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Biomedical subjects

S K Reddy

Publications and source records attributed to S K Reddy.

At least 37 records · Page 2Linked to original sources

Subarachnoid neurolytic block under general anesthesia in a 3-year-old with neuroblastoma.

CASE REPORT: A 3-year-old boy with neuroblastoma complained of severe pain in the left lower extremity. Pharmacologic management had previously been attempted, but severe pain continued, and further upward titration was complicated by sedative effects. METHODS AND RESULTS: Because the focus of treatment had become the controlling of pain, a lumbosacral subarachnoid neurolytic block was performed under general anesthesia. One-time neurolysis was more acceptable to the family than a procedure like epidural analgesia, that requires greater management. Contrast medium was used to monitor the spread of the neurolytic. An epidural catheter was inserted during the neurolytic block procedure for possible future use. The short-term results were good--pain reports and opioid doses decreased greatly, although with increased incontinence. The boy had new abdominal distention and pain 5 days after neurolysis. Opioid doses and sedatives were increased. He died 3 days later.

Anesthesia, General↗

Medical decision-making in a patient with a history of cancer and chronic non-malignant pain.

The selection of cancer pain treatment modalities depends on careful assessment to establish the pathophysiology of the pain complaint. Treatment may consist of a single modality--e.g., pharmacotherapy--or multiple modalities--e.g., pharmacotherapy, anesthetic intervention, and radiotherapy for bone pain. Cancer patients may present with pain and multiple concomitant medical problems related to their primary neoplastic disease, complications of cancer treatment, or unrelated conditions including preexisting pain of nonmalignant origin. We present the case of a patient with new onset of pain superimposed on chronic nonmalignant pain. This case emphasizes the need for careful assessment and the close cooperation required between the pain consultant and the referring oncology staff to make optimal treatment decisions in the context of a complex medical illness.

Carcinoma↗

Functional expression and peroxisomal targeting of rat urate oxidase in monkey kidney cells.

Humans and hominoid primates lack the enzyme urate oxidase, which catalyzes the oxidation of uric acid to allantoin. In rats and most other mammals, urate oxidase is present as a crystalloid core within the peroxisomes of liver parenchymal cells. To determine whether functionally active recombinantly expressed urate oxidase can be targeted to the peroxisome as well as display the crystalloid core-like structure, we expressed rat urate oxidase cDNA in African green monkey kidney cells (CV-1 cells) under the control of a cytomegalovirus promoter. Cell lines stably expressing urate oxidase were isolated. Northern blot analysis revealed a 1.3-kb transcript and immunoblot analysis confirmed the presence of urate oxidase in the stably transfected cells. The recombinant urate oxidase expressed in CV-1 cells was functionally active. Immunofluorescence microscopy revealed that the expressed protein was visualized as discrete granules in the cytoplasm. Electron microscopy and immunocytochemical localization studies showed that the recombinantly expressed protein formed distinct crystalloid core structures with bundles of tubules within single membrane limited cytoplasmic organelles. On cross section, the recombinant urate oxidase tubular structures are arranged as circles of 10 surrounding a slightly larger circle. This arrangement is reminiscent of urate oxidase-containing cores in rat liver peroxisomes. Immunocytochemical studies confirmed that the recombinantly expressed urate oxidase is correctly targeted to the catalase-containing peroxisomes in these CV-1 cells.

Allantoin↗

Amphibian allantoinase. Molecular cloning, tissue distribution, and functional expression.

The chain of enzymes necessary to convert uric acid to its metabolic products urea and glyoxylic acid in vertebrates is truncated through the successive loss of allantoicase, allantoinase, and urate oxidase during phylogenetic evolution. Previous studies have assigned the localization of both urate oxidase and allantinase to the peroxisome in the amphibian liver. This study reports the cloning of a cDNA encoding bullfrog (Rana catesbeiana) allantoinase, an enzyme that converts allantoin to allantoic acid. The cDNA is 2112 base pairs in length containing a 1449-base pair open reading frame which corresponds to a 483-residue protein (53,296 Da). Structural analysis of the deduced protein suggested two potential transmembrane segments and the presence of a putative mitochondrial localization sequence in the amino terminus. Immunocytochemical analysis revealed that allantoinase is localized to mitochondria and not to peroxisomes. On Northern blotting, a single mRNA species was detected in the liver and kidney of frog but not in other tissues; this distribution was confirmed by immunoblotting. The hepatic- and renal-specific expression of allantoinase coincides with the distribution of urate oxidase in these tissues in the frog. The allantoinase expressed in Saccharomyces cerevisiae and in Spodoptera frugiperda (Sf9) insect cells exhibits catalytic activity and is antigenically identical to the native frog enzyme.

