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Biomedical subjects

Raj Kumar

Publications and source records attributed to Raj Kumar.

At least 55 records · Page 3Linked to original sources
PubMed2004

Spinal tuberculosis: with reference to the children of northern India.

BACKGROUND: Tuberculosis is a necrotizing bacterial infection with protean manifestation and wide distribution. There has been a great fall in the prevalence of tuberculosis in the United States since 1990, although the impact of acquired immunodeficiency syndrome (AIDS) has increased the resurgence of tuberculosis (TB). Spinal tuberculosis is the commonest form of skeletal tuberculosis. In this article, an overview of spinal tuberculosis and the personal experience of 19 children with spinal tuberculosis are presented. All the children required surgical intervention, because they manifested neurological deficit. PATHOGENESIS AND CLINICAL FEATURES: The spinal tuberculosis is a result of hematogenous dissemination from primary focus in the lungs or the lymph nodes. The central type of vertebral tuberculosis spreads along with Batson's plexus of veins, while paradiscal infection spreads through the arteries. The anterior type of vertebral body tuberculosis results from the extension of the abscess beneath the anterior longitudinal ligament and periosteum. Two types of bone and joint tuberculosis are recognized: the caseous, exudative type with abscess formation, which is more common in children, and the granular type is frequent in adults. Only 7 of the 19 children had an abscess, while 10 manifested mainly granulation tissue. Although spinal tuberculosis is an extradural disease, 2 children had intramedullary granulomas and presented a tumor-like syndrome as rare manifestations. It was interesting to encounter intradural granulation and organized intradural granuloma causing cord compression in 2 children. A frank abscess with clumping of nerve roots was encountered in the cauda of another child without vertebral involvement. There is a controversy regarding the age predilection of the disease; it is documented that it is a disease of adults in affluent countries, and a disease of the first three decades in other regions. DIAGNOSIS: Magnetic resonance imaging is extremely useful in diagnosing the difficult and rare sites of disease like the craniovertebral junction. It detects the marrow changes, exudative and granulation types, extra- and intradural disease, and radiological response to treatment in the early follow-up period around 6-8 weeks. TREATMENT: Opinion varies regarding the operative indication for Pott's spine. A large group of surgeons perform debridement and decompression in all cases, irrespective of neurological involvement. Others perform operative decompression only in those patients who do not respond to chemotherapy. We did surgical interventions in children with moderate to severe neurological deficits manifesting radiological compression of their neuraxis. Depending on the site of involvement and type of disease the surgical approach was decided in individual cases. Two children with healed Pott's spine also required surgery because of their spinal deformations, which caused gradual neurological deficits and pain in both. Prognosis depends on many factors; the magnitude of cord compression, duration of neural complication, age and general condition of patient. Fifteen of our children made a remarkable recovery. Children with paraplegia also made an excellent recovery of their strength and sensations.

Child↗
PubMed2004

Childhood choroid plexus papillomas: operative complications.

METHODS: Eight children (below 12 years of age) operated on for intraventricular choroid plexus papilloma (CPP) were retrospectively reviewed to identify the factors responsible for their high postoperative morbidity and mortality. Seven of these patients were aged between 2 months and 2 years and 1 was aged 12 years. Six CPP lesions were in the lateral ventricles and the remaining 2 were in the anterior third ventricle. All children presented with features of raised intracranial pressure. Due to gross hydrocephalus with severe manifestations at admission two patients required CSF diversion before definitive surgery. RESULTS: Microsurgical excision of CPPs was achieved in 7 and near total removal of the tumor in an 8th child. Brain shift was noted during operation and was attributed to acute CSF drainage and/or tumor excision in all cases. External ventricular drainage was postoperatively placed in 2 patients, who ultimately required shunt installation. One child died during definitive surgery. Due to neurological deterioration 6 of the remaining 7 patients had a postoperative CT scan within a week of surgery. One had an uneventful recovery, and pneumocephalus and subdural effusion were found in all 6 scanned children. Pneumocephalus was significant enough in 4 of them to warrant a surgical evacuation. CONCLUSION: Acute CSF drainage leading to significant intraoperative brain shift, postoperative external ventricular drainage, pneumocephalus, subdural effusion, and persistent postoperative hydrocephalus were identified as chief factors for higher morbidity in these children.

