Diagnosis of candidiasis was based on clinical signs and examination of PAS-stained smears. The frequency of candidiasis was 24/71 (34%). The clinical presentations were pseudomembranous 8 (11%), erythematous 14 (20%), angular cheilitis 3 (4%). Twenty-six patients (37%) had candidiasis or were receiving antifungal treatment for recurrent pseudomembranous type. Twelve of 13 (92%) patients with AIDS and 14/58 (24%) without AIDS were affected. Bivariate analyses showed significant associations with AIDS, the use of zidovudine, low T4-count, xerostomia: marital status (sometime married), restricted performance status and age of >35 yr. Multivariate logistic regression analysis showed that the presence of xerostomia was an independent and statistically significant predictor of HIV-related oral candidiasis. T4-count and restricted performance status were the second and third most important predictors.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, Jan 15, 2003
HOPA is a 25 kb Xq13 gene that codes for a member of the thyroid receptor co-activator protein (T... more HOPA is a 25 kb Xq13 gene that codes for a member of the thyroid receptor co-activator protein (TRAP) family of nuclear receptor co-activators. In our prior research, polymorphisms in the opposite paired (Opa) domain of HOPA have been associated with a syndrome of aberrant behavior, most prominently psychosis, and hypothyroidism. These Opa domain polymorphisms are intriguing because subsequent research has demonstrated that changes in the Opa domain of the C. elegans orthologue of HOPA results in altered neurogenesis and release of transcriptional suppression. In an effort to determine whether other allelic polymorphisms in this gene exist and may potentially contribute to increased susceptibility to neuropsychiatric illness, we have performed single stranded conformational polymorphism (SSCP) analysis of all 45 exons and each of the two potential promoter regions of HOPA using DNA from a panel of patients with psychosis. We found a rare promoter polymorphism in an individual with schizoaffective disorder and extremely low thyroid stimulating hormone (TSH). The most common exonic polymorphism in HOPA is the previously demonstrated HOPA 12 bp polymorphism.Transmissiondisequilibrium analysis of the HOPA 12 bp polymorphism showed segregation with affected status in six of eight instances. We suggest that this evidence supports previous associations of HOPA 12 bp with a broad range of neuropsychiatric illness and conclude that further studies of this uncommon polymorphism are merited. ß
Psychiatric genetics, 2004
PCQAP is a member of the mediator family of transcription co-activators that is found in the regi... more PCQAP is a member of the mediator family of transcription co-activators that is found in the region of 22q11, which is consistently deleted in DiGeorges/velocranialfacial (VCF) syndrome. As such, it is a gene of interest to behavioral geneticists because VCF is also associated with a high rate of psychosis and because defects in other mediator genes have been linked to psychosis and abnormal neurodevelopmental abnormalities. Recently, DeLuca and colleagues reported that polymorphisms in a trinucleotide repeat in exon 7 of PCQAP were associated with schizophrenia in a case-control study of Italian schizophrenics. To confirm and extend the prior findings, we conducted a case-control association analysis using DNA from 233 schizophrenics and 371 random controls. Unfortunately, we did not find any significant differences in the distribution of CAG repeat alleles between subjects and controls. These findings limit the role of exon 7 PCQAP polymorphisms in the pathogenesis of schizophrenia.
American Journal of Medical Genetics Part B-neuropsychiatric Genetics, 2007
In attempts to isolate genetic vulnerability factors for panic disorder (PD), a number of investi... more In attempts to isolate genetic vulnerability factors for panic disorder (PD), a number of investigators have used genome-wide linkage or association analyses. But these attempts have been only modestly successful which suggests that alternative approaches may be needed to define the biology of PD. Therefore, using recently developed genome-wide gene expression profiling, we explored whether transcriptional signatures associated with PD are present in lymphoblast cell line. The expression of 2,469 transcripts in lymphoblast cell lines from 16 subjects was arithmetically increased in every line and significantly increased overall and 354 transcripts was arithmetically decreased in every cell line and significantly decreased overall as compared to those lymphoblast lines from 17 subjects without a history of behavioral illness. Further sex specific analyses showed that in those 10 lines derived from female probands, the expression of a further 67 transcripts was arithmetically increased in every line and significantly increased overall and a further 332 transcripts was arithmetically decreased in every cell line and significantly decreased. Conversely, in cell lines from the six male probands, the expression of an additional 212 was arithmetically increased in every line and significantly increased overall and a further 332 transcripts was arithmetically decreased in every cell line. We conclude that lymphoblast cell lines derived from subjects with PD have significant, partially sex dependent changes in gene transcription. Further studies are necessary to correlate these changes in these hemopoetically derived cells with those changes postulated to occur in the CNS in association with PD. © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B-neuropsychiatric Genetics, 2007
