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Biomedical subjects

D Peterson

Publications and source records attributed to D Peterson.

At least 109 records · Page 6Linked to original sources

Analysis of cell type and radiographic presentation as predictors of the clinical course of patients with bronchioalveolar cell carcinoma.

STUDY OBJECTIVES: Bronchioloalveolar carcinoma is a primary lung neoplasm of variable histopathologic, radiologic, and clinical expression. There are three cell types described in bronchioloalveolar carcinoma: Clara cells, mucin-producing cells, and alveolar type II epithelial cells. It is unclear whether these three tumor cell types are associated with a specific radiologic presentation and clinical course. In this study, we investigated whether tumor cell type, identified by transmission electron microscopy, correlated with a specific radiologic pattern, and whether tumor cell type or radiologic presentation correlated with the patient's clinical course and outcome. DESIGN: Transmission electron microscopy was used to restudy tissue blocks from the original surgical histopathologic specimens in 54 patients with primary bronchioloalveolar carcinoma diagnosed over a 10-year period (1980 to 1990). The pretreatment radiographs were reviewed in each case, and the first chest radiograph obtained at the time of the discovery of the tumor in each patient was compared with the results of the ultrastructural study. The medical records of each patient were examined to obtain pertinent radiologic, clinical, and patient outcome information. MEASUREMENT AND RESULTS: There were 32 Clara cell tumors, 10 mucin-producing cell tumors, and 1 alveolar type II epithelial cell tumor in this series. Eleven additional tumors had mixtures of two or more cell types. No statistically significant relationship was detected between tumor cell type and radiologic presentation or patient mortality pattern. There was increased mortality among patients who presented radiologically with segmental, lobar, multifocal, or diffuse disease compared with those patients exhibiting a solitary pulmonary nodule at presentation. CONCLUSION: Radiologic presentation, rather than tumor cell type, provides prognostic information that aids in predicting patient outcome.

Adenocarcinoma, Bronchiolo-Alveolar↗

Diagnosis and surgical repair of partial atrioventricular septal defects in two dogs.

Partial atrioventricular (AV) septal defects consist of an ostium primum defect and malformation of the septal cusp of the mitral valve. A partial AV septal defect was diagnosed by means of echo-cardiography in 2 dogs. Transatrial septal blood flow was high enough in both dogs to warrant surgical correction. Defects were repaired through right fifth intercostal thoracotomies, with the aid of cardiopulmonary bypass. An incision was made in the right atrium to expose the AV septal defect, and the mitral valve was inspected through the septal defect. The cleft in the septal cusp of the mitral valve was repaired with mattress sutures of 6-0 polypropylene. The septal defect was closed with autogenous pericardium harvested from the right aspect of the pericardial sac. Both dogs survived surgery and were alive 15 and 42 months, respectively, after surgery, however, 1 dog developed progressive mitral regurgitation after surgery. Partial AV septal defects can be successfully repaired in dogs. Long-term prognosis probably depends on the adequacy of the mitral valve repair.

Animals↗

Mutations of critical amino acids affect the biological and biochemical properties of oncogenic A-Raf and Raf-1.

The catalytic domains of the Raf family of protein kinases (deltaRaf) differ in their ability to activate MEK in vitro and in vivo and in their ability to oncogenically transform mammalian cells. The kinase domain of B-Raf is more active than the equivalent portion of Raf-1 which in turn is more active than A-Raf. In Raf-1 the phosphorylation or mutation to aspartic acid of two key tyrosine residues upstream of the ATP binding site has been demonstrated to significantly potentiate catalytic activity. In A-Raf the analogous amino acids are also tyrosine whereas in B-Raf they are aspartic acid. To determine if these differences in amino acid sequence influence the relative catalytic activity of the Raf kinase domains we constructed forms of deltaA-Raf, deltaB-Raf and deltaRaf-1 that encode either aspartic acid [DD], phenylalanine [FF] or tyrosine [YY] at these positions. These proteins were expressed both in mammalian cells as fusions with the hormone binding domain of the estrogen receptor and as epitope-tagged proteins in Sf9 insect cells to test their oncogenic and catalytic potentials. When expressed in Rat1 or 3T3 cells in the presence of hormone all of the deltaRaf-1:ER and deltaA-Raf:ER proteins were transforming with the exception of the [FF] form of deltaA-Raf. In general the [DD] forms of the deltaRaf-1:ER and deltaA-Raf:ER proteins were the most potently oncogenic which correlated with their ability to elicit activation of the MAP kinase pathway. Consistent with the transformation data, the catalytic activity of the [DD] forms of deltaA-Raf:ER and deltaRaf-1:ER was about ten times greater than the cognate [FF] and [YY] forms of the proteins. By contrast all of the deltaB-Raf:ER proteins were highly transforming and deltaB-Raf catalytic activity was largely unaffected by mutation of the aforementioned aspartic acids to either tyrosine or phenylalanine. Similar results were obtained with epitope-tagged forms of deltaA-Raf, deltaB-Raf and deltaRaf-1 expressed in Sf9 cells. These data provide support for the model that key tyrosine residues in the protein kinase domains of A-Raf and Raf-1 are important in the regulation of catalytic activity. In addition they demonstrate that the higher intrinsic activity of B-Raf cannot be explained simply by the presence of aspartic acids at the analogous positions.

