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Biomedical subjects

M Freeman

Publications and source records attributed to M Freeman.

At least 55 records · Page 3Linked to original sources
PubMed1987

Human preproparathyroid hormone synthesized in Escherichia coli is transported to the surface of the bacterial inner membrane but not processed to the mature hormone.

cDNA encoding human preproPTH (hpreproPTH) was expressed in Escherichia coli to study the processing of the precursor to hPTH and its secretion by the bacterial secretory apparatus. We first constructed hybrid genes that differed randomly in the distance between the E. coli lac promoter's ribosomal binding site and DNA encoding a fusion protein with beta-galactosidase activity and the prepro sequence of hpreproPTH on the aminoterminus. Starting with clones identified as efficient producers of beta-galactosidase on indicator agar plates, the coding sequence for hpreproPTH was reconstituted intact. In a different construction we placed the hpreproPTH coding sequence downstream from the lac promoter at a distance of 12 base pairs from the ribosomal binding site. PTH immunoreactive proteins from multiple clones were identified by protein gel electrophoresis and by protein microsequencing. PTH-related proteins encoded by different plasmids were shown to be hpreproPTH with amino-terminal extensions of either two or four amino acids and as authentic hpreproPTH. Two hPTH fragments, hPTH(3-84) and hPTH(8-84), were also observed. The trypsin accessibility of hpreproPTH and of the two hPTH fragments in pulse-chase, cell-fractionation experiments using intact and lysed spheroplasts lets us conclude that the mammalian signal sequence directs hpreproPTH to the surface of the spheroplast membrane but is not appropriately cleaved by the signal peptidase.

Animals↗
PubMed1987

The distribution of a 'mitosis-specific' antigen during Drosophila development.

We have used MPM-2, a monoclonal antibody raised against mitotic HeLa cells, to stain a Drosophila cell line, whole mounts of Drosophila embryos, and sectioned tissue from embryonic and larval stages of development. MPM-2 recognizes a major phosphoprotein of approximately 125 X 10(3) Mr in Drosophila tissue culture cells that, like the mammalian MPM-2 antigen, appears to be recognized only in mitotic cells. During early embryogenesis, when the embryonic nuclei divide as a syncytium with a very short nuclear division time, MPM-2 antigen is observed within the spindle compartment at all stages of the nuclear division cycle. Upon cellularization of the embryo and lengthening of the duration of the cycle, the antigen is predominantly seen in mitotic cells. Drosophila larvae contain both diploid and polytene tissues: in diploid tissue MPM-2 staining is specifically observed over mitotic cells, as expected from its distribution in cellularized embryos. Surprisingly, antigen is also detected in the nuclei of polytene cells that replicate their DNA but do not undergo mitosis.

Animals↗
PubMed1987

Concurrent validity of equilibrium tests in boys with learning disabilities with and without vestibular dysfunction.

Six equilibrium measures were administered to 50 boys with learning disabilities, 25 with and 25 without suspected vestibular system dysfunction. Pearson product moment correlations were computed between test scores for the total sample and for each subgroup to establish concurrent validity between tests. Four correlations for the total sample and three for each of the subgroups were statistically significant. However, only 3 of the 10 correlation coefficients mentioned were greater than r = 0.5. The relatively low magnitude of many of the correlations obtained demonstrates that different tests of equilibrium measure different balance-related competencies, and that competence in one area does not indicate competence in another. Therapists evaluating equilibrium should administer more than one test. The tilt test used in this investigation did not correlate significantly with any other test. This suggests that tilt tests should routinely be included in the evaluation of equilibrium.

Adolescent↗
PubMed1987

Eosinophilic fasciitis with atypical features.

Eosinophilic fasciitis has been reported to be a syndrome distinct from progressive systemic sclerosis, due to the absence of Raynaud's phenomenon, visceral disease, and autoantibodies as well as steroid responsiveness and an abnormal histopathologic appearance that primarily involves the lower subcutis and fascia. More recent studies, however, have noted considerable overlap in the clinical, pathologic, and laboratory features of these two entities. We report a case that further blurs the distinction between eosinophilic fasciitis and progressive systemic sclerosis.

Aged↗
PubMed1986

The dissociation of nuclear and centrosomal division in gnu, a mutation causing giant nuclei in Drosophila.

We describe a recessive, maternal-effect lethal mutation of Drosophila, gnu. gnu uncouples nuclear division from many cytoplasmic events of mitosis in the Drosophila embryo. Embryos from homozygous females are defective in nuclear division, but not in DNA replication, and therefore develop a small number of giant nuclei. Centrosomes divide independently of nuclear division and migrate to the surface of the syncytial blastoderm. There they nucleate microtubules into asters, which appear normal at first but become very large. Only later, when the giant nuclei begin to break down, are spindles sometimes formed. The cortical actin of these embryos develops into a characteristic network.

Actins↗
PubMed1986

Should the intent of testing influence its interpretation?

