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Biomedical subjects

P K Patnaik

Publications and source records attributed to P K Patnaik.

18 recordsLinked to original sources
PubMed2000

Plasmodium chabaudi-infected erythrocytes adhere to CD36 and bind to microvascular endothelial cells in an organ-specific way.

Adherence of erythrocytes infected with Plasmodium falciparum to microvascular endothelial cells (sequestration) is considered to play an important role in parasite virulence and pathogenesis. However, the real importance of sequestration for infection and disease has never been fully assessed. The absence of an appropriate in vivo model for sequestration has been a major barrier. We have examined the rodent malaria parasite Plasmodium chabaudi chabaudi AS in mice as a potential model. Erythrocytes infected with this parasite adhere in vitro to purified CD36, a critical endothelium receptor for binding P. falciparum-infected erythrocytes. P. c. chabaudi-infected erythrocytes adhere in vitro to endothelial cells in a gamma interferon-dependent manner, suggesting the involvement of additional adhesion molecules in the binding process, as is also the case with P. falciparum-infected cells. Furthermore, plasma or sera from infected and hyperimmune mice, respectively, have the ability to block binding of infected erythrocytes to endothelial cells. In vivo, erythrocytes containing mature P. c. chabaudi parasites are sequestered from the peripheral circulation. Sequestration is organ specific, occurring primarily in the liver, although intimate contact between infected erythrocytes and endothelial cells is also observed in the spleen and brain. The results are discussed in the context of the use of this model to study (i) the relationship between endothelial cell activation and the level of sequestration and (ii) the primary function of sequestration in malaria infection.

Animals↗
PubMed1999

Progress towards elimination of leprosy as a public health problem in India and role of modified leprosy elimination campaign.

India (population 943 million) has seen a highly significant decrease in the prevalence of leprosy since the introduction of multi-drug therapy (MDT) in 1981. From a prevalence rate of 57/10,000 of the population in March 1981, the figure has declined to 5.2/10,000 in March 1999. This was possible due to the creation of a completely vertical (specialized) infrastructure for leprosy control in the 218 endemic districts of the country and skeleton vertical staff in the remaining districts, coupled with the recruitment of additional staff on contract basis to provide MDT through vertical staff in endemic districts and mobile treatment units in the moderate and low endemic districts. Despite all efforts, however, new case detection has not shown a decline over the last 14 years due to the presence of hidden (and undiagnosed) cases. Therefore, in order to intensify and hasten progress towards elimination (less than 1 case per 10,000 of the population) in the whole country, it was decided to implement a massive leprosy elimination campaign (LEC) in all the States/Union Territories (UTs). The reports of 22 States/UTs indicate that 415 out of the total of 490 districts in the country were covered by modified LEC (MLEC), with 85% coverage of the population. The campaign used in India was modified from the pattern previously described by the World Health Organization. The detection of hidden or suspected cases took place within a short, intensive period of 6-7 days and relied heavily on house-to-house searches by General Health Care staff trained in leprosy detection and confirmation was made by appropriately trained staff. This MLEC received widespread Government and public support, resulting in the detection of 454,290 hidden cases of leprosy, whilst providing training to a large number of General Health Care staff and volunteers and creating widespread awareness about leprosy and the availability of treatment free of charge for all cases. This programme proved to be one of the most successful health care interventions undertaken in India in recent years, particularly in the states of Bihar and Orissa. Although a few states in India are unlikely to reach the current WHO goal of elimination before end of the year 2000, the results of the MLEC strongly support the possibility that elimination levels will be achieved in the majority of states by the end of the year 2000 and at national level by the end of the year 2002.

Health Promotion↗
PubMed1999

Modified leprosy elimination campaign (MLEC) in the State of Orissa, India.

As part of a country-wide modified leprosy elimination campaign (MLEC) carried out in 21 selected States in India in 1998, the State of Orissa launched activities in early January of that year, during which 28.9 million people were examined, giving 85% coverage of the enumerated population. Using general health care staff and volunteers, 416,604 suspect cases were identified and 62,804 of these were confirmed as leprosy by experience observers. The period of intensive search activity lasted 1 week only, but this was preceded by several months of community mobilization and involvement, health education, training of government and voluntary staff, media messages and the involvement of all relevant health departments, officials and politicians. Both this and the intensive search period were characterized by a high level of interest and cooperation by all concerned. The total of new cases detected and put on treatment (multi-drug therapy; MDT) during the period of only 7 days was approximately equal to that which, on routine population survey by the leprosy services, would be recorded over a period of 2 years. The MLEC in Orissa is judged to have been not only an historic step forward in the control of leprosy in a State previously classified as highly endemic for leprosy, but also one of the most successful State health interventions ever mounted. In the 5 months after completion of the campaign, the voluntary reporting rate increased from 50 to 90%. As a direct result of the campaign, facilities for the diagnosis and treatment of leprosy are now available daily in an additional 1639 institutions, over and above those in existence before the campaign was launched. The achievements in terms of detecting hidden (and thus undiagnosed and untreated) cases exceeded the outset predictions, underlining the importance of continued vigilance and the need to maintain involvement of general health care staff. It is anticipated that the rise in prevalence due to the addition of 62,884 cases will be reduced by the implementation of MDT by 80% by about March 1999. Overall the results of the MLEC in Orissa strongly support the likelihood that an elimination level of less than 1 case per 10,000 of the population will be reached in this State by the year 2000.

