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Biomedical subjects

B Shapiro

Publications and source records attributed to B Shapiro.

At least 37 records · Page 2Linked to original sources
PubMed2001

Molecular dynamics simulations of the denaturation and refolding of an RNA tetraloop.

Tetraloops are very abundant structural elements of RNA that are formed by four nucleotides in a hairpin loop which is closed by a double stranded helical stem with some Watson-Crick base pairs. A tetraloop r(GCGAAGGC) was identified from the crystal structure of the central domain of 16S rRNA (727-730) in the Thermus thermophilus 30S ribosomal complex. The crystal structure of the 30S complex includes a total of 104 nucleotides from the central domain of the 16S rRNA and three ribosomal proteins S6, S15 and S18. Independent biochemical experiments have demonstrated that protein S15 plays the role in initiating the formation of the central domain of this complex. In the crystal, the tetraloop interacts with the protein S15 at two sites: one of them is associated with hydrogen bond interactions between residue His50 and nucleotide G730, and the other is associated with the occurrence of residue Arg53 beside A728. This paper uses molecular dynamics (MD) simulations to investigate the protein-dependent structural stability of the tetraloop and demonstrates the folding pathway of this tetraloop via melting denaturation and its subsequent refolding. Three important results are derived from these simulations: (i) The stability of nucleotide A728 appears to be protein dependent. Without the interaction with S15, A728 flips away from stacking with A729. (ii) The melting temperature demonstrated by the simulations is analogous to the results of thermodynamic experiments. In addition, the simulated folding of the tetraloop is stepwise: the native shape of the backbone is formed first; this is then followed by the formation of the Watson- Crick base pairs in the stem; and finally the hydrogen bonds and base stacking in the loop are formed. (iii) The tetraloop structure is similar to the crystal structure at salt concentrations of 0.1 M and 1.0 M used for the simulations, but the refolded structure at 0.1 M salt is more comparable to the crystal structure than at 1.0 M. The results from the simulations using both the Generalized Born continuum model and explicit solvent model (Particle Mesh Ewald) generate a similar pathway for unfolding/refolding of the tetraloop.

Arginine↗
PubMed2001

Parathyroid carcinoma. A concise review.

Parathyroid carcinoma is a very rare malignancy and the least common among endocrine malignat tumors. Its etiology is still unclear and some hypotheses have been suggested: previous external radiation to the neck, pregression from benign to malignant lesion, familial hyperparathyroidism. An early accurate diagnosis is very important since surgery is the most effective therapeutic approach to parathyroid carcinoma. Prognosis is quite variable and stress is laid on the early diagnosis and radical surgery which seem to be most favorable prognostic factors. An accurate follow-up should include frequent measurements of serum calcium and PTH levels to promptly detect recurrence or metastases which are usually associated with severe hyeprcalcemia.

Carcinoma↗
PubMed2001

Clinical role of 99mTcO4/MIBI scan, ultrasound and intra-operative gamma probe in the performance of unilateral and minimally invasive surgery in primary hyperparathyroidism.

