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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 397 records · Page 22Linked to original sources
PubMed2000

Classification and the need to classify epilepsy.

Epilepsies are a diverse group of disorders with both shared and distinct features. Classification allows a coherent, systematic approach and serves as a 'universal language' between neurologists all over the world. There are two systems of classifications of epilepsies in use today. The International League Against Epilepsy (ILAE) Classification of Epileptic Seizures 1981 divides seizures into 3 morphologic types--generalised, partial and unclassifiable, with subtypes of each. This system has the advantage that seizures can be classified relatively easily and choice of antiepileptic is dictated by seizure type. However, the same patient may have more than one type of seizure either together or sequentially and many patients show a distinct evolution of their illness. This paved the way for another system of classification--the ILAE Classification of Epilepsies & Epileptic Syndromes 1989, which is meant to supplement the previous classification. An epileptic syndrome is defined as an epileptic disorder characterised by a cluster of signs and symptoms occurring together. According to this system, epilepsies are divided into 4 broad groups--localisation related and generalised, undetermined whether localised or generalised and special syndromes. Within the generalised and localised groups, there are further subdivisions into idiopathic, cryptogenic or symptomatic. This classification is complex and many syndromes are not adequately defined. At initial presentation, it may not be possible to identify the syndrome. Only a small proportion of patients fit into specific syndromes and a large proportion fall into non specific categories. For the present then, classification of epilepsy is still being refined. A brief description of major childhood epileptic syndromes according to age at onset is presented.

Adolescent↗
PubMed2000

Infected Ewing's sarcoma of spine.

An unusual case of extradural, intraspinal Ewing's sarcoma with significant extraspinal extension is reported. In view of associated constitutional symptoms, suggestive signs, leucocytosis, elevated ESR and operative findings, the initial diagnosis of Pott's spine was entertained. The lesion however turned out to be infected Ewing's sarcoma on histopathology and bacteriological examination.

Child↗
PubMed2000

Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson's disease.

Pallidotomy is now widely performed for the treatment of advanced Parkinson's disease (PD). Preliminary reports of the effect of globus pallidus pars interna deep brain stimulation (GPi DBS) have also been promising. We have analyzed a cohort of 22 consecutive patients enrolled in a multicenter study. Surgery was bilateral in 17 and unilateral in five patients. At 6-month follow-up, the bilaterally GPi-implanted patients demonstrated a marked improvement when examined after drug withdrawal ("off") and under optimal medication ("on") using the Unified Parkinson's Disease Rating Scale (UPDRS). The benefit induced by the stimulation in the "off" medication condition in the total motor score was 31% and in the activities of daily living (ADL) scores was 39%. During the "on" medication period, the reduction in the total "on" dyskinesias score was 66% and in the ADL score was 32%. A similar pattern of improvement was seen in the group of patients with unilateral GPi stimulation, although a second cohort of 12 patients not included in the multicenter study showed greater improvements in "on" motor functioning. Although the effect of DBS is predominantly reversible, electrode insertion alone resulted in measurable clinical effects in the absence of stimulation. Thus, at 6-month follow-up, the benefit observed without stimulation was up to 44% in the "on" dyskinesias score and 29% in timed tapping scores undertaken in the "off" medication state. Complications among 34 patients from all centers included perioperative infection (n=3), hardware fracture (n=2), and premature battery failure (n=3). These results show a positive antiparkinsonian effect of pallidal DBS. No specific complications were observed with bilateral procedures.

Adult↗
PubMed2000

Pharmacological and surgical options for the treatment of cervical dystonia.