Child↗
PubMed2004

Subependymal giant cell astrocytoma: a report of five cases.

Five cases of intraventricular subependymal giant cell astrocytomas (SEGCA) were retrospectively reviewed. Records and detailed work-up of all five cases were well maintained in view of rare occurrence of these tumors. The five patients were males aged 10, 12 (2 cases), 14 and 18 years. The 18-year-old aged male had no stigmata of tuberous sclerosis (TSC) on examination, while the rest presented with features of TSC, intraventricular tumors and hydrocephalus. None of the five cases had renal tumors and did not reveal cardiac tumors. Skin manifestations like shagreen patches were present in two, facial angiofibromas in three, periungal fibromas in two, hypopigmented macules in two and ash-leaf spot in two patients. Fundoscopic examination revealed retinal astrocytomas in two cases only. Two of the five children did not have mental compromise. A child who started throwing seizures early (at 5 months of age) had severe mental retardation. Although SEGCA is a less vascular tumor, one tumor bled profusely intraoperatively; it was excised rapidly via the transcortical route to salvage the life of the child, though he was planned for the transcallosal route like the other cases. The tumor of another child was also very vascular. Four children survived surgery and required no shunt CSF diversion, while one died of severe ventriculitis and septicemia 3 weeks after surgery.

Adolescent↗
PubMed2004

Association of IL4 gene polymorphisms with asthma in North Indians.

BACKGROUND: Asthma is a complex airway disorder, and a number of genetic loci have been found to be associated with asthma. The 5q31-33 region is one of the most important loci linked to asthma and atopic disorders. However, association studies with candidate genes in this region, such as IL4, were inconclusive, as both positive and negative results were obtained in several populations studied. The aim of our case-control study was to determine the association between IL4 and asthma in North Indians. PATIENTS AND METHODS: Polymorphisms in the promoter and a dinucleotide repeat in the 2nd intron in IL4 were genotyped by sequencing and GeneScan analysis, respectively, in ethnically matched, unrelated patients (n = 171) and controls (n = 128), following the guidelines of the American Thoracic Society. RESULTS: The proximal promoter region of the IL4 gene was found to be invariant. Previously reported polymorphisms, -590 C/T and +33 C/T, were found to be absent in our population. The chi2 test using only large expected cell counts (more than 5% of the sample size) showed a significant association between allele size and disease status (chi2 = 38.08, d.f. = 6, p < 0.05). In addition, a significant difference was observed for the allele and genotype frequencies (p < 0.0005 and p = 0.0009, respectively) in the patient and the control groups using the Fisher-Freeman-Halton test. CONCLUSION: Our studies indicate that the promoter of the IL4 gene is invariant in our population. The case-control studies on the CA repeat polymorphism in the 2nd intron of the IL4 gene have shown interesting results and indicate the need for further family-based studies.

Adult↗
PubMed2004

Induced alpha-helix structure in AF1 of the androgen receptor upon binding transcription factor TFIIF.

In recent years, it has become clear that in many proteins, significant regions are encoded by amino acid sequences that do not automatically fold into their fully condensed, functional structures. Characterization of the conformational propensities and function of the nonglobular protein sequences represents a major challenge. Striking among proteins with unfolded regions are numbers of transcription factors, including steroid receptors. In many cases, the unfolded or partially folded regions of such proteins take shape when the protein interacts with its proper binding partner(s), that is, the molecules to which it must bind to carry out its function. The AF1 domain of the androgen receptor (AR) shows little structure, when expressed as a recombinant peptide. It has been shown previously that AF1 interacts with transcription factor TFIIF in vitro. Using Fourier transform infrared (FTIR), we tested whether this interaction can induce structure in the AR AF1. Our results demonstrate that the recombinant AR AF1 can acquire significantly higher helical content after interacting with RAP74, a subunit of the TFIIF complex. We further show that this induced conformation in the AR AF1 is well-suited for its interaction with SRC-1.

