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Biomedical subjects

J Samuel

Publications and source records attributed to J Samuel.

At least 37 records · Page 2Linked to original sources
PubMed1994

A retrospective study of clinical and laboratory characteristics of ovine footrot.

The infection of the feet of sheep by the anaerobic bacterium Dichelobacter nodosus results in a spectrum of diseases ranging from virulent through intermediate to benign footrot. By examining the clinical characteristics of various forms of footrot from 22 properties in Victoria, Australia in association with the results of several laboratory tests including the gene probe-based dot blot hybridisation, it was shown that virulent footrot could not be differentiated from intermediate footrot using the clinical characteristics alone. In addition, D. nodosus isolates from sheep with benign footrot as diagnosed by the clinical manifestations might in fact show characteristics associated with those causing virulent, intermediate or benign footrot as determined by the laboratory tests. Although the elastase test, gelatin gel test and dot blot were in agreement with isolates from 9 of the 22 properties under investigation, they displayed differences from one another in many other cases, especially those with clinical benign footrot. The results of the elastase test appeared to be slightly closer to those of the dot blot compared with the gelatin gel test. Like any other tests based on the measurements of phenotypic characteristics of D. nodosus bacteria, the elastase test and gelatin gel test are subject to changes with factors that affect bacterial growth and metabolism. The use of DNA based detection methods would eliminate many of the problems associated with the conventional tests for differentiating strains causing virulent, intermediate and benign footrot.

Animals↗
PubMed1994

Life-threatening hypotension associated with emergency intubation and the initiation of mechanical ventilation.

To determine the incidence of life-threatening hypotension (LTH) suffered by patients in the initial hours after emergency intubation and mechanical ventilation, prospective, consecutive case series of patients undergoing endotracheal intubation and mechanical ventilation were evaluated in the adult emergency department of a large urban hospital. Eight-four medical patients who received intubation and mechanical ventilation for ventilatory failure, respiratory failure, or airway protection (trauma patients exluded) were included. LTH, defined as a decrease in mean arterial pressure of 60 mm Hg or an absolute decrease to a systolic blood pressure < 80 mm Hg in the first 2 hours after intubation, was observed in 24 of the 84 patients who met study criteria (incidence 28.6%). Eleven patients (incidence 13.1%) required treatment for LTH with vasopressors. There was one cardiac arrest, and there were no deaths. There was a statistically significant association between LTH and hypercarbic (PCO2 > 50 mm) chronic obstructive pulmonary disease (COPD) (P = .004). There was also a weaker statistical association between LTH and hypoxemic respiratory failure (P = .019). No association could be established between LTH and the other diagnoses, arterial blood gas (ABG) derangements, or the administration of sedatives or paralytic medications. LTH represents a serious complication of emergency intubation in the initial phase of mechanical ventilation. Because it occurs in more one quarter of all cases, it should be anticipated during intubation and the initial phase of ventilator management, especially in high-risk patients such as those with hypercarbic COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Gas Analysis↗
PubMed1993

Antibody-targeted delivery of doxorubicin entrapped in sterically stabilized liposomes can eradicate lung cancer in mice.

Cancer chemotherapy is limited by adverse side effects resulting from toxicities to normal tissues. Targeted delivery of drugs to diseased tissues in vivo would help to reduce these side effects. Liposomes containing lipid derivatives of polyethylene glycol have circulation times sufficiently long to allow for effective in vivo drug delivery. Polyethylene glycol liposomes, containing entrapped doxorubicin, targeted to KLN-205 squamous cell carcinoma of the lung by means of specific antibodies attached at the liposome surface were capable of reducing tumor burden to a high degree and eradicating tumor in a significant percentage of mice.

Animals↗
PubMed1993

Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant.

We have synthesized various formulations that have potential for active specific immunotherapy (ASI) of human cancers. Sialyl-Tn (STn) is a potentially important target structure for ASI because its expression on mucins is a strong, independent predictor of poor prognosis, suggesting that it may have functional significance in the metastatic process. In this first pilot study of synthetic sialyl-Tn hapten conjugated to keyhole limpet hemocyanin (STn-KLH), with Detox adjuvant, toxicity and humoral immunogenicity were assessed in 12 patients with metastatic breast cancer. Toxicity was minimal, restricted to local cutaneous reactions (apart from transient nausea and vomiting following single low-dose cyclophosphamide treatment). Using STn-conjugated human serum albumin in a solid-phase enzyme-linked immunosorbent assay, it was shown that all patients developed IgM and IgG specific for the synthetic STn hapten. Following immunization, most patients were shown to develop increased titres of complement-mediated cytotoxic antibodies, partially inhibited by synthetic STn hapten, but not by the related TF hapten. We also detected IgM and IgG antibodies reactive with natural STn determinants expressed on ovine submaxillary mucin, the STn specificity of this reactivity being confirmed by hapten inhibition. Evaluation of clinical efficacy in a small pilot study is difficult. Five patients are alive 12 or more months after entry, and another 4 patients are alive 6 or more months after entry into the study. All 3 patients with known widespread bulky disease progressed despite ASI, 2 having died from widespread cancer. Two patients had partial responses, each lasting 6 months. While several patients had disease stability for 3-10 months, 1 patient with pulmonary metastases remains stable 15 months after entry into the program.

