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D R Jacobson

Publications and source records attributed to D R Jacobson.

At least 37 records · Page 2Linked to original sources
PubMed1994

A double-variant transthyretin allele (Ser 6, Ile 33) in the Israeli patient "SKO" with familial amyloidotic polyneuropathy.

Transthyretin (TTR) isolated from amyloid fibrils from an Israeli patient ("SKO") with familial amyloidotic polyneuropathy has been studied by two groups of investigators. Originally, a position 49 Thr-->Gly substitution was reported; subsequently, a position 33 Phe-->Ile substitution was found instead. We have studied DNA from this patient by single strand conformation polymorphism analysis, restriction analysis, and DNA sequencing. On one allele, exon 2 contained both a T-->A transversion at the first position of codon 33, encoding the previously described Phe-->Ile substitution, and a G-->A transition at the first position of codon 6, encoding a Gly-->Ser substitution. The originally reported position 49 mutation was not encoded in the genomic DNA. This is the first report of a TTR double-variant allele in a patient with TTR amyloidosis.

Alleles↗
PubMed1994

A highly sensitive assay for mutant ras genes and its application to the study of presentation and relapse genotypes in acute leukemia.

Most studies of ras oncogene activation use assays for ras mutations based on the polymerase chain reaction (PCR) of DNA segments containing ras exons 1 and 2, followed by allele-specific oligonucleotide (ASO) hybridization or direct sequencing, which require that to be detectable, a mutation must be present in at least 3-25% of ras alleles. Thus, studies of tissues in which only a fraction of cells contains a ras mutation risk false negative results. To minimize this risk, we have developed a highly sensitive, non-radioactive assay for ras mutations. Ras genes were PCR-amplified using mismatched primers, to introduce restriction sites into products derived from normal alleles. Repeated restriction digestion and PCR enriched for mutant alleles, visualized by agarose gel electrophoresis. Serially diluted DNA samples containing ras mutations demonstrated detection of 1 mutant/10(6) normal alleles (four orders of magnitude more sensitive than PCR/ASO hybridization). This assay was applied to DNA from four patients with relapsed acute leukemia in whom ras mutations present at diagnosis were not detectable by PCR/ASO hybridization at relapse. In one case, the mutation present at diagnosis was demonstrated at relapse. In the others, loss of the mutation was confirmed, at a greatly increased sensitivity. This method is widely applicable to detection of mutant ras alleles admixed with larger numbers of normal alleles.

Alleles↗
PubMed1992

Transthyretin Pro55, a variant associated with early-onset, aggressive, diffuse amyloidosis with cardiac and neurologic involvement.

Mutations in the protein transthyretin cause amyloidosis involving the heart, peripheral nerves, and other organs. A family from West Virginia developed an unusually aggressive form of widespread transthyretin amyloidosis. Single-strand conformation polymorphism analysis revealed a variant in the transthyretin gene, which was found on sequencing to be a T----C transversion at position 2 of codon 55, corresponding to a Leu----Pro substitution. The variant sequence was confirmed by restriction analysis and polymerase chain reaction (PCR)-primer introduced restriction analysis.

Amyloidosis↗
PubMed1992

Radiographic exposure calculator and mammographic dose calculator.

A set of dose calculators has been designed to facilitate quick and easy calculation of surface exposure (or skin dose) for routine radiography and average glandular dose in mammographic studies. Acceptance by technologists has been good, and in two inspections by the Joint Commission for Accreditation of Health Care Organizations, the calculators were deemed adequate to satisfy the diagnostic radiology standards that doses be monitored.

Humans↗
PubMed1992

A specific test for transthyretin 122 (Val----Ile), based on PCR-primer-introduced restriction analysis (PCR-PIRA): confirmation of the gene frequency in blacks.

The variant transthyretin (TTR) allele, TTR (122 Val----Ile), associated with cardiac amyloidosis in blacks, is caused by a G----A transition which destroys a MaeIII site. This variant has previously been detected by PCR around codon 122, followed by MaeIII digestion, but this test is not specific: any of 12 mutations in the MaeIII recognition site, each of which yields a different amino acid change, would also destroy this site. A modification of PCR, termed "PCR-primer-introduced restriction analysis," was used to introduce a new FokI site into the PCR products derived from the variant (122 Ile) but not wild-type (122 Val) allele. This test demonstrated that each of six previously identified MaeIII(-) alleles had lost its MaeIII site because of a G----A transition encoding TTR (122 Val----Ile), confirming that the same TTR variant was present both in 4/177 healthy black individuals and as a homozygous variant in an individual with cardiac amyloidosis.

