Search PubMed⌕ Search

Biomedical subjects

M A Simon

Publications and source records attributed to M A Simon.

At least 109 records · Page 6Linked to original sources
PubMed1992

Evaluation, prognosis, and medical treatment considerations of metastatic bone tumors.

Metastatic cancer can cause severe pain and disability. Metastases can occur in any bone, but usually are located in the axial or proximal appendicular skeleton. The most frequently encountered primary tumors that spread to bone are those of the prostate, breast, kidney, lung, and thyroid. When the origin of the primary cancer is known, skeletal metastases are more often from breast or prostate. When the primary site is unknown, the lung and kidney should be suspected as sites of origin. The nonoperative management of skeletal metastases from multiple myeloma and from carcinomas of the prostate, breast, kidney, lung, and thyroid are discussed.

Bone Neoplasms↗
PubMed1992

Simian virus 40-induced disease in rhesus monkeys with simian acquired immunodeficiency syndrome.

Simian virus 40 (SV40) disease was diagnosed in four rhesus monkeys that died with SIV-induced acquired immunodeficiency syndrome (AIDS). One juvenile monkey seroconverted for SV40 6 months after inoculation with SIV and developed severe bilateral tubulointerstitial nephritis. In contrast, progressive multifocal leukoencephalopathy (PML) occurred in two adult monkeys that were seropositive for SV40 before SIV inoculation, as well as a third adult that was naturally infected with SIV and seropositive for SV40 5 years before death. Large intranuclear inclusions containing abundant polyomavirus particles were limited to either renal tubular epithelial cells or oligodendrocytes. In situ DNA hybridization for SV40 large T antigen further demonstrated that SV40 nucleic acid was localized to either kidney or brain tissue. By immunohistochemical analysis, areas of central nervous system inflammation and demyelination were shown to contain CD68+ macrophages (gitter cells), aggregates of CD8+ T lymphocytes, and numerous gemistocytic astrocytes that labeled for glial fibrillary acidic protein. These observations indicate that rhesus monkeys with SIV-induced AIDS are predisposed to polyomaviral disease, in which SV40 nucleic acid is observed in renal tissue in primary infections and brain tissue after viral reactivation. Furthermore, this organ-specific replication suggests that tissue-tropic strains of SV40 may develop in immunodeficient monkeys.

Animals↗
PubMed1992

Arteriopathy in macaques infected with simian immunodeficiency virus.

BACKGROUND: An arteriopathy characterized by intimal and medial thickening and fibrosis was seen in 19 of 85 rhesus monkeys infected with simian immunodeficiency virus (SIV), a lentivirus with morphologic, genetic, and biologic similarities to HIV-1 and HIV-2. EXPERIMENTAL DESIGN: All cases of simian AIDS in rhesus monkeys at the New England Regional Primate Research Center, resulting from either experimental or naturally acquired SIV infection, were retrospectively examined for evidence of histopathologic changes to the vasculature. Of the 85 SIV-related deaths recorded in the pathology files to date, tissues from 19 animals were chosen for further study because of thickening, disruption, inflammation, or other abnormality to any layer of the vascular wall. The lesion was characterized by special stains, immunoperoxidase procedures, and ultrastructural examination. RESULTS: Affected monkeys of both sexes varied in age from 4 months to 17 years at the time of inoculation and survived from 41 days to 4 years after infection. Pulmonary arteries were affected in all 19 animals, while vessels in other parenchymal organs were involved less frequently. In addition to sometimes marked intimal thickening with luminal occlusion, the internal elastic laminae were fragmented and interrupted. Seven of 19 animals had pulmonary thromboses with varying degrees of organization and recanalization. Immunohistochemical studies, special stains, and ultrastructural analyses revealed the thickened intimae to be composed predominantly of collagen, extracellular matrix, and smooth muscle cells. Ultrastructurally, endothelial cells from both early (no intimal thickening) and advanced lesions were plump, vacuolated, and often disorganized and detached from the subendothelial space. Increased numbers of macrophages (CD68+) were found in the adventitia and occasionally in the thickened intima and media. Rare, fully differentiated macrophages (CD68+, 25F9+) were demonstrated in lumina of affected vessels, some of which expressed p27 SIV gag protein. However, the lesion was not uniformly associated with localization of either viral protein or RNA at the site using immunohistochemistry or in situ hybridization, respectively. A similar arterial lesion has been described in children with AIDS. CONCLUSIONS: The morphologic findings in macaques and their similarity to arteriosclerotic changes induced by experimental endothelial damage in other species collectively suggest that arteriopathy in AIDS may represent a manifestation secondary to primary endothelial injury.

