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Biomedical subjects

E M Gabriel

Publications and source records attributed to E M Gabriel.

9 recordsLinked to original sources
PubMed1999

Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter.

Toxic multinodular goiter (TMNG) represents a frequent cause of endogenous hyperthyroidism, affecting 5-15% of such patients (with higher frequencies reported in iodine-deficient areas of the world). Although mutations of human TSH receptor (hTSHR) have been described in autonomously functioning thyroid nodules (AFTN), the role of such mutations in the pathogenesis of TMNG remains unclear. To search for alterations of hTSHR in AFTN and TMNG, we performed bidirectional, dye primer automated fluorescent DNA sequencing of the entire transmembrane domain and cytoplasmic tail of hTSHR (TMD+CT-hTSHR) using DNA extracted from nodular regions of 24 patients with TMNG and 7 patients with AFTN. Eight of the 24 patients (33.3%) showed heterozygote polymorphism of codon 727 on the cytoplasmic tail of hTSHR with an amino acid substitution of aspartic acid to glutamic acid. Three of 24 (12.5%) patients with TMNG were found to carry a heterozygote mutation of codon 703, resulting in substitution of alanine with glycine. One patient had multiple heterozygote mutations including I606M (Ile to Met), A703G (Ala to Gly), Q720E (Gln to Glu), and D727E (Asp to Glu). Two patients exhibited silent polymorphism of codons 460 and 618. We found no mutation of the TMD+CT-hTSHR in 7 patients with AFTN, except for a silent polymorphism of codon 460 in 1. DNA fingerprinting of codon 727 using restriction enzyme NlaIII and genomic DNA confirmed the sequencing results in all cases, indicating that the sequence alterations were not somatic in nature. This technique was also used to examine peripheral blood genomic DNA from 52 normal individuals and 49 patients with Graves' disease; 33.3% of TMNG (P = 0.019 vs. normal subjects), 16.3% of Graves' disease patients (P = 0.10 vs. normal subjects), and 9.6% of normal individuals were heterozygous for the D727E polymorphism. Expression of the D727E hTSHR variant in eukaryotic cells (COS-7) resulted in an exaggerated cAMP response to TSH stimulation compared to that of the wild-type hTSHR. These findings indicate that a germline polymorphism of codon D727E of hTSHR is associated with TMNG, suggesting that its presence is an important predisposing genetic factor in the pathogenesis of TMNG.

Adolescent↗
PubMed1998

Ischemic injury and extracellular amino acid accumulation in hippocampal area CA1 are not dependent upon an intact septo-hippocampal pathway.

The septo-hippocampal pathway contains a major gamma-aminobutyric acid (GABA) projection to dendritic fields within the hippocampus. To determine the importance of the septo-hippocampal pathway in ischemia-induced accumulation of GABA and subsequent cell death in area CA1 of hippocampus, septo-hippocampal deafferentation of adult gerbils was performed. Electrolytic lesions were produced in the medial or medial plus lateral septal regions in gerbils 7 days prior to being subjected to 5 min forebrain ischemia. The extent of deafferentation of the dorsal hippocampus was determined histochemically by acetylcholinesterase staining. Both the medial and medial plus lateral septal lesions produced nearly complete loss of acetylcholinesterase staining in the dorsal hippocampus indicating relatively complete deafferentation. During and following ischemia, in vivo microdialysis was used to measure extracellular GABA accumulation, which reached concentrations up to 1060 +/- 143% of basal. Septo-hippocampal deafferentation in both groups of lesioned animals failed to prevent the accumulation of GABA (and glutamate) induced by ischemia, indicating that ischemia-induced GABA accumulation in area CA1 arises principally from intrinsic GABAergic interneurons. Ischemic animals with medial septal lesions did not demonstrate neuroprotection or increased damage in the stratum pyramidale 7 days after reperfusion. Since the septo-hippocampal pathway provides the source of GABAergic disinhibition within the hippocampus, neither disinhibition nor the septo-hippocampal input appear to play an important role in the development of ischemia-induced neuronal death in the hippocampus.

Acetylcholinesterase↗
PubMed1998

Evolution of neuroablative surgery for involuntary movement disorders: an historical review.

Surgical therapy of involuntary movement disorders has evolved during the past century from gross destructive ablations of the central nervous system to refined, accurate, discrete lesioning of sites deep within the brain. The understanding of neuroanatomic and physiological systems improved tremendously through experimentation in animals and empirical observations of surgery in humans. A continuum of accumulated knowledge has been achieved through ablation or lesioning of virtually all aspects of the central and peripheral nervous system predicated on previous successes or failures. This compilation of surgical history of involuntary movement disorders has provided present neurosurgeons with the foundations on which they base their therapeutic measures and will direct future endeavors within this field.