Adjuvants, Immunologic↗
PubMed1993

Immunogenicity of synthetic peptides related to the core peptide sequence encoded by the human MUC1 mucin gene: effect of immunization on the growth of murine mammary adenocarcinoma cells transfected with the human MUC1 gene.

The immune response of CAF1 mice to various synthetic peptides (SP) related to the amino acid sequence (PDTRPAPGSTAPPAHGVTSA) of the tandem repeat of the MUC1 human breast mucin core peptide was evaluated. The most immunogenic preparations of the synthetic peptides were those conjugated to keyhole limpet hemocyanin (KLH) or clustered in a dendritic multiple antigenic peptide (MAP-4) configuration. The mice were immunized subcutaneously with synthetic peptides emulsified in RIBI adjuvant, employing various immunization protocols. Equivalently high IgG responses were induced using SP-KLH conjugates (GVTSAPDTRPAPGSTA-KLH) or an SP--MAP-4 chimeric configuration (SP1-6), which also included a universal malarial CST-3 T-helper epitope (SP1-6 = SAPDTRPAEKKIAKMEKASSVFNVVNS--MAP-4). These IgG antibodies bound both the appropriate MUC1 synthetic peptides and the cell surface expressed MUC1 mucin on murine mammary cells that had been transfected with the human MUC1 gene and a human breast cancer cell line that expresses cell-surface MUC1. A MAP-4 molecule, which included the entire 20-amino-acid sequence of the MUC1 tandem repeat (SP1-5 = PDTRPAPGSTAPPAHGVTSA-MAP-4) induced a poor IgG response. In contrast, all three types of molecule: SP-KLH, SP1-6 and SP1-5, were found to be good immunogens for the induction of specific delayed-type hypersensitivity (DTH) reactions measured using either synthetic peptides or MUC1-transfected cells. In addition, immunization with irradiated MUC1-transfected cells induced strong DTH reactions measured using synthetic peptides that expressed the PDTRP sequence, which has been shown to be, or to overlap, a T cell epitope in humans and a B cell epitope in mice. Finally, it was demonstrated that synthetic MUC1 peptide "vaccines" could be used both prophylactically and therapeutically to inhibit the growth of MUC1-transfected tumor cells and prolong the survival of tumor-bearing mice.

Adenocarcinoma↗
PubMed1993

Recurrent massive bleeding from an intercostal artery aneurysm through an empyema chest tube.

Intercostal artery aneurysms can be of congenital, posttraumatic, or mycotic type. Intercostal arterial aneurysmal bleeding can be brisk enough to lead into shock or sudden death. Bleeding through chest tubes has been reported due to various causes; it is commonly due to injury to intercostal or pulmonary vessels and is occasionally due to leaking aortic aneurysms. We describe a patient who had development of repeated episodes of brisk bleeding through an empyema chest tube leading to shock episodes requiring resuscitations. After extensive search, the bleeding source was found to be an intercostal artery aneurysm. Transcatheter embolization of that intercostal artery with absorbable gelatin sponge (Gelfoam) was successful in obliterating the blood flow to the aneurysm and in preventing further bleeding.

Adult↗
PubMed1992

Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenreich) determinant using a synthetic carbohydrate antigen.

