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Biomedical subjects

S Mohan

Publications and source records attributed to S Mohan.

At least 19 recordsLinked to original sources

Fourier transform infrared and Raman spectral assignments and analysis of 7-amino-4-trifluoromethylcoumarin.

FTIR and FT-Raman spectra of 7-amino-4-trifluoromethylcoumarin (ATMC) have been recorded in the range 4000-400 and 3500-100 cm(-1), respectively, using Bruker IFS 66 V spectrometer. A detailed vibrational analysis has been carried out and assignments of the observed fundamental bands have been proposed on the basis of peak positions, relative intensities, fundamentals, overtones and combination bands. With hope of providing more and effective information on the fundamental vibrations, a normal co-ordinate analysis has been performed by assuming C(S) point group symmetry. The simple valance force field (SVFF) has been employed in normal co-ordinate analysis and to calculate the potential energy distribution (PED) for each fundamental vibration are reported. The PED contribution to each of the observed frequencies shows the reliability and precision of the spectral analysis.

Coumarins↗

Disruption of four-and-a-half LIM 2 decreases bone mineral content and bone mineral density in femur and tibia bones of female mice.

Four-and-a-half LIM 2 (FHL2) is a member of a family of LIM domain proteins which mediate protein-protein interactions. FHL2 acts as a coactivator and binds to important regulators of bone formation such as insulin-like growth factor binding protein (IGFBP)-5, androgen receptor, and beta-catenin. We hypothesized that FHL2 is an important regulator of bone formation. We evaluated growth and skeletal parameters in FHL2 knockout (KO) and wild-type (WT) mice at 4, 8, and 12 weeks of age. At 4 weeks of age, lack of FHL2 reduced femur, tibia, and total bone mineral content (BMC) and body weight in all mice. A gender-by-treatment interaction (P <or= 0.05) was observed for several parameters due to a greater reduction in females. Specifically, femur BMC was reduced 11-27% at 8 and 12 weeks of age and BMD was reduced 7-13% at all ages in female KO mice (P < 0.05). A similar reduction was observed in the tibias at 8 weeks of age. A 6% reduction (P = 0.07) in femur cortical thickness was observed at 12 weeks of age in female KO mice. Interestingly, a gender-specific reduction in IGFBP-5 expression was observed in the femurs of female KO mice. During differentiation of bone marrow stromal cells into osteoblasts, expression of osteocalcin, alkaline phosphatase, and bone sialoprotein was reduced 47-96% in FHL2 KO cells (P < 0.001). In conclusion, FHL2 is an important regulator of peak bone mass, lack of FHL2 produces gender- and site-specific effects on bone accretion and IGFBP-5 expression, and FHL2 is important for optimal osteoblast differentiation in vitro.

Animals↗

Preparation and characterization of Nd3+ doped sodium leadbismuthate glass.

Nd(3+) doped unconventional sodium leadbismuthate glass is prepared through the melt quenching method. The amorphous nature of the glass is confirmed through the X-ray diffraction study. The differential thermal study was performed to identify the glass transition and approximate glass thermal stability measurements. To identify the local structure of the glass, Fourier transform infrared spectral analysis was also carried out. By performing the Judd-Ofelt theory, the theoretical and experimental oscillator strengths were calculated.

Absorption↗

An evaluation of the darkroom prone provocative test in family members of primary angle closure glaucoma patients.

PURPOSE: To compare ocular biometric parameters with darkroom prone provocative test (DRPPT) in family members of primary angle closure glaucoma (PACG) patients. METHODS: One hundred and forty-nine family members of 46 PACG patients underwent ocular examination included slit lamp biomicroscopy, gonioscopy, fundus examination using +90 D lens, Goldmann applanation tonometry, darkroom prone provocative test, perimetry on Humphrey's field analyzer II and optic disc evaluation using HRT II. Ultrasonic ocular biometry and the DRPPT were then performed. IOP>or=8 mmHg rise from baseline with iridocorneal touch was considered as a positive test. RESULTS: Of the 149 family members examined, 55 (36.9%) were found to have PACG. Forty (72.7%) of these had subacute PACG and 15 (27.3%) were found to have chronic PACG. Thirty-nine (70.3%) of the affected members showed a positive DRPPT. Mean anterior chamber depth (ACD) was 2.03+/-0.3, 2.3+/-0.4, 2.7+/-0.3 mm (P=0.0001) and mean lens thickness was 4.41+/-0.39, 3.99+/-0.5, 3.93+/-0.4 mm (P=0.0001) in DRPPT positives, borderlines and negatives respectively. ROC curve (ACD) plotted showed cutoff value of 2.07 mm (sensitivity 88.57%) for screening. CONCLUSION: Anterior chamber is shallowest, lens is thickest and axial length is shortest in affected and DRPPT positive, family members of PACG patients.

