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Biomedical subjects

V G Rao

Publications and source records attributed to V G Rao.

At least 19 recordsLinked to original sources

Malnutrition and high childhood mortality among the Onge tribe of the Andaman and Nicobar Islands.

OBJECTIVES: A study was conducted among the Onge tribe of the Andaman and Nicobar Islands with the objectives of identifying demographic factors responsible for the decline in their population and assessing their nutritional status, which is an important determinant of child survival. STUDY DESIGN AND SUBJECTS: The study included estimation of indices of fertility and child mortality, and assessment of nutritional status. All individuals of the Onge community settled on Little Andaman Island were included. RESULTS: The mean total marital fertility rate was estimated to be 5.15 live births per woman and the general fertility rate was 200 live births per 1000 married-woman-years. Although the gross reproduction rate was estimated to be 2.2 female children per married woman, the net reproduction rate was only 0.9 surviving female child per married woman. The mean infant mortality rate during the past 30 years was 192.7 per 1000 live births, and the child survival rate was found to be only 53.2%. A mild to moderate degree of malnutrition was found in 85% of children of pre-school age and severe malnutrition in 10%. The Onges had low intakes of iron, vitamin A and vitamin C. All the screened Onges were found to be infested with one or more intestinal parasites. CONCLUSIONS: High childhood mortality appears to be the predominant demographic factor responsible for the decline in the Onge population. The high prevalence of undernutrition and micronutrient deficiency disorders could be important factors contributing to the high childhood mortality.

Adolescent↗

HIV epidemic in Central India: trends over 18 years (1986-2003).

In this report, we present the occurrence of HIV seropositivity and trends over last 18 years in a heterogenous group of people attending Voluntary Counselling and Testing Centre (VCTC) in Central India. The first Indian HIV positive person was reported in 1992 at the Centre. The occurrence of HIV infection increased from nil in 1986 to 19.9% in 2003. The HIV seropositivity was higher in males (6.9%) than in females (3.3%). Highest prevalence was seen in the age group of 25-29 years in both males and females. Heterosexual route was the commonest route of transmission. Relative decline was observed as regards to the blood borne transmission. No intravenous drug abuser was reported. The study highlights a need for comprehensive policies to control the HIV epidemic in Central India.

Adolescent↗

Undernutrition & childhood morbidities among tribal preschool children.

BACKGROUND & OBJECTIVE: Undernutrition and various morbidities go hand in hand, particularly in children. Nutritional status is a sensitive indicator of community health and nutrition. The present study is an attempt to assess the nutritional status of pre-school children of Gond tribal community in Madhya Pradesh. METHODS: The study was a community-based, cross- sectional survey carried out in tribal preschool children. Anthropometric measurements were taken. Various indices of nutritional status were expressed in standard deviation units (z scores) from the reference median. The children were examined for nutritional deficiencies and other morbidities. The haemoglobin concentration was measured and the children were classified into various grades of nutritional anaemias. Data on socio-cultural and hygienic practices were also collected. RESULTS: More than 60 per cent children were underweight. Micronutrient deficiency disorders such as anaemia and vitamin A deficiency were common among them. Unhygienic personal habits and adverse cultural practices relating to child rearing, breast-feeding and weaning were also prevalent among them. INTERPRETATION & CONCLUSION: The findings of the present study revealed the widespread prevalence of undernutrition among pre-school tribal children and highlight a need for an integrated approach towards improving the child health as well as nutritional status in this area.

Anemia↗

Worm infestation and anaemia: a public health problem among tribal pre-school children of Madhya Pradesh.

A study to assess the status of intestinal parasitosis and anaemia was carried out among the pre-school children of Gond tribal community in Kundam block of Jabalpur district, Madhya Pradesh. A total of 985 pre-school children were covered. The results revealed that 48% pre-school children had intestinal parasitic infections. Common parasites observed among them were Hymenolepis nana, hookworms and roundworms. Mean epg for these parasites ranged from 371.2 to 1221.8. High prevalence of anaemia (86.7%) was also observed among them. This high prevalence of intestinal parasitic infections and anaemia could be due to indiscriminate defecation, low socio-economic status, ignorance and low standard of personal hygiene. Comprehensive control strategy with specific intervention measures need to be evolved and implemented specially in tribals as serious efforts are being madeby the Govt. for their overall development.

