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Biomedical subjects

M K Kan

Publications and source records attributed to M K Kan.

14 recordsLinked to original sources

Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors.

A novel Mr 17,000 heparin-binding protein was purified from culture medium conditioned by A431 human epidermoid carcinoma cells. This protein, designated HBp17, was found to bind the heparin-binding peptide growth factors HBGF-1 and HBGF-2 in a noncovalent, reversible manner. In addition HBp17 was found to inhibit the biological activities of both HBGF-1 and HBGF-2. Both the binding and inactivation of HBGF-1 and HBGF-2 by HBp17 were abolished by heparin. Full-length 1163-base pair HBp17 cDNA was cloned and sequenced by using the polymerase chain reaction technique. The deduced primary structure of HBp17 consisted of 234 amino acids including each of five partial peptide sequences obtained from proteolytic fragments of purified HBp17. The encoded protein included a 33-residue N-terminal signal sequence for secretion and a single potential N-linked glycosylation site. No homology with any known protein was found for the deduced primary structure of HBp17. The expression of HBp17 mRNA was found to occur preferentially in normal human keratinocytes and in squamous cell carcinomas. This pattern of HBp17 gene expression suggests that this binding protein for HBGFs 1 and 2 has a physiological role in squamous epithelia.

Amino Acid Sequence

Fibroblast growth factor receptors from liver vary in three structural domains.

Changes in heparin-binding fibroblast growth factor gene expression and receptor phenotype occur during liver regeneration and in hepatoma cells. The nucleotide sequence of complementary DNA predicts that three amino-terminal domain motifs, two juxtamembrane motifs, and two intracellular carboxyl-terminal domain motifs combine to form a minimum of 6 and potentially 12 homologous polypeptides that constitute the growth factor receptor family in a single human liver cell population. Amino-terminal variants consisted of two transmembrane molecules that contained three and two immunoglobulin-like disulfide loops, as well as a potential intracellular form of the receptor. The two intracellular juxtamembrane motifs differed in a potential serine-threonine kinase phosphorylation site. One carboxyl-terminal motif was a putative tyrosine kinase that contained potential tyrosine phosphorylation sites. The second carboxyl-terminal motif was probably not a tyrosine kinase and did not exhibit the same candidate carboxyl-terminal tyrosine phosphorylation sites.

Amino Acid Sequence

Measurement of liver volume by emission computed tomography.

In 22 volunteers without clinical or laboratory evidence of liver disease, liver volume was determined using single-photon emission computed tomography (ECT). This technique provided excellent object contrast between the liver and its surroundings and permitted calculation of liver volume without geometric assumptions about the liver's configuration. Reproducibility of results was satisfactory, with a root-mean-square error of less than 6% between duplicate measurements in 15 individuals. The volume measurements were validated by the use of phantoms.

Adult

Scintillation-camera simulator for remote-data acquisition testing.

A device based on an 8080 microprocessor was assembled for the generation of image data in a manner similar to that of the scintillation camera. This "simulator" thus permits testing of the integrity of systems for the acquisition of data over long transmission lines, without tying up the portable scintillation camera. The simulator has improved the reliability of remote-data collections and has increased the efficiency of utilization of the camera.

Amplifiers, Electronic

Evaluation of the mediastinum by gallium-67 scintigraphy in lung cancer.

Delineation of the metastatic spread of lung cancer has been attempted by a variety of means. Controversy as to the indications for organ surveys, mediastinoscopy, scintillation scanning, and biopsy techniques still exists. Since definition of the micrometastatic state is yet unachieved, the staging of disease for therapy continues to be predicted on documented spread beyond the site of the origin. The records of 75 patients in whom the presence or absence of mediastinal metastases was known were retrospectively reviewed to establish the sensitivity, specificity, predictive values, and accuracy of 67Ga scintigrams. Comparisons were made with chest roentgenograms, mediastinal tomograms, and endoscopic findings. Five patients had 67Ga-negative studies. In the 70 patients having 67Ga-positive lung lesions, mediastinal 67Ga uptake had a sensitivity of 88%, a specificity of 86%, predictive values of 93% for a positive test and 76% for a negative test, and a test accuracy of 87%. These studies, plus those of others, permit selectivity of choosing candidates for mediastinoscopy. If the primary is 67Ga positive, a negative mediastinal scan obviates mediastinoscopy. If the mediastinum is 67Ga positive, mediastinal exploration is indicated. The level of involvement dictates whether resection is undertaken in suitable surgical candidates. This approach, employed since 1976, has lowered the costs of staging, and 67Ga has become our scintigram of choice.

