The structure and function of nodavirus particles: a paradigm for understanding chemical biology.
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Insect Viruses↗
Biomedical subjects
V Reddy
Publications and source records attributed to V Reddy.
Evaluation and comparison of three mobilization methods for the collection of granulocytes.
BACKGROUND: Cancer chemotherapeutic regimens have become more potent and myeloablative. As a consequence, morbidity and mortality due to opportunistic infections have become a major challenge. The provision of adequate doses of viable granulocytes has thus become an important approach for circumventing the problem. A schedule for collecting therapeutic numbers of cells with minimal donor toxicity has yet to be established. STUDY DESIGN AND METHODS: An investigation of three mobilization schedules for the collection of granulocytes for transfusion--granulocyte-colony-stimulating factor (G-CSF) 5 micrograms per kg daily; G-CSF 5 micrograms per kg every other day, and prednisone 60 mg given orally (20 mg doses at 17 hours, 12 hours, and 2 hours before the collection). RESULTS: A total of 464 apheresis procedures involving 163 healthy donors were analyzed. Prednisone caused a small increase in the white cell (WBC) counts over the collection days, while G-CSF every other day and daily schedules improved WBC counts to 145 and 160 percent, respectively (p = 0.004). Similarly, administration of G-CSF daily and every other day mobilized higher yields of granulocytes over the collection days, compared to the prednisone schedule (170% and 180% vs. 105%; p = 0.02). CONCLUSION: Compared with prednisone, higher WBC yields were achieved by G-CSF stimulation; G-CSF given every other day is as effective as daily G-CSF administration for the recruitment of granulocytes, which makes the mobilization procedure more cost-effective.
Administration, Oral↗
An initial trial of a prototype telepathology system featuring static imaging with discrete control of the remote microscope.
Routine diagnosis of pathology images transmitted over telecommunications lines remains an elusive goal. Part of the resistance stems from the difficulty of enabling image selection by the remote pathologist. To address this problem, a telepathology microscope system (TelePath, TeleMedicine Solutions, Birmingham, Ala) that has features associated with static and dynamic imaging systems was constructed. Features of the system include near real time image transmission, provision of a tiled overview image, free choice of any fields at any desired optical magnification, and automated tracking of the pathologist's image selection. All commands and images are discrete, avoiding many inherent problems of full motion video and continuous remote control. A set of 64 slides was reviewed by 3 pathologists in a simulated frozen section environment. Each pathologist provided diagnoses for all 64 slides, as well as qualitative information about the system. Thirty-one of 192 diagnoses disagreed with the reference diagnosis that had been reached before the trial began. Qf the 31, 13 were deferrals and 12 were diagnoses of cases that had a deferral as the reference diagnosis. In 6 cases, the diagnosis disagreed with the reference diagnosis yielding an overall accuracy of 96.9%. Confidence levels in the diagnoses were high. This trial suggests that this system provides high-quality anatomic pathology services, including intraoperative diagnoses, over telecommunications lines.
Diagnostic Imaging↗
Late referral of end-stage renal failure.
We studied all new patients accepted for renal replacement therapy (RRT) in one unit from 1/1/96 to 31/12/97 (n = 198), to establish time from nephrology referral to RRT, evidence of renal disease prior to referral and the adequacy of renal management prior to referral. Sixty four (32.3%, late referral group) required RRT within 12 weeks of referral. Fifty-nine (29.8%) had recognizable signs of chronic renal failure > 26 weeks prior to referral. Patients starting RRT soon after referral were hospitalized for significantly longer on starting RRT (RRT within 12 weeks of referral, median hospitalization 25.0 days (n = 64); RRT > 12 weeks after referral, median 9.7 days (n = 126), (p < 0.001)). Observed survival at 1 year was 68.3% overall, with 1-year survival of the late referral and early referral groups being 60.5% and 72.5%, respectively (p = NS). Hypertension was found in 159 patients (80.3%): 46 (28.9%) were started on antihypertensive medication following referral, while a further 28 (17.6%) were started on additional antihypertensives. Of the diabetic population (n = 78), only 26 (33.3%) were on an angiotensin-converting-enzyme inhibitor (ACEI) at referral. Many patients are referred late for dialysis despite early signs of renal failure, and the pre-referral management of many of the patients, as evidenced by the treatment of hypertension and use of ACEI in diabetics, is less than optimal.
Adult↗
Effect of levamisole on the immune status of malnourished children.
Levamisole is known to enhance an impaired immune response. Its function as an immunostimulant was assessed in malnourished children. A total of 26 children suffering from severe protein-calorie malnutrition were selected for the study. Serum immunoglobulins were estimated in these subjects and to assess cell-mediated immunity, enumeration of T lymphocytes and the lymphocyte proliferative response were carried out. The results show an increase in the cell-mediated immunity response in the levamisole-treated group, thereby suggesting that levamisole may help to speed the recovery of malnourished children suffering from various infections.