Cervical dystonia (CD) is a condition in which patients experience involuntary and abnormal head movements, such as tilting, twisting, or extension, often accompanied by pain. Although the exact pathologic mechanisms underlying idiopathic CD have not yet been identified, a number of therapeutic strategies have been developed to alleviate the symptoms of this disorder. Oral medications include anticholinergic agents, dopamine receptor antagonists, and GABAmimetic agents. These drugs are employed in a trial-and-error manner and have a low rate of efficacy. Localized therapy using botulinum toxin injections has revolutionized the treatment of CD, providing a high rate of response with a low incidence of side effects. However, as with oral medications, neurotoxin therapy is palliative, not curative, and repeated injections are required. In patients who develop resistance to botulinum toxin therapy and who do not achieve an adequate response to, or are intolerant of, oral medications, surgical approaches are appropriate. Among the options for peripheral surgery, the greatest experience and most consistent results have been achieved with selective dorsal ramisectomy. Recent developments in stereotactic surgery suggest that, for more complex forms of CD or when more widespread dystonia is present, bilateral pallidotomy or globus pallidus deep brain stimulation may be the treatment of choice.

Botulinum Toxins, Type A↗
PubMed2000

New insights into anti-HER-2 receptor monoclonal antibody research.

Abnormalities in the expression, structure, or activity of proto-oncogene products contribute to the development and maintenance of the malignant phenotype. For example, c-erbB-2 encodes the HER-2 receptor (also known as c-erbB-2 or c-neu) that is overexpressed, amplified, or both in a number of human malignancies including breast, ovarian, colon, lung, prostate, and cervical cancers. In addition to deregulation of cell-surface HER receptors, cancer cells often show excessive activation and/or nonattenuation of growth factor--inducible signaling components, as well as their downstream transcription factors. Current approaches to target HER-2 pathways include downregulation of HER-2 by the adenovirus 5E1A, antisense phosphothionate oligonucleotides, ribozyme, and targeting tyrosine kinase using specific inhibitors. Because growth factors regulate the proliferation of cancer cells by activating receptors on the surface of cells, one obvious approach to control cell proliferation is to interfere with the growth factor receptor-mediated autocrine/ paracrine growth stimulation by antireceptor-blocking monoclonal antibodies. Therefore, a large number of scientists are attempting to control the growth of cancer cells using agents that inhibit one or more of the above steps of growth factor action. Recently completed clinical trials established the usefulness of a humanized form of 4DS monoclonal antibody, trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA), against some forms of breast tumors overexpressing HER-2 receptors. Using in vitro models, recent studies have shown that HER-2 overexpression may not be a prerequisite for invasion of breast cancer cells, as HER-2 activation by heregulin, which binds to HER-3 or HER-4 and transphosphorylates HER in noninvasive breast cancer cells, could lead to increased motility, enhanced gelatinolytic activity, and invasion. Furthermore, these ligand-driven phenotypic changes were completely suppressed by trastuzumab, which also blocked interactions between HER-2 and HER-3 receptors in heregulin-treated breast cancer cells, and inhibited the phosphatidylinositol-3' kinase-dependent pathway, but not the mitogen-activated protein kinase pathway. These phenotypic effects of anti-HER-2 monoclonal antibody are of special interest, because they point to potential therapeutic effects of trastuzumab in inhibiting the invasion and metastasis of breast cancer with low receptor expression.

Animals↗
PubMed2000

Comparison of various conventional methods with a polymerase chain reaction assay for detecting methicillin-resistant & susceptible Staphylococcus aureus strains.

BACKGROUND & OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA), a major nosocomial pathogen world-wide, is often difficult to detect due to the heterogeneous nature of expression of oxacillin resistance. In the present study, various conventional methods were compared with polymerase chain reaction on 106 clinical isolates of Staph. aureus for detection of oxacillin resistance. METHODS: A total of 106 clinical isolates of Staph. aureus were tested for oxacillin resistance by disc diffusion, screen agar plates (3 micrograms and 6 micrograms/ml of oxacillin), oxacillin broth (3 micrograms/ml) and mecA based PCR. RESULTS: PCR detected mecA gene amplified product of 604 bp in 57 strains. Disc diffusion failed to detect 7 mecA positive strains but identified 5 mecA negative strains as oxacillin resistant. Screen agar 3 micrograms, screen agar 6 micrograms and oxacillin broth 3 micrograms detected 55, 53 and 55 respectively of the 57 mecA positive strains; however, they also falsely identified 5, 3 and 3 strains of mecA negative strains respectively as oxacillin resistant. The sensitivity, specificity and accuracy of disc diffusion, 3 micrograms screen agar, 6 micrograms screen agar and 3 micrograms oxacillin broth against PCR as gold standard were as follows: 87.7, 89.9 and 88.7 per cent; 96.5, 89.8 and 93.4 per cent; 93.0, 93.9 and 93.4 per cent; 96.5, 93.9 and 95.3 per cent respectively. INTERPRETATION & CONCLUSIONS: The present study demonstrated that disc diffusion test was least reliable and 3 micrograms broth had the highest sensitivity and specificity when compared with PCR for detection of oxacillin resistance. Because of variations among the methods, a combination of tests should be used for the accurate detection of MRSA till new guidelines by an appropriate body are formulated.

