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Biomedical subjects

A K Aggarwal

Publications and source records attributed to A K Aggarwal.

At least 55 records · Page 3Linked to original sources

Total partnership for primary health care provision: a proposed model--Part II.

This is the second part in a paper which studied the dynamics of primary health care provision. This paper examines external factors related to the management of General Practices. The study revealed that there are major problems at GP/FHSA interfaces involving poor communications, needs evaluation and understanding, and the lack of teamwork. The paper argues that attempts by FHSAs in terms of initiatives are so far failing and have not effectively been able to build strong partnerships between the parties concerned. The paper concludes by proposing a Model of Total Partnership for effective primary health care provision. The model suggests that structures need to be modified in a horizontal way, focusing on patients and building a collaborative way between FHSAs and GPs in a seamless fashion. The model is based on Total Quality Management (TQM) principles and is represented by the building of a customer-supplier chain, the spirit of continuous improvement and synergy through teamwork with the ultimate goal of Total Patient Satisfaction.

Attitude of Health Personnel↗

Body temperatures of home delivered newborns in north India.

In this prospective study, axillary temperature of newborns delivered at home were recorded by a field worker once within a period of 24 h after the birth in 10 villages of Haryana, India, during 1992-1993. Room air temperature was measured at the same time. Family members were interviewed to record newborn care practices. Of the 189 babies, 11.1% were found to be hypothermic (temperature < 35.6 degrees C) and 22.8% were hyperthermic (temperature > 37.3 degrees C). During winter months 19.1% were hypothermic as compared to only 3.1% in summer whereas 8.5% were hyperthermic in winter compared to 36.8% in summer. Room air temperature of < 24 degrees C was recorded in 41%. A strong correlation was observed between room air temperature and neonatal temperature. At the time of birth, 13.2% of the delivery rooms in summer and 73.6% in winter were reported to have heat source: 58.2% babies were reported to be wiped soon after birth; 97.3% were wrapped in cloth; the head was covered in 59.1% cases in winter and 10.5% in summer; 97.3% babies were kept with mother in same bed but not in skin-to-skin contact; and 65% were bathed within 24 h after delivery. Neonatal hypothermia is a common problem in developing countries. It is important that information, education and communication strategy about appropriate technologies for prevention and management of neonatal hypothermia is provided at domiciliary level. A significant proportion of babies are likely to suffer from hyperthermia in warm countries, specially in summer. Therefore, guidelines for thermal control in home births should be tailored to the specific environmental situation.

Fever↗

Expression, purification, and co-crystallization of IRF-I bound to the interferon-beta element PRDI.

Interferon regulatory factor 1 (IRF-1) is an essential factor involved in the regulation of type I interferon (IFN) and IFN-inducible genes. The protein consists of 329 amino acids that are highly conserved from mouse to human. Similar to other transcription factors, the protein is modular in nature with a basic N-terminal region involved in DNA binding and an acidic C-terminal region required for activation. We report here the expression, purification and co-crystallization of the minimal N-terminal region of IRF-1 involved in DNA binding (amino acids 1-113) with a 13 bp DNA fragment from the IFN-beta promoter. The crystals diffract to at least 3.0 A in resolution and belong to space group R3 with unit cell parameters of a = b = 84.8 A, c = 203.7 A.

Base Sequence↗

Structure of the multimodular endonuclease FokI bound to DNA.

FokI is a member of an unusual class of bipartite restriction enzymes that recognize a specific DNA sequence and cleave DNA nonspecifically a short distance away from that sequence. Because of its unusual bipartite nature, FokI has been used to create artificial enzymes with new specificities. We have determined the crystal structure at 2.8A resolution of the complete FokI enzyme bound to DNA. As anticipated, the enzyme contains amino- and carboxy-terminal domains corresponding to the DNA-recognition and cleavage functions, respectively. The recognition domain is made of three smaller subdomains (D1, D2 and D3) which are evolutionarily related to the helix-turn-helix-containing DNA-binding domain of the catabolite gene activator protein CAP. The CAP core has been extensively embellished in the first two subdomains, whereas in the third subdomain it has been co-opted for protein-protein interactions. Surprisingly, the cleavage domain contains only a single catalytic centre, raising the question of how monomeric FokI manages to cleave both DNA strands. Unexpectedly, the cleavage domain is sequestered in a 'piggyback' fashion by the recognition domain. The structure suggests a new mechanism for nuclease activation and provides a framework for the design of chimaeric enzymes with altered specificities.

Amino Acid Sequence↗

Crystallization and preliminary X-ray analysis of restriction endonuclease FokI bound to DNA.