Histone Acetyltransferases↗
PubMed2004

Expression and secretion of a prokaryotic protein streptokinase without glycosylation and degradation in Schizosaccharomyces pombe.

Streptokinase (SK) is an important thrombolytic protein that is secreted by pathogenic strains of Streptococcus. Expression of streptokinase has been so far attempted in Pichia pastoris, Escherichia coli and Bacillus subtilis and shown to yield protein that was either highly glycosylated or degraded. Since the fission yeast, Schizosaccharomyces pombe, shares several molecular characteristics with higher eukaryotes, we decided to express the streptokinase gene in this yeast. A chimeric gene comprising the signal sequence of the Plus pheromone of Sz. pombe fused in-frame with the mature streptokinase from Streptococcus sp. was constructed and inserted into the expression vector containing the thiamine-regulated promoter. We obtained a high level of expression of streptokinase comparable to that in E. coli and P. pastoris, with 50-100% processing of the signal sequence and secretion of the mature streptokinase into the periplasmic fraction. The mature enzyme co-migrates with the authentic mature SK in SDS gels, lacks any major modification and is functional. Importantly, a higher level of expression under stationary phase conditions and improved extractability of the mature and undegraded streptokinase was achieved in a novel mutant of Sz. pombe defective for a potent extracellular protease activity. We suggest that the unique vector/strain system developed here could be advantageous for large-scale production of prokaryotic proteins without significant modification or degradation in Sz. pombe.

Amino Acid Sequence↗
PubMed2004

Overview of the structural basis for transcription regulation by nuclear hormone receptors.

The mechanism of action of the nuclear hormone receptors (NHRs) as gene- regulatory molecules has become a major focus of current biological interest. NHRs belong to the superfamily of ligand-activated transcription factors, which are involved in the regulation of homoeostasis, reproduction, development and differentiation. To fully understand their functions, it is important to know the functional three-dimensional structure of these proteins. Molecular cloning and structure-function analyses have revealed that NHRs commonly have three functional regions: the N-terminal, DNA-binding and ligand-binding domains. Structures of some of these domains expressed independently have been solved. However, to date the three-dimensional structure remains unknown for full-length and even for any two domains together of any NHR family member. The available structures nevertheless begin to give clues of how site-specific DNA binding takes place, and how ligand binding alters the ligand-binding domain, consequently affecting potential interactions of the NHRs with co-activators/co-repressors and other components of basal transcriptional machinery. However, precisely how signals from a ligand through its NHR are passed to specific genes is still unknown. Herein, we present a broad overview of current knowledge on the structure and functions of the NHRs.

Animals↗
PubMed2003

Hyperostotic paraganglioma of occipitotemporal bone.

A 25-year-old male presented with off-and-on vertigo of 10-year duration. He had left-sided cerebellar signs, left vocal cord paresis, and minimal left-sided hearing impairment. Computed tomography of the head revealed significant hyperostosis of squamous occipital, mastoid, and petrous temporal bone with no adjacent soft tissue mass. On excision, it turned out to be paraganglioma. Paraganglioma as a pure bony mass is not reported in the literature. The site of origin of such a tumor could not be ascertained, even on generous screening. The tumor remained nonsecretory on clinical and biochemical investigations.

Adult↗
PubMed2003

Uncommon manifestations of shunt infection.