Evaluation Studies as Topic

Scintigraphic assessment of left ventricular aneurysms.

Thirty-five patients with coronary artery disease and possible left ventricular aneurysm underwent routine clinical examination, gated cardiac blood pool scintigraphy, and radionuclide cineangiography. Thirty-three of the 35 patients had coronary angiography and contrast left ventriculography. Sixteen patients had segmental left ventricular akinesia or dyskinesia, and 17 demonstrated left ventricular hypokinesis on contrast ventriculograms. Two patients had aneurysm confirmed at autopsy. Routine clinical evaluation was not sufficient to separate patients with aneurysm from those with hypokinesis. Radionuclide cineangiography correctly identified all cases of aneurysm or hypokinesis. The cinescintigraphic technique was preferable to the gated cardiac blood pool technique for qualitatively assessing and classifying abnormal ventricular wall motion. There was good correlation of the left ventricular ejection fraction by contrast ventriculograms and gated scintigrams in patients with either aneurysm or hypokinesis.

Cineangiography

Analysis of wall motion abnormalities of the heart and great vessels by computer generated cine-radionuclide-equilibrium study.

Cardiac wall motion was evaluated in 54 patients by ECG-gated blood pool scintigraphy (GBPS) and computer assisted cine-radionuclide-equilibrium study (CRES). The cine format in CRES enhances the subtle aspects of great vessel and cardiac chamber motion and volume abnormalities. An off-line system using a general purpose computer permitted CRES to be initiated in smaller nuclear medicine facilities without large financial investiments.

Adult

Edge enhancement of ECG-gated cardiac images using directional masks.

ECG-gated images were processed by a computer using a nonlinear digital filter and directional masks to improve delineation of cardiac chamber boundaries and identification of the aortic and mitral valve planes. This technique proved to be satisfactory in 30 patients with documented coronary or valvular heart disease.

Coronary Disease

Scintigraphic evaluation of suspected acute myocardial infarction.

Ninety-one patients with chest pain suggestive of acute myocardial infarction were studied by static technetium Tc 99m stannous pyrophosphate scintigraphy and dynamic sodium pertechnetate Tc 99m cardioangiography. Twenty-three of 26 patients (88%) with acute transmural infarcts and 12 of 17 patients (71%) with nontransmural infarcts had abnormal static studies. In 45 patients with negative scintigrams, ECG or serum enzyme changes consistent with acute infarction failed to develop. Three false-positive static studies (6%) were recorded. Twenty of 43 (47%) patients with acute infarction had hemodynamic or structural abnormalities identified by cardioangiography. The dynamic study also proved helpful in localizing the site of infarction and in ruling out certain causes of false-positive static scintigrams.

Acute Disease

Unilateral breast uptake of 67Ga from breast feeding.

Unilateral 67Ga uptake was observed in the left breast of a 23-year-old woman who had nursed her infant on that side for 10 months. Careful clinical examination and follow-up failed to reveal any evidence of breast disease. Unilateral breast feeding should be considered in the differential diagnosis of asymmetric 67Ga localization in the breast.

Breast

Marked suppression of thyroid function in rats with gram-negative septicemia.

Gram-negative septicemia was induced in rats by two daily injections of fecal mixture into the thigh, after which the thyroid function was markedly suppressed for 2 days. Iodine metabolism was studied by organ radioassay and by imaging with a multiwire proportional chamber (MWPC) at various time intervals after intravenous injection of 125I. Plasma T3, T4, and TSH, measured by radioimmunoassays, were suppressed, as were the T3-resin uptakes. Fractional blood supply to the thyroid glands of the infected rats, studied by the 81Rb uptake method, was also found to be markedly reduced. Sections of the thyroid glands showed little structural change during the period of marked thyroid suppression. There was no biochemical evidence of renal failure in the septicemic rats.

Animals