A test is often interpreted as "normal" or "abnormal" by a single criterion, regardless of the intent of testing. The discriminate accuracy of this convention was critically analyzed using information content (I), likelihood ratio and the area under the receiver-operating characteristic curve. Three ejection fraction variables were assessed--ejection fraction at rest, exercise ejection fraction and the change in ejection fraction from rest to exercise--each relative to three intentional goals: diagnosis of coronary artery disease in 929 patients without previous myocardial infarction, prediction of multivessel disease in these same 929 patients and prediction of multivessel disease in 507 patients with previous myocardial infarction. The information content of exercise ejection fraction (IEX) was higher than for ejection fraction at rest (IR) or for the change from rest to exercise (IEX-R), and was relatively constant regardless of the goal of testing. In contrast, neither IR nor IEX-R was constant. IR was lowest for diagnosis of coronary artery disease, whereas IEX-R was highest for this same goal. These empiric observations are consistent with the quantitative relation predicted by information theory: IEX = IR + IEX-R. Thus, ejection fraction at rest has little discriminate value relative to the diagnosis of coronary artery disease, but does have value in evaluating the extent of disease in patients after myocardial infarction. Exercise ejection fraction and change in ejection fraction are nearly equally useful for purposes of diagnosis, whereas the former is most useful for functional evaluation in postinfarction patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Acute renal rejection versus acute tubular necrosis in a canine model: MR evaluation.

Findings of magnetic resonance (MR) imaging in acute renal rejection and acute tubular necrosis (ATN) were studied in dogs. On T1-weighted images, corticomedullary differentiation was absent in kidneys undergoing acute rejection. The loss of corticomedullary differentiation in these kidneys was secondary to a decrease in the relative signal intensity of the cortex, indicating prolongation of the T1 relaxation time of the cortex. In contrast, corticomedullary differentiation was preserved on T1-weighted images of autotransplanted kidneys and kidneys with ATN. MR imaging findings correlated with changes in water content in these three groups of kidneys. Kidneys undergoing acute rejection showed a marked increase in water content compared with kidneys in the other two groups. No change in fat content was found in any group.

Acute Kidney Injury↗
PubMed1986

On computer-assisted analysis of biological sequences: proline punctuation, consensus sequences, and apolipoprotein repeats.

During the past several years, the use of computer programs in the analysis of protein and DNA sequences has become commonplace. In all but the simplest procedures, the ability to critically review the results obtained with computer methods requires a basic knowledge of the algorithms employed (and the assumptions upon which they are based), an awareness of the capabilities and limitations of the particular program that implements an algorithm, and some familiarity with probability and statistics. We describe a number of computer methods that have been applied to the analysis of apolipoprotein sequences. We discuss the suitability of these methods for particular problems, how the choice of initial "parameters" can affect the results, and what the results can tell us about protein or gene sequences. We also identify some outstanding problems of apolipoprotein sequence analysis where further work is needed.

Amino Acid Sequence↗
PubMed1985

Malignant "Triton" tumors. Natural history and immunohistochemistry of nine new cases with literature review.

Malignant schwannomas with rhabdomyoblastic differentiation have been termed malignant "Triton" tumors (MTT). To define the natural history of MTT, we have analyzed our experience (9 cases, the largest series reported) in combination with the 27 previously described in the literature (total 36 cases). This study was initiated due to the unusual presentation of MTT as a polypoid esophageal mass. Rhabdomyoblastic differentiation in these tumors was confirmed using myoglobin immunohistochemistry. Two groups of patients were identified: those with Von Recklinghausen's Neurofibromatosis (Group I, VRN cases); and those without (Group II, sporadic, non-VRN cases). Group I patients accounted for over 70% of cases and displayed a marked male predominance, young age, and common head and neck presentation. By contrast, Group II patients were older, had a female predominance, and tumors frequently located on the trunk. Both groups fared equally poorly: local recurrence was common and the 5-year survival rate for all cases was 12%. Our data support the view that the natural history of MTT, whether in VRN patients or not, is much more aggressive than sporadic malignant schwannoma and similar to VRN sarcomas in general. This poor outlook could not be attributed to site; rather, it appeared to reflect the high frequency of Grade III histology in this disease.

Adult↗
PubMed1985

Cerebrospinal fluid levels of angiotensin-converting enzyme in Alzheimer's disease, Parkinson's disease and progressive supranuclear palsy.

Angiotensin-converting enzyme (ACE, E.C. 3.4.15.1) has been identified as a normal constituent of human cerebrospinal fluid (CSF). ACE activity in CSF from adult subjects without known neurologic disorder correlated positively (P = 0.002) with age between 50 and 90 years. Patients with moderate degrees of senile dementia of the Alzheimer's type and comparably demented patients with Parkinson's disease or progressive supranuclear palsy exhibited mean levels of ACE activity that were decreased 41, 27 and 53% respectively, compared to the mean level in an age and sex-matched group of neurologically intact individuals. These results raise the possibility that ACE activity in CSF may be an index of neuronal dysfunction in certain central neurodegenerative disorders.

Aged↗
PubMed1985

A format for integrating the interpretation of exercise ejection fraction and wall motion and its application in identifying equivocal responses.