UNLABELLED: Shunt infection is one of the commonest and most troublesome cause of shunt failure. According to the etiology and clinical presentations it has been divided into external and internal types. METHOD: We hereby present four pediatric cases, who presented with atypical manifestations not coinciding with the above mentioned types of shunt infection. Three patients developed round, globular or diffuse fluctuant CSF filled swellings at the burr hole site, one of whom had involvement of the entire pericatheteral extent upto the abdomen. RESULT: The fourth child developed spontaneous expulsion of ventricular end of shunt tube through the dehiscent and infected chest wall incision site. CONCLUSION: First three of the above children were diagnosed as having internal type of shunt infections, while the fourth had mixed manifestations of external and internal type.

Anti-Bacterial Agents↗
PubMed2003

Ascites in ventriculoperitoneal shunt.

OBJECTIVE: To fetch out the factors responsible for ascites, following shunt CSF diversion in cases of intracarnial lesions. Four children developing ascites/abdominal psuedocyst following ventriculoperitoneal shunt were analyzed to see the factors responsible for such complication. METHODS: Records of 4 cases developing ascites were studied retrospectively. These children developed ascites at 8 months, 6 months, 1 year and 1 year 2 months interval following their shunt installation. RESULTS: The primary etiology of hydrocephalus was demonstrated as thalamic glioblastoma, choroid plexus papillomas of third ventricle, post tubercular meningitis hydrocephalus and suprasellar craniopharyngioma. CONCLUSION: The proposed etiology of ascites in these cases was peritoneal metastasis from thalamic glioblastoma through ventriculoperitoneal shunt in first case, excessive production of CSF by choroid plexus papilloma in second, infection in the third case and craniopharyngioma causing excessive production of CSF in the fourth child. All the children were treated by reasonable laparotomy and fenestration of cyst along with the repositioning of shunt tip at another site.

Ascites↗
PubMed2003

Spinal dysraphism: trends in northern India.

OBJECTIVE: To evaluate the clinical profiles, image findings and surgical outcome of 155 cases of spinal dysraphism. METHODS: 155 patients were studied prospectively (143) or retrospectively (12). The male to female ratio was 1.5:1. Mean age at presentation was 5.7 years. Out of 155 cases of spinal dysraphism, 119 had open spina bifida [meningomyelocele (MMC) in 113 (72%), meningocele in 3 (2%) and myelocystocele in 3 (2%)] and 36 had occult spina bifida [split cord malformation (SCM) without overt MMC sac (pure SCM) in 29 (19%) and midline dermal sinus in 7 (4.5%)]. Lipomeningomyelocele constituted 73 of the 113 cases of MMC (65%). Twenty cases of MMC (18%) had associated SCM (complex spina bifida). The total number of cases with SCM was 49 (32%). Twenty-four children with MMC presented with an operative scar from previous surgery, performed at the periphery. After a detailed clinical evaluation of all patients, craniospinal MRI was the preferable mode of investigation. All patients underwent surgery and were clinically assessed over a mean follow-up period of 3.6 years. RESULTS: MMC sac was the commonest skin manifestation seen in 89/155 cases (57%). Hypertrichosis and previous operative scar were noticed in 24 cases each (15%). Cutaneous hemangioma, skin tag and multiple neurofibroma were the other common superficial skin manifestations. Clinically, 103 patients (66.5%) had variable weakness of the lower limbs, and muscle atrophy was noticed in 56 cases (41%). Graded sensory loss, sphincteric dysfunction, trophic ulcer and backache were present in 89 (57%), 64 (36%), 17 (11%) and 9 cases (6%), respectively. Significant scoliosis in 56 cases (36%) and congenital talipes equinovarus in 51 cases (33%) were the most frequent neuroorthopedic deformities apart from high-arched foot, leg length discrepancy and flat foot. Common image findings were low-lying cord in 101 (65%), neural placode in 76/113 (49%), hydrosyrinx in 42 (27%), hydrocephalus in 71 (46%) and Chiari malformation in 62 cases (45%). The lumbosacral region in 56 cases (38%), followed by the lumbar region in 47 (30%), were the most common sites of occurrence of spina bifida. Of 71 hydrocephalic patients, 39 (55%) needed shunting before definitive surgery and 21 (30%) after the surgery. Eleven patients (15%) did not require shunting at all. CSF leak in 51 patients (33%), pseudomeningocele in 26 (17%), wound infection in 22 (14%) and meningitis in 13 (8%) were the most common postoperative complications. Two patients died in the postoperative period. During an average follow-up of 3.6 years (range 1.5-8 years), motor weakness improved in 47 children (45%) and remained static in 53 (52%), and 3 children showed deterioration in motor power. Sensory dysfunction improved in 43 (48%), remained static in 42 (47%) and deteriorated in 4 patients (4%). Sphincteric function clinically improved in 26 patients (41%) and was static in 38 (59%), and 6 patients (4%) had deterioration. Backache was dramatically relieved in all 9 patients with this complaint (100%). In 13 children with trophic ulcer (76%), it completely healed. CONCLUSION: A significant proportion of patients with open spinal dysraphism harbor an underlying SCM, an entity coined complex spina bifida (in our previous study). The incidence of hydrocephalus in spinal dysraphism is low in India in comparison to the Western world. Some patients with mild hydrocephalus on scan may not require a shunt operation. Surgical intervention should be early after entire neural axis screening by MRI.