Acute Disease↗

Comparison of ultrasound biomicroscopic parameters after laser iridotomy in eyes with primary angle closure and primary angle closure glaucoma.

PURPOSE: To study changes in anterior segment morphology after laser peripheral iridotomy (LPI) in primary angle closure (PAC) and primary angle closure glaucoma (PACG) using ultrasound biomicroscopy (UBM). METHODS: Ninety-three eyes of 93 patients underwent anterior segment evaluation including gonioscopy, disc evaluation with + 90D lens, applanation intraocular pressure, and standard achromatic perimetry. UBM was performed before and 2 weeks after Nd:YAG LPI to measure the trabecular-iris angle (TIA), the angle-opening distance (AOD 250/500), and the central anterior chamber depth (ACD). RESULTS: The superior TIA widened from a mean of 7.54+/-3.15 to 15.66+/-6.69 degrees (P=0.0001), the inferior TIA increased from a mean of 9.0+/-4.7 to 15.9+/-6.8 degrees (P=0.0001) after LPI in PAC. In PACG, the mean superior angle changed from 4.55+/-2.5 to 6.12+/-3.8 degrees (P=0.4) and the inferior angle increased from 4.75+/-2.0 to 7.9+/-3.7 degrees (P=0.1). The mean ACD increased from 2.19+/-0.36 to 2.30+/-0.36 mm in PAC group (P=0.0003), with no significant change seen in the PACG group (1.79+/-0.32 vs 1.82+/-0.33 mm, P=0.13). CONCLUSION: LPI leads to a widening of the anterior chamber angle and a deepening of the anterior chamber in eyes with PAC. It does not significantly change any anterior segment parameters in eyes with PACG.

Adult↗

High osteoblastic activity in C3H/HeJ mice compared to C57BL/6J mice is associated with low apoptosis in C3H/HeJ osteoblasts.

This study sought to confirm that osteoblasts of C3H/HeJ (C3H) mice, which have higher differentiation status and bone-forming ability compared to C57BL/6J (B6) osteoblasts, also have a lower apoptosis level and to test whether the higher differentiation status and bone-forming ability of C3H osteoblasts were related to the lower apoptosis. C3H mice had 50% fewer (P < 0.01) apoptotic osteoblasts on the endocortical bone surface than B6 mice as determined by the TUNEL assay. Primary C3H osteoblasts in cultures also showed a 50% (P < 0.05) lower apoptosis level than B6 osteoblasts assayed by acridine orange/ethidium bromide staining of apoptotic osteoblasts. The lower apoptosis in C3H osteoblasts was accompanied by 22% (P < 0.05) and 56% (P < 0.001) reduction in the activity of total caspases and caspases 3/7, respectively. C3H osteoblasts also displayed greater alkaline phosphatase (ALP) activity (P < 0.001) and higher expression of Cbfa1, type-1 collagen, osteopontin, and osteocalcin genes (P < 0.05 for each). To assess if an association existed between population apoptosis and the differentiation status (ALP-specific activity) and/or bone-forming activity (insoluble collagen synthesis), C3H and B6 osteoblasts were treated with several apoptosis enhancers (tumor necrosis factor-alpha, dexamethasone, lipopolysaccharide, etoposide) and inhibitors (parathyroid hormone, insulin-like growth factor I, transforming growth factor beta1, estradiol). Both ALP (r = -0.61, P < 0.001) and insoluble collagen synthesis (r = -0.61, P < 0.001) were inversely correlated with apoptosis, suggesting that differentiation (maturation) and/or bone-forming activity of these mouse osteoblasts were inversely associated with apoptosis. In conclusion, these studies support the premise that higher bone density and bone formation rate in C3H mice could be due in part to lower apoptosis in C3H osteoblasts.