FokI is a type IIs restriction endonuclease which recognizes an asymmetric DNA sequence and cleaves DNA a short distance away from the sequence. The enzyme is bipartite in nature with its DNA recognition and cleavage functions located on distinct domains. We report here cocrystals of the complete FokI enzyme (579 amino acids) bound to a 20-bp DNA fragment containing its recognition sequence. The complex is amongst the largest protein-DNA complexes to be crystallized, and required macroseeding techniques for optimal crystal growth. The cocrystals diffract to at least 2.8 A in resolution and belong to space group P2(1) with unit cell dimensions of a=67.9 A, b=119.8 A, c=69.1 A, beta = 96.6 degrees. Using specific amino acid analysis we show that asymmetric unit contains a single FokI molecule bound to the 20-bp DNA fragment. This paper reports the first cocrystals of a type IIs restriction endonuclease.

Crystallography, X-Ray↗

Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.

Pit-1, a member of the POU domain family of transcription factors, characterized by a bipartite DNA-binding domain, serves critical developmental functions based on binding to diverse DNA elements in its target genes. Here we report a high resolution X-ray analysis of the Pit-1 POU domain bound to a DNA element as a homodimer. This analysis reveals that Pit-1 subdomains bind to perpendicular faces of the DNA, rather than opposite faces of the DNA as in Oct-1. This is accomplished by different spacing and orientation of the POU-specific domain. Contrary to previous predictions, the dimerization interface involves the carboxyl terminus of the DNA recognition helix of the homeodomain, which in an extended conformation interacts with specific residues at the amino terminus of helix alpha1 and in the loop between helices alpha3 and alpha4 of the POU-specific domain of the symmetry related monomer. These features suggest the molecular basis of disease-causing mutations in Pit-1 and provide potential basis for the flexible allostery between protein domains and DNA sites in the activation of target genes.

Amino Acid Sequence↗

Factors influencing psychosocial development of preschool children in a rural area of Haryana, India.

In a cross-sectional survey, 3746 children aged less than 6 years residing in 47 randomly selected villages of district Ambala (India), were studied to find out the environmental risk factors influencing psychosocial development. A culture appropriate test battery comprising 67 test items was administered, and psychosocial development score of each child was computed by scoring each test item passed as 1 and failed as 0. At each age level children having score in lower quartile were categorised as having slow psychosocial development and those in upper quartile were labelled as having accelerated development. Logistic regression revealed that per capita income, education of mother, nutritional status of the child, number of rooms and environmental hygiene in the house, presence of a high school within easy travel distance, availability of a caretaker when mother is busy, child attending a nursery (anganwadi), households having access to newspaper, child having toys or toy substitutes, TV, books, story telling by the mother were found to have a significant association with psychosocial development of preschool children. The risk factors identified in this survey can be used for screening families at risk in rural communities and for selection of interventions for promotion of psychosocial development of children.

Analysis of Variance↗

Total partnership for primary health care provision: a proposed model: Part I.

Presents the first of a two part paper, based on a study which examined the dynamics of primary health care provision. The study examined 49 general practices in the Kirklees area, UK, through a detailed questionnaire mode. The response was 67 per cent covering the views of 106 doctors. To capture further input for the study, an in-depth seminar with nine doctors from a range of practices was conducted. Examines internal factors for managing general practices and the levels of competence in addressing financial, strategic, quality issues and whether general practices get involved in any external activities for new learning and benchmarking. Comprehensively covers common areas of concern and areas where expertise may be inadequate or lacking.

Benchmarking↗

Reproductive tract infections--and associated difficulties.

In addition to financial constraints there are significant social, educational, moral and religious barriers to the prevention and treatment of reproductive tract infections in rural India. A pilot project aimed at achieving progress in this field is reported below.

Adult↗

Crystallization and preliminary X-ray analysis of Pit-1 POU domain complexed to a 28 base pair DNA element.

The POU domain, representing an approximately 150 amino acid conserved region, serves as the DNA-recognition domain for a large number of eukaryotic transcription factors. Bipartite in nature, the POU domain is comprised of a N-terminal POU-specific domain connected by a linker of variable length to a C-terminal homeodomain. We report here co-crystals of pituitary-specific factor Pit-1 POU domain bound as a dimer to a 28 bp DNA fragment. The crystals diffract to at least 2.3 angstroms in resolution and belong to space group P1 with unit cell dimensions of a = 42.5 angstroms, b = 50.1 angstroms, c = 55.8 angstroms, alpha = 76.7 degrees, beta = 79.3 degrees, and gamma = 67.2 degrees.

Base Sequence↗

The relevance of hearing a crack in ankle injuries.

OBJECTIVE: To examine the predictive value of a crack noise or sensation in the history of injury in the diagnosis of ankle fracture. METHODS: A short questionnaire was filled in on 464 patients with isolated ankle injuries attending the accident and emergency department in a three month period from July to September. These patients were seen in the usual way in the department and the need for x ray assessed according to clinical judgement and existing departmental guidelines. Cases which subsequently proved to be other than ankle injuries, for example, fractured calcaneus, were excluded from the study. RESULTS: A positive history of hearing or feeling a crack did not indicate the need for an x ray or increase the possibility of a fracture; indeed the history of a crack made the presence of a fracture less likely. The clinical diagnosis of absence of fracture without radiological examination may require careful explanation to the patient. CONCLUSIONS: Hearing a crack in the ankle does not suggest a fracture.