Transcriptional profiling has been used to identify gene expression patterns indicative of genera... more Transcriptional profiling has been used to identify gene expression patterns indicative of general medical illnesses such as atherosclerosis. However, whether these methods can identify common psychiatric disorders has not been established. To answer this question with respect to nicotine use, we used genome-wide expression profiling lymphoblast cell lines from six actively smoking Iowa Adoption Studies (IAS) subjects and nine “clean” control subjects, followed by real-time PCR (RT-PCR) of gene expression patterns in lymphoblast derived RNA from 94 subjects in the IAS. As compared to those from controls without a history of smoking (n = 9), the expression levels of 579 of 29,098 genes were significantly up-regulated and expression levels of 584 of 29,098 genes were significantly down-regulated in lymphoblast lines from currently smoking subjects (n = 6). RT-PCR confirmation of four select RNA levels confirmed the validity of the overall profile and revealed highly significant relationships between the expression of some of these transcripts and (1) major depression, (2) antisocial personality, (3) nicotine dependence, and (4) cannabis dependence. We conclude that the use of expression profiling may contribute significant insights into the biology of complex behavioral disorders. © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2008
Serotonin Transporter (5HTTor SLC6A4) mRNA transcription is regulated by both genetic and epigene... more Serotonin Transporter (5HTTor SLC6A4) mRNA transcription is regulated by both genetic and epigenetic mechanisms. Unfortunately, despite intense scrutiny, the exact identity and contribution of each of these regulatory mechanisms, and their relationship to behavioral illness remain unknown. This lack of knowledge is critical because alterations in SLC6A4 function are posited to be central to a wide variety of CNS disorders. In order to address this shortcoming, we quantified 5HTTLPR genotype, SLC6A4 mRNA production and CpG methylation using biomaterial from 192 lymphoblast cell lines derived from subjects who participated in the latest wave of the Iowa Adoption Studies. We then analyzed the resulting data with respect to clinical characteristics. We confirmed prior findings that the short (s) 5HTTLPR allele is associated with lower amounts of mRNA transcription, but there was no significant effect of the "Long G" allele on mRNA transcription. We also found that CpG methylation was higher (P< 0.0008) and mRNA production (P< 0.0001) was lower in females as compared to males. Those subjects with a lifetime history of Alcohol Dependence had higher levels of SLC6A4 mRNA. There was a trend for an association of increased overall methylation with lifetime history of major depression. Finally, we confirm our prior findings that the exact levels of 5HTT mRNA expression are dependent on how it is measured. We conclude that both genetic variation and epigenetic modifications contribute to the regulation of SLC6A4 function and that more in-depth studies of the molecular mechanisms controlling gene activity and the relationship of these mechanisms to behavioral illness are indicated.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2007
In attempts to isolate genetic vulnerability factors for panic disorder (PD), a number of investi... more In attempts to isolate genetic vulnerability factors for panic disorder (PD), a number of investigators have used genome-wide linkage or association analyses. But these attempts have been only modestly successful which suggests that alternative approaches may be needed to define the biology of PD. Therefore, using recently developed genome-wide gene expression profiling, we explored whether transcriptional signatures associated with PD are present in lymphoblast cell line. The expression of 2,469 transcripts in lymphoblast cell lines from 16 subjects was arithmetically increased in every line and significantly increased overall and 354 transcripts was arithmetically decreased in every cell line and significantly decreased overall as compared to those lymphoblast lines from 17 subjects without a history of behavioral illness. Further sex specific analyses showed that in those 10 lines derived from female probands, the expression of a further 67 transcripts was arithmetically increased in every line and significantly increased overall and a further 332 transcripts was arithmetically decreased in every cell line and significantly decreased. Conversely, in cell lines from the six male probands, the expression of an additional 212 was arithmetically increased in every line and significantly increased overall and a further 332 transcripts was arithmetically decreased in every cell line. We conclude that lymphoblast cell lines derived from subjects with PD have significant, partially sex dependent changes in gene transcription. Further studies are necessary to correlate these changes in these hemopoetically derived cells with those changes postulated to occur in the CNS in association with PD.
The induction motor is without doubt the most used electrical motor because of its unique charact... more The induction motor is without doubt the most used electrical motor because of its unique
characteristics. Most of its applications need fast and intelligent speed control system. This paper presents
comparison of the intelligent and advanced speed control methods based on PWM technique and PI
controller to achieve maximum torque and efficiency. Simulation is carried out in MAT LAB environment
and results are investigated for speed control of induction motor without any controller and with PI
controller on full load condition.