Animals↗

FT-IR and FT-RAMAN investigations of nicotinaldehyde.

The Fourier transform Raman and infrared spectra of nicotinaldehyde were recorded and the observed frequencies were assigned to various modes of vibration in terms of fundamentals by assuming Cs point group symmetry. A normal coordinate analysis was also carried out using a simple valence force field. A complete vibrational analysis is presented here for this molecule and the results are briefly discussed.

Aldehydes↗

Fourier transform infrared and Raman spectral investigations of 5-aminoindole.

Fourier transform infrared (FT-IR) and Raman (FT-Raman) spectra of 5-aminoindole has been recorded and analysed. The FT-IR spectrum of the compound was recorded in a BrukerIFS 66 V spectrometer in the range 4000-400 cm(-1) and the FT-Raman spectrum was also recorded in the same instrument in the region 3500-100 cm(-1). Observed frequencies for normal modes are compared with those calculated form normal co-ordinate analysis. The shift in the frequencies of the fundamental modes with the substituent amino group and the mixing of different normal modes are discussed with the help of potential energy distribution (PED) calculated through normal co-ordinate analysis.

Carbon↗

Vibrational spectra and normal co-ordinate analysis of 2-aminopyridine and 2-amino picoline.

The Fourier transform infrared (FT-IR) and Raman (FT-R) spectra of 2-aminopyridine and 2-amino picoline were recorded and the observed frequencies were assigned to various modes of vibration in terms of fundamentals by assuming Cs point group symmetry. A normal co-ordinate analysis was also carried out for the proper assignment of the vibrational frequencies using simple valence force field. A complete vibrational analysis is presented here for the molecules and the results are briefly discussed.

Aminopyridines↗

Serum levels of insulin-like growth factor (IGF); IGF-binding proteins-3, -4, and -5; and their relationships to bone mineral density and the risk of vertebral fractures in postmenopausal women.

We previously found that serum levels of insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP)-3, but not IFGBP-2, were associated with bone mineral density (BMD) and the risk of vertebral fractures. The aim of the present study was to investigate the roles of IGFBP-4 and -5 in age-dependent bone loss and vertebral fracture risk in postmenopausal Japanese women and to compare them with those of IGF-I and IGFBP-3. One hundred and ninety-three Japanese women aged 46-88 years (mean 62.5) were enrolled in the cross-sectional study. BMD was measured at the lumbar spine, femoral neck, ultradistal radius (UDR), and total body by dual-energy X-ray absorptiometry. Serum levels of IGFBP-4 and -5 as well as IGF-I and IGFBP-3 were measured by radioimmunoassay. Serum levels of IGF-I, IGFBP-3, and IGFBP-5 declined with age, while serum IGFBP-4 increased with age. Multiple regression analysis was performed between BMD at each skeletal site and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, and serum creatinine. BMD at the UDR was significantly and positively correlated with all serum levels of IGF-I and IGFBPs measured (P < 0.01), while BMD at the femoral neck was correlated with none of them. Serum IGF-I level was significantly and positively correlated with BMD at all sites except the femoral neck (P < 0.01), while serum IGFBP-3 and -4 levels were significantly and positively correlated with only radial BMD (P < 0.01). Serum IGFBP-5 level was positively correlated with UDR BMD (P < 0.001) and negatively correlated with total BMD (P < 0.05). Serum IGF-I, IGFBP-3, and IFGBP-5 levels were significantly lower in women with vertebral fractures than in those without fractures (mean +/- SD: 97.1 +/- 32.1 vs. 143.9 +/- 40.9 ng/dl, P < 0.0001; 2.18 +/- 1.02 vs. 3.23 +/- 1.07 microg/ml, P < 0.0001; 223.6 +/- 63.3 vs. 246.5 +/- 71.5 ng/ml, P = 0.0330, respectively). When multivariate logistic regression analysis was performed with the presence of vertebral fractures as a dependent variable and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, serum creatinine, and serum alubumin as independent variables, IGF-I and IGFBP-3 were selected as indices affecting the presence of vertebral fractures [odds ratio (OR) = 0.29, 95% confidential interval (CI) 0.15-0.57 per SD increase, P = 0.0003 and OR = 0.31, 95% CI 0.16-0.61 per SD increase, P = 0.0007, respectively]. To compare the significance values, IGF-I, IGFBP-3, and age were simultaneously added as independent variables in the analysis. IGFBP-3 was more strongly associated with the presence of vertebral fractures than IGF-I and age (P = 0.0006, P = 0.0148, and P = 0.0013, respectively). Thus, after comprehensive measurements of serum levels of IGF-I and IGFBPs, it seems that serum IGF-I level is most efficiently associated with bone mass and that serum IGFBP-3 level is most strongly associated with the presence of vertebral fractures in postmenopausal women among the IGF system components examined.

