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J Baron

Publications and source records attributed to J Baron.

At least 145 records · Page 8Linked to original sources

Bacterial proteins that mediate the association of a defined subset of T cell receptor:CD4 complexes with class II MHC.

We have examined the responses of cloned T cell lines and of normal T cells to staphylococcal enterotoxins A, B, and C1 (SEA, SEB, and SEC1). SEA, SEB, and SEC1 are all very potent mitogens for T cells in the presence of Ia+ APC. The minimal activating dose of all these SE varies from 1 to 100 ng/ml. As determined by mAb blocking of the responses of both normal T cells and cloned T cell lines, SEA required either the I-A or the I-E molecule on APC for stimulating T cells, whereas SEB required the I-E molecule predominantly over I-A molecule. The TCR:CD4 complex is also involved in the response to SE. The responses to SEB and SEC1 were inhibited by anti-V beta 8 antibody F23.1, whereas the response to SEA and to PHA was not affected by this antibody. Anti-CD4 effectively inhibited responses to all SE but not to PHA. The involvement of the TCR was also confirmed by flow microfluorimetry analysis of T cell blasts responding to SE and the responses of a panel of cloned T cell lines, both of which showed that V beta 8+ T cells preferentially responded to SEB, whereas V beta 8+ T cells failed to respond to SEA. By using fixed APC, it could be shown that processing is not required for the presentation of SE. Furthermore, pulsing experiments showed that SEB can bind to relevant sites on either B cells or T cells, whereas with conventional Ag only prepulsing of the APC has worked. In one case, SEB activates a cloned T cell line in the absence of APC, and this same clone also responds directly to anti-V beta 8 antibody. Thus, SEB appears to bring together V beta 8-expressing TCR with the I-E molecule, whereas SEA apparently has the same effect on TCR expressing different V beta with either the I-A or the I-E molecule, probably depending upon which TCR is bound. The close resemblance between T cell responses to SE and those to mixed-lymphocyte stimulating (Mls) locus suggests to us that a novel SE-like protein that binds both to class II MHC molecules on the APC surface and to V beta gene products on TCR could be the product of the Mls locus.

Animals↗

Localization, distribution, and induction of xenobiotic-metabolizing enzymes and aryl hydrocarbon hydroxylase activity within lung.

The metabolism of xenobiotics within lung often leads to toxicity, although certain pulmonary cells are more readily damaged than others. This differential susceptibility can result from cell-specific differences in xenobiotic activation and detoxication. The localization and distribution of xenobiotic-metabolizing enzymes (cytochromes P-450, NADPH-cytochrome P-450 reductase, epoxide hydrolase, glutathione S-transferases, UDP-glucuronosyltransferases, and a sulfotransferase) and of aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity determined immunohistochemically and histochemically, respectively, within lung are discussed. Findings reveal that xenobiotics can be metabolized in situ, albeit to different extents, by bronchial epithelial cells, Clara and ciliated bronchiolar epithelial cells, and type II pneumocytes and other alveolar wall cells and that enzymes and activities are not necessarily induced uniformly among these cells.

Animals↗

Short-term effect of a new portable extracorporeal lithotripter on renal function.

Extracorporeal shock wave lithotripsy has become the treatment of choice for upper urinary tract stones. We evaluated the impact of a new lithotripter on the kidneys of 14 nonobstructed patients treated for renal stones, using several physiological parameters and renal ultrasonography. Glomerular filtration rates (GFR) were estimated from the renal scan. Complete disintegration of the stone was accomplished in all but one patient. Treatment did not alter the serum parameters or the renal ultrasonography. Also, no changes were found in the GFR on the follow-up renal scans in both kidneys. The implications of these findings are discussed.

Adult↗

In situ localization and distribution of xenobiotic-activating enzymes and aryl hydrocarbon hydroxylase activity in lungs of untreated rats.

The present investigation was undertaken to more precisely establish where xenobiotics can be oxidatively metabolized and bioactivated within the lung. To accomplish this, antibodies raised against NADPH-cytochrome P-450 reductase (EC 1.6.2.4) and cytochromes P-450 BNF-B, PB-B, and PCN-E (the major forms of cytochrome P-450 induced by beta-naphthoflavone, phenobarbital, and pregnenolone-16 alpha-carbonitrile, respectively) that had been purified to apparent homogeneity from rat liver microsomes were used to determine the localizations and distributions of these enzymes immunohistochemically at the light microscopic level within lungs of untreated rats. Additionally, the intrapulmonary sites at which benzo(alpha)pyrene undergoes hydroxylation were identified in situ by means of fluorescence histochemistry. Immunohistochemical staining for NADPH-cytochrome P-450 reductase and cytochromes P-450 BNF-B, PB-B, and PCN-E was detected in bronchial epithelial cells, both ciliated and nonciliated (Clara) bronchiolar epithelial cells, and type II pneumocytes as well as other cells in the alveolar wall. Results of microfluorometric analyses of the immunofluorescence staining intensities of bronchial epithelial cells, Clara cells, and type II pneumocytes demonstrated further that Clara cells bound the antibodies raised to NADPH-cytochrome P-450 reductase and cytochrome P-450 PB-B to significantly greater extents than did bronchial epithelial cells and type II pneumocytes. Thus, in lungs of untreated rats, Clara cells contain the greatest amounts of these two enzymes. In marked contrast, the antibodies directed against cytochromes P-450 BNF-B and PCN-E were each bound to similar extents by bronchial epithelial cells, Clara cells, and type II pneumocytes. In agreement with immunohistochemical observations on the intrapulmonary localizations of NADPH-cytochrome P-450 reductase and cytochromes P-450 BNF-B, PB-B, and PCN-E in untreated rats, benzo(alpha)pyrene was hydroxylated in situ by bronchial and bronchiolar epithelial cells and alveolar wall cells, especially type II pneumocytes. These immunohistochemical and histochemical findings, thus, demonstrate that bronchial epithelial cells, Clara and ciliated bronchiolar epithelial cells, and type II pneumocytes as well as other alveolar wall cells represent sites for the in vivo oxidative metabolism and bioactivation of xenobiotics in lungs of untreated rats.