Anemia↗

A neural network approach to identifying adolescent adjustment.

This study examined the relationship between the quality of adjustment in adolescents and a set of psychiatric diagnoses, personality traits, parental bonding, and social support variables. One hundred fifty adolescents were administered the Millon Adolescent Personality Inventory, the Parental Bonding Questionnaire, the Social Support Questionnaire, and the Diagnostic Interview for Children and Adolescents. A neural network approach was then utilized, and it was found that several of the variables (e.g., Major Depressive Disorder, Conduct Disorder, and Societal Conformity) had a significant role in classifying adolescents into three groups: maladjusted, nominally adjusted, and well-adjusted.

Adolescent↗

Functional role of the slow activation property of ERG K+ channels.

ERG (ether-à-go-go-related gene) K+ channels are crucial in human heart physiology (h-ERG), but are also found in neuronal cells and are impaired in Drosophila 'seizure' mutants. Their biophysical properties include the relatively fast kinetics of the inactivation gate and much slower kinetics of the activation gate. In order to elucidate how the complex time- and voltage-dependent activation properties of ERG channels underlies distinct roles in excitability, we investigated different types of ERG channels intrinsically present in cells or heterologously expressed in mammalian cells or Xenopus oocytes. Voltage-dependent activation curves were highly dependent on the features of the eliciting protocols. Only very long preconditioning times produced true steady-state relationships, a fact that has been largely neglected in the past, hampering the comparison of published data on ERG channels. Beyond this technical aspect, the slow activation property of ERG can be responsible for unsuspected physiological roles. We found that around the midpoint of the activation curve, the time constant of ERG open-close kinetics is of the order of 10-15 s. During sustained trains of depolarizations, e.g. those produced in neuronal firing, this leads to the use-dependent accumulation of open-state ERG channels. Accumulation is not observed in a mutant with a fast activation gate. In conclusion, it is well established that other K+ channels (i.e. Ca2+-activated and M) control the spike-frequency adaptation, but our results support the notion that the purely voltage-dependent activation property of ERG channels would allow a slow inhibitory physiological role in rapid neuronal signalling.

Animals↗

The cardiac troponin C isoform and the length dependence of Ca2+ sensitivity of tension in myocardium.

The Ca2+ sensitivity of tension in cardiac muscle is length dependent, such that the sensitivity is diminished with decreasing sarcomere length below 2.4 microm. This length dependence of Ca2+ sensitivity of tension also forms the basis for the Frank-Starling mechanism in the heart. The fast-twitch skeletal muscle has a much lower length dependence of Ca2+ sensitivity. In a recent study of skinned cardiotrabeculae, we indicated that the exchange of endogenous cardiac troponin C (TnC) for skeletal troponin C also resulted in a major reduction in the length dependence to the level of skeletal muscle. These findings suggested that cardiac troponin C has a key role in the length-sensing mechanism. The present investigation supports this conclusion and delineates the specific domain in cardiac TnC responsible for the length effect. Chimeras splicing either 41, 61, or 96 N-terminal cardiac amino acids with the remaining skeletal residues have indicated that while Ca2+ binding in all three constructs is similar to that in wild type cardiac TnC, the functional responsiveness of the 96-cardiac residue construct is improved over the other two. This 96-cardiac residue construct yielded a tension response indistinguishable from that of wild-type cardiac TnC. A tryptophan variant of the chimera indicated fluorescence characteristics indistinguishable from cardiac troponin C. The findings provide further support for the idea that cardiac troponin C in situ is modified in response to sarcomere length change and thereby participates in the Frank-Starling mechanism. Moreover, the study indicates that the tropinin C length-sensing attribute originates within the N-terminal domain constituted by these 96 residues.