The main purposes of this study were: (a) to investigate the efficacy of an imaging protocol based on the combination of 99mTcO4/MIBI scintigraphy and neck ultrasound (US) in selecting patients with primary hyperparathyroidism (HPT) for unilateral neck exploration, and (b) to help define the role of the intraoperative MIBI gamma probe (IMGP) technique in the performance of minimally invasive radio-guided surgery (MIRS). One hundred and forty-three consecutive patients with primary HPT were enrolled in the study. We used a modified 99mTcO4/MIBI scintigraphic procedure which included the oral administration of potassium perchlorate to cause rapid 99mTcO4 washout from the thyroid tissue, thereby permitting the acquisition of high-quality early MIBI images. A single-photon emission tomography (SPET) acquisition was also obtained in 21 patients, of whom seven had an enlarged parathyroid gland (EPG) in the mediastinum at planar scintigraphy and 14 had discordant scan/US findings for the presence of a cervical EPG. Neck US was performed in the same session as scintigraphy using a small-parts, high-resolution 10-MHz transducer. All patients were then operated on by the same surgical team. Quick PTH assay (QPTH) was used to measure PTH intraoperatively to confirm successful parathyroidectomy. In patients with scan/US evidence of a solitary EPG and with a normal thyroid gland, limited, unilateral neck surgery or, more recently, MIRS was planned (n=91). In patients with scan/US evidence of multiglandular disease (MGD) (n=21) or concomitant nodular goitre (n=24) or in patients with a negative scan/US evaluation (n=7), extensive bilateral neck exploration was planned (n=52). In 87 of the 91 patients (95.6%) in whom preoperative imaging indicated the presence of a solitary EPG and a normal thyroid gland, a single parathyroid adenoma was found at surgery, and these patients were treated by unilateral neck exploration or MIRS. In the remaining four patients of this group, conversion to bilateral neck exploration was required because parathyroid carcinoma (n=3) or MGD (n=1) was diagnosed at operation. In some cases SPET was helpful in better localising the EPG. In particular, in 5 of the 21 patients evaluated, SPET localised an EPG deep in the neck or mediastinum and at surgery a parathyroid adenoma was found in the paratracheal or para-oesophageal space. In 43 of the 46 patients (93.5%) who were candidates for MIRS, the IMGP technique allowed parathyroidectomy to be performed through a small, 2- to 2.5-cm skin incision with a short duration of intervention (mean 34 min). We conclude that: (a) The integrated scan/US imaging protocol that we used appears to be accurate in selecting patients with primary HPT for unilateral neck exploration. (b) In our series the most prevalent cause of bilateral neck exploration was the co-existence of a nodular goitre; thus accurate preoperative evaluation of the thyroid gland by dual-tracer scintigraphy and US imaging is strongly recommended in all patients with HPT. (c) SPET can provide the surgeon with useful information when an EPG is located deep in the neck or mediastinum. (d) IMGP appears to be a useful intraoperative device in HPT patients with solitary parathyroid adenomas and a normal thyroid gland, since it permits minimally invasive and time-saving surgery.

Adenoma↗
PubMed2001

Imaging of human infection with (131)I-labeled recombinant human interleukin-8.

UNLABELLED: The chemotactic cytokine interleukin-8 (IL-8) plays an important role in attraction and activation of polymorphonuclear leukocytes in infection and inflammation. A pilot study was conducted to determine if radiolabeled IL-8 would depict infection in humans. METHODS: Human recombinant IL-8 (rhIL-8) labeled with (131)I (specific activity, 0.4-0.7 MBq [11-18 microCi] (131)I/microg IL-8) was injected intravenously into 8 diabetic patients with active foot infections and evidence of osteomyelitis, 2 patients with successfully treated osteomyelitis, and 1 patient with cellulitis of the thumb. RESULTS: Focal accumulation of (131)I-rhIL-8 was seen in 8 of 8 patients with active foot infection and diffuse uptake was seen in the thumb of the 1 patient with cellulitis. In the 2 patients with successfully treated bone infection, multiphase (99m)Tc-hydroxyethylene diphosphonate bone scans were negative early, but late-phase (>3 h) uptake depicted degenerative lesions that did not image with (131)I-rhIL-8. CONCLUSION: (131)I-rhIL-8 accumulates rapidly within infected foci in osteomyelitis and cellulitis but not in successfully treated infections or degenerative joint disease.

Adult↗
PubMed2001

Perioperative hypoxia. The clinical spectrum and current oxygen monitoring methodology.

When searching for the source of hypoxia, the anesthesiologist and intensivist one served best by treating the patient in an organized approach--beginning with the environmental and pulmonary sources, searching for anemic and circulatory sources, and finally ruling out the less common histocytic causes. When treating hypoxia, the first maneuver should be to administer oxygen, ensure airway, ventilation, and circulation (the ABCs of basic life support). Further monitoring is addressed at global assessments and specific organ systems (especially in high-risk patients or during high-risk procedures). The ability to directly measure the oxygenation, blood flow, and function in each individual organ of the body is not yet available. Efforts are advancing in the ability to measure the function of important tissue beds, such as the brain and splanchnic circulation. In this regard, Table 5 provides a summary of the spectrum of monitoring technology available for various organs.

Anemia↗
PubMed2000

Mutations in a conserved enteroviral RNA oligonucleotide sequence affect positive strand viral RNA synthesis.

We showed earlier that a transition mutation U234C, located within the completely conserved 5 nucleotide (nt) tract 5'-CGUUA (nt232-236) in the 5' non-translated region (NTR) of the coxsackievirus B3 (CVB3) genome, attenuated CVB3 cardiovirulence in mice. To further explore the role of the sequence, we induced two single and one double transversion mutations in the conserved 5mer in a cardiovirulent CVB3 genome. The mutated sites partially or totally reverted to parental wild-type when progeny viruses were passaged at 37 degrees C, but remained stable when transfection and subsequent passages were performed at 33.5 degrees C. Viral replication in cell culture was attenuated at 37 degrees C or 39.5 degrees C relative to replication at 33.5 degrees C. While Western blot analysis demonstrated the level of protein translation consistent with virus replication, the ratios of positive to negative strand viral RNA at 37 degrees C in murine cells demonstrated a 2-5 fold diminution from those measured at 33.5 degrees C. Mutant CVB3 strains failed to replicate productively when inoculated into mice. The biological data are consistent with an hypothesis that proposes a lesion with primary effects at the level of positive strand viral RNA synthesis that results in attenuation of viral replication at physiologic temperature.