In a phase I study, ten ovarian cancer patients with extensive metastatic disease despite chemotherapy were immunized three to eight times subcutaneously with the synthetic form of the immunodominant disaccharide (beta Gal1----3 alpha GalNAc) of the Thomsen-Friedenreich antigen conjugated to KLH (TF alpha-KLH) plus DETOX adjuvant. Six patients were given a "low" dose of TF alpha-KLH (100 micrograms/injection) and four patients were given a "high" dose (500 micrograms/injection). All patients received a single low-dose cyclophosphamide treatment (200 mg/m2 i.v.) 3 days prior to commencement of the series of immunizations. Immunizations were 2 weeks apart. Little or no toxicity was noted. As expected, all patients (prior to immunization) had naturally occurring IgM antibodies against the synthetic TF alpha hapten. None of the patients had detectable pre-existing IgG or IgA antibodies against synthetic TF alpha hapten. Nine of the ten ovarian cancer patients showed a significant increase in IgM titer above pre-existing levels following immunizations with TF alpha-KLH plus DETOX adjuvant. These same patients also produced IgG anti-TF alpha and eight of these also produced IgA anti-TF alpha, although the IgA responses were weaker. Most of the IgG responses followed the IgM responses by 2-4 weeks. Two patients produced a vigorous IgG response after their first TF alpha-KLH injection, suggesting a recall response. Both direct ELISAs on various solid-phase synthetic carbohydrate antigens and hapten inhibition experiments confirmed the TF alpha hapten specificity of the antibodies. IgM and IgG anti-TF alpha-specific antibodies reacted with natural TF antigen, by ELISA and FACS analysis, although the titers were generally lower than the titers against the immunizing TF alpha hapten. Increased levels of cytotoxic antibodies against TF-expressing tumor cell targets were detected in eight of the ten patients following immunization. One patient who had no detectable cytotoxic antibodies prior to immunization developed increasingly strong cytotoxic antibodies as a function of the number of immunizations. The low antigen dose patients showed as good or better humoral immune responses than the high antigen dose patients. All four high-dose and four of six low-dose patients developed moderate to strong DTH reactions at the vaccination sites. Our results demonstrate that KLH is an acceptable carrier for carbohydrate haptens in humans and that DETOX is an appropriate nontoxic adjuvant for the generation of high-titer specific anti-carbohydrate responses in human cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1991

Postoperative neuromuscular function in pediatric day-care patients.

After anesthesia employing nondepolarizing muscle relaxants, 30%-40% of adult patients demonstrate residual paralysis with a train-of-four ratio less than 70%, but it is not known if the same is true for children. This study was designed to investigate neuromuscular transmission in 91 ASA physical status I or II day-care children (aged 0-10 yr) after halothane anesthesia in which pancuronium (n = 34), atracurium (n = 32), or vecuronium (n = 25) was administered. Peripheral nerve stimulation was used clinically to assess neuromuscular blockade during surgery. In the recovery room, the evoked response of the adductor pollicis muscle was measured by train-of-four stimulation of the ulnar nerve. This measurement was made (mean +/- SEM) at 18.0 +/- 1.5, 15.0 +/- 1.3, and 15.0 +/- 1.7 min after pharmacologic antagonism with 0.02 mg/kg atropine and 0.06 mg/kg neostigmine in the pancuronium, atracurium, and vecuronium groups, respectively. There were no differences in the ages of the patients in the three groups at 4.3 +/- 0.4, 4.0 +/- 0.4, and 5.0 +/- 0.5 yr, with 17 children less than 2 yr. Recovery from neuromuscular blockade in all three groups was almost complete. The train-of-four ratio (height of fourth twitch compared with the first) was similar in patients who had received pancuronium (96.7% +/- 0.9%), atracurium (95.5% +/- 0.9%), or vecuronium (96.3% +/- 1.3%). Therefore, postoperative muscle weakness or respiratory impairment is unlikely in pediatric day-care surgical patients more than 2 yr old when these anesthetic techniques are used.

Ambulatory Surgical Procedures↗
PubMed1990

Analysis of human tumor associated Thomsen-Friedenreich antigen.

The Thomsen-Friedenrich (TF) antigen is a precursor structure of MN blood group antigens and is also expressed by about 90% of human carcinomas. The immunodominant group of TF antigen [beta-galactosyl(1-3)-alpha-N-acetylglactosamine] is present in cryptic form in normal RBC and is revealed by neuraminidase treatment. A murine monoclonal antibody (Mab 49H.8) developed against neuraminidase treated human RBC was reactive against a variety of human tumors. We have characterized the human tumor associated TF antigen detected by this antibody from a human transitional bladder carcinoma cell line (647V), a human colon adenocarcinoma cell line (LS174T), and a pleural effusion fluid of a breast adenocarcinoma patient (PE 89). A heterologous sandwich radioimmunoassay for TF antigen was developed using Mab 49H.8 as the catcher and 125I-peanut agglutinin as the probe. Detergent extracts of 647V and LS174T cells, media conditioned by culturing these cells, and PE 89 were shown to contain the antigen by this assay. The specificity of the antigen capture by Mab 49H.8 in this assay was demonstrated by its selective inhibition by nitrophenyl-beta-D-galactoside, phenyl-beta-D-galactoside, and a TF hapten. Preliminary studies on TF antigen in serum samples using this assay showed that about 53.7% of the carcinoma samples contained an antigen concentration greater than 200 units/ml whereas for 90.9% of the normal samples the antigen concentration was below 200 units/ml. These studies demonstrated that the TF antigen is shed by the tumor cells both in vitro and in vivo. The TF antigen was sensitive to treatment with alkali (0.1 M NaOH for 5 h at 37 degrees C) and periodate (10 mM sodium periodate for 1 h at room temperature), was resistant to acidic pH (50 mM acetate buffer, pH 4.5, for 5 h at 37 degrees C), and could be extracted with perchloric acid (0.6 M for 1 h at 4 degrees C). The antigen was shown to be a high molecular weight glycoprotein (Mr greater than 1,000,000) by gel filtration chromatography. The density of the antigen was estimated to be about 1.35 g/ml by cesium chloride density gradient centrifugation. The antigen could be isolated from conditioned media by a combination of affinity chromatography and gel filtration with an overall purification of about 61,432-fold and a final recovery of 53.2%.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1990