Aged↗

Evolution of the soluble nitrate reductase: defining the monomeric periplasmic nitrate reductase subgroup.

Bacterial nitrate reductases can be classified into at least three groups according to their localization and function, namely membrane-bound (NAR) or periplasmic (NAP) respiratory and cytoplasmic assimilatory (NAS) enzymes. Monomeric NASs are the simplest of the soluble nitrate reductases, although heterodimeric NASs exist, and a common structural arrangement of NAP is that of a NapAB heterodimer. Using bioinformatic analysis of published genomes, we have identified more representatives of a monomeric class of NAP, which is the evolutionary link between the monomeric NASs and the heterodimeric NAPs. This has further established the monomeric structural clade of NAP. The operons of the monomeric NAP do not contain NapB and suggest that other redox partners are employed by these enzymes, including NapM or NapG predicted proteins. A structural alignment and comparison of the monomeric and heterodimeric NAPs suggests that a difference in surface polarity is related to the interaction of the respective catalytic subunit and redox partner.

Bacterial Proteins↗

Regulation of insulin-like growth factor binding protein-5, four and a half lim-2, and a disintegrin and metalloprotease-9 expression in osteoblasts.

The roles of insulin-like growth factors (IGFs) in regulating growth and their modulation by six IGF binding proteins (IGFBP) are well established. IGFBP-5, the most abundant IGFBP stored in bone, is an important regulator of bone formation via IGF-dependent and -independent mechanisms. Two new proteins, four and a half lim (FHL)-2, a transcription modulator that interacts with IGFBP-5, and a disintegrin and metalloprotease (ADAM)-9, an IGFBP-5 protease, have been identified as potential regulators of IGFBP-5 action in bone. We tested the hypothesis that agents which modulate bone formation by regulating IGFBP-5 expression would also regulate FHL-2 and ADAM-9 expression in a coordinated manner. We evaluated the expression of IGFBP-5, FHL-2, and ADAM-9 by real-time reverse transcriptase (RT)-PCR during differentiation of mouse bone marrow stromal cells into osteoblasts and in response to treatment with bone formation modulators in the LSaOS human osteosarcoma cell line. IGFBP-5 and FHL-2 increased 4.3- and 3.0-fold (P < or = 0.01), respectively, during osteoblast differentiation. Dexamethasone (Dex), an inhibitor of bone formation, decreased IGFBP-5 and FHL-2 and increased ADAM-9 in LSaOS cells (P < or = 0.05). Bone morphogenic protein (BMP)-7, a stimulator of bone formation, increased IGFBP-5 and decreased ADAM-9 (P<0.01). To determine if BMP-7 would eliminate Dex inhibition of IGFBP-5, cells were treated with Dex+BMP-7. The BMP-7-induced increase in IGFBP-5 was reduced, but not eliminated, in the presence of Dex (P < or = 0.01), indicating that BMP-7 and Dex may regulate IGFBP-5 via different mechanisms. Transforming growth factor (TGF)-beta, a stimulator of bone formation, increased IGFBP-5 and FHL-2 expression (P < or = 0.01). IGF-I and TNF-alpha decreased expression of ADAM-9 (P<0.05). In conclusion, our findings are consistent with the hypothesis that FHL-2 and ADAM-9 are important modulators of IGFBP-5 actions and are, in part, regulated in a coordinated manner in bone.

ADAM Proteins↗

Degradation of the S. frugiperda peritrophic matrix by an inducible maize cysteine protease.