Animals↗

[Intraoperative intracranial hypotension syndrome].

A case is described of intracranial hypotension after surgical removal of chronic subdural haematoma and hygroma resulting in apnoea lasting several hours. Fully effective anaesthesiological management of this complication is reported.

Apnea↗

Potential pitfalls in the obstructive renal scan in patients with double-pigtail ureteral catheters.

In 21 patients with a long-standing internal ureteral double-pigtail catheter we demonstrated the adverse effect of a full bladder on upper system drainage. A pseudo-obstructive pattern noted in these patients on routine scans was immediately rectified by mere bladder emptying and a normal pattern was demonstrated. We suggest the bladder be emptied in all patients with indwelling internal ureteral stents before renographic evaluation.

Catheters, Indwelling↗

Animal model of conjunctival primary acquired melanosis.

A condition clinically identical to human conjunctival primary acquired melanosis (PAM) was induced in 16 of 20 Dutch (pigmented) rabbits after weekly topical 60-microliters applications of a 1% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in acetone. Pigment stippling appeared in the conjunctiva as early as 5 weeks after the initial carcinogen application. Confluent patches of flat pigmentation appeared over the palpebral conjunctiva 18 weeks after the onset of treatment and showed progressive lateral enlargement and darkening. Histologically, a spectrum of changes from increased melanin production and melanocytic hyperplasia without atypia (resembling the human condition of PAM without atypia) through atypical melanocytic hyperplasia (resembling human PAM with atypia) was identified. The development of this model permits further investigations to explore and explain the clinically observed phenomenon of waxing and waning of PAM and its promotion to conjunctival malignant melanoma.

9,10-Dimethyl-1,2-benzanthracene↗

Prophylactic red-cell transfusions in pregnant patients with sickle cell disease. A randomized cooperative study.

Prophylactic blood transfusion has come to be regarded as necessary in the treatment of patients with sickle cell disease during pregnancy. Because of the risks associated with blood products and reports of successful outcomes without the use of blood transfusion, we conducted a prospective randomized controlled study of this issue. Seventy-two pregnant patients with sickle cell anemia were randomly assigned to one of two treatment groups: 36 received prophylactic transfusions of frozen red cells, and 36 received red-cell transfusions only for medical or obstetric emergencies. Twenty-eight patients with sickle cell anemia who did not qualify for randomization (mainly because they had other medical disorders), 66 with sickle cell-hemoglobin C disease, and 23 with sickle cell-beta-thalassemia were also followed and received transfusions only for emergencies. There was no significant difference in perinatal outcome between the offspring of mothers with sickle cell disease who were assigned to treatment with prophylactic transfusions and those who were not (15 vs. 5 percent). The occurrence of a perinatal death in a previous pregnancy and the presence of twins in the present pregnancy were two major risk factors for an unfavorable outcome; when they were present, perinatal mortality was 50 percent. Perinatal mortality was somewhat higher in the two groups that were randomized than in the three groups that were not. Prophylactic transfusion significantly reduced the incidence of painful crises of sickle cell disease (P less than 0.01) and substantially reduced the cumulative incidence of other complications of this disorder (P = 0.07). Other medical and obstetric complications occurred with nearly equal frequency in the two randomized groups. Increases in costs, the number of hospitalizations, and the risk of alloimmunization were disadvantages of prophylactic transfusion. We conclude that the omission of prophylactic red-cell transfusion will not harm pregnant patients with sickle cell disease or their offspring.

Adult↗

Further evidence of von Willebrand factor involvement in thrombotic thrombocytopenia purpura.