Adolescent↗
PubMed2003

Transactivation functions of the N-terminal domains of nuclear hormone receptors: protein folding and coactivator interactions.

The N-terminal domains (NTDs) of many members of the nuclear hormone receptor (NHR) family contain potent transcription-activating functions (AFs). Knowledge of the mechanisms of action of the NTD AFs has lagged, compared with that concerning other important domains of the NHRs. In part, this is because the NTD AFs appear to be unfolded when expressed as recombinant proteins. Recent studies have begun to shed light on the structure and function of the NTD AFs. Recombinant NTD AFs can be made to fold by application of certain osmolytes or when expressed in conjunction with a DNA-binding domain by binding that DNA-binding domain to a DNA response element. The sequence of the DNA binding site may affect the functional state of the AFs domain. If properly folded, NTD AFs can bind certain cofactors and primary transcription factors. Through these, and/or by direct interactions, the NTD AFs may interact with the AF2 domain in the ligand binding, carboxy-terminal portion of the NHRs. We propose models for the folding of the NTD AFs and their protein-protein interactions.

Animals↗
PubMed2003

Mild, moderate, and severe forms of allergic bronchopulmonary aspergillosis: a clinical and serologic evaluation.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disorder induced by Aspergillus species colonizing the bronchial tree. There are patients with asthma who fulfill the diagnostic criteria of ABPA by serologic evaluation (specific IgE/IgG to Aspergillus fumigatus), bronchography, CT, and or conventional linear tomography. OBJECTIVE: To identify different forms of ABPA based on various diagnostic criteria. METHODS: Eighteen patients with asthma fulfilling the criteria of ABPA were evaluated in the present study. Six patients each received a diagnosis of ABPA serologic positive (ABPA-S), ABPA with central bronchiectasis (ABPA-CB), and ABPA with central bronchiectasis and other radiologic features (ABPA-CB-ORF). RESULTS: The spirometric changes in the ABPA-S group (group 1) were mild, in the ABPA-CB group (group 2) were moderate, and in the ABPA-CB-ORF group (group 3) were severe. Absolute eosinophil count was raised in each group but was maximum (1,233 micro L) in severe form of disease (group 3). Specific IgE against A fumigatus was raised in each group, and the maximum was 47.91 IU/mL in ABPA-CB-ORF. CT scan findings of the ABPA-S group were normal without central bronchiectasis. The exacerbation in symptoms was maximum in group 3 compared to other groups. CONCLUSION: The present observations suggest that ABPA includes mild (ABPA-S), moderate (ABPA-CB), and severe (ABPA-CB-ORF) forms of disease. It is recommended, therefore, that the disease should be diagnosed early, treated at the mild form of disease (ABPA-S), and prevented from leading to ABPA-CB or ABPA-CB-ORF.

