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S Goldring

Publications and source records attributed to S Goldring.

At least 19 recordsLinked to original sources
PubMed1995

Downregulation of calcitonin receptor mRNA expression by calcitonin during human osteoclast-like cell differentiation.

Calcitonin inhibits both osteoclast formation and bone resorption, and is a primary treatment for patients with hypercalcemia and increased bone turnover. However, the clinical utility of calcitonin is limited because patients become refractory to calcitonin after several days (the calcitonin "escape phenomenon"). The molecular basis for calcitonin "escape" is unclear. To determine the regulatory mechanisms controlling calcitonin receptor (CTR) expression in osteoclasts and their precursors, we treated immature mononuclear precursors for human osteoclast-like multinucleated cells (MNC) formed in vitro with 1,25-(OH)2D3, to induce their differentiation to committed mononuclear precursors, and mature multinucleated osteoclasts, and used reverse transcriptase (RT)-PCR to assess expression of CTR mRNA in both committed mononuclear precursors and MNC. The PCR fragment produced was cloned and sequenced to confirm that it was derived from CTR mRNA. CTR mRNA expression was detected in mononuclear MNC precursors after 7 d of 1,25-(OH)2D3 treatment. It was also present in osteoclast-like MNC and highly purified giant cells from osteoclastomas, but not in monocytes or macrophage polykaryons formed in vitro. Calcitonin markedly decreased CTR but not actin mRNA expression in giant cells and MNC after 12 h, and removal of calcitonin restored CTR mRNA expression. Similarly, calcitonin decreased calcitonin-induced adenylate cyclase activity. These data suggest: (a) downregulation of CTR gene expression by calcitonin may in part explain the calcitonin "escape phenomenon"; and (b) expression of CTR mRNA occurs in mononuclear osteoclast precursors within 7 d after exposure to 1,25-(OH)2D3.

Base Sequence↗
PubMed1994

Distinctive electrophysiological characteristics of functionally discrete brain areas: a tenable approach to functional localization.

The direct cortical response (DCR), an electrical potential recorded in the immediate vicinity of a surface cortical stimulus, shows a configuration in the primary sensory areas of animals that is different from the one observed in association cortex. This suggested the possibility that systematic study of the DCR in the human brain might reveal a profile of configurations in which the form of the response provides functional information about the gyri being tested. Studies were carried out in subhuman primates and in patients undergoing surgery for tumors, occult vascular malformations, and epilepsy. In the animals, DCR's from somatosensory, motor, and association cortex are distinguishable; however, there are no differences in configuration between motor and premotor responses, or between association responses from prefrontal and parietal cortex. In patients with epilepsy due to nonspace-occupying pathology, the responses did not show distinguishing features. In contrast, in the patients with tumors or occult vascular malformations, DCR's from somatosensory, motor, and premotor cortex could be readily distinguished from each other. Responses along the mid and posterior sylvian fissure of the dominant hemisphere also had distinctive features, but more data are needed before the significance of this finding with respect to language function can be assessed. The accumulating results suggest that analysis of DCR's may prove to be a useful method for functional localization in individuals with focal space-taking pathology.

Animals↗
PubMed1992

Results of anterior temporal lobectomy that spares the amygdala in patients with complex partial seizures.

In December, 1980, the authors modified their anterior temporal lobectomies to exclude the amygdala from resection, a decision influenced by the dearth of pathology in the amygdala compared to the hippocampus. Furthermore, it had never been demonstrated that a good result was contingent upon including the amygdala per se in the lobectomy. Fifty-five (79%) of 70 patients in whom the amygdala was not resected were benefited by surgery. This result is similar to that achieved in series of anterior temporal lobectomies that include the amygdala in the resection. The results take on a special significance when considered together with those of amygdala-hippocampectomy which has been effective for controlling complex partial seizures of temporal mesiobasal origin (the region of the hippocampus, parahippocampal gyrus, and amygdala). A survey of the combined results strongly suggests that the anterior hippocampus and/or associated entorhinal cortex may be all that need be removed to control complex partial seizures caused by a temporal mesiobasal focus.

Adolescent↗
PubMed1991

Stromal cell-associated hematopoiesis: immortalization and characterization of a primate bone marrow-derived stromal cell line.