Fourteen patients diagnosed as having thrombotic thrombocytopenia purpura (TTP) were studied. Those who survived have been followed during a 1 to 7 year period. The clinical diagnosis was based on changing neurological findings, thrombocytopenia and evidence of microangiopathic hemolytic anemia. Laboratory tests included the determination of von Willebrand factor antigen (VWF:Ag), ristocetin cofactor (RiCof) and the electrophoretic mobility of von Willebrand factor (CIE VWF:Ag). The ratio of RiCof to VWF:Ag was then calculated. Control individuals included healthy subjects and patients with thrombocytopenia of several etiologies. Statistical differences between the values of RiCof, the ratio of RiCof:VWF:Ag and the CIE of VWF:Ag were found for samples comparing active disease and remission phase. The recovery from thrombocytopenia paralleled the correction of abnormal parameters. Similarly, significant differences were found when above parameters were compared between thrombocytopenia of TTP with other thrombocytopenic states. We suggest that these abnormal tests could be useful in distinguishing TTP from other disorders, and may have prognostic significance in patients already diagnosed as having TTP.

Adolescent↗

Arthropathy and surgery in congenital factor VII deficiency.

A 35-year-old woman with severe (less than 1 percent) factor VII deficiency had recurrent hemarthroses involving the left knee, leading to deformity, pain, and virtually complete loss of function. It was elected to perform a total knee replacement. In preparation for surgery, the patient received heat-treated prothrombin complex concentrate containing 870 units of factor VII per vial. A dose of 50 U/kg raised the factor VII level to 115 percent. At surgery, dense adhesions were found within the joint, the articular cartilage was overgrown with pannus extending out to the lateral patella, and there was extensive deformity of the femoral condyle and tibial plateau. The joint was excised and replaced by a cemented Microloc prosthesis. Postoperatively, factor VII levels were maintained above 10 percent by six-hourly infusions of concentrate. Beginning on Day 4, single daily infusions of 25 U/kg were given prior to physical therapy. No bleeding occurred, and the patient was ambulating at the time of discharge 20 days postoperatively. This experience indicates that despite its short half-life (less than four hours), factor VII levels sufficient to prevent bleeding can be maintained in factor VII-deficient patients undergoing major operative procedures.

Adult↗

Sites for xenobiotic activation and detoxication within the respiratory tract: implications for chemically induced toxicity.

Results of in situ immunohistochemical investigations on several enzymes which participate in the bioactivation and detoxication of xenobiotics and of histochemical studies on aryl hydrocarbon hydroxylase activity summarized in this report clearly demonstrate that there are numerous sites within the respiratory tract at which xenobiotics can be bioactivated and detoxicated. The data presented, however, also reveal that xenobiotic-metabolizing enzymes and benzo[a]pyrene hydroxylase activity may not be distributed uniformly within individual segments (e.g., the nasal mucosa) of this organ system. Thus, it should be apparent from these findings that one cannot generalize as to how a given xenobiotic-metabolizing enzyme or xenobiotic monooxygenase activity normally is distributed either within or among the different segments of the respiratory tract. Additionally, since enzymes catalyzing the bioactivation and detoxication of xenobiotics usually are present within the same respiratory tract cells, it obviously is difficult to predict from these results which cell types within individual segments of this organ system most likely would be damaged as a consequence of exposure to xenobiotics which are biotransformed into cytotoxic metabolites by cytochrome(s) P-450. Although the cellular localizations and intercellular distributions of cytochromes P-450 BNF-B and MC-B parallel those of benzo[a]pyrene hydroxylase activity within the different segments of the respiratory tract in untreated rats, immunohistochemical findings on the inductions of these cytochrome P-450 isozymes are not entirely consistent with histochemical observations on the enhancement of benzo[a]pyrene hydroxylase activity by Aroclor 1254 within the nasal mucosa and by both Aroclor 1254 and 3-methylcholanthrene within the lung. It must be appreciated, however, that other cytochrome P-450 isozymes undoubtedly are present and inducible in the nasal mucosa and lung and, further, that these hemeproteins, although being immunochemically unrelated to the cytochrome P-450 isozymes studied, also could catalyze aryl hydrocarbon hydroxylase activity. Nevertheless, these immunohistochemical and histochemical findings do demonstrate that one cannot generalize as to how chemicals which induce the same xenobiotic-metabolizing enzyme will affect that enzyme within different segments of the respiratory tract and, moreover, that inducers of cytochromes P-450 can alter differentially the extents to which different cells within a given segment of the respiratory tract (e.g., the nasal mucosa) participate in the oxidative metabolism of xenobiotics.

Animals↗

Outcome bias in decision evaluation.

In 5 studies, undergraduate subjects were given descriptions and outcomes of decisions made by others under conditions of uncertainty. Decisions concerned either medical matters or monetary gambles. Subjects rated the quality of thinking of the decisions, the competence of the decision maker, or their willingness to let the decision maker decide on their behalf. Subjects understood that they had all relevant information available to the decision maker. Subjects rated the thinking as better, rated the decision maker as more competent, or indicated greater willingness to yield the decision when the outcome was favorable than when it was unfavorable. In monetary gambles, subjects rated the thinking as better when the outcome of the option not chosen turned out poorly than when it turned out well. Although subjects who were asked felt that they should not consider outcomes in making these evaluations, they did so. This effect of outcome knowledge on evaluation may be explained partly in terms of its effect on the salience of arguments for each side of the choice. Implications for the theory of rationality and for practical situations are discussed.

Decision Making↗