Animals↗
PubMed1992

Medical management compared with operative treatment for osteoid-osteoma.

Twenty-four patients were evaluated and diagnosed, between August 1975 and July 1989, as having probable osteoid-osteoma. Fifteen patients had operative treatment (twelve immediate and three delayed); all fifteen had complete relief of pain. The remaining nine patients were treated with non-steroidal anti-inflammatory medications; all nine had complete relief of pain, and six had resolution of the symptoms without using non-steroidal anti-inflammatory drugs, after an average of thirty-three months (range, thirty to forty months) of treatment. Thus, long-term administration of non-steroidal anti-inflammatory drugs can often be as effective as excision for the treatment of osteoid-osteoma, without the morbidity that is associated with the operation, especially in patients in whom operative treatment would be complex or might lead to disability.

Adult↗
PubMed1991

Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase.

We have conducted a genetic screen for mutations that decrease the effectiveness of signaling by a protein tyrosine kinase, the product of the Drosophila melanogaster sevenless gene. These mutations define seven genes whose wild-type products may be required for signaling by sevenless. Four of the seven genes also appear to be essential for signaling by a second protein tyrosine kinase, the product of the Ellipse gene. The putative products of two of these seven genes have been identified. One encodes a ras protein. The other locus encodes a protein that is homologous to the S. cerevisiae CDC25 protein, an activator of guanine nucleotide exchange by ras proteins. These results suggest that the stimulation of ras protein activity is a key element in the signaling by sevenless and Ellipse and that this stimulation may be achieved by activating the exchange of GTP for bound GDP by the ras protein.

Amino Acid Sequence↗
PubMed1991

Limb salvage for osteosarcoma in the 1980s.

The incidence of local recurrences following limb salvage performed by experienced surgeons with wide surgical margins and with the use of neoadjuvant chemotherapy is sufficiently low (5%-10%) so as not to have a biologically statistically significant impact on the long-term survival rate. Following limb salvage, the incidence of morbidity increases with a few patients occasionally requiring prolonged or repeated hospitalizations and further surgical procedures, even amputation. The durability of the reconstructions is variable, and many of the mobile knee reconstructions may need to be revised if the patients become long-term survivors. The function of salvaged limbs is better than that after the alternative amputation, but none of the reconstructions will give normal function. Finally, no matter which type of surgery on the lower extremity is selected, patients will have a good early psychosocial adjustment if no premorbid psychosocial disorder is present.

Bone Neoplasms↗
PubMed1991

Limb-salvage surgery in the treatment of osteosarcoma in skeletally immature individuals.

Sacrifice of major growth plates during resection and fixed-length reconstruction of a limb in a skeletally immature child with osteosarcoma may result in a significant limb-length inequality as growth progresses. A limb-length discrepancy in the humerus may cause minor cosmetic problems but does not generally result in a significant functional deficit. In the lower extremity, tumors about the knee, including the distal femur and proximal tibia, usually present the dilemma of whether limb salvage by arthrodesis, osteoarticular allograft, or endoprosthetic replacement would result in a significant limb-length inequality and whether amputation of the extremity is a preferable procedure. The techniques of rotationplasty and an expandable endoprosthesis have been successfully used for treating skeletally immature patients with osteosarcoma of the distal femur. With regard to survival and function, the results obtained with these innovative methods are favorable compared with those of a high above-knee amputation.