Amino Acids↗

Low energy Helium-Neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial.

PURPOSE: To evaluate the efficiency of Helium-Neon (He-Ne) laser in the prevention of oral mucositis induced by high dose chemoradiotherapy before autologous bone marrow transplantation (BMT). METHODS AND MATERIALS: Between 1993 and 1995, 30 consecutive patients receiving an autologous peripheral stem-cell or bone marrow transplant (BMT) after high dose chemoradiotherapy were randomized to possibly receive prophylactic laser to the oral mucosa after giving informed consent. Chemotherapy consisted of cyclophosphamide, 60 mg/kg intravenously (I.V.) on day (d)-5 and d-4 in 27 cases, or melphalan 140 mg/kg I.V. on d-4 in three cases. Total body irradiation (TBI) consisted of 12 Gy midplane dose in six fractions (4 Gy/day for three days). He-Ne laser (632.8 nm wavelength, power 60 mW) applications were performed daily from d-5 to d-1 on five anatomic sites of the oral mucosa. Oral examination was performed daily from d0 to d + 20. Mucositis was scored according to an oral exam guide with a 16 item scale of which four were assessed by the patients themselves. Mean daily self assessment scores for oral pain, ability to swallow and oral dryness were measured. A daily mucositis index (DMI) and a cumulative oral mucositis score (COMS) were established. Requirement for narcotics and parenteral nutrition was recorded. RESULTS: The COMS was significantly reduced among laser treated (L+) patients (p = 0.04). The improvement of DMI in L+ patients was also statistically significant (p < 0.05) from d + 2 to d + 7. Occurrence and duration of grade III oral mucositis were reduced in L+ patients (p = 0.01). Laser applications reduced oral pain as assessed by patients (p = 0.05) and L+ patients required less morphine (p = 0.05). Xerostomia and ability to swallow were improved among the L+ patients (p = 0.005 and p = 0.01, respectively). Requirement for parenteral nutrition was not reduced (p = NS). CONCLUSION: Helium-Neon laser treatment was well tolerated, feasible in all cases, and reduced high dose chemoradiotherapy-induced oral mucositis. Optimal laser treatment schedules still needs to be defined.

Adolescent↗

Ectopic expression of A-myb in transgenic mice causes follicular hyperplasia and enhanced B lymphocyte proliferation.

The A-myb gene is a transcription factor that shares structural and functional similarities with the v-myb oncogene. To date, v-myb is the only myb gene directly implicated in tumorigenesis, a property attributed to its transactivating ability. Recent studies have demonstrated that A-myb, like v-myb, is a potent transcriptional activator, raising the possibility that A-myb may also participate in oncogenesis. To test this hypothesis, we generated fusion constructs that contained the human A-myb cDNA under control of the mouse metallothionein promoter and the mouse mammary tumor virus long terminal repeat. These constructs were inserted into the germ line of mice, and the functional consequences of ectopic A-myb expression were examined. Although transgene expression was detected in a wide range of tissues, abnormalities were confined primarily to hematopoietic tissues. After a 9-month latency, A-myb transgenic mice developed hyperplasia of the spleen and lymph nodes. Enlarged tissues contained a polyclonally expanded B lymphocyte population that expressed a germinal center-cell phenotype. Transgenic B lymphocytes showed increased DNA synthesis in response to low dose mitogen stimulation, suggesting that A-myb may contribute to hyperplasia by increasing the rate of B cell proliferation.

Animals↗

Soluble and membrane-bound forms of signaling lymphocytic activation molecule (SLAM) induce proliferation and Ig synthesis by activated human B lymphocytes.