Health Promotion↗
PubMed1997

Studies with artificial extrachromosomal elements in trypanosomatids: could specificity in the initiation of DNA replication be linked to that in transcription?

Historically, artificial replicons have served as useful models for the definition of regulatory elements involved in chromosomal replication and transmission in yeast and DNA replication in bacteria. Here, Pradeep Patnaik examines what we have learnt so far from the replicative behaviour of various artificial extrachromosomal elements available for trypanosomatids. He highlights the involvement of transcription regulatory elements in virtually every eukaryotic origin of replication analysed in detail and, by drawing upon the extensive literature supporting a close association between DNA replication and transcription, he speculates that the nature and organization of origins of replication on a chromosome also may hold clues to the manner by which an organism regulates gene expression.

Journal Article↗
PubMed1996

Artificial linear mini-chromosomes for Trypanosoma brucei.

We have constructed artificial linear mini- chromosomes for the parasitic protozoan Trypanosoma brucei. These chromosomes exist at approx. 2 copies per cell, are indefinitely stable under selection but are lost from 50% of the transformed population in approx. 7 generations when grown in the absence of selective pressure. Consistent with results obtained earlier with natural chromosomes in T.brucei, the telomeres on these artificial chromosomes grow, adding approx. 1- 1.5 telomeric repeats per generation. The activity of a procyclic acidic repetitive protein (parp) gene promoter on these elements is unaffected by its proximity to a telomere, implying the lack of a telomere-proximal position effect (TPE) in procyclic trypanosomes. Among other things, these autonomously replicating dispensable genetic elements will provide a defined system for the study of nuclear DNA replication, karyotypic plasticity and other aspects of chromosomal behavior in this ancient eukaryotic lineage.

Animals↗
PubMed1994

The region encompassing the procyclic acidic repetitive protein (PARP) gene promoter plays a role in plasmid DNA replication in Trypanosoma brucei.

We have previously reported the construction and characterization of an autonomously replicating plasmid in Trypanosoma brucei. In this plasmid the procyclic acidic repetitive protein (PARP) gene promoter drives the transcription of a selectable marker. Deletion of this promoter incapacitates the plasmid, suggesting its utilization as a promoter-trap. Three independent libraries were created by inserting variously digested T.brucei genomic DNA into this promoterless construct. Transfection of these libraries into procyclic T.brucei and the subsequent isolation of episomes led only to the reisolation of the PARP promoter. Additionally, a ribosomal RNA promoter failed to keep the construct as an episome, although it can sustain mRNA transcription in T.brucei and was shown to be an efficient promoter in this construct. Finally, by using a transient replication assay involving the methylation-sensitive restriction endonuclease DpnI to distinguish between input and replicated DNA, we showed that the PARP promoter-bearing construct could replicate autonomously in procyclic T.brucei, but the corresponding construct with the rRNA promoter could not. The close association between elements that sustain transcription and DNA replication in T.brucei mirrors results observed in several higher eukaryotes and their viruses and suggests an ancient origin of this feature.

Animals↗
PubMed1994

Spectrum of ulcerative colitis in north India.

We analyzed retrospectively the characteristics of 87 patients with ulcerative colitis seen in a tertiary care center in north India. Ulcerative colitis was diagnosed on the basis of clinical features, sigmoidoscopy, rectal biopsy, and exclusion of microbiological causes of colitis. Severe clinical disease was seen in 53 (60%) patients that correlated with extensive colonic involvement (p < 0.001), severe changes on sigmoidoscopy (p < 0.001) and histology (p < 0.001), erythrocyte sedimentation rate (ESR) of > 30 mm for the first hour, and serum albumin of < 3 g/dl (p < 0.001). Remission of the disease was maintained on sulfasalazine in 18 (20.7%) patients, whereas 47 (54%) required steroids. Proctocolectomy with ileoanal anastomosis was done in 22 (25.3%) patients in whom there was poor response to medical treatment. Postoperative complications were seen in seven (31.8%) patients, and death occurred in four (18.1%) patients. Ulcerative colitis thus commonly presents as severe disease, with the majority of patients requiring surgery due to poor response to medical therapy. This pattern of disease as seen in an academic referral hospital in north India is virtually indistinguishable from that seen in similar centers in the West. However, in our setting, proctocolectomy and ileoanal anastomosis is cost-effective in patients unresponsive to, or unable to afford, drug treatment.