A unique 33-kDa cysteine protease (Mir1-CP) rapidly accumulates at the feeding site in the whorls of maize (Zea mays L.) lines that are resistant to herbivory by Spodoptera frugiperda and other lepidopteran species. When larvae were reared on resistant plants, larval growth was reduced due to impaired nutrient utilization. Scanning electron microscopy (SEM) indicated that the peritrophic matrix (PM) was damaged when larvae fed on resistant plants or transgenic maize callus expressing Mir1-CP. To directly determine the effects of Mir1-CP on the PM in vitro, dissected PMs were treated with purified, recombinant Mir1-CP and the movement of Blue Dextran 2000 across the PM was measured. Mir1-CP completely permeabilized the PM and the time required to reach full permeability was inversely proportional to the concentration of Mir1-CP. Inclusion of E64, a specific cysteine protease inhibitor prevented the damage. The lumen side of the PM was more vulnerable to Mir1-CP attack than the epithelial side. Mir1-CP damaged the PM at pH values as high as 8.5 and more actively permeabilized the PM than equivalent concentrations of the cysteine proteases papain, bromelain and ficin. The effect of Mir1-CP on the PMs of Helicoverpa zea, Danaus plexippus, Ostrinia nubilalis, Periplaneta americana and Tenebrio molitor also was tested, but the greatest effect was on the S. frugiperda PM. These results demonstrate that the insect-inducible Mir1-CP directly damages the PM in vitro and is critical to insect defense in maize.

Animals↗

Rapid qualitative protease microassay (RPM).

A rapid qualitative protease microassay (RPM) was developed as an alternative to conventional assays of cysteine protease activity in HPLC fractions. Using this technique protease activity in samples could be visually determined within 5 min. The method was sensitive to 3.3x10(-7) U/mL of papain and detected cysteine protease activity in dilute HPLC fractions with activity of 5.4x10(-5) U/mL. Because the method monitors the decolorization of Coomassie Brilliant Blue stained substrate, it can be modified to detect other classes of proteases.

Chromatography, High Pressure Liquid↗

FTIR, FT-Raman spectra and ab initio DFT vibrational analysis of 2-bromo-4-methyl-phenylamine.

The FTIR and FT-Raman spectra of 2-bromo-4-methyl-phenylamine (BMP) have been recorded. From the standard geometrical parameters the geometry of BMP was optimized at ab initio and DFT levels of theory with complete relaxation in the potential energy surface using 6-311+g(d,p) and 6-311+g(2df,2p) basis sets. Several thermodynamic parameters were also calculated for the minimum energy conformer at ab initio and DFT level of theories. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FTIR and FT-Raman spectra. Majority of the computed wavenumbers were found to be in good agreement with the experimental observations. The experimental spectra also coincide satisfactorily with those of theoretically constructed bar type spectrograms.

Aniline Compounds↗

Homozygous and heterozygous expression of a novel insulin-like growth factor-I mutation.

IGF-I is a key factor in intrauterine development and postnatal growth and metabolism. The secretion of IGF-I in utero is not dependent on GH, whereas in childhood and adult life, IGF-I secretion seems to be mainly controlled by GH, as revealed from studies on patients with GHRH receptor and GH receptor mutations. In a 55-yr-old male, the first child of consanguineous parents, presenting with severe intrauterine and postnatal growth retardation, microcephaly, and sensorineural deafness, we found a homozygous G to A nucleotide substitution in the IGF-I gene changing valine 44 into methione. The inactivating nature of the mutation was proven by functional analysis demonstrating a 90-fold reduced affinity of recombinantly produced for the IGF-I receptor. Additional investigations revealed osteoporosis, a partial gonadal dysfunction, and a relatively well-preserved cardiac function. Nine of the 24 relatives studied carried the mutation. They had a significantly lower birth weight, final height, and head circumference than noncarriers. In conclusion, the phenotype of our patient consists of severe intrauterine growth retardation, deafness, and mental retardation, reflecting the GH-independent secretion of IGF-I in utero. The postnatal growth pattern, similar to growth of untreated GH-deficient or GH-insensitive children, is in agreement with the hypothesis that IGF-I secretion in childhood is mainly GH dependent. Remarkably, IGF-I deficiency is relatively well tolerated during the subsequent four decades of adulthood. IGF-I haploinsufficiency results in subtle inhibition of intrauterine and postnatal growth.

Heterozygote↗