Animals↗

Molecular basis of depression of Ca2+ sensitivity of tension by acid pH in cardiac muscles of the mouse and the rat.

BACKGROUND: Acid pH decreases the Ca2+ sensitivity of myocardial tension generation, and recent studies have suggested that regulatory proteins are involved. The current study defines the molecular basis of this effect on troponin C (TnC) and troponin I (TnI) and also addresses previous differences between the rat and mouse. METHODS AND RESULTS: Endogenous cardiac TnC and cardiac TnI in isolated trabeculae from mice and rats were exchanged with their fast-twitch skeletal muscle counterparts. A cardiac-skeletal TnC chimera was used to define the target region for proton action on cardiac TnC. Finally, cardiac TnC and skeletal TnC were genetically modified by insertion of a tryptophan for phenylalanine-26 to probe the pH effects with fluorescence spectroscopy. The pH 6.2 effects on Ca2+ sensitivity of force development in mouse and rat cardiotrabeculae are largely accounted for by the proton influences on TnC (23%) and TnI (53%). In cardiac TnC, residues 1 to 41 provide the target region. Comparison of the Ca(2+)-induced fluorescence in isolated cardiac TnC and skeletal TnC also indicated a greater pH effect in the cardiac isoform. CONCLUSIONS: The studies provide firm evidence that both TnC and TnI moieties are involved in the mechanism of acidosis causing reduction in the Ca sensitivity of force development in the myocardium. The findings rule out the possibility of interspecies variations in the underlying mechanisms. The genetically designed TnCs and a chimera demonstrate that the observed TnC-mediated difference in the pH effects on Ca2+ sensitivity of tension between cardiac and skeletal muscles is preserved in these isolated proteins. The N-terminal amino acid residues 1 to 41 in cardiac TnC are established as the pH sensor of this protein in the mouse as in the rat.

Animals↗

Relationship of personality, environmental, and DICA variables to adolescent hopelessness: a neural network sensitivity approach.

OBJECTIVE: This study identified critical factors from a set of psychiatric diagnoses, personality traits, and family and social support variables that relate to hopelessness in adolescents. METHOD: One hundred fifty adolescents were selected in a systematic sample from 1,700 high school students; they completed the Millon Adolescent Personality Inventory, the Parental Bonding Questionnaire, the Social Support Questionnaire, the Hopelessness Scale for Children and were interviewed by trained clinicians on the Diagnostic Interview for Children and Adolescents. Selected variables were chosen for a back-propagation neural network model and for subsequent sensitivity and statistical analysis. RESULTS: Sensitive adolescents and adolescents with less impulse control scored high on hopelessness. Forceful adolescents were less hopeless. CONCLUSIONS: Using the neural network models, the authors suggest that assertive training as well as group activities that increase cooperativeness may ameliorate hopelessness.

Adolescent↗

Molecular mobility of the Ca(2+)-deficient EF-hand of cardiac troponin C as revealed by fluorescence polarization of genetically inserted tryptophan.

To probe attitudinal features of the Ca(2+)-deficient site (site I) in the Ca2+ switch of cardiac troponin C (cTnC), we have examined steady-state fluorescence emission and polarization of a Trp26 inserted in a recombinant cardiac TnC (cTnC3.W) and compared these with the properties of the Ca(2+)-competent site I in skeletal TnC (sTnC4.W). The Ca(2+)-induced fluorescence emission in cTnC3.W was a fraction (25-30%) of that in sTnC4.W, in agreement with previous observations on the Ca(2+)-deficient site incorporated in a cardiac/skeletal chimera c1/s.W [Gulati, J. & Rao, V. G. (1994) Biochemistry 33, 9052-9056]. Thus, the fractional quantum yield reflected intrinsic properties of the cardiac metal ion-deficient site I. Conversely, in sTnC-1.W, where the skeletal site I also was made Ca(2+)-deficient by D27-->A substitution, the Ca(2+)-induced quantum yield was lower than that in cTnC3.W. Nevertheless, similar steady-state fluorescence polarizations for Ca(2+)-saturated sTnC4.W and cTnC3.W indicated indistinguishable final conformations in the two activated TnC isoforms. In EGTA, the polarization parameter (PEGTA) of sTnC4.W is greater than that of cardiac TnC, and the cardiac PEGTA value is closer to the activated PCa. Comparison of the chimera c1/s.W with sTnC-1.W indicated that the differences in conformation of the site I Trp for the EGTA-treated cardiac/skeletal isoforms were due to the structural disparities in this region. This contention was further supported by examination of the chimera CBc1/s.W, where the cardiac EF-hand was altered by 27VLGA30-->DAD substitution. Polarization of the relaxed form was similar to that for sTnC4.W. These findings suggest that the relaxed conformation of the cardiac Ca2+ switch is more favorably predisposed to activation than the skeletal switch.