Adult↗
PubMed1993

Autonomously replicating single-copy episomes in Trypanosoma brucei show unusual stability.

We have obtained several autonomously replicating plasmids in procyclic Trypanosoma brucei. Two of these have been analyzed in detail. Both exist as monomeric single-copy episomes, which nevertheless demonstrate significant stability. These episomes transform procyclics at frequencies that are at least 60-fold higher than those achieved earlier with non-replicating molecules. A modified version of one of these episomes is able to replicate autonomously in bloodstream form T. brucei but it is unstable in this developmental stage of the organism. These episomes will prove useful as shuttle vectors, in functional complementation studies, in the construction of promoter-traps for the isolation of transcriptional promoters in T. brucei, and importantly, as models for the analysis of DNA replication in this ancient eukaryotic lineage.

Animals↗
PubMed1993

Molecular species analysis of phospholipids from Trypanosoma brucei bloodstream and procyclic forms.

We present a quantitative description of the molecular species composition of the major phospholipid classes in bloodstream and procyclic forms of Trypanosoma brucei. Phospholipid classes were resolved by 2-dimensional thin-layer chromatography. Diradylglycerols were released from individual phospholipid classes by phospholipases C, converted into benzoate derivatives and separated into diacyl, alkylacyl and alk-1-enylacyl subclasses. Individual molecular species were quantitated and identified by HPLC and the assignments were confirmed by mass spectrometry. Comparison of the diacyl species of PC, PE and PI in bloodstream trypanosomes showed major differences in the relative amounts of individual molecular species between the different classes but not striking changes in the degree of saturation or overall chain length. In contrast, in procyclic trypanosomes the relative amounts of diacyl molecular species with polyunsaturated fatty acyl chains decreased in the order of PC > PE >> PI. Also, the alkylacyl and alk-1-enylacyl subclasses of PC and PE in bloodstream trypanosomes comprised a single molecular species, 18:0 18:2. Such exclusivity was not observed in procyclic trypanosomes among the same phospholipid subclasses, although 18:0 18:2 was the predominant species. Almost all the PI of bloodstream forms contained one 18:0 acyl species, which is consistent with the composition of the PI used for glycosylphosphatidylinositol synthesis.

Acetylglucosamine↗
PubMed1990

Effect of altering GATC sequences in the plasmid ColE1 primer promoter.

Plasmid ColE1 has three recognition sites for the Escherichia coli DNA adenine methylase in the immediate upstream region of the primer promoter. Two of these sites are conserved among all plasmid relatives of ColE1 and constitute parts of an inverted repeat that can conceivably form a cruciform structure. Recent experiments have indicated that hemimethylated ColE1-type plasmids are inefficiently replicated after transformation (D. W. Russell and N. Zinder, Cell 50:1071-1079, 1987). By mutating the three methylation sites, we found that disruption of all three GATC sites was necessary for complete relief of the hemimethylation-mediated inhibition of replication in vivo. We also found that these three methylation sites acted in a position-specific manner. The putative cruciform, if present, did not play a regulatory role in the hemimethylation-mediated inhibition of replication.

Base Sequence↗
PubMedDate not supplied

Massive lower intestinal bleeding--a decade of experience.

BACKGROUND: Lower gastrointestinal bleeding is defined as hemorrhage orginating distal to the ligament of Treitz. Its diagnosis is difficult, often requiring endoscopy, angiography and isotope scans. METHODS: All patients with massive lower gastrointestinal bleeding seen in three gastroenterology centers of Armed Forces during an 11 year period between 1988 and 1999 were retrospectively analysed. RESULTS: A total of 91 patients with massive lower gastro intestinal bleeding were seen during 11 years. The mean age of the patients was 38.9 years and 64 were males. Aetiological diagnosis was: Non-specific ulcers--11, Ileal tuberculosis--8, NSAID enteropathy--8, Enteric fever--7, Meckel's diverticulum--7, Polyps--6, Ulcerative colitis--5, Carcinoma colon--5, Colonic diverticulosis--5, No cause found--5, Polyposis coli--5, Jejunal diverticulae--3, Angiodysplasia colon--3, Radiation colitis--3, Ischaemic colitis--3, Ileal tumor--2, Ileal angiodysplasia--2, Intestinal Lymphoma--2, Bechet's syndrome--1. Bleeding stopped on conservative therapy in 18 patients (including 5 where no diagnosis could be made). Diagnosis was made in 36 patients on fiber-optic colonoscopy done during active bleeding. Remaining patients were subjected to emergency laparotomy and diagnosis was obvious on inspection of abdominal contents in 25 cases. The diagnosis was finally made in remaining 12 cases by intraoperative endoscopic examination through an ileotomy. Four patients died, only one of them due to rebleed after surgery from an additional lesion. CONCLUSIONS: Compared with experience in Western countries, massive lower gastro-intestinal hemorrhage in India affects younger patients, has different causes and carries a lower mortality. Colonoscopy is useful in making diagnosis during active lower intestinal bleeding in about one-third cases. Exploratory laparotomy and Intra-operative endoscopy are complimentary to above examination and can make the diagnosis in most of the remaining cases.