Adjuvants, Immunologic↗
Proliferation markers and prognosis in Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a frequently aggressive primary cutaneous neuroendocrine malignancy. We investigated 3 cell proliferation markers which may be useful in predicting the aggressiveness of MCC: 1) p53, a tumor suppressor protein, 2) Ki-67, a marker of cell cycling, and 3) proliferating cell nuclear antigen (PCNA). Twenty patients with MCC were studied. The 3 cell proliferation markers were studied by immunoperoxidase. Clinical and immunoperoxidase results were tabulated according to recurrence or death from disease. Of the 20 patients, 10 experienced recurrence, and 10 did not. Seven tumors were positive for p53. We found correlations between recurrence and death in MCC patients, between p53 positivity and recurrence/death, and between p53 positivity and head/neck primary sites. We found no correlation with recurrence by gender or primary site. PCNA was positive in only 1 patient, while Ki-67 was positive in all patients, making these 2 markers unsuitable for predicting recurrence. Further clinical studies will be helpful to confirm and refine the application of this test. Prognostic information from such studies may be useful in planning observation and treatment for patients in the future.
Aged↗
Immunologic and hematopoietic effects of CD40 stimulation after syngeneic bone marrow transplantation in mice.
CD40 is a molecule present on multiple cell types including B lymphocyte lineage cells. CD40 has been shown to play an important role in B cell differentiation and activation in vitro, although little is known concerning the effects of CD40 stimulation in vivo. We therefore examined the effects of CD40 stimulation in mice using a syngeneic bone marrow transplantation (BMT) model in an effort to augment B cell recovery after high dose therapy with hematopoietic reconstitution. After the BMT, mice were treated with or without 2-6 microg of a soluble recombinant murine CD40 ligand (srmCD40L) given intraperitoneally twice a week. A significant increase in B cell progenitors (B220+/ surface IgM-) was observed in the bone marrow of mice receiving the srmCD40L. The treated recipients also demonstrated improved B-cell function with increases in total serum immunoglobulin and increased splenic mitogen responsiveness to LPS being noted. Additionally, srmCD40L treatment promoted secondary lymphoid organ repopulation, accelerating germinal center formation in the lymph nodes. Total B cell numbers in the periphery were not significantly affected even with continuous srmCD40L administration. Lymphocytes obtained from mice treated with the ligand also had increases in T cell mitogen and anti-CD3 mAb responsiveness and acquired the capability to produce IL-4. Surprisingly, treatment with srmCD40L also produced hematopoietic effects in mice, resulting in an increase of BM and splenic hematopoietic progenitor cells in the mice after BMT. Treatment with srmCD40L significantly increased granulocyte and platelet recovery in the peripheral blood. Incubation of BMC with srmCD40L in vitro also resulted in increased progenitor proliferation, demonstrating that the hematopoietic effects of the ligand may be direct. Thus, stimulation of CD40 by its ligand may be beneficial in accelerating both immune and hematopoietic recovery in the setting of bone marrow transplantation.
Animals↗
Surgical management of traumatic aortic disruption.
BACKGROUND: Acute traumatic disruption of the descending thoracic aorta is a life-threatening injury that requires emergent operative intervention. From May 1988 to August 1996, 27 patients have undergone surgical repair at our institution. METHODS: Diagnosis of aortic disruption was confirmed in all patients by aortogram prior to aortic repair. A Gott shunt was used in 24 patients (89%) and partial femoral-femoral bypass in 1 patient (4%) for distal perfusion. A clamp-and-sew technique was used in 2 patients (7%). RESULTS: Mean aortic clamp time was 44 +/- 3 minutes (range 22 to 80 minutes) in patients with distal perfusion via a Gott shunt. One patient (4%) died within 30 days of aortic repair due to multisystem organ failure. Paraplegia occurred in 1 patient (4%). CONCLUSIONS: With a disciplined, diagnostic and surgical approach for patients with traumatic disruption of the descending thoracic aorta, it is possible to achieve excellent outcomes. The use of a Gott shunt is a simple and effective method for distal perfusion during the repair of traumatic aortic rupture.
Adolescent↗
Studies on section 2D1 monoclonal antibodies.
Monoclonal antibodies in "Other Blood Groups" were tested with random blood samples collected from the various ethnic groups in KwaZulu-Natal, South Africa, and with samples of selected red cell phenotypes. Standard red cell serological techniques were used.
Antibodies, Monoclonal↗
Studies on section 2D3 monoclonal antibodies.