Base Sequence↗
PubMed2000

Bone scanning for bone metastasis in carcinoma cervix.

AIM: Bone metastasis in cervical cancer is rare. With the aim of defining the frequency of bony metastasis in patients of carcinoma cervix, with clinical suspicion of metastasis, we performed bone scan in 38 such patients. RESULTS: Twelve out of the 38 patients were confirmed as having metastasis. All the patients were also detected by bone scan (100% sensitivity). CONCLUSION: Bone scan should be investigation of choice for screening patients of carcinoma cervix with symptoms suggestive of metastasis in all stage of the disease. Bone scan is the most sensitive method for detection of bone metastasis. Bone scan offers the additional advantages of allowing a review of the kidney size to look for ureteric involvement and subsequent hydronephrosis.

Adult↗
PubMed2000

Undifferentiated leukemia following treatment of gastric cancer with 5 fluorouracil, doxorubicin, mitomycin C chemotherapy.

Secondary leukemias are an increasingly well recognized complication of cancer chemotherapy. We report on the development of undifferentiated leukemia in a forty one year lady, eighteen months after treatment of gastric cancer with 5-fluorouracil (5 FU), doxorubicin and mitomycin C. She developed progressive weakness and pancytopenia over a period of few months. Leukemic blasts which were undifferentiated by immunophenotyping were seen in her peripheral blood. She died of intracranial haemorrhage during induction chemotherapy for the leukemia. Undifferentiated leukemia is a rare complication of FAM chemotherapy for gastric cancer.

Adenocarcinoma↗
PubMed2000

Prevalence of allergic bronchopulmonary aspergillosis in patients with bronchial asthma.

Two Hundred patients with bronchial asthma were studied to identify the prevalence of allergic bronchopulmonary aspergillosis (ABPA). The patients selected required intermittent short courses of steroids and their mean duration of illness was 12 years. Absolute eosinophil count was > 500/mm3 in 53% of the cases. Chest X-rays showed small homogenous shadows with patchy infiltrations in 25% and fluctuating pneumonic shadows in 14% of the cases. Raised specific IgG and positive serum precipitin against Aspergillus fumigatus (AF) were present in 24% and 13%, respectively. Cases with radiological and immunological suspicion were further investigated for ABPA. Skin tests for Type-I and Type-III reactivity were positive with AF extract in 87% (n = 47) and 36% (n = 47) of the cases. A thorax CT of 31 patients showed central bronchiectasis in 24 cases, labeling these patients as ABPA-CB (ABPA with central bronchiectasis) and an other 7 as ABPA-S (serological positive). CT was not done in one case who, because of other positive findings, was also labeled as ABPA-S. Thus, these 32 asthmatics were found to have ABPA. Among them, there was raised specific IgG (100%) and raised specifc IgE against AF (100%), positive skin test for Type-I and Type-III reactivity (100% and 53%) against AF. There was elevated total IgE (100%, n = 29), a positive family history of asthma (63%), peripheral eosinophilia (100%) and a history of passage of brownish plugs (31%). Radiological findings suggested soft shadow with infiltration in 31% and fluctuating pneumonic shadows in 69% of cases. CT Thorax (n = 31) showed central bronchiectasis in 78% of theses patients. Based on the present data, the prevalence of ABPA in bronchial asthma patients is 16% (12% with central bronchiectasis and 4% only serologically positive). Therefore, patients should be investigated and diagnosed in an early phase of ABPA (ABPA-S) and should be treated to prevent permanent lung damage.

