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Biomedical subjects

K Peterson

Publications and source records attributed to K Peterson.

At least 91 records · Page 5Linked to original sources

Structure and chromosomal localization of the mammalian agrin gene.

Agrin, a component of the synaptic basal lamina, has been shown to induce clustering of ACh receptors on the surface of muscle fibers. Analysis of cDNAs isolated from a rat embryonic spinal cord library demonstrated that agrin contains domains similar to regions of protease inhibitors, laminin and epidermal growth factor. The domain structure of agrin is further revealed here in an analysis of the agrin gene. Two additional internal repeated sequences are defined: one rich in cysteine residues with no homology to other proteins, and another similar to the laminin G domain, which is involved in heparin binding. Alternative RNA splicing at two positions in the gene predicts up to eight possible forms of the agrin protein. The gene (symbol AGRN/Agrn) has been assigned to chromosome 1 region pter-p32 in human and to mouse chromosome 4.

Agrin↗

Caring for people, not profits, brings success.

The path to success in healthcare institutions must become more centered on caring for people instead of caring about profits, says Kristine Peterson, a longtime consultant taking a sabbatical from the industry.

Consumer Behavior↗

Blood phenylalanine estimation for the patient with phenylketonuria using a portable device.

A simple and reliable method is described which is suitable for estimation of a whole blood phenylalanine concentration for the patient with PKU in various settings including the physician's office and the home. Excellent correlations were obtained between this method and weighed phenylalanine standards, as well as with measurement of phenylalanine in serum, plasma, and whole blood, using the McCaman-Robins fluorometric assay. Increasing the frequency and rapidity of feedback to the patient should improve metabolic control, just as home glucose monitoring has for the patient with diabetes mellitus. This method is immediately adaptable to monitoring patients with tyrosinemia, and with substitution of the appropriate amino acid ammonia lyase could be used for other amino acidemias.

Ammonia↗

Safe, live Vibrio cholerae vaccines?

Mutants of Vibrio cholerae defective in intestinal colonization have been constructed. Characterization of these mutants has led to the identification of a gene cluster involved in the assembly of a pilus colonization factor called TCP. The tcp operon has been cloned and strains of V. cholerae have been constructed that overproduce this pilus and the B subunit of cholera toxin. Together these studies may contribute to the eventual construction of efficient live and killed, oral cholera vaccines.

Administration, Oral↗

Molecular cloning of Treponema pallidum outer envelope fibronectin binding proteins, P1 and P2.

Phages directing the synthesis of Treponema pallidum fibronectin binding adhesin proteins, P1 and P2, were isolated from an EMBL-3 bacteriophage lambda library of T pallidum deoxyribonucleic acid (DNA). The recombinant phages were identified using antisera generated to treponemal proteins purified in fibronectin-Sepharose. Recombinant P1 and P2 proteins possessed the same relative molecular weights as the native surface polypeptides of spirochaetes. The structural genes for these proteins were subcloned into the plasmid vector pUC19, and transformed Escherichia coli expressed and translocated recombinant P1 and P2 to their outer membranes. Finally, the recombinant adhesin proteins, P1 and P2, were purified from detergent solubilised E coli outer membrane preparations using fibronectin-Sepharose affinity chromatography, which confirmed that the fibronectin binding properties of the cloned proteins were retained.

Adhesins, Bacterial↗

Expression of A9 antigen and loss of blood group antigens as determinants of survival in patients with head and neck squamous carcinoma.