Monoclonal antibodies (MAbs) directed against CD-related antigens were tested with various red cell samples from different ethnic groups in KwaZulu-Natal. The MAbs were tested by standard red cell serological techniques. The MAbs with specificities CD44, CD58 and RBC, reacted with all the samples tested. CD99 was non-reactive. The two Rh?related MAbs showed possible Rh specificity by saline technique, as did one CD47, MAb 2D3-6.
Antibodies, Monoclonal↗
Genetic similarity among Mycobacterium avium isolates from blood, stool, and sputum of persons with AIDS.
Large-restriction-fragment pattern comparison of Mycobacterium avium from 85 blood, stool, and respiratory specimens from 25 human immunodeficiency virus-infected San Francisco patients revealed 4 strains that infected multiple people (3 groups of 2 patients and 1 group of 3 patients). Most patients harbored a single M. avium strain, but 2 strains were recovered from 8 patients. The significance of recovering 2 strains is not clear, since the second strain was seldom recovered more than once. The strain recovered from blood was recovered from stool of 4 patients and respiratory secretions of 6 patients >4 weeks before detection of bacteremia, indicating that the intestinal and respiratory tracts are entry portals from which M. avium can disseminate. M. avium from 21 cities outside of California served as controls. Thus, a single M. avium strain can cause disseminated infection in multiple patients. This may represent infection from a common environmental source or person-to-person spread.
AIDS-Related Opportunistic Infections↗
Identification of amino acids in the transmembrane and juxtamembrane domains of the platelet-derived growth factor receptor required for productive interaction with the bovine papillomavirus E5 protein.
The bovine papillomavirus E5 protein forms a stable complex with the cellular platelet-derived growth factor (PDGF) beta receptor, resulting in receptor activation and cell transformation. Amino acids in both the putative transmembrane domain and extracytoplasmic carboxyl-terminal domain of the E5 protein appear important for PDGF receptor binding and activation. Previous analysis indicated that the transmembrane domain of the receptor was also required for complex formation and receptor activation. Here we analyzed receptor chimeras and point mutants to identify specific amino acids in the PDGF beta receptor required for productive interaction with the E5 protein. These receptor mutants were analyzed in murine Ba/F3 cells, which do not express endogenous receptor. Our results confirmed the importance of the transmembrane domain of the receptor for complex formation, receptor tyrosine phosphorylation, and mitogenic signaling in response to the E5 protein and established that the threonine residue in this domain is required for these activities. In addition, a positive charge in the extracellular juxtamembrane domain of the receptor was required for E5 interaction and signaling, whereas replacement of the wild-type lysine with either a neutral or acidic amino acid inhibited E5-induced receptor activation and transformation. All of the receptor mutants defective for activation by the E5 protein responded to acute treatment with PDGF and to stable expression of v-Sis, a form of PDGF. The required juxtamembrane lysine and transmembrane threonine are predicted to align precisely on the same face of an alpha helix packed in a left-handed coiled-coil geometry. These results establish that the E5 protein and v-Sis recognize distinct binding sites on the PDGF beta receptor and further clarify the nature of the interaction between the viral transforming protein and its cellular target.
Amino Acid Sequence↗
Stroke rehabilitation.
Stroke is the leading cause of brain damage and resultant disability. Rehabilitation measures help to restore lost abilities, improve quality of life and decrease the long-term economic cost of stroke. Proper patient selection, realistic goal setting, the active participation of both the patient and family, and the use of an interdisciplinary team approach are important for the success of stroke rehabilitation. Functional demand and intensive training are believed to trigger central nervous system reorganization, which is responsible for late functional recovery after stroke. The outcome following a stroke is most likely to be positive when patients have bladder and bowel continence, are able to feed themselves and have a healthy and caring spouse. Stroke rehabilitation must include the prevention or early diagnosis of medical complications as well as patient and family education concerning the prevention of recurrent stroke.
Cerebrovascular Disorders↗
After a stroke: strategies to restore function and prevent complications.
Mortality and morbidity are high in elderly stroke patients. Early mobilization and prevention of stroke-related complications improve their ability to participate in a more intense and comprehensive rehabilitation program. An interdisciplinary approach to stroke rehabilitation restores functional loss, improves quality of life, and decreases long-term economic costs. Important parts of stroke rehabilitation include patient and family education, treatment of stroke-related complications, and prevention of recurrent stroke. A healthy and caring spouse, continence of bladder and bowel, and ability to feed oneself are the most positive predictors of stroke outcome.
Aged↗
Body-mind-spirit responses.
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Acupuncture Therapy↗
Preclinical assessment of human hematopoietic progenitor cell transduction in long-term marrow cultures.