The conventional interpretation of ejection fraction change with exercise may be limited because it does not consider the rest value, define equivocal responses or integrate wall motion data reproducibly. Thus, a format was developed for combined interpretation of rest and exercise radionuclide ejection fraction and wall motion by reviewing the reported data for the exercise responses of patients without prior myocardial infarction. The ejection fraction data of 202 normal patients and of 259 patients with coronary artery disease were first fitted to beta distributions. The true positive and false positive rates for coronary disease for each combination of rest and exercise ejection fraction were then determined directly from these distributions. A given rest/exercise ejection fraction combination was "normal" if the false positive rate was greater than the true positive rate, or "abnormal" if the true positive rate was greater than the false positive rate, and "equivocal" when the rates were similar (within a 50% confidence interval). This analytic format, which predicted an inverse relation between rest ejection fraction and the change required with exercise, was then validated prospectively in 854 patients without myocardial infarction (557 with and 297 without angiographic coronary artery disease). Using the conventional criterion of an abnormal test result (less than 0.05 absolute rise in ejection fraction with exercise or a wall motion abnormality), sensitivity was 85 +/- 2% and specificity only 42 +/- 3%. The statistical format had a sensitivity of 70 +/- 2% and specificity of 70 +/- 3%, resulting in a twofold increase in information content. This format has at least two advantages over conventional interpretation: 1) it provides an explicit definition of equivocal responses; and 2) it reproducibly integrates discordant ejection fraction and wall motion responses and allows for the combined analysis of other nonscintigraphic observations, such as age and sex.

Adult↗
PubMed1985

Doughnut sign on bone scintigraphy in angioblastic meningioma.

Bone imaging was performed in a patient with a rapidly expanding parietal bone lesion. The findings on the nuclear medicine study showed a doughnut type lesion. The underlying abnormality was found to be an angioblastic meningioma causing local bone destruction.

Diphosphonates↗
PubMed1979

Immunity of children to diphtheria, tetanus, and poliomyelitis.

A survey of titres of diphtheria and tetanus antitoxins and of antibodies to polioviruses in the sera of 291 schoolchildren aged 15, 11, and 7 years showed that high immunisation rates can evoke protective concentrations of tetanus antitoxin in 98% of children and protective levels of the antibodies to diphtheria and all three types of poliomyelitis in 85% of children. Reinforcing immunisation at school entry appeared to be necessary to maintain adequate titres of diphtheria antitoxin in children up to 15 years of age, not essential to maintain adequate titres of tetanus antitoxin, and to have little effect on the titres of antibodies to poliomyelitis.

Adolescent↗
PubMed1978

Training visual-spatial ability in EMR children.

Educable mentally retarded children were randomly assigned to either a visual-spatial training condition or a control group. The children who received training showed a gain from pretest to posttest on the Children's Embedded Figures Test that corresponds to approximately 4 years of maturation in nonretarded children. The performance of the children in the control group on the posttest was not significantly different from their performance on the pretest. Correlations between measures of visual-spatial ability and the employment adjustment of retarded persons obtained by other investigators suggest the potential importance of developing the visual-spatial skills of this population.

Adolescent↗
PubMed1977

Hepatic triglyceride lipase deficiency in liver disease.

The activity of post-heparin lipases in patients with alcoholic hepatitis and viral hepatitis was evaluated. Lipoprotein lipase and hepatic triglyceride lipase were differentiated by assay under high and low salt conditions and also by separation on heparin-agarose affinity chromatography columns. The mean activity of hepatic triglyceride lipase in the sera of liver disease patients was only 21-24% of the mean of controls, but lipoprotein lipase in patients' sera was not different from normal levels. Hepatic triglyceride lipase deficiency may partially account for the accumulation of a triglyceride-rich low density lipoprotein in liver disease.

Alcoholism↗
PubMed1976

The uptake of pyrimidine nucleosides in Tetrahymena. I. Uridine.

Uridine uptake was examined in Tetrahymena pyriformis GL-7 in defined medium under conditions where food vacuole formation is not a significant factor in solute acquisition by the cell. The results indicate the presence of a saturable mechanism which follows Michaelis-Menten kinetics. When corrected for diffusion the apparent Km for the carrier is 2.3 +/- 0.6 muM and the Vmax is 7.3 +/- 0.2 X 10(-7) nmoles/cell/min. It is evident from nucleotide pool analysis that most of the radioactivity of externally supplied [3H]uridine appears in UMP with the remainder in UTP. Uridine is apparently phosphorylated immediately upon entry into the cell and neither uridine-cytidine kinase activity nor RNA synthesis are rate-limiting in the uptake process. Uridine transport is competitively inhibited by a variety of ribo- and deoxyribonucleosides as well as several nucleoside analogs. Neither uracil nor ribose or deoxyribose are effective inhibitors of uridine transport indicating the carrier is specific for the nucleoside. There is little difference between the Ki values for ribo- as opposed to deoxyribonucleosides except in the case of deoxyguanosine which is much less effective as an inhibitor under the conditions of this study, than all the other nucleosides, including guanosine.

Animals↗