Basal Ganglia↗
PubMed1997

Neuropsychiatric complications after temporal lobe limbic system surgery.

Although control of seizure activity is the main goal of temporal lobectomies for complex partial epilepsy, the results of surgery must be viewed within the larger context of possible ramifications of limbic system disruption. The neuropsychiatric complications may be significant and influence the patient's perceived qualify of life, thus detracting from the benefits of seizure control. It is apparent from the previous studies that the modalities affected are influenced by the laterality of the resection, with left-sided lobectomies more often affecting verbal memory and learning, whereas right-sided resections may cause visual/spatial memory and cognitive declines. Preoperative neuropsychologic testing may help to predict these possible complications. General psychosocial function, memory, and cognition all seem to be less affected when complete seizure control is attained, with nearly 80% experiencing no significant change in neuropsychologic testing and the gain and losses being equal in magnitude. Also, younger patients and those with a shorter history of seizure activity may fare better after surgery because of a greater capacity for neuronal plasticity to subserve these functions. These findings support the contention that early diagnosis and surgical treatment may help to minimize potential neuropsychiatric complications in conjunction with improved postoperative seizure control.

Age Factors↗
PubMed1996

Recurrence of a cerebral arteriovenous malformation after surgical excision. Case report.

Complete excision of a cerebral arteriovenous malformation (AVM) should eliminate the future risk of an associated intracranial hemorrhage. Because total removal of an AVM may be difficult to assess at the time of surgery, postoperative angiography has become the accepted standard for documenting that the removal has been accomplished. However, even angiography confirmed excision of an AVM does not completely ensure against rebleeding. Regrowth of an AVM with subsequent hemorrhage can occur. This has been documented in children and is attributed to forces acting on the immature vasculature of these younger patients. The authors report the case of an older patient whose AVM recurred when he was 28 years of age, despite an angiography proven complete excision, and emphasize that, even in adults, angiography documentation of total removal does not always eliminate the risk of reformation of an AVM.

Adult↗
PubMed1996

History of spinal cord stereotaxy.

Stereotactic and functional neurosurgery has experienced a remarkable degree of development during the last 50 years, from the plaster of Paris frame of Spiegel and Wycis to the technology of frameless stereotaxis. Although predominantly used for intracranial procedures, stereotaxy has its roots in experimental studies of the spinal cord. The field of spinal cord stereotaxy has not received the same amount of attention as supratentorial surgery, but there have been significant contributions to the field that have helped to further our understanding of spinal cord anatomy and physiology. Now that frameless stereotaxis has reached clinical practice, there may be further developments in the field of spinal surgery: this technique may prove useful for spinal fusion operations and, possibly, intramedullary operations as well.

History, 20th Century↗
PubMed1995

Glomus jugulare tumor metastatic to the sacrum after high-dose radiation therapy: case report.

A 47-year-old woman with left ear pain and hearing loss was diagnosed with a glomus jugulare tumor for which she received radiation therapy as the primary treatment. Over a period of 20 years, she developed temporal bone necrosis, brain stem calcifications, local tumor recurrence, and eventually metastases to her lungs and sacrum. This case underscores the often indolent nature of glomus jugulare tumors, the late sequelae of radiation therapy for benign intracranial tumors, and the potential of these tumors to metastasize. This patient's history suggests that aggressive surgical resection should be considered early for such tumors, particularly because radiation treatment does not ablate the tumor. This is only the second reported case of a glomus jugulare tumor metastatic to the sacrum.

Aged↗
PubMed1982

Failure to detect conventional enterotoxins in classical enteropathogenic (serotyped) Escherichia coli strains of proven pathogenicity.

Ammonium sulfate-precipitated supernatants of classical enteropathogenic Escherichia coli strains were negative when investigated for enterotoxin production in rabbit ligated ileal loops, rabbit skin vascular permeability factor tests, suckling mice, and Y-1 adrenal cells. They also failed to stimulate guanylate cyclase activity in homogenates of rabbit, rat, and infant mouse intestines. Furthermore, DNA from enteropathogenic E. coli lacked sequences that encode heat-labile and heat-stable enterotoxins. These studies fail to show conventional enterotoxin synthesis by classical enteropathogenic E. coli.

Animals↗