Journal of Oral Pathology & Medicine, 1991
HIV-related oral candidiasis was investigated in 71 HIV-seropositive patients who received interv... more HIV-related oral candidiasis was investigated in 71 HIV-seropositive patients who received interviews, oral examinations and hematologic investigation. Diagnosis of candidiasis was based on clinical signs and examination of PAS-stained smears. The frequency of candidiasis was 24/71 (34%). The clinical presentations were pseudomembranous 8 (11%), erythematous 14 (20%), angular cheilitis 3 (4%). Twenty-six patients (37%) had candidiasis or were receiving antifungal treatment for recurrent pseudomembranous type. Twelve of 13 (92%) patients with AIDS and 14/58 (24%) without AIDS were affected. Bivariate analyses showed significant associations with AIDS, the use of zidovudine, low T4-count, xerostomia: marital status (sometime married), restricted performance status and age of >35 yr. Multivariate logistic regression analysis showed that the presence of xerostomia was an independent and statistically significant predictor of HIV-related oral candidiasis. T4-count and restricted performance status were the second and third most important predictors.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, Jan 15, 2003
HOPA is a 25 kb Xq13 gene that codes for a member of the thyroid receptor co-activator protein (T... more HOPA is a 25 kb Xq13 gene that codes for a member of the thyroid receptor co-activator protein (TRAP) family of nuclear receptor co-activators. In our prior research, polymorphisms in the opposite paired (Opa) domain of HOPA have been associated with a syndrome of aberrant behavior, most prominently psychosis, and hypothyroidism. These Opa domain polymorphisms are intriguing because subsequent research has demonstrated that changes in the Opa domain of the C. elegans orthologue of HOPA results in altered neurogenesis and release of transcriptional suppression. In an effort to determine whether other allelic polymorphisms in this gene exist and may potentially contribute to increased susceptibility to neuropsychiatric illness, we have performed single stranded conformational polymorphism (SSCP) analysis of all 45 exons and each of the two potential promoter regions of HOPA using DNA from a panel of patients with psychosis. We found a rare promoter polymorphism in an individual with schizoaffective disorder and extremely low thyroid stimulating hormone (TSH). The most common exonic polymorphism in HOPA is the previously demonstrated HOPA 12 bp polymorphism.Transmissiondisequilibrium analysis of the HOPA 12 bp polymorphism showed segregation with affected status in six of eight instances. We suggest that this evidence supports previous associations of HOPA 12 bp with a broad range of neuropsychiatric illness and conclude that further studies of this uncommon polymorphism are merited. ß
Psychiatric genetics, 2004
PCQAP is a member of the mediator family of transcription co-activators that is found in the regi... more PCQAP is a member of the mediator family of transcription co-activators that is found in the region of 22q11, which is consistently deleted in DiGeorges/velocranialfacial (VCF) syndrome. As such, it is a gene of interest to behavioral geneticists because VCF is also associated with a high rate of psychosis and because defects in other mediator genes have been linked to psychosis and abnormal neurodevelopmental abnormalities. Recently, DeLuca and colleagues reported that polymorphisms in a trinucleotide repeat in exon 7 of PCQAP were associated with schizophrenia in a case-control study of Italian schizophrenics. To confirm and extend the prior findings, we conducted a case-control association analysis using DNA from 233 schizophrenics and 371 random controls. Unfortunately, we did not find any significant differences in the distribution of CAG repeat alleles between subjects and controls. These findings limit the role of exon 7 PCQAP polymorphisms in the pathogenesis of schizophrenia.