5' Untranslated Regions↗
PubMed2000

Artifacts, anatomical and physiological variants, and unrelated diseases that might cause false-positive whole-body 131-I scans in patients with thyroid cancer.

The whole body 131-I scan remains an important component in the postoperative treatment of patients with well-differentiated thyroid cancer. Because normal thyroid tissue remnants and residual or metastatic foci of well-differentiated thyroid cancer have the unique ability to concentrate, organify, and store 131-I, the whole body scan provides a depiction of those tissues that can be ablated with therapeutic doses of 131-I. Over time, it has become obvious that the whole body scan may also reveal foci of 131-i uptake owing to a wide variety of other causes. We provide a detailed pathophysiological classification of the artifacts, anatomic and physiological variants, and nonthyroidal diseases that may give rise to false-positive whole body scans in postoperative patients with thyroid cancer. These include ectopic foci of normal thyroid tissue; nonthyroidal physiological sites (eg, choroid plexus, salivary glands, gastric mucosa, urinary tract); contamination by physiological sections; ectopic gastric mucosa; other gastrointestinal abnormalities; urinary tract abnormalities; mammary abnormalities; serous cavities and cysts; inflammation and infection; nonthyroidal neoplasms; and currently unexplained causes. This article also provides a detailed review of the widely scattered English language literature in which these phenomena were originally described.

Artifacts↗
PubMed2000

Redistribution of Bax is an early step in an apoptotic pathway leading to germ cell death in rats, triggered by mild testicular hyperthermia.

Programmed cell death occurs spontaneously during spermatogenesis and can be induced in a cell- and stage-specific manner by mild testicular hyperthermia. Studies using transgenic mice suggest the involvement of Bcl-2 proteins in regulating germ cell apoptosis. To delineate further the pathways involved, we examined the temporal changes in proapoptotic Bax and antiapoptotic Bcl-2 in rat testes after transient exposure to heat (43 degrees C for 15 min). Germ cell apoptosis, involving exclusively early (I-IV) and late (XII-XIV) stages, was activated within 6 h. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to perinuclear localization within 0.5 h of heating as assessed by immunocytochemical methods. In contrast, Bcl-2 is distributed both in the cytoplasm and nucleus in those cell types susceptible to heat-induced apoptosis. Despite the striking redistribution, Bax levels remained unchanged as determined by Western analysis; Bcl-2 levels increased significantly by 6 h after heat exposure. Reverse transcription-polymerase chain reaction analysis indicated no change in either Bax or Bcl-2 mRNA levels in response to heat, suggesting the involvement of post-transcriptional rather than transcriptional mechanisms mediating their activity. The marked subcellular redistribution of Bax prior to activation of apoptosis and the increase in Bcl-2 suggest an involvement of Bcl-2 family members in heat-induced apoptotic death of germ cells.

Animals↗
PubMed1999

Students' perceptions of their psychiatric mental health clinical nursing experience: a personal construct theory exploration.

Personal construct theory and repertory grid technique provides a suitable framework for exploring Registered Nursing students' perceptions of their psychiatric practicum. This descriptive research was designed to understand students' own ways of constructing knowledge during their mental health clinical experience. A constructivist conceptual perspective and George Kelly's personal construct psychology were the theoretical bases of the research. A qualitative case study methodology allowed creation of and reflection on personal construct changes as provided in participants' review of repertory grid ideas about psychiatric nursing. The participants were six Canadian second-year nursing students in a Baccalaureate programme that integrated psychiatric and medical surgical nursing curricula. The following three overarching themes were identified and are used to explain and describe significant features of the psychiatric clinical experience: 1) students' anxiety related more to feeling unable to help than to interactions with mentally ill patients; 2) students' feelings of a lack of inclusion in staff nurse groups; 3) student emphasis on the importance of nonevaluated student-instructor discussion time.

Anxiety↗
PubMed1999

Stem Trace: an interactive visual tool for comparative RNA structure analysis.