Adolescent↗
PubMed2003

Molecular regulation of cholesterol biosynthesis: implications in carcinogenesis.

Cholesterol synthesis was demonstrated to be mandatory for cellular growth and serves to supply one of the necessary building blocks for new membranes demanded by dividing cells during growth. The mevalonate pathway, which is regulated through a finely tuned mechanism, is responsible mainly for cholesterol enrichment to cells. Among the various steps, the production of mevalonate from 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) is the most critically regulated step catalyzed by HMG-CoA reductase. The ability of sterols to regulate both the transcriptional rates of the reductase gene and the degradative machinery for the reductase protein provides a multilevel system for controlling the expression of this enzyme. Much convincing evidence indicates that cells manifest a higher flux through the mevalonate pathway when proliferating than when they are in the cell cycle arrest condition; furthermore, tumors undergo deregulated cholesterogenesis mainly at the critical rate-controlling juncture (i.e., the reaction catalyzed by HMG-CoA reductase). The mevalonate component of the cholesterol biosynthesis plays a key role in controlling cell proliferation by generating prenyl intermediates, particularly farnesyl and geranyl-geranyl moieties. These isoprenoids covalently modify and thus modulate the biological activity of signal transducing proteins, such as that of the Ras superfamily. The prenylated Ras-mediated signal transduction pathway provides much of the molecular information needed to trigger cell proliferation. Therefore, depletion of mevalonate can block both the processing and the transforming activities of Ras, indicating that drugs such as lovastatin and compactin, which had previously been exploited for lowering cholesterol levels, may be useful chemotherapeutic agents for treating tumors harboring oncogenic Ras mutation. In addition, Ras prenylation, which provides much of the molecular information needed to trigger cell proliferation, represents an inviting target for the design of chemotherapeutic drugs that would interrupt such signaling events and arrest tumor cell proliferation.

Acyl Coenzyme A↗
PubMed2003

Cancer chemoprevention by resveratrol: in vitro and in vivo studies and the underlying mechanisms (review).

Cancer, next only to heart diseases, is the second leading cause of deaths in the United States of America and many other nations in the world. The prognosis for a patient with metastatic carcinoma of the lung, colon, breast, or prostate (four of the most common and lethal forms of cancer, which together account for more than half of all deaths from cancer in the USA), remains dismal. Conventional therapeutic and surgical approaches have not been able to control the incidence of most of the cancer types. Therefore, there is an urgent need to develop mechanism-based approaches for the management of cancer. Chemoprevention via non-toxic agents could be one such approach. Many naturally occurring agents have shown cancer chemopreventive potential in a variety of bioassay systems and animal models, having relevance to human disease. It is appreciated that an effective and acceptable chemopreventive agent should have certain properties: (a), little or no toxic effects in normal and healthy cells; (b), high efficacy against multiple sites; (c), capability of oral consumption; (d), known mechanism of action; (e), low cost; and (f), acceptance by human population. Resveratrol is one such agent. A naturally occurring polyphenolic antioxidant compound present in grapes, berries, peanuts and red wine. In some bioassay systems resveratrol has been shown to afford protection against several cancer types. The mechanisms of resveratrol's broad cancer chemopreventive effects are not completely understood. In this review, we present the cancer chemopreventive effects of resveratrol in an organ-specific manner. The mechanisms of the antiproliferative/cancer chemopreventive effects of resveratrol are also presented. We believe that continued efforts are needed, especially well-designed pre-clinical studies in the animal models that closely mimic/represent human disease, to establish the usefulness of resveratrol as cancer chemopreventive agent. This should be followed by human clinical trials in appropriate cancer types in suitable populations.

Animals↗