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Biomedical subjects

L Berman

Publications and source records attributed to L Berman.

At least 19 recordsLinked to original sources

Fuzzy classification of hemodynamic trends and artifacts: experiments with the heart rate.

Fuzzy set theory allows one to map inexact data, concepts, and events to fuzzy sets via user-defined membership functions. This paper describes a method for (1) robustly estimating the mean and slope of an arbitrary number of data points, (2) developing a set of fuzzy membership functions to classify various properties of heart rate trends, and (3) finding the longest consecutive sequence of heart rate data that fit a particular fuzzy membership function. Preliminary results indicate that fuzzy set theory has significant potential in the development of a clinically robust method for classifying heart rate data, trends, and artifacts.

Data Interpretation, Statistical

Molecular genetic analysis of the mldr mouse: a spontaneous revertant at the mld locus containing a recombinant myelin basic protein gene.

The mld mutation is a complex genetic lesion affecting the myelin basic protein (MBP) locus in the mouse. The mutation consists of a variety of DNA rearrangements including: tandem duplication of the MBP structural gene, partial inversion of the 3' end of the upstream gene copy, duplication of a region flanking the rearrangement junction in the upstream copy and insertion between the two gene copies of a segment of extraneous DNA not associated with the wild-type MBP locus. The net result of the mutation is a dysfunctional MBP locus. Homozygous mld/mld mice produce very little MBP and consequently very little myelin. They exhibit a clinical phenotype characteristic of hypomyelination (shaking, convulsions). We have discovered a revertant mld mouse which does not exhibit clinical symptoms of hypomyelination. Genetic analysis indicates that the reversion is allelic to mld. We have designated the revertant locus mldr. Restriction analysis of mldr genomic DNA indicates that there is a single intact MBP gene. Analysis of various junction regions using the polymerase chain reaction indicates that the single MBP gene in mldr is derived by recombination from the 5' end of the upstream gene and the 3' end of the downstream gene. Studies on MBP expression in mldr mice indicate that the developmental regulation, level of expression and pattern of post-transcriptional processing of MBP gene products in mldr are similar to wild type. These results indicate that the recombinant MBP gene in mldr is fully functional. From this we infer that the MBP-deficient phenotype of the original mld mutant is attributable to the complex rearrangements in the upstream gene copy which render the locus dysfunctional.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles

Automated integration of external databases: a knowledge-based approach to enhancing rule-based expert systems.

Expert system applications in the biomedical domain have long been hampered by the difficulty inherent in maintaining and extending large knowledge bases. We have developed a knowledge-based method for automatically augmenting such knowledge bases. The method consists of automatically integrating data contained in commercially available, external, on-line databases with data contained in an expert system's knowledge base. We have built a prototype system, named DBX, using this technique to augment an expert system's knowledge base as a decision support aid and as a bibliographic retrieval tool. In this paper, we describe this prototype system in detail, illustrate its use and discuss the lessons we have learned in its implementation.

Asthma

Recombinant soluble human complement receptor type 1 inhibits inflammation in the reversed passive arthus reaction in rats.

The human CR1 was genetically engineered by site directed mutagenesis into a truncated form which was secreted from transfected Chinese hamster ovary cells. This soluble recombinant CR1 (sCR1) was purified from the supernatants of the Chinese hamster ovary cells cultured in a hollow fiber bioreactor. sCR1 inhibits the C3 and C5 convertases of the classical and the alternative pathways in vitro. The ability of sCR1 to inhibit the immune complex-mediated inflammation in vivo was tested in a rat reversed passive Arthus reaction model. Administration of sCR1 at the dermal sites reduced the Arthus vasculitis in a dose-dependent manner as judged by both gross and microscopic examination, as well as by immunohistologic localization of C3 and C5b-9 neoantigen deposits. These data suggest that sCR1 inhibits the Arthus reaction by interrupting the activation of the C cascade, hence limiting the detrimental immune complex-induced tissue damage in vivo.

Animals

Problem area formation as an element of computer aided diagnosis: a comparison of two strategies within quick medical reference (QMR).

INTERNIST-I's use of "partitioning" to group related diagnoses into problem areas (for competitive consideration and elimination during case analysis) is felt to be the source of many of its strengths as well as some of its weaknesses. QMR, INTERNIST-I's successor program, embodies a homology function which can act as an alternative to the partitioner for problem area formation. This study undertakes a comparison of the problem areas generated by the INTERNIST-I partitioning algorithm, the QMR homology function, and expert clinicians; it finds the correlation to be poor. The authors then discuss another method of problem area formation which might better mimic a human clinician and provide an alternative approach in diagnostic computer-aided decision making.

Algorithms

Mercury concern.

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Canada

The late-presenting pediatric Morgagni hernia: a benign condition.

Data concerning 15 infants and children with late-presenting (more than 8 weeks) Morgagni hernias over the last 20 years (1966 to 1986) have been reviewed. Ten of the cases were clinically normal on presentation, and the most common symptoms and signs were gastrointestinal and respiratory. Only one child presented with acute symptoms. Five had previously normal chest x-rays, and two others had an incorrect initial radiologic assessment. Chest x-ray was the most common diagnostic test; preoperative barium studies were performed in three patients. Twelve patients had other major congenital abnormalities. Fourteen of the 15 had surgery, usually within days of presentation. At operation, 10 of the 14 hernias contained a hollow viscus, nine had a sac, and four had abnormal bowel fixation. Postoperatively, two children had radiologic evidence of impaired diaphragmatic motility. There was no mortality in this series. Overall, late-presenting Morgagni hernias are relatively benign.

Child

Primary structure of the leukocyte function-associated molecule-1 alpha subunit: an integrin with an embedded domain defining a protein superfamily.