An elucidation of the interaction between the bone marrow microenvironment and hematopoietic stem cells is critical to the understanding of the molecular basis of stem cell self renewal and differentiation. This interaction is dependent, at least in part, on direct cell to cell contact or cellular adhesion to extracellular matrix proteins. Long-term bone marrow cultures (LTMC) provide an appropriate microenvironment for maintenance of primitive hematopoietic stem cells and a means of analyzing this stem cell-stromal cell interaction in vitro. Although LTMC have been successfully generated from murine and human bone marrow, only limited success has been reported in a primate system. In addition, few permanent stromal cell lines are available from nonmurine bone marrow. Because the primate has become a useful model for large animal bone marrow transplant studies and, more specifically, retroviral-mediated gene transfer analysis, we have generated immortalized bone marrow stromal cell lines from primate bone marrow using gene transfer of the Simian virus large T (SV40 LT) antigen. At least one stromal cell line has demonstrated the capacity to maintain early hematopoietic cells in long-term cultures for up to 4 weeks as measured by in vitro progenitor assays. Studies were undertaken to characterize the products of extracellular matrix biosynthesis and growth factor synthesis of this cell line, designated PU-34. In contrast to most murine bone marrow-derived stromal cell lines capable of supporting hematopoiesis in vitro that have been examined, the extracellular matrix produced by this primate cell line includes collagen types I, laminin. Growth factor production analyzed through RNA blot analysis, bone marrow cell culture data, and factor-dependent cell line proliferation assays includes interleukin-6 (IL-6), IL-7, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, leukemia inhibitory factor, and a novel cytokine designated IL-11. This immortalized primate bone marrow stromal cell line may be useful in maintaining early progenitor cells for experimental manipulation without the loss of reconstituting capacity and as a potential source of novel hematopoietic growth factors.

Animals↗
PubMed1987

Pediatric epilepsy surgery.

The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.

Brain↗
PubMed1986

Comparison of multinucleated cells elicited in rats by particulate bone, polyethylene, or polymethylmethacrylate.

Osteoclasts, the multinucleated resorbing cells of bone, are identified by their characteristic morphology, unique cell membrane specializations, and more recently by the presence of cell surface antigens recognized by monoclonal antibodies. They are derived from mononuclear precursor cells of hematogenous origin. The precise relationship between osteoclasts and other types of tissue giant cells is unknown. This study was designed to examine factors involved in the recruitment and differentiation of multinucleated cells and to investigate the relationship between so-called foreign body giant cells and bone-resorbing osteoclasts. Particles of various materials were implanted into subcutaneous pockets in rats. Histological, histochemical, and electron microscopic evaluations were made of specimens harvested 12 days after implantation. Large, foamy multinucleated cells were evident around particles of devitalized bone, polyethylene, and polymethylmethacrylate. Bone particles showed scalloped surfaces and were partially resorbed. Those cells adjacent to the bone particles stained positive for tartrate-resistant acid phosphatase, in contrast to the multinucleated cells adjacent to the other materials. All the cell types had extensive rough endoplasmic reticulum, abundant mitochondria, cytoplasmic vacuoles and dense bodies, giant centrospheres, and areas of fusion of plasma membranes. Cells in lacunae on the surface of the bone particles showed a clear zone of attachment to the bone substrate and ruffled borders, a feature characteristic of in osso osteoclasts. Although the giant cells occasionally displayed an extensive clear zone of attachment to the polyethylene and polymethylmethacrylate particles, no ruffled borders were detected. The results of these studies show that the multinucleated cells elicited in response to different materials, although sharing many common features, do demonstrate certain features that are substrate specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1985

Computed tomography in chronic seizure disorder caused by glioma.

Since the introduction of computed tomography (CT) in 1974, 137 patients underwent cortical resection for intractable epilepsy. The CT scans of 32 of these patients demonstrated an isolated calcified or hypodense lesion of unknown origin. The mean interval from onset of the seizure disorder to surgery was 11 years. The referring physicians frequently considered these lesions to be of nonneoplastic origin, which usually delayed surgical management. Twenty-six of the 32 patients, however, proved to have a cerebral glioma, seven showing anaplastic changes. Because the majority of these patients were found to have a neoplasm and especially because the CT scan could not distinguish between a well-differentiated glioma and those with anaplastic changes, we recommend early surgical treatment in patients with chronic seizure disorders who are found to have an isolated lesion of unknown origin on CT scan.

Adolescent↗
PubMed1985

The need to trace our roots in difficult times. The 1985 AANS presidential address.

Several important events that have played a major role in shaping the destiny of neurological surgery are recounted: the birth of neurosurgery; the founding of scientific surgery; the origin and evolution of microvascular technique in cerebrovascular surgery. In each case, the clinical breakthroughs stemmed from an apparently irrelevant basic laboratory investigation. Also, in each case, the transfer of the laboratory results to the bedside required clinicians who were prepared by training and knowledge to recognize the clinical significance of the fundamental observations. History tells us that if we are to sustain neurological surgery as a vibrant surgical specialty, we must continue to give top priority to the preparation of young minds through education and research. It is more important to understand this now than ever before, because never before have we been so preoccupied with social and economic issues: a preoccupation that is threatening to divert our attention from the main determinants of our specialty's future viability--the acquisition and application of new knowledge.

History, 19th Century↗
PubMed1984

Surgical management of epilepsy using epidural recordings to localize the seizure focus. Review of 100 cases.