Long-term marrow cultures (LTMCs) were established from 27 human marrows. Hematopoietic cells were subjected to multiple rounds of exposure to retroviral vectors during 3 weeks of culture. Seven different retroviral vectors were evaluated. LTMCs were assessed for viability, replication-competent retrovirus, progenitors capable of proliferating in immune-deficient mice, and gene transfer. The average number of adherent cells and committed granulocyte-macrophage progenitors (CFU-GM) recovered from LTMCs was 28% and 11% of the input totals, respectively. There was no evidence by marker rescue assay or polymerase chain reaction (PCR) of replication-competent virus production during LTMC. No toxicity to cellular proliferation due to the transduction procedure was observed. The adherent layers of LTMCs exposed to retroviral vectors were positive for proviral DNA by PCR and by Southern blot analysis. Fifty-three percent of 1,427 individual CFU-GM from transduced LTMC adherent layers were positive for vector-derived DNA. For neocontaining vectors, the average G418 resistance was 28% of 1,393 LTMC-derived CFU-GM. Forty percent of 187 tissues from 30 immune-deficient mice injected with human LTMC cells were positive for human DNA 4-5 weeks after adoptive transfer. These studies indicate that multiple exposures of human LTMCs to retroviral vectors result in consistent and reproducible LTMC viability and gene transfer into committed progenitors. Our results further support the use of transduced LTMC cells in clinical trials of hematopoietic stem cell gene transfer.
Animals↗
The 2.8 A structure of a T = 4 animal virus and its implications for membrane translocation of RNA.
Simple RNA animal viruses generally enter cells through receptor-mediated endocytosis followed by acid pH dependent release and translocation of RNA across the endosomal membrane. The T = 3 nodaviruses contain prefabricated pentameric helical bundles that are cleaved from the remainder of the subunits by an assembly-dependent auto-proteolysis and they are positioned for release through 5-fold axes of the particle. We previously proposed that these bundles may serve as conduits for RNA membrane translocation. Additional support for this hypothesis is now provided by the first atomic resolution structure of a T = 4 RNA virus, where we find cleavage sites and helical bundles nearly identical with those observed in T = 3 nodaviruses. The helices are of sufficient length to span a membrane bilayer and the internal diameter of the coiled bundle could accommodate ssRNA. The T = 4 particle has a mean outer diameter of 410 A and is formed by 240 copies of a single subunit type. The subunit is composed of a helical inner domain (where the cleavage occurs) containing residues preceding and following a canonical, viral, eight-stranded beta-sandwich that forms the contiguous shell. Inserted between two strands of the shell domain are 133 residues with an immunoglobulin c-type fold. The initial gene product consists of 644 amino acid residues and is cleaved between residues Asn570 and Phe571 in the mature particle determined in this analysis.
Biological Transport↗
Do excimer laser angioplasty and rotational atherectomy facilitate balloon angioplasty? Implications for lesion-specific coronary intervention.
OBJECTIVES: This study sought to determine whether adjunctive balloon angioplasty after rotational atherectomy and excimer laser angioplasty provides better lumen enlargement ("facilitated angioplasty") than angioplasty alone. BACKGROUND: Adjunctive angioplasty is often used immediately after atherectomy and laser angioplasty to further enlarge lumen dimensions, but it is not known whether this practice is superior to angioplasty alone. METHODS: Balloon angioplasty was performed in 1,266 native coronary lesions alone (n = 541) or after extraction atherectomy (n = 277), rotational atherectomy (Rotablator) (n = 211) or excimer laser angioplasty (n = 237). Quantitative angiographic analysis included final lumen diameter, final diameter stenosis and efficiency of balloon-mediated lumen enlargement. RESULTS: Compared with angioplasty alone (33 +/- 12% [mean +/- SD]), final diameter stenosis was higher for adjunctive angioplasty after extraction atherectomy (37 +/- 16%, p < 0.001) and excimer laser angioplasty (37 +/- 16%, p < 0.001) and lower after rotational atherectomy (27 +/- 15%, p < 0.001). However, there was significant undersizing of balloons after all three devices. To correct for differences in balloon size, the efficiency index (final lumen diameter/balloon diameter ratio) was calculated and was higher for adjunctive angioplasty after the Rotablator (0.78 +/- 0.14, p < 0.001) than after angioplasty alone (0.69 +/- 0.12). The efficiency indexes suggested facilitated angioplasty after rotational atherectomy for ostial, eccentric, ulcerated and calcified lesions and lesions > 20 mm long. Facilitated angioplasty was also observed after extraction atherectomy and excimer laser angioplasty for ostial lesions, but not for any other lesion subsets. CONCLUSIONS: Rotational atherectomy, extraction atherectomy and excimer laser angioplasty can facilitate the results of balloon angioplasty. However, the extent of facilitated angioplasty is dependent on the device and baseline lesion morphology, consistent with the need for lesion-specific coronary intervention.
Aged↗