The leukocyte function-associated molecule 1 (LFA-1, CD11a/CD18) is a membrane glycoprotein which functions in cell-cell adhesion by heterophilic interaction with intercellular adhesion molecule 1 (ICAM-1). LFA-1 consists of an alpha subunit (Mr = 180,000) and a beta subunit (Mr = 95,000). We report the molecular biology and protein sequence of the alpha subunit. Overlapping cDNAs containing 5,139 nucleotides were isolated using an oligonucleotide specified by tryptic peptide sequence. The mRNA of 5.5 kb is expressed in lymphoid and myeloid cells but not in a bladder carcinoma cell line. The protein has a 1,063-amino acid extracellular domain, a 29-amino acid transmembrane region, and a 53-amino acid cytoplasmic tail. The extracellular domain contains seven repeats. Repeats V-VII are in tandem and contain putative divalent cation binding sites. LFA-1 has significant homology to the members of the integrin superfamily, having 36% identity with the Mac-1 and p150,95 alpha subunits and 28% identity with other integrin alpha subunits. An insertion of approximately 200 amino acids is present in the NH2-terminal region of LFA-1. This "inserted/interactive" or I domain is also present in the p150,95 and Mac-1 alpha subunits but is absent from other integrin alpha subunits sequenced to date. The I domain has striking homology to three repeats in human von Willebrand factor, two repeats in chicken cartilage matrix protein, and a region of complement factor B. These structural features indicate a bipartite evolution from the integrin family and from an I domain family. These features may also correspond to relevant functional domains.

Amino Acid Sequence

Generalised lymphangiomatosis with chylothorax.

A 9 month old boy presented with acute respiratory distress and was found to have a left pleural effusion. The chylous nature of the effusion, multiple bony lytic lesions, and splenic cysts lead to the diagnosis of congenital lymphangiomatosis with chylothorax. Surgical intervention including pleurectomy was required after unsuccessful conservative management.

Bone Neoplasms

Anti-KJ: a new antibody associated with the syndrome of polymyositis and interstitial lung disease.

Antibodies to aminoacyl-tRNA synthetases (anti-Jo-1, anti-PL-7, anti-PL-12) have been found in the serum of some patients with polymyositis (PM). Patients with these antibodies have an unusually high rate of interstitial lung disease (ILD) in association with their PM. Two patients (K.J. and B.T.) with severe ILD and PM were found to have antibodies to a cytoplasmic antigen, but tests to determine whether the antigen was an aminoacyl-tRNA synthetase were negative, including tests of KJ serum for inhibitory effects on the 20 synthetases. KJ immunoprecipitates did not contain tRNA, in contrast to antisynthetase sera. When IgG samples were added to a reticulocyte in vitro translation system at a concentration of 0.3 mg/ml, KJ IgG inhibited globin mRNA translation by 98%, while anti-Jo-1 IgG inhibited 62% and normal IgG had little effect. Thus, both anti-KJ and the antisynthetases are directed at antigens that are involved in translation and protein synthesis, and both are associated with the syndrome of lung disease and PM. This syndrome may be associated with antibodies to translation-related proteins in general, which may have implications for the link of PM and enteroviruses, which are mRNA viruses.

Adult

Childhood diaphragmatic hernias presenting after the neonatal period.

Twenty-six patients with Bochdalek hernias and 15 with Morgagni hernias were evaluated in a survey of children presenting over the age of 8 weeks during a 20 year period. Ten of the children had previously normal chest radiographs. Radiological assessment at presentation was incorrect with 15 Bochdalek and two Morgagni hernias. These errors were more common in interpretations by general radiologists. Inappropriate thoracocentesis had been performed in four cases misdiagnosed as pneumothoraces. Barium studies, fluoroscopy, erect views and plain radiographs after nasogastric intubation were helpful investigations. Post-operative evidence of lobar collapse and pulmonary hypoplasia was frequently not appreciated at the time of clinical and radiological follow-up. Other congenital anomalies were commonly seen, particularly with Morgagni hernias. Bowel malfixation and malrotation, an important association, was frequently present but was occasionally overlooked at operation, necessitating further surgery for bowel obstruction.

Child

The late-presenting pediatric Bochdalek hernia: a 20-year review.

A 20-year retrospective study was made of children with congenital posterolateral (Bochdalek) hernias presenting more than 8 weeks after birth. The records of 26 patients (16 boys and 10 girls) were evaluated. Sixteen infants and children (62%) were originally misdiagnosed clinically and radiologically as having either infective lung changes, congenital lung cysts, or pneumothoraces; inappropriate thoracentesis occurred in four patients misdiagnosed as having a pneumothorax. Five patients had previously normal chest radiographs. The most useful investigation was a plain radiograph following passage of a nasogastric tube. Coexisting abnormalities (in particular, gut malfixation and malrotation) were common. All patients except one were operated on within days of presentation, and as emergencies if symptoms were acute. More than one third of our patients were left with a smaller than normal ipsilateral lung after their diaphragmatic hernia repair, and these lungs must be considered hypoplastic to some degree. Chest tubes made no difference in the lung's eventual expansion. Two deaths occurred as a result of acute cardiorespiratory arrest in previously well children. Therefore, the symptoms, signs, and radiologic findings of patients with diaphragmatic hernias presenting after the neonatal period may be difficult to interpret, and may result in diagnostic delay, misguided therapy, and a potentially fatal outcome.

Child

The ultrasound appearance of positive hip instability tests.

In a study assessing the use of ultrasound in the detection of neonatal hip abnormalities, the clinical findings in unstable hips were correlated with the ultrasound appearance during the instability provocation tests. Both hip displacement and concentric reduction of the femoral head in relation to the acetabulum could be defined with the ultrasound image.

Hip