Animals↗

Disparate contributions of Tyr10 and Tyr109 to fluorescence intensity of rabbit skeletal muscle troponin C identified using a genetically engineered mutant.

Intrinsic tyrosines, as monitored by fluorescence spectroscopy, are sensitive reporters of local, Ca(2+)-induced conformational changes in troponin C (TnC). Rabbit skeletal TnC contains two tyrosines (Y10 in the N-helix, and Y109 in site 3 in the C-terminal domain) in distinct microenvironments: their individual contributions to total fluorescence intensity are elucidated here utilizing bacterially synthesized rabbit skeletal TnC (sTnC4) and a genetically engineered variant, termed 109YF, lacking one of the tyrosines (Y109 replaced with F109). The steady-state fluorescence emission spectra following excitation at 280 nm were recorded in EGTA (Ca(2+)-free) and Ca(2+)-saturated (pCa4) solutions. For the wild-type sTnC4, pCa4 causes a significant (46%) increase in the peak fluorescence intensity over the value in EGTA. For the mutant 109YF, the EGTA fluorescence is only marginally affected (74% of the wild-type FEGTA), but interestingly the Ca2+ effect is completely suppressed (delta F = FpCa4-FEGTA = 2% of the wild-type value). These results indicate that the two tyrosines make disparate contributions to the fluorescence spectrum of wild-type sTnC, both in the presence and absence of Ca2+; whereas Y10 in the N-helix is dominant in Ca(2+)-free solution, Y109 is the sole contributor to the Ca2+ effect. Furthermore, to explain the biphasic fluorescence response of Y109 obtained during Ca2+ titrations, the findings yield the most unequivocal evidence that Ca(2+)-induced conformational changes in the trigger sites operating the contractile switch modify properties of the C-terminal sites in TnC pari passu.

Animals↗

The cardiac Ca(2+)-deficient EF-hand governs the phenotype of the cardiac-skeletal TnC-chimera in solution by Sr(2+)-induced tryptophan fluorescence emission.

In the development of force during Sr2+ activation, phenotypically cardiac muscle is more sensitive than fast-twitch skeletal muscle, and TnC is central in this mechanism. The uncertainty has remained, however, whether such functional manifestations in situ relied critically on protein-protein interactions in the fiber or whether the Sr2+ sensitivities were governed intrinsically within the TnC molecule. To resolve this, we substituted a tryptophan for phenylalanine-26 in both rabbit sTnC (sTnC.W26) and in a chimera (c1/s.W26) where the 41 N-terminal amino acid residues were of bovine cTnC and the remaining 42-160 residues of rabbit sTnC. The metal ion dependent fluorescence emissions of the constructs could be examined in solution isolated from the protein-protein interactions found in situ. The Sr2+ sensitivities of these proteins differed by 0.55 +/- 0.02 pSr unit, but Ca2+ sensitivities were indistinguishable, as in the fiber. In another mutant, where the 27VLGA30 cluster was replaced with D-AD to enable site 1 to coordinate metal ion binding despite closely preserved cardiac structure, the Sr(2+)-sensitivity response was transformed into the skeletal-type. The Hill coefficients were also characteristically distinct for the various constructs. The findings indicate that cardiac N-terminal 41 residues define TnC performance in solution similar to that in situ. Moreover, the study provides unambiguous evidence that TnC isoforms intrinsically dominate the phenotype in the switching mechanisms for both cardiac and skeletal contractilities.