MOTIVATION: Stem Trace is one of the latest tools available in STRUCTURELAB, an RNA structure analysis computer workbench. The paradigm used in STRUCTURELAB views RNA structure determination as a problem of dealing with a database of a large number of computationally generated structures. Stem Trace provides the capability to analyze this data set in a novel, visually driven, interactive and exploratory way. In addition to providing graphs at a high level of ion, it is also connected with complementary visualization tools which provide orthogonal views of the same data, as well as drawing of structures represented by a stem trace. Thus, on top of being an analysis tool, Stem Trace is a graphical user interface to an RNA structural information database. RESULTS: We illustrate Stem Trace's capabilities with several examples of the analysis of RNA folding data performed on 24 strains of HIV-1, HIV-2 and SIV sequences around the HIV dimerization region. This dimer linkage site has been found to play a role in encapsidation, reverse transcription, recombination, and inhibition of translation. Our examples show how Stem Trace elucidates preservation of structures in this region across the various strains of HIV. AVAILABILITY: The program can be made available upon request. It runs on SUN, SGI and DEC (Compaq) Unix workstations.

Algorithms↗
PubMed1999

Treatment of malignant pheochromocytomas with 131-I metaiodobenzylguanidine and chemotherapy.

Malignant pheochromocytomas have exhibited partial responses to treatments with 131-I metaiodobenzylguanidine (MIBG) and with chemotherapy. The authors combined these two therapeutic methods to determine if beneficial effects from each would be additive. Patients with documented malignant pheochromocytomas were recruited with the intent of administering 131-I MIBG in three substantial amounts of radioactivity at 3-month intervals followed by a year of chemotherapy in which cyclophosphamide, dacarbazine, and vincristine were to be given in 21-day cycles. Six patients entered the protocol. After the 131-I MIBG treatments, three patients manifested declines in the presence of tumor (smaller tumor volume or abnormalities on bone and 131-I MIBG scans) and the function of tumor (decreased rate of normetanephrine excretion as the major index). Two patients completed at least 9 months of chemotherapy and showed further reductions in the presence and function of tumors and were classified as having partial responses. Progressive disease afflicted three of the other four subjects. Even though toxicity was minimal from 131-I MIBG, it was sufficient to force reduction in the dosages or duration of chemotherapy. A combination of 131-I MIBG treatments and chemotherapy produced additive effects in reducing malignant pheochromocytomas. Toxicity moderately curtailed the proposed chemotherapy protocol.

3-Iodobenzylguanidine↗
PubMed1999

Pheochromocytomas: imaging with 2-[fluorine-18]fluoro-2-deoxy-D-glucose PET.

PURPOSE: To assess the sensitivity of positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in pheochromocytomas and, secondarily, to compare images obtained with FDG PET to those obtained with metaiodobenzylguanidine (MIBG) scintigraphy. MATERIALS AND METHODS: Twenty-nine patients with one or more known or subsequently proved pheochromocytomas underwent FDG PET (35 scans) and MIBG scintigraphy (35 scans). Tumor uptake of FDG was quantified on positive PET scans. RESULTS: Tumor uptake of FDG was detected in 22 of 29 patients. Most benign (seven of 12 patients) and most malignant (15 of 17 patients) pheochromocytomas and their metastases avidly concentrated FDG. In four patients whose pheochromocytomas failed to accumulate MIBG, uptake of FDG in the tumors was intense. For the majority of the 16 patients whose tumors concentrated both agents, however, ratings for MIBG images compared to FDG PET images for delineation of the tumor in comparison to background and normal organ accumulation were superior for nine patients (56%) and as good or better for 14 (88%). CONCLUSION: Most pheochromocytomas accumulate FDG. Uptake is found in a greater percentage of malignant than benign pheochromocytomas. FDG PET is especially useful in defining the distribution of those pheochromocytomas that fail to concentrate MIBG.

3-Iodobenzylguanidine↗
PubMed1999

Somatostatin receptor scintigraphy of a patient with a giant invasive prolactinoma.

A 41-year-old with a giant prolactinoma underwent in-111 pentetreotide (Octreotide) imaging showing very intense tracer uptake in the region of the anterior skull base. In contrast, there was no significant response to Octreotide therapy. Prediction of clinical responsiveness to Octreotide therapy in patients with pituitary adenomas may depend on the presence of somatostatin receptor subtype 5. Pentetreotide does not avidly bind to this receptor subtype and therefore, cannot be used clinically to predict therapeutic Octreotide responsiveness in patients with large prolactinomas.

Adult↗