In this study it is shown that both membrane-bound and soluble forms of signaling lymphocytic activation molecule (SLAM) induce proliferation and Ig synthesis by activated human B cells. Activated B cells express the membrane-bound form of SLAM (mSLAM), the soluble (s) and the cytoplasmic (c) isoforms of SLAM, and the expression levels of mSLAM on B cells are rapidly upregulated after activation in vitro. Importantly, recombinant sSLAM and L cells transfected with mSLAM efficiently enhance B cell proliferation induced by anti-mu mAbs, anti-CD40 mAbs or Staphylococcus aureus Cowan I (SAC) in the presence or absence of IL-2, IL-4, IL-10, IL-12, or IL-15. sSLAM strongly enhances proliferation of both freshly isolated B cells and B cells derived from long-term in vitro cultures, indicating that SLAM acts not only during the initial phase of B cell activation but also during the expansion of preactivated B cells. In addition, sSLAM enhances production of IgM, IgG, and IgA by B cells activated by anti-CD40 mAbs. SLAM has recently been shown to be a high affinity self-ligand, and the present data suggest that signaling through homophilic SLAM-SLAM binding during B-B and B-T cell interactions enhances the expansion and differentiation of activated B cells.

Animals↗

Factors contributing to recurrent carotid disease following carotid endarterectomy.

BACKGROUND: Retrospective analysis was performed to assess the effect of gender, age, hypertension, diabetes, and smoking upon residual disease, recurrent disease, and progression of disease following carotid endarterectomy (CE). The effect of patch versus primary closure was also studied. METHODS: Postoperative duplex studies were performed following 323 CEs at months 1, 6, 12, and 24. Residual disease was defined as luminal stenosis >59% at 1 month. Progression of disease was defined as stenosis at any month that was greater than stenosis at month 1. Recurrent disease was nonresidual stenosis >79%. RESULTS: Correlation was found between age at operation <65 years and cigarette smoking; both also correlated with progression of disease on serial studies, as well as recurrent stenosis <79%. Primary closure of the arteriotomy correlated with residual disease. CONCLUSION: Primary closure of the arteriotomy following CE increases the likelihood of residual disease. Smokers and those aged <65 years are predisposed to progression of postoperative disease, and to development of recurrent stenosis.

Age Factors↗

Liposome-mediated gene transfer to lung isografts.

OBJECTIVES: Our objective were to determine the feasibility, efficacy, and safety of in vivo and ex vivo liposome-mediated gene transfer to lung isografts. METHODS: Fischer rats were divided into three main groups: (1) Nontransplant setting: Liposome-chloramphenicol acetyl transferase cDNA was intravenously injected, and lungs were harvested at different time points: 2, 6, 12, and 24 hours; 2, 5, 8, and 21 days (n = 3). Chloramphenicol acetyl transferase activity was determined in lungs, hearts, livers, and kidneys. The distribution and type of transfected cells were evaluated by in situ hybridization. Lung toxicity was assessed by arterial oxygen tension, histology, and tumor necrosis factor-alpha levels. (2) In vivo graft transfection: Left lungs were transplanted 6 hours, 4 hours, and 15 minutes after intravenous injection and were assessed for chloramphenicol acetyl transferase activity and arterial oxygen tension on postoperative day 2. (3) Ex vivo graft transfection: Grafts were infused ex vivo with either 660 micrograms (n = 3) or 330 micrograms (n = 3) of DNA complexed to liposomes and stored at 10 degrees C for 4 hours. Chloramphenicol acetyl transferase activity was assessed 44 hours after transplantation. RESULTS: Transgene expression was detected in endothelial cells, macrophages, and interstitial cells. Chloramphenicol acetyl transferase activity was present as early as 2 hours, increased significantly between 6 hours and 8 days, and then decreased to minimal levels by 21 days. Chloramphenicol acetyl transferase activity was greatest in donor lungs and hearts and minimal in livers and kidneys. Arterial oxygen tension was normal in treated animals. Inflammation was minimal, and tumor necrosis factor-alpha levels increased only sevenfold in treated animals. CONCLUSION: In vivo and ex vivo liposome-mediated gene transfer to lung isografts allows significant transgene expression with minimal effects on graft function.

Animals↗

Immunization with hybrid hepatitis B virus core particles carrying circumsporozoite antigen epitopes protects mice against Plasmodium yoelii challenge.