Amino Acid Sequence↗

Detecting dysfunctional behavior in adolescents: the examination of relationships using neural networks.

We describe a neural network that models the effect of personality, social, and environmental variables on hopelessness in adolescents. A sensitivity analysis suggests the effect that variation in each of the input variables will have on the output. Clinical implications are that health professionals can focus their attention on the variables most likely to impact upon the outcome.

Adolescent↗

Critical minimum length of the central helix in troponin C for the Ca2+ switch in muscular contraction.

In the troponin C (TnC) dumbbell, the NH2- and COOH-terminal lobes are well delineated, but the role of the central helix and especially the function of its long length remain doubtful. To study this, we used a cDNA construct encoding rabbit fast-twitch muscle TnC, comprising multiple restriction sequences to facilitate mutagenesis (Babu, A., Su, H., Ryu, Y. & Gulati, J. (1992) J. Biol. Chem. 267, 15469-15474). Systematically, we have deleted 3-12 amino acid residues from the central helix and examined their effects in maximally activated skinned muscle fibers. Limiting the deletions to 7 amino acid residues manifested little change in maximal force development (Sheng, Z., Francois, J. M., Hitchcock, S. E. & Potter, J. D. (1991) J. Biol. Chem. 266, 5711-5715). However, with further deletions, we now find that contractility was inhibited pari passu; by 12 deletions, the inhibition was complete. The critical minimum length for the central helix is thereby estimated as 27 A. The Ca2+ binding capacity (4 mol of Ca2+/mol of protein) as well as the structural characteristics (alpha-helicity by CD measurements and the fluorescence emitted by Tyr-109) indicated a well preserved global conformation of the short mutant. However, surprisingly, two of these short mutants filled each TnC slot under highly specific superloading conditions: one short molecule was taken up in EGTA solution, and the second molecule was captured and retained with Ca2+. They also rescued the contractile switch, evidently in a bimolecular reaction. Another short variant (putative skeletal fast muscle TnC-I-II), in which the NH2-terminal Ca(2+)-binding sites were incapacitated, failed to respond to superloading, indicating that sites III and IV could not substitute for sites I and II. The results suggest that a critical role of the central helix linker in TnC is to keep the two lobes optimally apart, evidently in proximity of their respective target sites on troponin I in the fiber.

Amino Acid Sequence↗

Filariasis control in rural areas through detection and treatment with diethylcarbamazine.

A pilot study for control of bancroftian filariasis through detection and treatment of microfilaria (mf) carriers and filaria disease cases with Diethylcarbamazine (DEC) undertaken in the rural areas of Srikakulam and Vizianagaram of Andhra Pradesh showed that this chemotherapeutic method of control of filaria in rural areas is feasible and acceptable to society. During first round of detection and treatment 20,300 mf carriers (90.6 per cent of detected) and 6,588 disease persons (86 per cent of detected) in Srikakulam and 7,097 mf carriers (94.8 per cent of detected) and 1,436 disease persons (93.4 per cent of detected) in Vizianagaram were treated with DEC tablets. These areas were again surveyed after five years and detected cases were treated with DEC with coverage of treatment ranging from 82.3 per cent to 95 per cent for both mf & disease cases and decline in mf and disease rate was noted to be 52.4 per cent and 50.9 per cent respectively in Srikakulam and 42.2 per cent for mf rate in Vizianagaram. The mf reduction was appreciably high (50 per cent or more) in 11 PHCs of Srikakulam and 4 PHCs of Vizianagaram. The mf rate reduction was the highest in the age group of 1 to 4 year indicating that the transmission has been cut down significantly. The vector infection rate showed reduction by 50 per cent during second round of detection and treatment as compared to first round, indicating significant reduction in transmission potential.

Animals↗