Adolescent↗
PubMed1991

Mobile knee reconstructions after resection of malignant tumors of the distal femur.

Limb-salvage surgery involving mobile knee reconstructions for malignant tumors about the distal femur is a desirable and achievable goal. With limb salvage, the survival rate does not decrease significantly, and the resulting function is superior to when an amputation plus a prosthesis are used. Immediate and delayed morbidity is greater after limb-salvage surgery than after amputation. However, with thorough preoperative planning, use of neoadjuvant chemotherapy as indicated, and an experienced team of surgeons, limb-salvage surgery can provide a mobile knee with excellent function in the vast majority of cases for patients with malignant tumors of the distal femur.

Bone Transplantation↗
PubMed1991

The effects of resection of the proximal part of the fibula on stability of the knee and on gait.

We studied six patients to determine the effects of unilateral marginal resection of the proximal part of the fibula on stability of the knee and on gait. At the time of the operation, the fibular collateral ligament and the tendon of the biceps femoris were reattached, but no attempt was made to stabilize the fibula otherwise. The patients were tested an average of sixty-one months after operation. Stability of the knee was measured with an instrumented system. Gait was evaluated with an optical electronic three-dimensional digitizing system and a multicomponent force-platform. The gait of six healthy control subjects of similar age was also studied, and the reproducibility of measurements of stability of the knee was investigated in four healthy adults. There were significant differences between the side on which an operation had been done and the contralateral side with regard to the extent of anterior translation and of total anterior-posterior translation of the tibia at both 20 and 90 degrees of flexion of the knee, and in total varus and valgus rotation of the knee (the number of degrees from a position of maximum varus to one of maximum valgus angulation) at 20 degrees of flexion. The measurements of gait and of motion of the knee were found to be normal when compared with those in the control subjects. In the ground-reaction measurements, there were some significant differences from normal in the medial-lateral plane, but they were clinically unimportant. Resection of the proximal part of the fibula can lead to instability of the knee.

Adult↗
PubMed1990

Radiobiological characterization of head and neck and sarcoma cells derived from patients prior to radiotherapy.

The radiobiological parameters of 33 tumor cell lines were studied in biopsy samples obtained from patients prior to radiotherapy. Epithelial tumor cells derived from head and neck cancer patients were more radioresistant than tumor cell lines derived from patients with sarcoma regardless of method of analysis. The presence of radioresistant tumor cell lines was associated with local failure in some patients. However, the presence of radiosensitive tumor cells did not necessarily predict local control. Our data suggest radiocurability is complex and inherent radiobiological parameters of tumor cells may be only one factor in radiotherapy outcome.

Carcinoma, Squamous Cell↗
PubMed1990

Tubular sodium handling in cirrhotic patients with ascites as analysed by the renal lithium clearance method.

The proximal and distal sodium reabsorption were calculated from lithium clearance in 21 healthy controls and 24 cirrhotic patients with ascites after 4 days under a sodium-restricted diet. The values of fractional lithium clearance were lower in patients than in controls (7.37 +/- 0.87 vs. 18.13 +/- 1.76%, P less than 0.001). Fractional proximal sodium reabsorption was increased in patients compared with controls (92.8 +/- 1.1 vs. 81.8 +/- 1.7%, P less than 0.001). No differences were found in fractional distal sodium reabsorption between controls and patients (96.9 +/- 0.8 vs. 98.6 +/- 0.1%). When patients were separated into two subgroups according to their sodium balance, it was found that fractional distal sodium reabsorption was increased in patients whose balance remained positive, compared with patients on a negative sodium balance (98.99 +/- 0.26 vs. 94.11 +/- 1.50%, P less than 0.05). In addition, the natriuretic response to a specific dose of spironolactone was higher in patients on positive sodium balance compared with patients on negative sodium balance (per cent increase in natriuresis after spironolactone 300 mg day-1: 355.24 +/- 73.98 vs. 84.21 +/- 15.8%, P less than 0.01). We conclude that proximal sodium reabsorption is increased in cirrhotics with ascites. In addition, distal sodium reabsorption is enhanced only in those patients which exhibit avid sodium retention.

