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Biomedical subjects

K Peterson

Publications and source records attributed to K Peterson.

At least 19 recordsLinked to original sources
PubMed1992

SV2, a brain synaptic vesicle protein homologous to bacterial transporters.

Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein specifically localized to secretory vesicles in neurons and endocrine cells. As a first step toward understanding the function of SV2 in neural secretion, a rat brain complementary DNA (cDNA) that encodes SV2 was isolated and characterized. Analyses of this cDNA predict that SV2 contains 12 transmembrane domains. The NH2-terminal half of the protein shows significant amino acid sequence identity to a family of bacterial proteins that transport sugars, citrate, and drugs. Expression of the SV2 cDNA in COS cells yielded a high level of SV2-like immunoreactivity distributed in a reticular and punctate pattern, which suggests localization to intracellular membranes. Its localization to vesicles, predicted membrane topology, and sequence identity to known transporters suggest that SV2 is a synaptic vesicle-specific transporter.

Amino Acid Sequence↗
PubMed1992

Loss of heterozygosity for chromosomes 1 or 14 defines subsets of advanced neuroblastomas.

Neuroblastomas have been characterized genetically by N-myc amplification and by deletions or loss of heterozygosity (LOH) for the short arm of chromosome 1. However, recent studies have suggested deletion or allelic loss involving at least three other chromosome arms, 11q, 14q, and 17p. Therefore, we undertook an analysis of allelic loss for these respective chromosomal arms to determine the frequency and pattern of LOH as well as the correlation of these findings with other biological and clinical variables. A group of 24 pairs of normal and tumor DNAs was chosen that were representative of patients of different ages and stages. A substantial frequency of LOH (greater than or equal to 20%) was found only for 1p and 14q, whereas LOH for the other chromosome arms occurred in less than or equal to 5% of cases. On the basis of these results, we extended the analysis to a total of 59 neuroblastomas, and we found 1p LOH in 15 of the 59 cases (25%) and 14q LOH in 10 of 43 informative cases (23%). N-myc amplification was found in 15 of the 59 cases (25%). This analysis confirmed that 1p LOH and 14q LOH occurred almost exclusively in patients with advanced stages of disease. Furthermore, LOH for 1p and 14q usually occurred independent of each other, and 1p LOH frequently was associated with N-myc amplification, whereas 14q LOH was not. Thus, our results demonstrate that neuroblastomas are complex genetically and that there are at least two distinct loci for putative suppressor genes that are deleted independently in this tumor, both of which are associated with advanced stages of disease.

Blotting, Southern↗
PubMed1992

Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients.

We reviewed the clinical findings in 55 patients with cerebellar degeneration associated with the anti-Yo antibody (an anti-Purkinje cell antibody identified in this study by histochemistry and Western blot). The patients were all women, 26 to 85 years old. Fifty-two of them proved to have malignancies, almost exclusively breast or gynecologic cancers and usually confined to the involved organs and local lymph nodes. One woman had adenocarcinoma of the lung, and in three no malignancy has yet been identified. In 34 of 52 patients with cancer, the neurologic syndrome preceded the diagnosis of cancer and in many led to that diagnosis. Patients subacutely developed a pancerebellar disorder that was substantially disabling in most, with 37 of 48 assessable patients being unable to walk or sit unassisted. Laboratory evaluation revealed lymphocytic pleocytosis in 35 patients, with eventual cerebellar atrophy on imaging studies in seventeen. The disabling neurologic syndrome generally did not respond to treatment, but the cancer was often successfully treated. The presence of the anti-Yo antibody in patients with cerebellar symptoms warrants an aggressive approach to diagnosis and treatment of the underlying cancer, as many are curable at the time neurologic symptoms develop.

Adult↗
PubMed1992

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1979

Assessment of early ventricular systole by first pass radionuclide angiography: useful method for detection of left ventricular dysfunction at rest in patients with coronary artery disease.