Alleles↗
PubMed1991

Frequency and genetic background of the position 122 (Val----Ile) variant transthyretin gene in the black population.

Transthyretin (TTR) (122 Val----Ile), caused by a point mutation which destroys a MaeIII restriction site, is associated with cardiac amyloidosis in black individuals. To estimate the frequency of the MaeIII(-) gene in the black population without overt cardiac disease, DNA from 177 black individuals without amyloidosis was amplified by the PCR around TTR codon 122 and was digested with MaeIII. The MaeIII(-) gene frequency was 4/354 (1.1%; 95% confidence interval 0.32%2.7%), suggesting that the variant is relatively common in blacks. HLA genotype testing did not suggest that the TTR (122 Val----Ile) heterozygotes were of a closely related genetic background.

Amino Acid Sequence↗
PubMed1990

Display of CT studies on a two-screen electronic workstation versus a film panel alternator: sensitivity and efficiency among radiologists.

Prototype electronic workstations incorporated in networks linking computed tomographic (CT) and magnetic resonance imaging systems are being developed. The authors compared observer efficiency and sensitivity in reading body CT studies from a two-screen workstation (1,000-line monitors and 12-bit dynamic range in image memory) and conventional film panel alternator. The two-screen workstation displayed 32 images at a matrix resolution of 256 x 256 or eight images at a matrix resolution of 512 x 512 simultaneously. Ninety-six images with a matrix resolution of 512 x 512 could be displayed simultaneously at the film panel alternator. Four observers read images from 20 cases, 10 with repeat examinations, in a randomized viewing sequence. There was an average of 32 images per case. Reporting time was less with the film panel alternator (average, 5.08 minutes) than with the workstation (average, 6.66 minutes). There was improved sensitivity for all observers in reading from the film panel alternator (range, 1%-12%) (P less than .05). In complex cases evaluated by means of body CT, the current prototype two-screen electronic workstation is limited by display capabilities.

Data Display↗
PubMed1990

A homozygous transthyretin variant associated with senile systemic amyloidosis: evidence for a late-onset disease of genetic etiology.

Senile systemic amyloidosis (SSA) is a late-onset disease characterized by deposition of amyloid fibrils containing transthyretin (TTR). Amino acid sequencing of protein isolated from the amyloid fibrils of a patient with SSA identified TTR containing a position - 122 isoleucine-for-valine substitution. This change led to the prediction of a genomic G-to-A transition, destroying an MaeIII restriction site. We confirmed the presence of the variant DNA fragment both by Southern blotting and by visualization of MaeIII digests of DNA amplified around codon 122, by using the polymerase chain reaction. The patient's DNA was entirely resistant to MaeIII cleavage; therefore, only the mutant sequence was present. DNA from none of either 24 controls or six other SSA patients contained the variant. Quantitative Southern blotting demonstrated that the patient's DNA contained two copies of the TTR gene per genome; the mutation was therefore homozygous rather than hemizygous. In the present case, the homozygous mutation TTR (122 Val----Ile) is associated with SSA, a finding which is consistent with autosomal recessive inheritance of this condition.

Age Factors↗
PubMed1988

Restriction fragment analysis confirms the position 33 mutation in transthyretin from an Israeli patient (SKO) with familial amyloidotic polyneuropathy.

Transthyretin isolated from amyloid fibrils from an Israeli patient with Familial Amyloidotic Polyneuropathy was sequenced by two research groups. One laboratory reported a position 49 Thr----Gly substitution, while the other noted a Phe for Ile interchange at amino acid 33. We used a transthyretin cDNA probe to study DNA from this patient by Southern blotting. The DNA displayed the unique Bcl I restriction site predicted by the mutation in codon 33. Because of the close size of the normal (6.40 kb), and variant (6.27 kb) fragments, the variant was more easily demonstrated after digestion with both Bcl I and Sph I, which generated two easily resolvable fragments of 2.39 and 2.27 kb.

Amyloidosis↗
PubMed1986

Immunosuppression and infection in multiple myeloma.

Patients with multiple myeloma are at increased risk of severe bacterial infection. A variety of immune deficits has been described in such patients, including a decreased primary antibody response and defects in complement and granulocyte function. The depressed humoral response appears to result primarily from the activity of suppressor monocytes. Pneumovax (Merck Sharp & Dohme, West Point, Penn) should be administered to patients with myeloma, although its effectiveness in this population has not been proven. The role of other potential modalities of treatment and prophylaxis, such as IV gamma globulin, requires further study.

Bacterial Infections↗