American Journal of Medical Genetics Part B-neuropsychiatric Genetics, 2007
In attempts to isolate genetic vulnerability factors for panic disorder (PD), a number of investi... more In attempts to isolate genetic vulnerability factors for panic disorder (PD), a number of investigators have used genome-wide linkage or association analyses. But these attempts have been only modestly successful which suggests that alternative approaches may be needed to define the biology of PD. Therefore, using recently developed genome-wide gene expression profiling, we explored whether transcriptional signatures associated with PD are present in lymphoblast cell line. The expression of 2,469 transcripts in lymphoblast cell lines from 16 subjects was arithmetically increased in every line and significantly increased overall and 354 transcripts was arithmetically decreased in every cell line and significantly decreased overall as compared to those lymphoblast lines from 17 subjects without a history of behavioral illness. Further sex specific analyses showed that in those 10 lines derived from female probands, the expression of a further 67 transcripts was arithmetically increased in every line and significantly increased overall and a further 332 transcripts was arithmetically decreased in every cell line and significantly decreased. Conversely, in cell lines from the six male probands, the expression of an additional 212 was arithmetically increased in every line and significantly increased overall and a further 332 transcripts was arithmetically decreased in every cell line. We conclude that lymphoblast cell lines derived from subjects with PD have significant, partially sex dependent changes in gene transcription. Further studies are necessary to correlate these changes in these hemopoetically derived cells with those changes postulated to occur in the CNS in association with PD. © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B-neuropsychiatric Genetics, 2007
Transcriptional profiling has been used to identify gene expression patterns indicative of genera... more Transcriptional profiling has been used to identify gene expression patterns indicative of general medical illnesses such as atherosclerosis. However, whether these methods can identify common psychiatric disorders has not been established. To answer this question with respect to nicotine use, we used genome-wide expression profiling lymphoblast cell lines from six actively smoking Iowa Adoption Studies (IAS) subjects and nine “clean” control subjects, followed by real-time PCR (RT-PCR) of gene expression patterns in lymphoblast derived RNA from 94 subjects in the IAS. As compared to those from controls without a history of smoking (n = 9), the expression levels of 579 of 29,098 genes were significantly up-regulated and expression levels of 584 of 29,098 genes were significantly down-regulated in lymphoblast lines from currently smoking subjects (n = 6). RT-PCR confirmation of four select RNA levels confirmed the validity of the overall profile and revealed highly significant relationships between the expression of some of these transcripts and (1) major depression, (2) antisocial personality, (3) nicotine dependence, and (4) cannabis dependence. We conclude that the use of expression profiling may contribute significant insights into the biology of complex behavioral disorders. © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2008
Serotonin Transporter (5HTTor SLC6A4) mRNA transcription is regulated by both genetic and epigene... more Serotonin Transporter (5HTTor SLC6A4) mRNA transcription is regulated by both genetic and epigenetic mechanisms. Unfortunately, despite intense scrutiny, the exact identity and contribution of each of these regulatory mechanisms, and their relationship to behavioral illness remain unknown. This lack of knowledge is critical because alterations in SLC6A4 function are posited to be central to a wide variety of CNS disorders. In order to address this shortcoming, we quantified 5HTTLPR genotype, SLC6A4 mRNA production and CpG methylation using biomaterial from 192 lymphoblast cell lines derived from subjects who participated in the latest wave of the Iowa Adoption Studies. We then analyzed the resulting data with respect to clinical characteristics. We confirmed prior findings that the short (s) 5HTTLPR allele is associated with lower amounts of mRNA transcription, but there was no significant effect of the "Long G" allele on mRNA transcription. We also found that CpG methylation was higher (P< 0.0008) and mRNA production (P< 0.0001) was lower in females as compared to males. Those subjects with a lifetime history of Alcohol Dependence had higher levels of SLC6A4 mRNA. There was a trend for an association of increased overall methylation with lifetime history of major depression. Finally, we confirm our prior findings that the exact levels of 5HTT mRNA expression are dependent on how it is measured. We conclude that both genetic variation and epigenetic modifications contribute to the regulation of SLC6A4 function and that more in-depth studies of the molecular mechanisms controlling gene activity and the relationship of these mechanisms to behavioral illness are indicated.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2007
In attempts to isolate genetic vulnerability factors for panic disorder (PD), a number of investi... more In attempts to isolate genetic vulnerability factors for panic disorder (PD), a number of investigators have used genome-wide linkage or association analyses. But these attempts have been only modestly successful which suggests that alternative approaches may be needed to define the biology of PD. Therefore, using recently developed genome-wide gene expression profiling, we explored whether transcriptional signatures associated with PD are present in lymphoblast cell line. The expression of 2,469 transcripts in lymphoblast cell lines from 16 subjects was arithmetically increased in every line and significantly increased overall and 354 transcripts was arithmetically decreased in every cell line and significantly decreased overall as compared to those lymphoblast lines from 17 subjects without a history of behavioral illness. Further sex specific analyses showed that in those 10 lines derived from female probands, the expression of a further 67 transcripts was arithmetically increased in every line and significantly increased overall and a further 332 transcripts was arithmetically decreased in every cell line and significantly decreased. Conversely, in cell lines from the six male probands, the expression of an additional 212 was arithmetically increased in every line and significantly increased overall and a further 332 transcripts was arithmetically decreased in every cell line. We conclude that lymphoblast cell lines derived from subjects with PD have significant, partially sex dependent changes in gene transcription. Further studies are necessary to correlate these changes in these hemopoetically derived cells with those changes postulated to occur in the CNS in association with PD.
The induction motor is without doubt the most used electrical motor because of its unique charact... more The induction motor is without doubt the most used electrical motor because of its unique
characteristics. Most of its applications need fast and intelligent speed control system. This paper presents
comparison of the intelligent and advanced speed control methods based on PWM technique and PI
controller to achieve maximum torque and efficiency. Simulation is carried out in MAT LAB environment
and results are investigated for speed control of induction motor without any controller and with PI
controller on full load condition.