The hepatitis B virus nucleocapsid antigen (HBcAg) was investigated as a carrier moiety for circumsporozoite protein (CS) repeat B cell epitopes of the rodent malaria agent Plasmodium yoelii. A vector expressing a hybrid gene coding for the dominant CS repeat epitope (QGPGAP)4 was constructed and transformed into avirulent Salmonella typhimurium. The resulting hybrid HBcAg-CS polyproteins were purified from recombinant Salmonella typhimurium. They purified as particles and displayed HBc as well as P. yoelii CS antigenicity. To investigate immunogenicity and protective efficacy, BALB/c mice were immunized with the hybrid HBcAg-CS particles. Immunization resulted in high titered antinative CS serum IgG antibody litres. BALB/c mice immunized with hybrid HBcAgCS particles were between 90-100% protected against subsequent P. yoelli challenge. Protective immunity persisted for a minimum of three months. These data confirm the previous suggestion (Schödel et al., 1994), that hybrid HBcAg particles could become a useful component of future human malaria vaccines.

Amino Acid Sequence↗

Identification of a novel selD homolog from eukaryotes, bacteria, and archaea: is there an autoregulatory mechanism in selenocysteine metabolism?

Escherichia coli selenophosphate synthetase (SPS, the selD gene product) catalyzes the production of monoselenophosphate, the selenium donor compound required for synthesis of selenocysteine (Sec) and seleno-tRNAs. We report the molecular cloning of human and mouse homologs of the selD gene, designated Sps2, which contains an in-frame TGA codon at a site corresponding to the enzyme's putative active site. These sequences allow the identification of selD gene homologs in the genomes of the bacterium Haemophilus influenzae and the archaeon Methanococcus jannaschii, which had been previously misinterpreted due to their in-frame TGA codon. Sps2 mRNA levels are elevated in organs previously implicated in the synthesis of selenoproteins and in active sites of blood cell development. In addition, we show that Sps2 mRNA is up-regulated upon activation of T lymphocytes and have mapped the Sps2 gene to mouse chromosome 7. Using the mouse gene isolated from the hematopoietic cell line FDCPmixA4, we devised a construct for protein expression that results in the insertion of a FLAG tag sequence at the N terminus of the SPS2 protein. This strategy allowed us to document the readthrough of the in-frame TGA codon and the incorporation of 75Se into SPS2. These results suggest the existence of an autoregulatory mechanism involving the incorporation of Sec into SPS2 that might be relevant to blood cell biology. This mechanism is likely to have been present in ancient life forms and conserved in a variety of living organisms from all domains of life.

Amino Acid Sequence↗

A novel technique for laminoplasty augmentation of spinal canal area using titanium miniplate stabilization. A computerized morphometric analysis.

STUDY DESIGN: Titanium miniplates are used to secure the posterior elements in the open position after expansive open-door laminoplasty. Preoperative and postoperative spinal canal dimensions are measured to assess the effectiveness of this technique. OBJECTIVES: To develop a simple yet effective technique to stabilize the posterior elements after laminoplasty and to compare preoperative and postoperative spinal canal dimensions to accepted normal values. SUMMARY OF BACKGROUND DATA: Expansive open-door laminoplasty has been offered as a simple alternative to laminectomy, which has been associated with postoperative kyphosis. Although the technique of laminoplasty is effective, a simple and reliable method of holding the posterior elements open has not been described. METHODS: Ten myelopathic patients with multilevel cervical canal stenosis secondary to spondylosis or ossification of the posterior longitudinal ligament were treated with an expansive open-door laminoplasty. The posterior elements were stabilized in the open position with titanium miniplates. Computer-assisted morphometric analysis was performed on preoperative and postoperative computed tomography scans to obtain spinal canal dimensions. Plain radiographs were used to monitor construct integrity. RESULTS: The preoperative sagittal canal diameter was 8.2 +/- 0.96 mm, and the canal area was 180.6 +/- 33.7 mm2. These dimensions increased after surgery to 16.6 +/- 1.5 mm and 321.9 +/- 29.7 mm2, respectively. The titanium miniplate constructs did not fail during the follow-up period (mean, 26.4 months), and the decompression was maintained. The single significant complication was transient C5 radiculopathy. CONCLUSIONS: Normal canal dimensions can be reestablished with open-door laminoplasty. Achieving and maintaining an increased sagittal canal diameter is probably the most important change in anatomic parameters to facilitate neurologic recovery. The use of titanium miniplates to stabilize the posterior elements after laminoplasty is a simple, durable, and effective technique to maintain the increased sagittal diameter of the spinal canal.