Ankle Injuries↗

Nutritional status of children: validity of mid-upper arm circumference for screening undernutrition.

OBJECTIVES: To determine the nutritional status and validity of mid upper arm circumference (MAC) in diagnosing malnutrition among preschool children. DESIGN: Cross-sectional household survey. SETTING: 47 villages in District Ambala, Haryana. SUBJECTS: 3747 children aged less than six years. METHODOLOGY: Trained field workers recorded age, weight, length/ height and MAC of children. Prevalence of underweight, stunting, and wasting were calculated in reference to National Centre for Health Statistics (NCHS) standards. Sensitivity and specificity of MAC for detecting underweight, wasting and stunting among children aged 1 to 4 years were determined. RESULTS: At the cut-off level of < -2.00 SD of Z-scores, 48.8% children were stunted, 49.6% were underweight and 9.1% were wasted whereas 47.6% children had neither wasting nor stunting. Prevalence of severe stunting, underweight, and wasting (Z-score < -3 SD) was 18.1%, 11.5% and 0.6%, respectively. Undernutrition showed a significant rise after 12 months of age (p < 0.0001). Stunting and underweight were significantly more among girls compared to boys (p < 0.01) but wasting was not significantly different in them. Compared to the conventional MAC cut off levels of < 13.5 cm and < 12.5 cm, sensitivity and specificity in our setting were optimum at < 13.5 cm for detection of wasting and < 14.0 cm for diagnosis of underweight and stunting, and < 13.0 cm for detection of severe wasting and < 13.5 cm for diagnosis of severe underweight and severe stunting. CONCLUSIONS: Almost every second child was undernourished. Optimum cut off level of MAC in our setting were higher than the conventional cut off points for detection of undernutrition among children.

Anthropometry↗

Structure of the even-skipped homeodomain complexed to AT-rich DNA: new perspectives on homeodomain specificity.

even-skipped is a homeobox gene important in controlling segment patterning in the embryonic fruit fly. Its homeobox encodes a DNA binding domain which binds with similar affinities to two DNA consensus sequences, one AT-rich, the other GC-rich. We describe a crystallographic analysis of the Even-skipped homeodomain complexed to an AT-rich oligonucleotide at 2.0 A resolution. The structure reveals a novel arrangement of two homeodomains bound to one 10 bp DNA sequence in a tandem fashion. This arrangement suggests a mechanism for the homeoproteins' regulatory specificity. In addition, the functionally important residue Gln50 is observed in multiple conformations making direct and water-mediated hydrogen bonds with the DNA bases.

Amino Acid Sequence↗

Structure of Bam HI endonuclease bound to DNA: partial folding and unfolding on DNA binding.

The crystal structure of restriction endonuclease Bam HI complexed to DNA has been determined at 2.2 angstrom resolution. The DNA binds in the cleft and retains a B-DNA type of conformation. The enzyme, however, undergoes a series of conformational changes, including rotation of subunits and folding of disordered regions. The most striking conformational change is the unraveling of carboxyl-terminal alpha helices to form partially disordered "arms." The arm from one subunit fits into the minor groove while the arm from the symmetry related subunit follows the DNA sugar-phosphate backbone. Recognition of DNA base pairs occurs primarily in the major groove, with a few interactions occurring in the minor groove. Tightly bound water molecules play an equally important role as side chain and main chain atoms in the recognition of base pairs. The complex also provides new insights into the mechanism by which the enzyme catalyzes the hydrolysis of DNA phosphodiester groups.

Base Composition↗

Purification, crystallization, and preliminary X-ray diffraction analysis of even-skipped homeodomain complexed to DNA.

Embryonic development in metazoa, to a significant extent, is directed by genes which contain a conserved sequence motif named the homeobox. This sequence encodes a polypeptide called the homeodomain which has sequence specific DNA-binding activity. We report the purification, crystallization, and preliminary diffraction analysis of the Drosophila Even-skipped homeodomain (Eve HD) bound to two different oligonucleotides. Crystals of Eve HD complexed with an AT-rich sequence belong to space group P2(1), a = 34.06, b = 61.61, c = 39.99 Angstrom, beta = 90.0 degrees. These crystals diffract to at least 2.0 Angstrom and both native and derivative data sets have been collected. Crystals of Eve HD complexed with a GC-rich sequence belong to space group P6(3), a = b = 124.52, c = 66.78 Angstrom and diffract to 3.5 Angstrom resolution. A native data set has been collected.

Amino Acid Sequence↗