To identify abnormal left ventricular function without exercise stress in patients with coronary artery disease first-pass radionuclide angiograms were analyzed in 32 normal subjects (Group I); 31 patients with coronary disease and normal contrast ventriculograms (Group II); and 17 patients with coronary disease and depressed left ventricular function (Group III). Total ejection fraction (EF) was computed with standard angiographic methods and from each time-activity curve. During the first third of systole, ejection fraction was determined manually by averaging three to five beats and the value compared with that obtained with contrast ventriculography: (Formula: see text). Both total radionuclide ejection fraction (r = 0.95) and first-third ejection fraction (r = 0.91) correlated well with angiography. Intraobserver and interobserver variation was small, averaging 0.02 +/- 0.02 (range 0 to 0.05). The radionuclide first-third ejection fraction was 0.25 or greater in normal subjects and less than 0.25 in 29 of 31 patients (94 percent) in Group II and in all patients in Group III. It is concluded that the first-third ejection fraction obtained with first pass angiography identifies subtle abnormalities of left ventricular function at rest in more than 90 percent of patients with coronary disease that may not be recognized by total ejection fraction alone.

Adult↗
PubMed1979

Left ventricular volumes by gated equilibrium radionuclide angiography: a new method.

To compare radionuclide end-diastolic (EDV) and end-systolic (ESV) volumes with angiographic volume, we studied 52 patients with equilibrium radionuclide angiography using 99mTc-human serum albumin within 48 hours of contrast angiography. Each RR interval was divided into 20--28 equally timed frames and a time-activity curve generated. End-diastolic counts were taken at the early peak of the curve and end-systolic counts at its nadir. Counts were divided by the total number of processed heart beats and normalized for: 1) dose per body surface area; 2) plasma volume; and 3) counts/ml of plasma. A cardiac phantom was developed and serial volumes were studied using a normalization factor. Radionuclide values were expressed as dimensionless units and compared with either biplane angiographic volumes (in the patient studies) or known phantom volumes. Good correlations were obtained with methods 1 and 2 in 35 patients (r greater than 0.84), but the best correlation was obtained in 17 patients when normalization for counts/ml of plasma was used (r = 0.98; y = 0.255 x -0.121). The standard error of the estimate (SEE) was +/- 11.5 ml for EDV and +/- 7.3 ml for ESV. The phantom study also showed an excellent correlation (r = 0.99), with a SEE of +/- 6.5 ml. We conclude that a radionuclide method independent of geometric assumptions can be used to estimate left ventricular volume in man.

Adult↗
PubMed1978

Active valvulitis associated with chronic rheumatic valvular disease and active myocarditis.

From ten patients aged 15 to 40 years with chronic rheumatic valvular disease and histologically proved Aschoff bodies of active rheumatic myocarditis, the valves were evaluated for incidence, distribution and degree of severity of active inflammation. Prior to death, there had been clinical evidence of active rheumatic fever. In each case, active rheumatic valvulitis was present in at least one valve. Of the individual valves studied, 83% were involved by active inflammation of the leaflets or the anulus or both. The aortic valves was involved in 100% of cases, the mitral valve in 86%, the tricuspid valve in 78% and the pulmonary valve in 70%. The mitral and aortic valves were most frequently involved, but the mitral and tricuspid valves were most severely involved when affected. In every case, active rheumatic lesions of the left atrial appendage were present, but these tended to be less widely distributed than the myocardial Aschoff bodies. The high incidence of active valvulitis supports the concept that chronic fibrosing rheumatic valvular disease results from recurrent active inflammation. Such inflammation may occur without clinical suspicion of active rheumatic fever.

Adult↗
PubMed1978

Evaluation of the in vivo function of the Hancock porcine xenograft in the aortic position.

We evaluated the vivo hemodynamic function of the stent-mounted glutaraldehyde-fixed porcine xenograft in 23 patients who had undergone aortic valve replacement from 2 days to 24 months prior to the study. Functional aortic valve orifice areas for the porcine xenograft ranged from 0.58 to 3.0 sq. cm., the average area being 1.36 sq. cm. Six patients had calculated prosthetic valve orifice areas less than 1.0 sq. cm. Valve orifice area did not correlate significantly with valve size or the time interval from surgery to postoperative study. Left ventricular stroke volume showed a significant, positive correlation with calculated xenograft orifice area. Systemic thromboembolism was not encountered. One patient required reoperation for xenograft stenosis caused by dense fibrin deposition on the aortic leaflets. We conclude that use of the stent-mounted glutaraldehyde-fixed porcine xenograft can be associated with significant functional stenosis which may be related to annulus size or inertial properties of the valve. These factors should be taken into consideration when considering use of the stent-mounted glutaraldehyde-fixed porcine xenograft in individual patients.

Adult↗