Adult↗

Hybrid hepatitis B virus core antigen as a vaccine carrier moiety: I. presentation of foreign epitopes.

Hepatitis B virus (HBV) core antigen (HBcAg) is a highly immunogenic subviral particle. Here, we review recent progress in the use of HBcAg as a carrier moiety for heterologous epitopes. To define surface exposed and immunogenic insertion sites for foreign epitopes in HBcAg, peptidic epitopes representing binding sites for virus neutralizing antibodies on the HBV surface antigens were inserted at different positions within HBcAg using genetic engineering in an Escherichia coli expression system (Schödel et al. (1992) J. Virol. 66, 106-114). While fusion to the N-terminus required a linker to become surface accessible, both fusion to the N-terminus and to the C-terminus was compatible with particle assembly and preserved the native antigenicity and immunogenicity of HBcAg. Fusion to an immunodominant internal site of HBcAg reduced the HBcAg immunogenicity and antigenicity and most drastically enhanced the immunogenicity of the inserted foreign epitope. This internal site of HBcAg was used to express circumsporozoite antigen (CS) repeat epitopes of two rodent malaria parasites and of Plasmodium falciparum (Schödel et al. (1994b) J. Exp. Med. 180, 1037-1046 and Schödel et al. (1995a) 95th ASM General Meeting, Washington DC, Abstr. E61). When purified from recombinant Salmonella typhimurium, the hybrid HBcAg-CS proteins were particulate and displayed CS antigenicity as well as reduced HBc antigenicity, as compared to native HBcAg. Immunization of several mouse strains with HBcAg-CS hybrid particles resulted in high titered serum anti-CS antibodies representing all murine IgG isotypes. Immunization of mice with HBcAg or HBcAg-CS particles formulated on alum, complete Freunds or incomplete Freunds adjuvant resulted in equivalent anti-CS and anti-HBc serum antibody titres. The possible influence of carrier-specific immunosuppression was examined and pre-existing immunity to HBcAg did not significantly alter the immunogenicity of hybrid HBcAg particles suggesting that they would be useful carrier moieties for repeated immunizations against multiple haptens or in immune subjects after HBV infection. Examination of T cell recognition of HBcAg-CS particles revealed that HBcAg-specific T cells were universally primed and CS-specific T cells were primed if the insert contained a CS-specific T cell recognition site. This indicates that the internal amino acid position in HBcAg is permissive for the inclusion of heterologous functional T helper as well as B cell epitopes. BALB/c mice immunized with HBcAg-CS1 were protected against P. berghei challenge to 90% and 100%, respectively, in two independent experiments.

Animals↗

The maize caffeic acid O-methyltransferase gene promoter is active in transgenic tobacco and maize plant tissues.

The pattern of expression directed by the promoter of the maize caffeic acid O-methyltransferase (COMT) gene was studied by histochemical and fluorometric beta-glucuronidase (GUS) analysis in transgenic maize and tobacco plants. The COMT promoter directs GUS expression to the xylem and the other tissues undergoing lignification, and it responds to wounding and to elicitors. In transgenic maize plants, expression of GUS corresponds to the pattern of expression of the endogenous COMT gene as determined by northern analysis and in situ hybridization. The pattern in transgenic tobacco plants clearly shows that the maize promoter sequence is recognized by tobacco transcriptional factors, in spite of the anatomical differences and the evolutionary distance between these two species. The results suggest that the most significant promoter signals that induce the specific expression of the lignin COMT are conserved in different species.

Gene Expression Regulation, Enzymologic↗

Bronchoscopic findings in post-obstructive pulmonary oedema.

PURPOSE: To present the first photographed bronchoscopic findings associated with negative pressure pulmonary oedema (NPPE). CLINICAL FEATURES: A previously healthy patient underwent anterior C3-C4 disc removal and arthrodesis. Following tracheal extubation he developed acute respiratory distress manifested as stridor, tachypnoea, restlessness, and desaturation. Once the trachea was reintubated, he displayed the classic findings of pulmonary oedema. Bronchoscopy was performed to confirm tracheal tube position and to rule out tracheal injury secondary to surgical manipulation. Diffuse punctate haemorrhages were noted throughout the visualised tracheobronchial tree. CONCLUSION: We believe that these haemorrhages represent disruption of the bronchial vasculature and may contribute to the clinical presentation of NPPE.

Acute Disease↗