Adolescent↗
PubMedDate not supplied

Dieulafoy's lesion: a rare cause of massive upper gastrointestinal haemorrhage.

Out of 900 cases of Upper Gastrointestinal haemorrhage seen during 1985-1989, 6 (0.67%) cases had Dieulafoy's lesion as the causative factor. All patients presented with massive upper gastrointestinal haemorrhage. The mean age of the patients was 46.3 year (32-60 yrs) and 4 were males and 2 females. No consistent associated medical factors could be identified. The diagnosis was established by emergency endoscopy which showed an active arterial spurter in 4 patients and located the bleeding site to be close to the fundus in other 2 patients. Injection sclerotherapy tried in 3 patients was not successful. Four patients had bleeding lesion along the greater curvature close to the fundus and two had on posterior wall but all within 6 cm. of gastroesophageal junction. All patients underwent curative emergency surgery with wedge resection of the lesion. We conclude that Dieulafoy lesion should be suspected in a patient with massive, recurrent and obscure upper gastrointestinal bleeding. Emergency endoscopy for diagnosis and prompt surgical intervention can cure the lesion which is potentially fatal if untreated.

Adult↗
PubMedDate not supplied

Portal hypertension in a western Indian hospital.

The profile of Portal Hypertension (PHT) in India is different from the west. Despite a good liver our patients are prone to die due to massive haematemesis as they are located far away from the referral centres. Drugs have a limited role and endoscopic sclerotherapy has its own limitations in our setting. Surgery (proximal lieno-renal shunt) is a one time treatment, removes the injury prone huge spleen and cures hypersplenism. We report our experience of 36 patients managed by this procedure.

Humans↗
PubMedDate not supplied

The contribution of "cure by dapsone monotherapy' to the reduction of prevalence of leprosy in the State of Orissa, India, 1983-1993.

The implementation of multiple drug therapy (MDT) in the State of Orissa, India, started in early 1983 and was extended in a phased manner to nine out of the then total of 13 districts by 1993. As part of a programme to bring the remaining four districts under MDT, an intensive screening of the registers was carried out in early 1993. From a total of 28,855 cases registered in these districts, 26,113 (90.5%) were examined and 18,008 (69.9%) deleted. The deleted included patients who had died, emigrated, double (or occasionally treble) entries for the same patient and those in whom careful re-assessment suggested that the original diagnosis of leprosy had been wrong. In addition, however, 8,260 (45.8%) of the 18,008 cases deleted were considered to have been cured by dapsone monotherapy. This figure, from districts with a relatively poor development of services for leprosy control, prompted a retrospective examination of data from the other (more privileged) nine districts. This revealed that from a total of 264,000 patients screened, prior to the implementation of MDT from 1983 onwards, 75,590 (28.6%) were removed from the registers, and that of these, 63,562 (84.0%) were considered to have been cured by dapsone monotherapy. Thus from a total of 93,598 patients removed from registeres in this State since 1983, 71,822 (76.7%) have been assessed as cured by dapsone monotherapy. The significance of this finding and its apparently considerable contribution to the overall reduction in the prevalence of leprosy in Orissa, 1983-1993, is discussed.

Dapsone↗
PubMedDate not supplied

Selection of donors and organization of a donor system for liver transplantation in India.

Organ transplantation has been a major scientific advance of this century. There is an attempt to start liver transplantation (LTx) in India in the near future. Donor selection is an integral part of the transplantation programme. Donor organs are a scarce resource and optimising their use will not only contribute to the success of the programme but also will ensure a steady flow of donors in the long term. Various factors essential for consideration while selecting a donor for liver transplantation are discussed. I have suggested guidelines for organising a viable donor system in the Indian setting to make the transplant programme long lasting.

Adult↗