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Biomedical subjects

P A Goodman

Publications and source records attributed to P A Goodman.

7 recordsLinked to original sources
PubMed1992

Growth factor receptor regulation in the Minn-1 leprechaun: defects in both insulin receptor and epidermal growth factor receptor gene expression.

Leprechaunism is a disorder characterized by intrauterine growth retardation, distinctive dysmorphology, and extreme insulin resistance due to structural abnormalities of the insulin receptor (IR). In addition to the IR, it has been suggested that abnormalities of the other growth factor receptors may occur in this syndrome. Using fibroblasts from the Minn-1 leprechaun, we have now investigated the expression of three different growth factor receptor genes: the IR, the insulin-like growth factor-I receptor (IGF-IR), and the epidermal growth factor receptor (EGFR). In agreement with previous studies, we found decreased insulin binding to fibroblasts from the Minn-1 leprechaun. In these cells, the IR transcription rate was not decreased, and sequence analysis of the IR promoter region of the patient showed no abnormalities. Both single-stranded conformational polymorphism analysis (SSCP) and DNA sequencing confirmed a previously reported nonsense mutation in one of the patient's two IR alleles at exon 14. mRNA levels for the IR were markedly decreased, suggesting that IR mRNA turnover was enhanced. We then studied the expression of the closely related IGF-IR Ligand binding, mRNA content, and transcription rate were all normal. In contrast to the IGF-IR, when the EGFR was studied, ligand binding and mRNA content were markedly decreased. These studies therefore raise the possibility that the phenotypic expression of leprechaunism results from defects in the expression of both the IR and the EGFR.

Abnormalities, Multiple↗
PubMed1991

Production of inhibitor of insulin-receptor tyrosine kinase in fibroblasts from patient with insulin resistance and NIDDM.

Although non-insulin-dependent diabetes mellitus (NIDDM) is associated with defects in insulin action, the molecular basis of this resistance is unknown. We studied fibroblasts from a markedly insulin-resistant patient with NIDDM but without acanthosis nigricans. Her fibroblasts were resistant to insulin when alpha-aminoisobutyric acid uptake was measured. Fibroblasts from this patient demonstrated normal insulin-receptor content as measured by both insulin-receptor radioimmunoassay and by Scatchard analysis. However, when compared with nondiabetic control subjects, insulin-receptor kinase assays of wheat-germ-purified receptors prepared from her fibroblasts showed very low basal and no insulin-stimulated tyrosine kinase activity. The insulin receptor was then removed from the wheat-germ fraction by monoclonal antibody affinity chromatography. This insulin-receptor-deficient fraction inhibited both basal and insulin-stimulated tyrosine kinase activity of highly purified insulin receptors. When the specificity of this inhibition was tested, less inhibition was seen with insulinlike growth factor I-receptor tyrosine kinase, and even less inhibition was seen with the proto-oncogene p60c-src tyrosine kinase. Thus, these studies indicate that fibroblasts from an insulin-resistant patient with NIDDM produce a relatively specific glycoprotein inhibitor of insulin-receptor tyrosine kinase. Therefore, these studies raise the possibility that this inhibitor may play an important role in the insulin resistance seen in this patient.

Adult↗
PubMed1978

Nitrogen-containing compounds in foundry mold emissions.

Nitrogen compounds have been identified in the decomposition products from several commonly used foundry sand binders. These compounds include nitrogen oxides, hydrogen cyanide, ammonia, simple aromatic amines, and isocyanates. The concentrations of these compounds in foundry mold emissions do not appear to be directly related to the nitrogen content of the organic binders. Measurable concentrations were observed in some cases, indicating the necessity for periodic, monitoring in the foundry. Adequate ventilation will permit the use of these binders. The substitution of nitrogen-free binders suggests another possible control strategy.

Air Pollutants↗
PubMed1978

Metastatic disease of the paraspinal muscles: electromyographic and histopathologic correlation in early detection.

Electromyographic examination may demonstrate severe segmental compromise of the posterior primary ramus and relative sparing of the anterior ramus as the earliest objective evidences of spinal and paraspinal metastases. Antecedent studies, including roentgenographic, radioisotopic and neurologic investigations, are often initially normal, failing to reveal the underlying cause of the progressive back pain. The present report demonstrates metastatic spread both through the paravertebral venous plexus and by direct extension in contiguous muscle. In this special instance, segmental 4+ fibrillations in the paraspinal muscles are electrophysiologic manifestations of a local, active process of denervation rather than a remote effect of the malignant disease, as has been suggested by others.

Adenocarcinoma↗
PubMed1976

Glioblastoma multiforme with extraneural metastases in the absence of previous surgery.

A 63-year-old man was found to have an intracerebral glioblastoma multiforme and preoperative roentgenographic evidence of a mass in the middle lobe of the right lung. Because of the rarity of extraneural metastases from glioblastoma, especially in the absence of prior surgery, the lesions were considered to be separate neoplasms until death. The histologic appearance of the lung tumor obtained at autopsy was identical to the cerebral tumor. Additional metastases were found to bronchial lymph nodes and a lumbar vertebra. This case demonstrates that a glioblastoma can spontaneously metastasize extraneurally. Invasion of the glioblastoma into the lumen of a blood vessel was demonstrated within the primary tumor. Embolization of cells to the lung and beyond is the suspected mode of spread.

Brain Neoplasms↗