Amidohydrolases↗

Flow cytometric analysis of the neutralizing immune response against infectious bursal disease virus using reticuloendotheliosis virus-transformed lymphoblastoid cell lines.

Infectious bursal disease virus (IBDV) is a lymphotropic virus with cytocidal effect on B lymphocytes of the bursa of Fabricius. We investigated the susceptibility of clonal populations of reticuloendotheliosis virus-transformed chicken B lymphocytes of both spleen and bursal origin to IBDV infection. The infected cells were metabolically-labelled and the viral polypeptides were analyzed by immunoprecipitation using monoclonal antibodies (MAbs). Virus adsorption and the effects of neutralizing convalescent antisera and MAbs on virus attachment were studied using flow cytometry. The results of the study indicate firstly that the transformed B cells support virus replication and provide an efficient system for studying IBDV-lymphocyte interactions. Secondly, results obtained also showed that the most potent neutralizing antibodies may not be those involved in preventing the receptor-mediated viral attachment but rather those involved in the inhibition of downstream events such as virus penetration or uncoating.

Animals↗

Radioimmunoprecipitation of avian reovirus polypeptides using virus-specific IgM and IgG murine monoclonal and chicken polyclonal antibodies.

A simple and improved procedure for radioimmunoprecipitation (RIPA) for the identification of major immunogenic proteins of avian reovirus using murine monoclonal and chicken polyclonal antibodies is described. Bacterial proteins (Staphylococcus aureus-Protein A or Streptococcus species-Protein G) commonly used in RIPA procedures lack reactivities with low avidity monoclonals belonging to immunoglobulin (Ig)G or IgM subtypes, as well as avian Ig. Hence we used an indirect approach utilizing species-specific anti-IgM, IgG or chicken Ig antibodies followed by the precipitation of the immune complexes using Protein A. This improved the sensitivity of the RIPA enabling the antigenic analysis of the major antigenic proteins of avian reovirus. The results indicated that the virus is highly immunogenic in the natural host, chicken than in mice. Furthermore, there exists a direct correlation between a strong neutralizing antibody response and an increased precipitation of the sigma (sigma) proteins of the virus. The results also demonstrate a strong association between the conformational viral epitopes of the three classes of proteins, large (lambda), medium (mu) and small (sigma).

Animals↗

Biological roles of the major capsid proteins and relationships between the two existing serotypes of infectious bursal disease virus.

Neutralizing monoclonal antibodies (n-MAbs) were produced against infectious bursal disease virus (IBDV) of serotypes 1 and 2. The n-MAbs recognizing the major antigenic proteins VP2 and VP3, were characterized using different strains of IBDV representing the existing two serotypes and a variant subtype of serotype 1. The biological properties of these viral antigens as defined by the MAbs in vitro, were studied utilizing post-adsorption virus neutralization tests and fluorescence-activated cell sorter analysis. The MAbs directed against the immunodominant epitopes on VP2 were capable of enhanced virus neutralization but did not inhibit the virus attachment to susceptible cells. These MAbs were able to neutralize the virus by interfering with an event subsequent to virus adsorption, possibly inhibiting virus penetration or uncoating. On the contrary, a MAb that immunoprecipitated the other capsid protein VP3 was able to prevent virus attachment although it possessed lower neutralization titers. Cross-immunoprecipitations of various virus strains by these MAbs and antisera revealed interrelationships between the two serotypes of IBDV.

Antibodies, Monoclonal↗

Analysis of inter-serotypic structural relationships of infectious bursal disease virus using detergent solubilization and radioimmunoprecipitation with monoclonal antibodies.