Adult↗
PubMed1990

Function after amputation, arthrodesis, or arthroplasty for tumors about the knee.

We studied the function of twenty-two patients who had had a malignant skeletal tumor adjacent to the knee. An above-the-knee amputation was done in seven; a resection arthrodesis, in nine; and a replacement arthroplasty, in six. The patients all walked at a similar speed (sixty-one to sixty-six meters per minute), which is slower than normal (eighty meters per minute). They all walked with comparable efficiency at three velocities: the mean consumption of oxygen was 0.210 milliliter per kilogram of body weight per meter at free velocity, 0.215 milliliter per kilogram of body weight per meter when they walked 25 per cent faster, and 0.211 to 0.240 milliliter per kilogram of body weight per meter when they walked 50 per cent faster. The three groups of patients and a normal control group consumed oxygen at similar rates. The patients who had had an amputation were very active, and they were the least worried about damaging the affected limb, but they had difficulty walking on steep, rough, or slippery surfaces. The patients who had had an arthrodesis had a more stable limb and performed the most demanding physical work and recreational activities, but they had difficulty sitting. The patients who had had an arthroplasty led sedentary lives and were the most protective of the limb, but they were the least self-conscious about the limb.

Adolescent↗
PubMed1989

Ommatidia in the developing Drosophila eye require and can respond to sevenless for only a restricted period.

The sevenless gene encodes a putative cell surface receptor that is expressed in a highly specific and complex pattern in the developing Drosophila eye. We show here that this pattern is not required for the development of either the R7 cell or any other cell in the retina. By transiently expressing sevenless protein, we show that there is only a brief period during eye development when the sevenless protein is required for the formation of the R7 photoreceptor. Our results indicate that the specificity of the cell-cell signaling mediated by the sevenless protein is not achieved by regulating the distribution of the sevenless protein, but rather must reside in some combination of the temporal and spatial distributions of the sevenless ligand or other components of the sevenless signaling pathway.

Animals↗
PubMed1989

Regulation of the complex pattern of sevenless expression in the developing Drosophila eye.

The sevenless gene encodes a cell surface receptor that has protein-tyrosine kinase activity and is expressed in a highly specific and complex pattern in the developing Drosophila eye. We have coupled the sevenless promoter to the reporter gene lacZ and have examined the pattern of beta-galactosidase expression in the developing eyes of transgenic larvae. Our results indicate that the dynamic pattern of sevenless protein expression is regulated transcriptionally. Promoter sequences located 5' of the coding region are insufficient for the wild-type level of gene expression but appear to be able to confer the correct pattern of expression. In contrast, enhancer sequences within the body of the gene can confer both the correct pattern and a normal level of expression on either the sevenless promoter or heterologous promoters. Thus the complex pattern of sevenless expression is redundantly encoded within proximal promoter sequences and enhancer elements internal to the gene but relies on these enhancer sequences for correct quantitative expression.

Animals↗
PubMed1989

Structure and activity of the sevenless protein: a protein tyrosine kinase receptor required for photoreceptor development in Drosophila.

The sevenless gene encodes a putative protein tyrosine kinase receptor that is required for the proper differentiation of the R7 photoreceptor cells of the Drosophila eye. We have expressed the sevenless protein in Drosophila tissue culture cells and studied its synthesis, processing, and activity. Our results show that the sevenless protein possesses protein tyrosine kinase activity. The protein is first synthesized as a 280-kDa glycoprotein precursor that is subsequently cleaved into 220-kDa amino-terminal and 58-kDa carboxyl-terminal subunits that remain associated by noncovalent interactions. The 220-kDa subunit is glycosylated and contains most of the extracellular portion of the protein, and the 58-kDa subunit is composed of a small portion of the extracellular sequences and the intracellular protein tyrosine kinase domain. This complex is subsequently cleaved into either 49- or 48-kDa carboxyl-terminal fragments with concomitant degradation of the rest of the protein.

Animals↗