One hundred patients with focal epilepsy (44 were children) were evaluated with extraoperative electrocorticography via epidural electrode arrays. Localization of the epileptogenic focus was derived predominantly from recordings made during spontaneously occurring seizures. All resection procedures were carried out under general anesthesia. During anesthesia, the recording of sensory evoked responses made it possible to readily identify the sensorimotor region. Of the 100 patients, 72 underwent resection of an epileptogenic focus, and 33 of these were children. Those who did not have a resection either exhibited a diffuse seizure focus, failed to show an electrical seizure discharge in association with the clinical seizure, failed to have a seizure during the period of monitoring, or failed to exhibit conclusive changes for identifying a focus in the interictal record. Fifty-seven patients (29 children and 28 adults) who had a resection have been followed for between 1 and 12 years. Eighteen (62%) of the 29 children and 18 (64%) of the 28 adults enjoyed a good result. Twenty of the 100 patients reported here had temporal lobe epilepsy. They were candidates for recordings with depth electrodes to identify their focus, but they were evaluated instead with epidural recordings; the method is described. In 15 of them, a unilateral focus was identified and they underwent an anterior temporal lobectomy. Pathological changes were found in every case and, in 11 patients, the epidural recordings distinguished between a medial and a lateral focus. Ten of these patients have been followed for 9 months to 3 1/2 years, and seven have had a good result. The observations suggest that epidural electrodes may be used in lieu of depth electrodes for identifying the symptomatic temporal lobe.

Adolescent↗
PubMed1984

Localization of function in the excision of lesions from the sensorimotor region.

A method is described which utilizes the recording of somatosensory evoked responses and cortical stimulation to localize the sensorimotor area under general anesthesia. It has been used in 31 patients who had lesions located in or near the somatosensory or motor gyri. Twenty-six of these patients had a tumor, and the remaining five had a tuberculoma, cysticercoid cyst, thrombosed arteriovenous malformation, cystic infarct, and astrocytic proliferation, respectively. Case histories of selected patients are briefly reported to demonstrate how the method can be used to improve the safety of surgical excisions in the sensorimotor area. The neurological results are discussed in relation to recent physiological studies, demonstrating multiple and spatially separate, sensory and motor representations of the body in the somatosensory and motor gyri.

Adenocarcinoma↗
PubMed1983

Epilepsy surgery.

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Adolescent↗
PubMed1982

The Grass prize.

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Animals↗
PubMed1980

Comparative study of cerebral cortical potentials associated with voluntary movements in monkey and man.

Eight monkeys (Macaca mulatta) were taught to squeeze and release a handgrip. The movement simulated the brisk squeeze of a hand dynamometer performed by 7 human subjects. Monkey. During the performance of the voluntary movements, slow cortical potentials (motor potentials or MPs) were studied with monopolar, surface bipolar, transcortical and intracortical recordings. A survey of the dorsal expanse of cerebral cortex showed that the contralateral motor hand area, somatosensory hand area and area 6 adjacent to the supplementary motor area became active with movement. MPs also were seen in the motor and somatosensory cortex medial to the hand area, but we concluded that those potentials were probably related to adventitious movements in the arm and leg. That area 6 became active with movement was further verified with extracellular unit recording; the behavior of area 6 units was compared with that recorded from units in the motor hand area. Using simultaneous transcortical recordings a sequence of cortical activation was observed in those areas generating an MP. The motor hand area became active first, followed in turn by area 6 and the somatosensory hand area. The monosynaptic cortico-cortical connections of the motor hand area were studied with autoradiographic and horseradish peroxidase techniques and compared to the distribution of the MP. The hand area demonstrated reciprocal connectivity with portions of the somatosensory hand area, the supplementary motor area in area 6 and the cortex adjacent to the intraparietal sulcus. The distribution of the MPs correlated with the connectivity to the supplementary motor and somatosensory areas. Our physiologic studies did not adequately investigate the area adjacent to the intraparietal sulcus. Man. Motor potentials were studied using surface bipolar recordings with closely spaced electrodes (inter-electrode distances 1 cm or 2 cm). Recordings were made directly from the cortex in one subject studied under local anesthesia during an operation for epilepsy, and epidurally in 6 subjects in whom epidural electrode arrays had been inserted for the purpose of localizing an epileptogenic focus. Similar to the findings in the animals, MPs were recorded from the contralateral motor and somatosensory hand area with activity in motor cortex appearing first; area 6 just anterior to the motor hand area probably also generated a response. In addition, a locally generated potential not seen in monkey was recorded anterior to area 6. This difference in response distribution is viewed as possibly relating to the different significance which the seemingly comparable hand movements have for the animal and human subjects. No response was seen in motor and somatosensory hand area with ipsilateral movements. We have no information for the anteriorly recorded response with ipsilateral movement.

Animals↗