Monoclonal antibodies (MAbs) neutralizing only the infectious bursal disease virus strains (IBDV) belonging to serotype 1 also immunoprecipitated the heterologous major antigenic proteins of serotype 2 IBDV. Detergent-solubilization followed by radioimmunoprecipitation assays (RIPA) using the MAbs revealed structural similarities between the conformation-dependent antigenic determinants of IBDV of the two existing serotypes. The presence of non-ionic detergent Triton X-100 determined the binding of altered proteins by MAbs in RIPA.

Animals↗

Comparison of neutralizing antigens of recent isolates of infections bursal disease virus.

Monoclonal antibodies (MAbs) to a local turkey isolate (QT-1) of infectious bursal disease virus (IBDV) were produced to identify the virus-specific neutralizing proteins. Radioimmunoprecipitation assays showed that all the MAbs were specific for major viral protein, VP2. Two of the MAbs neutralized the local turkey and chicken isolates along with a reference strain belonging to serotype 1 but not the reference strain of serotype 2. The reactivities of the neutralizing MAbs against two reference strains and some recent field strains of IBDV isolated in the province of Québec were studied by indirect enzyme-linked immunosorbent assay and virus neutralization tests. The variations in the reactivities of the MAbs observed suggest differences in the neutralizing epitopes of the different isolates. Competitive binding assay using the MAbs revealed the presence of a third epitope involved in the neutralization of IBDV belonging to serotype 1.

Animals↗

Sudden death due to unsuspected coronary vasculitis.

Coronary artery vasculitis is a well-recognized complication of polyarteritis nodosa and is occasionally seen in other forms of systemic vasculitis. However, involvement of the major epicardial coronary arteries leading to myocardial infarction and death is uncommon. Isolated coronary arteritis is even more rare. We report three cases of sudden death due to myocardial ischemia associated with arteritis of the major coronary arteries. All three decedents were previously healthy young to middle-aged men who had died suddenly after complaints of chest pain and shortness of breath. The autopsy findings and differential diagnoses are presented. Such cases are of particular interest to the medical examiner because of the sudden, unexpected nature of the deaths. An approach to the correct diagnosis is discussed.

Adult↗

Effects of the Taser in fatalities involving police confrontation.

Sixteen deaths associated with the use of the Taser were examined. All involved young males who had a history of abuse of controlled substances; all but three were under the influence of cocaine, phencyclidine [phenylcyclohexylpiperidine (PCP)], or amphetamine. All were behaving in a bizarre or unusual fashion which necessitated calling the police. The cause of death was an overdose of drugs in eleven, gunshot wounds in three, heart disease and Taser shock in one, and an undetermined cause in one. All were considered to be under the influence of PCP by the police at the time of the incident. All were unarmed, which was the reason a Taser was used instead of a more lethal weapon. The conclusion reached after evaluation of these cases is that the Taser in and of itself does not cause death, although it may have contributed to death in one case.

Adult↗

Rhabdomyolysis following violent behavior and coma.

An individual suspected of being under the influence of phencyclidine (PCP) exhibited acute psychotic and violent behavior which was followed by cardiac arrest, coma, and renal failure. Sections of the damaged muscle showed rhabdomyolysis, and sections of the kidneys showed myoglonin casts positive for immunoperoxidase stain. Extensive toxicology studies for narcotics, PCP, and cocaine were negative. Therefore, a correlation between PCP and rhabdomyolysis associated with acute psychotic and violent behavior could not be made with certainty. The etiology and pathogenesis of rhabdomyolysis are discussed in depth.

Adult↗

Cyclic alternating combination chemotherapy for small cell lung cancer.

Sixty-two patients with small cell carcinoma of lung received cyclic alternating non-cross-resistant combination chemotherapy. Radiation to the chest was given to all the patients. Patients were given a course of VP16, adriamycin and vincristine (VAV) followed by radiation (3,000 rads) to the chest and then a second course of VAV. Three weeks later, a course of cytoxan, CCNU, and methotrexate (CCM) was given (6 weeks). Subsequently, the treatment was cycled between two courses of VAV (6 weeks) and one course of CCM (6 weeks). Overall objective response rate of 73%, with 45% complete response, was noted. Overall median survival was 50 weeks, with 83 weeks for complete responders. Median survival for patients with regional disease was 58 weeks compared to 40 weeks for extensive disease. All the patients headed for complete response did so prior to receiving CCM. These results were not superior to conventional combination chemotherapy regimens.

Adult↗