The murine monoclonal antibody (A9), raised to the human squamous cell carcinoma (SCC) cell-line UM-SCC-1, defines a squamous cell antigen associated with aggressive biologic behavior of SCC cell lines in vivo and in vitro. In the present investigation, A9 antigen was detected in tissue sections from 37 consecutive, previously untreated patients with SCC of the head and neck. All tumors were positive for A9 binding, although three distinct patterns (reflecting different intensities of A9 expression) were identified. The intensity of A9 expression was independent of primary tumor site, tumor differentiation, keratinization, or growth pattern. The frequency of high expression (Pattern 1) grew with increasing T class, N class, and tumor stage, and was associated with loss of blood group expression in the tumor and with low levels of lymphocyte infiltration in the tumor. Strong A9 expression had a statistically significant association with low nuclear grade (i.e., tumors with more mature and fewer enlarged nuclei, P = 0.019), low vascular/stromal response (i.e., patchy response rather than continuous, P = 0.014), and impaired in vitro lymphokine production by peripheral blood leukocytes (P = 0.0011). Of greatest interest, however, was the strong association of high A9 expression with shortened disease-free interval (DFI) (P = 0.085) and survival (P = 0.081) relative to patients with weak A9 tumor staining (Patterns 2 and 3). Similarly, the loss of blood group antigen expression was strongly associated with decreased DFI (P = 0.038) and survival (P = 0.062). While neither Pattern 1 A9 expression nor loss of blood group reach statistical significance in prediction of survival, the combination of Pattern 1 A9 expression and loss of blood group expression in primary tumors was significantly associated, both with decreased disease-free interval (P = 0.017) and with decreased overall survival (P = 0.011) (median length of follow-up = 22 months). The length of follow-up (LFU) ranged from 2 to 38 months, with a median LFU of 22 months. While the number of patients (37) is small, the significant association between the expression of these cell-surface markers with relapse and survival indicates that immunohistologic staining of the primary tumor will be an important prognostic indicator useful in identification of individual patients at greatest risk of recurrence or early death from head and neck cancer, independent of tumor size, site, or stage at presentation. These markers may thus provide means of selecting patients who should receive adjuvant therapy and more intensive monitoring for the early detection of recurrent disease.

ABO Blood-Group System↗

Thromboendarterectomy for chronic, major-vessel thromboembolic pulmonary hypertension. Immediate and long-term results in 42 patients.

Since 1970, forty-two patients with pulmonary hypertension due to chronic, thromboembolic obstruction of the major pulmonary arteries have had pulmonary thromboendarterectomy at the University of California, San Diego, and the San Diego Veterans Medical Centers. Duration of symptoms before admission averaged 4.4 years, with many alternative diagnoses having been made. At admission, 29 patients had class IV disease by New York Heart Association criteria, and 12, class III. Immediately after surgery, pulmonary vascular resistance declined significantly (p less than 0.001) from 897 +/- 352 dynes/s.cm-5 to 278 +/- 135 dynes/s.cm-5. Seven patients with class IV disease died in the postoperative period. Of the 35 survivors (mean follow-up, 28 months), 16 had class I disease; 18, class II; and 1, class III. Of the 17 patients who have returned for cardiac catheterization at 4 to 12 months after surgery, a further decline (p less than 0.05) in pulmonary vascular resistance has occurred. This experience indicates that the disorder is commoner than we previously suspected and that thromboendarterectomy is feasible, even in patients with severe and protracted hemodynamic compromise.

Adult↗

Pulmonary angiography in severe chronic pulmonary hypertension.

We have analyzed the safety of doing pulmonary angiography in 67 consecutive patients with moderate-to-severe primary pulmonary hypertension or hypertension secondary to chronic thromboembolic occlusions of the pulmonary arteries. The average (+/- SD) pulmonary arterial systolic and diastolic pressures were 74 +/- 19 and 34 +/- 10 mm Hg, respectively. Fourteen patients had a right ventricular end-diastolic pressure of 20 mm Hg or more. Selective left and right main pulmonary artery injections were done using ionic contrast agents in 56 patients and nonionic contrast agents in 11. No major rhythm disturbances or systemic hypotension requiring therapy occurred, and there were no deaths. Thrombotic occlusions of the pulmonary arteries were identified in 52 patients and confirmed in all 42 of those who had a thromboendarterectomy. At autopsy, 3 of the 15 patients who had normal angiograms were found not to have had thrombotic occlusions. We conclude that pulmonary angiography can be done safely despite the presence of severe pulmonary hypertension and right ventricular failure, and that the procedure leads to the identification of chronic, major-vessel thromboembolic pulmonary hypertension that may be alleviated by thromboendarterectomy.

Adolescent↗

Distal splenorenal (Warren) shunt in the management of actively bleeding oesophageal varices.