Effective drug-antibody targeting using a novel monoclonal antibody against the proliferative compartment of mammalian squamous carcinomas.

mAb 174H.64, which selectively recognizes an epitope expressed on the proliferating cells of mammalian squamous carcinomas, was covalently coupled to daunomycin (DM) by an acid-sensitive linker and tested for its selective cytotoxicity for squamous carcinomas. A murine lung squamous carcinoma model for chemoimmunotherapy using mAb 174H.64-DM conjugates was developed. This model utilizes the KLN-205 cell line, which metastasizes to the lungs following i.v. injection and shows a pattern of growth similar to those of spontaneous squamous carcinomas, characterized by highly proliferative cells at the periphery of the tumor (reactive with 174H.64) with the keratinized differentiated cells toward the center (not reactive with 174H.64). 174H.64-DM conjugates showed marked and specific cytotoxicity against KLN-205 cells both in vitro and following i.v. injection of the immunoconjugate in mice with established lung metastases. The conjugate was nearly as effective as daunomycin alone when incubated in vitro with KLN-205 cells and much more effective than daunomycin alone in vivo or other control immunoconjugates, which were ineffective. Finally, while the free 174H.64 mAb produced a significantly increased time of survival of mice bearing KLN-205 metastases, a much greater survival was found with mice treated with the 174H.64-DM immunoconjugate, some mice apparently demonstrating long-term survival (greater than 100 days). We conclude that mAb 174H.64 may have potential therapeutic benefit against squamous carcinoma.

Animals↗
PubMed1989

A novel marker for basal (stem) cells of mammalian stratified squamous epithelia and squamous cell carcinomas.

We have developed a monoclonal antibody (174H.64) which selectively recognizes antigens shared by the basal cells of mammalian stratified squamous epithelium and squamous cell carcinoma (SCC). Histopathological studies of the frozen tissue sections demonstrated selective binding of this antibody to SCCs of human, bovine, canine, feline, and murine origin. Tumors of other histological types did not show reactivity with the antibody. In well-differentiated SCCs the peripheral layer of the tumor showed preferential binding of the antibody, suggesting that the antigens are associated with the proliferative compartment of the tumor. Studies on normal human tissues showed selective binding of the antibody to the basal layer of stratified squamous epithelia, thymic epithelial cells, and myoepithelial cells around breast ducts, while no antibody binding was observed for the suprabasal layers of stratified epithelia, simple epithelia, or tissues of nonepithelial origin. A similar pattern of antibody binding was also observed for bovine and murine skin with staining of the basal layer. The antigens detected by monoclonal antibody 174H.64 were characterized from cytoskeletal protein extracts of normal human keratinocytes as well as human and bovine SCC tissues by using an immunoblotting technique. The antigens detected in normal human keratinocytes consisted of two major protein bands of approximate molecular weights of 48,000-50,000 and 57,000. In bovine SCC tumor the antigen detected was the Mr 48,000-50,000 band and in the human SCC tumor it was the Mr 57,000 band. A murine lung SCC model was developed with a murine SCC cell line KLN-205. The lung tumor obtained was reactive against the antibody and showed selective staining of the peripheral layer of the tumor containing the stem cell population. The antigens described by monoclonal antibody 174H.64 appear to be molecules associated with the stem cell populations of normal stratified epithelium and squamous cell carcinoma.

Animals↗
PubMed1989

Tuning forks: the problem of striking.

Tuning fork tests have accompanied us from the beginning of otology. Various methods of striking have been used during the century and the efforts to attain standardization appear to have been forgotten since audiology became available. The article reviews the history of the standardization and throws a new light on the production of overtones and air, compared to bone, conduction frequency. The article stresses the importance of tuning fork testing in clinical practice.

Hearing Tests↗