Adolescent↗
PubMed2000

Anthocyanin, bisabolol and phenylammonialyase activity in cell cultures of Populus deltoides.

Phenolics, anthocyanin and alpha-bisabolol production from poplar (Populus delotides) in tissue culture was determined. A number of phenolic acids were identified by HPLC. PAL activity in response to phytohormones, cells growth and anthocyanin production showed a positive correlation. A component, alpha-bisabolol, was identified using gas chromatography and UV spectroscopy. In vitro production of said metabolites was influenced by phytohormones.

Ammonia-Lyases↗
PubMed2000

Meningococcal meningitis outbreak control strategies.

Meningococcal meningitis has been occurring worldwide in both endemic and epidemic forms. Serogroup A accounts for majority of cases of epidemic as well as endemic Meningococcal meningitis in developing nations, whereas group C and group B causes epidemic and endemic meningococcal meningitis in developed countries. Person to person spread of N. meningitides generally occurs through inhalation of droplets of infected nasopharyngeal secretions by direct or indirect oral contact. Incubation period varies from 2 to 10 days. N. meningitides typically causes acute infective illness characterized by sequential development of upper respiratory tract infection, meningococcemia, meningitis and focal neurological deficit. Over 90 per cent cases of adult meningococcal infections have cerebrospinal meningitis, whereas in children prevalence of meningitis is much lower (50 per cent). Acute meningitis manifests with fever, severe headache, vomiting and neck stiffness. Presentations may be non-specific in infants, elderly and in patients with fulminant meningococcemia. Diagnosis is confirmed with cerebrospinal fluid analysis. Overall mortality due to meningitis is usually around 10 per cent. In meningococcal septicemia, the case fatality rate may exceed 50 per cent. Preventive strategies include vaccination, chemoprophylaxis and early detection and treatment. Mass vaccination campaign, if appropriately carried out, has been documented to halt an epidemic of meningococcal disease due to serogroup A or C. In the present review we have discussed the available evidence with regards to prevention at primary, secondary and tertiary level. Public health approach to an outbreak of meningococcal meningitis in a community or an organization is also outlined.

Disease Outbreaks↗
PubMed1999

Adhesion and invasion of a mutant Shigella flexneri to an eukaryotic cell line in absence of the 220-kb virulence plasmid.

A Shigella flexneri strain, cured of the large 220-kb virulence plasmid, expresses adhering and invading ability in confluent monolayers of HeLa cells similar to its parent strain. Invasion by both the parent and the cured strains resulted in alteration of the monomeric actin (G) in the total actin pool of HeLa cells. Other indicators of invasive characteristics of virulent Shigella strains such as production of keratoconjunctivitis in guinea pig eye in vivo, Congo red binding and expression of contact hemolysin however, indicated loss of invasive properties in the plasmid cured strain. Further, pretreatment of bacterial cells with para-bromophenacyl bromide (p-BPB), a specific chemical inhibitor of phospholipase A, adversely affected adhesion to and invasion of HeLa cells in vitro, irrespective of the presence of the 220-kb plasmid indicating the possible involvement of the enzyme phospholipase A in the invasion process. Adherence of both the strains to guinea pig colonic epithelial cells (CECs) in vitro was reduced significantly on pretreatment of bacteria or CECs with p-BPB. Expression of exocellular enzymes viz. protease, elastase, phospholipase A and phospholipase C were not related to the large plasmid.

Acetophenones↗
PubMed1999

Serine phosphorylation of paxillin by heregulin-beta1: role of p38 mitogen activated protein kinase.