Distal splenorenal shunts have been performed on 53 patients during or soon after variceal haemorrhage. In 38 patients active haemorrhage was occurring at the time of operation or was controlled by tamponade and 12 of these patients died. There was no mortality in the semi-elective group. A higher mortality was found in patients with poor liver reserve and in whom prolonged conservative management had been attempted. Rebleeding occurred in 20 per cent of patients in the early postoperative period and this was a significant factor in the death of three patients. Of 39 patients with longer term follow-up, 8 suffered minor encephalopathy. Subsequent mortality could be related to the progression of liver disease and was no worse than that seen in a population of cirrhotic patients.

Adolescent↗

Pulmonary blood volume: relationship to changes in left ventricular end-diastolic pressure during atrial pacing.

Little data exist about the relationship between changes in cardiac end-diastolic pressure and changes in pulmonary blood volume. To assess this relationship, we studied 11 patients with coronary heart disease during atrial pacing in an attempt to produce multiple pressure-volume points. During catheterization, we obtained Millar pressure recordings of end-diastolic pressure along with equilibrium radionuclide angiograms. Cardiac output, ejection fraction, and pulmonary blood volume were obtained by means of recently validated radionuclide techniques. During pacing, substantial changes in pulmonary blood volume occurred only with marked increase in end-diastolic pressure volume (greater than or equal to 15 mm Hg) and rarely exceeded 15% of control pulmonary blood volume. Cardiac output did not change, while ejection fraction declined during pacing. There was a fair correlation between the absolute change in pulmonary activity (or pulmonary blood volume) or the percentage of change in pulmonary activity over the control value with end-diastolic pressure when all the data points were evaluated (n = 74, r greater than 0.70). However, the scatter in the data precluded making accurate estimates of pressure changes from changes in radionuclide volume changes. We conclude that large changes in cardiac filling pressure must occur during atrial pacing, where cardiac output does not change, before visible pulmonary blood volume changes occur. This may limit the extrapolation of presumed pressure changes from known pulmonary blood volume when changes are small.

Blood Pressure↗

Electrophysiologic changes associated with potassium depletion of frog skin.

Skins from the frog Rana pipiens pipiens were studied under short-circuited conditions during the course of removing and replacing potassium in the inner bathing media in 14 experiments. The intracellular potential (Vsc), fractional resistance (FR), short-circuit current (Isc) and total tissue conductance (gr) were constantly monitored during impalements of the epithelial cells. The mean value (+/- SE) for Vsc was --79 (+/- 3) mV under baseline conditions. Removal of potassium from the inner bathing solution transiently stimulated the short-circuit current and hyperpolarized the basolateral membrane; with sufficiently long incubations, the basolateral membrane was eventually depolarized. Restoration of potassium to the inner solution within 43 min after initiating the perfusion with K+-free solution depolarized the basolateral membrane. However, restoration of potassium after at least 1 1/2 hr of incubation hyperpolarized the membrane. Ouabain consistently depolarized the basolateral membrane, even after extended periods of potassium depletion as long as 320 min. In the presence of ouabain, restoration of potassium depolarized the basolateral membrane. The data provide further evidence for the concept that the Na--K exchange pump of frog skin is rheogenic. Furthermore, the results suggest that the pump continues to be active even during prolonged periods of potassium depletion, reaccumulating potassium which has leaked out of the epithelial cells.

Animals↗

Relationship of transient electrical properties to active sodium transport by toad urinary bladder.

Application of voltage pulses of 10 mV for periods of 9 sec across toad urinary bladder elicits a rapid deflection in transepithelial current. Frequently, the current decays back towards its baseline value during the course of the polarizing pulse. This transient phenomenon can be induced, or its magnitude increased, by raising the mucosal or serosal Na+ concentration. The transient can be abolished by sufficiently hyperpolarizing the tissue (rendering serosa positive to mucosa), by inhibiting transcellular Na+ transport with amiloride or ouabain, and by increasing the serosal K+ concentration. Vasopressin increases net Na+ movement across toad bladder but does not elicit these transients. It is proposed as a working hypothesis for further study that the transient behavior characterized in this study reflects: (1) the partition of Na+ between the apical plasma membrane and contiguous fluid layers, (2) the partition of K+ between the basolateral plasma membrane and adjacent submucosal fluid layer, and (3) the negative feedback interaction between intracellular Na+ activity and Na+ permeability of the apical plasma membrane of the transporting cells.

Amiloride↗