The mechanisms through which heregulin (HRG) regulates the progression of breast cancer cells to a more invasive phenotype are currently unknown. Recently we have shown that HRG treatment of breast cancer cells leads to the formation of lamellipodia/filopodia, and increased cell migration and invasiveness through the phosphatidylinositol 3-kinase (PI-3 kinase). Since the process of cell migration must involve changes in adhesion, we explored the potential HRG regulation of paxillin, a major cytoskeletal phosphoprotein of focal adhesion. We report that HRG stimulation of non-invasive breast cancer cells resulted in stimulation of p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinases (ERK) and PI-3K, and a concurrent unexpected increase in the level of paxillin phosphorylation on serine residue which was sensitive to protein-phosphatase 2b but not to protein tyrosine phosphatase 1. In addition, HRG triggered a rapid redistribution of paxillin to the perinuclear regions from the tyrosine-phosphorylated focal adhesions, and increased cell scattering. There was no effect of HRG on the state of phosphorylation and localization of focal adhesion kinase. The HRG-induced increase in serine phosphorylation of paxillin and cell scattering were selectively inhibited by a specific inhibitor of p38MAPK or a dominant-negative p38MAPK mutant, but not by inhibitors of p42/44MAPK or PI-3 kinase pathways. For the first time our results have shown that HRG, a potent migratory growth factor stimulates serine phosphorylation of paxillin. These findings suggest a role of p38MAPK-dependent signal transduction pathway(s) in serine phosphorylation and disassembly of the paxillin from the focal complexes during HRG-induced cell shape alterations and motility.

Breast Neoplasms↗
PubMed1999

Dynamic DNA hybridization on a chip using paramagnetic beads.

Dynamic DNA hybridization is presented as an approach to perform gene expression analysis. The method is advantageous because of its dynamic supplies of both DNA samples and probes. The approach was demonstrated on a microfluidic platform by incorporating paramagnetic beads as a transportable solid support. A glass chip was fabricated to allow simultaneous interrogation of eight DNA target samples by DNA probes. DNA targets were immobilized on beads via streptavidin-biotin conjugation or base pairing between oligonucleotide residues. The DNA/bead complex was introduced into the device in which hybridization took place with a complementary probe. The hybridized probe was then removed by heat denaturation to allow the DNA sample to be interrogated again by another probe with a different sequence of interest. A pneumatic pumping apparatus was constructed to transport DNA probes and other reagents into the microfluidic device while hydrostatic pumping was used for the introduction of paramagnetic beads with samples. After investigating three types of paramagnetic beads, we found Dynabeads Oligo(dT)25 best suited this application. Targets on the beads could be sequentially interrogated by probes for 12 times, and the hybridization signal was maintained within experimental variation. Demonstration of specific hybridization reactions in an array format was achieved using four synthesized DNA targets in duplicate and five probes in sequence, indicating the potential application of this approach to gene expression analysis.

Actins↗
PubMed1999

SHP-1 regulates Lck-induced phosphatidylinositol 3-kinase phosphorylation and activity.

Ligation of the T cell antigen receptor (TCR) activates the Src family tyrosine kinase p56 Lck, which, in turn, phosphorylates a variety of intracellular substrates. The phosphatidylinositol 3-kinase (PI3K) and the tyrosine phosphatase SHP-1 are two Lck substrates that have been implicated in TCR signaling. In this study, we demonstrate that SHP-1 co-immunoprecipitates with the p85 regulatory subunit of PI3K in Jurkat T cells, and that this association is increased by ligation of the TCR complex. Co-expression of SHP-1 and PI3K with a constitutively activated form of Lck in COS7 cells demonstrated the carboxyl-terminal SH2 domain of PI3K to inducibly associate with the full-length SHP-1 protein. By contrast, a truncated SHP-1 mutant lacking the Lck phosphorylation site (Tyr(564)) failed to bind p85. Wild-type but not catalytically inactive SHP-1 induced dephosphorylation of p85. Furthermore, expression of SHP-1 decreased PI3K enzyme activity in anti-phosphotyrosine immunoprecipitates and phosphorylation of serine 473 in Akt, a process dependent on PI3K activity. These results indicate the presence of a functional interaction between PI3K and SHP-1 and suggest that PI3K signaling, which has been implicated in cell proliferation, apoptosis, cytoskeletal reorganization, and many other biological activities, can be regulated by SHP-1 in T lymphocytes.

Amino Acid Substitution↗