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Biomedical subjects

G Rosen

Publications and source records attributed to G Rosen.

At least 91 records · Page 5Linked to original sources
PubMed1991

Endoprosthetic replacement for stage IIB osteosarcoma.

Over an eight-year period, 100 patients with IIB osteosarcoma have been managed. Eighty-one were treated with limb-salvage procedures, 78 of which involved reconstruction utilizing endoprostheses. Only 19 patients received amputation as the primary treatment for local control. Since 1984, all patients received preoperative and post-operative adjuvant chemotherapy. Those patients who received chemotherapy had a statistically significant improvement in five-year survival over those who did not (57% and 32%, respectively, p = 0.014). The functional results were good overall, with excellent results seen in distal femoral reconstruction. Twenty-eight of the 78 patients treated with endoprosthetic reconstruction experienced 30 complications (36%). Mechanical failure was the most common complication (10%) but was generally correctable. The local recurrence rate was 5% and the infection rate was 3%. Local complications were manageable. A statistical analysis revealed that the relative risk of patient death was 2.5 times higher than prosthesis failure for the 78 patients with endoprosthetic reconstruction. The intermediate-term results, with a median follow-up period of 43 months, remains encouraging.

Adolescent↗
PubMed1990

Effect of glycolipids of Leishmania parasites on human monocyte activity. Inhibition by lipophosphoglycan.

Lipophosphoglycan (LPG) and glycosyl phosphatidylinositol Ag (GPI), are glycolipids present on the membrane of Leishmania parasites. Both glycolipids have been chemically characterized. LPG is a polysaccharide of repeating phosphorylated units linked to a phosphocarbohydrate core that is anchored to the membrane by lysoalkyl phosphatidylinositol (PI). The GPI are smaller glycolipids with a structure resembling the phosphocarbohydrate core of the LPG. They are anchored to the membrane by alkyl acyl PI. Their relative abundance, uniqueness of structure, and cellular location suggest a role in interactions of the parasites with host cells. In the present study we examined the effect of LPG and GPI on the activation of human peripheral blood monocytes. Three parameters were studied: the production of IL-1, chemotactic locomotion, and oxidative burst. We found that whereas neither GPI nor LPG directly affected monocyte activity, preincubation of the monocytes with LPG strongly inhibited further activation: The production of IL-1, after stimulation with LPS, was decreased in a dose-dependent manner. Previous incubation with LPG also inhibited chemotactic locomotion of monocytes and neutrophils in response to diacylglycerol, zymosan-activated serum, FMLP and LTB4. Luminol-dependent chemiluminiscence caused by stimulation of the monocytes with streptococci and histone was also inhibited. After fragmentation of the LPG into phosphoglycan and 1-O-alkylglycerol by phosphatidylinositol-phospholipase C, only the phosphoglycan retained inhibitory activity. No difference in inhibitory activity was found between LPG prepared from Leishmania major or Leishmania donovani promastigotes. These results show that the phosphoglycan of LPG inhibits the immunologic response of normal human monocytes and neutrophils, and suggest that LPG may influence the nature of the inflammatory response surrounding infected cells.

Animals↗
PubMed1990

Progress in the recognition and treatment of soft tissue sarcomas.

Over the past 10 years there has been significant progress made in the recognition and treatment of soft tissue sarcomas. With the advent of CAT scans and MRI, preoperative delineation of soft tissue tumors has become readily available. The diagnostic use of these modalities in patients presenting with an ill-defined asymptomatic mass has been extremely helpful in terms of screening patients to decide whether or not a biopsy is indicated. These techniques have also provided a much clearer delineation of the anatomic extent of the primary tumor, which has been of great assistance both in radiation therapy treatment calculations as well as in preoperative surgical planning. The recognition that tumor grade is the dominant prognostic variable has resulted in the more common use of a grading system, and a more uniform reporting and stratification of end results. Recent studies with immunohistochemical staining have proven of value in determining the histogenesis of many tumors that in the past were difficult to classify accurately. Most recently the use of flow cytometry suggests that this will also be a valuable adjunct in determining tumor grade and thereby prognosis. The most recent investigations of molecular biologic evaluation of genetic DNA and RNA sequences, as well as of oncogenes are extremely interesting from a diagnostic standpoint and in demonstrating the potential of molecular biologic evaluation for understanding the origin of these tumors. Multimodality therapy with surgery, radiation, chemotherapy, or all three has resulted in a marked improvement in local tumor control for patients with soft tissue sarcomas. The combination of modalities has allowed smaller surgical excisions of the tumor and thereby preservation of the extremity and much of its function. There are currently several different methods of multimodality therapy used including neoadjuvant therapy and postoperative therapy, both of which have been proven efficacious. Chemotherapy is now playing an increased role in clinical investigation and treatment. The availability of Adriamycin, DTIC, cisplatin, and most recently ifosfamide has added several chemotherapeutic agents for use by the clinician. Combination chemotherapy and radiation is of value in the neoadjuvant setting, and several studies are now underway to determine whether postoperative adjuvant chemotherapy is of similar value in reducing systemic spread of disease. Finally, surgical resection of pulmonary metastases has been proven of value in 20% to 25% of patients who subsequently develop metastatic disease. As a result of these advances in several different treatment disciplines, the overall survival rate and quality of life of patients with soft tissue sarcoma have improved markedly over the past 10 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Thallium-201 scintigraphy in bone sarcoma: comparison with gallium-67 and technetium-MDP in the evaluation of chemotherapeutic response.

This study attempts to characterize thallium-201 (201TI) uptake in patients with bone and soft-tissue sarcoma and to compare these findings with gallium-67 (67Ga) and bone scintigraphy with emphasis on evaluating tumor viability before and after chemotherapy. Thirty-eight patients with surgically-proven sarcomas were evaluated. All patients had gallium and thallium studies. Nineteen patients underwent pre- and post-chemotherapy thallium and evaluation. Seven patients also had technetium-99m-MDP (99mTc-MDP) bone scintigraphy comparisons. Pathologic changes pre- and postchemotherapy were graded on the basis of %tumor necrosis as defined histologically. Scintigraphic comparisons demonstrated a high degree of correlation with 201TI and poor correlation with 99mTc-MDP. Thallium-201 was superior to 99mTc-MDP and 67Ga in predicting tumor response to chemotherapy as determined by %tumor necrosis determined histologically. Gallium was superior to Tc-MDP in predicting response to chemotherapy. However, both 67Ga and 99mTc-MDP appear to be affected by factors other than tumor activity.

Adolescent↗
PubMed1989

Structural analysis of glycosyl-phosphatidylinositol antigens of Leishmania major.

Three glycosyl-phosphatidylinositol glycolipids recognized by antibodies from patients with cutaneous leishmaniasis were extracted from Leishmania major promastigotes by hexane:isopropanol and then purified by thin layer chromatography and LH-20 gel chromatography. Structural analysis was carried out using chemical analyses, fast atom bombardment mass spectrometry, and 1H NMR. The major structures deduced can be summarized as follows: (formula: see text) where n = 0, 1, 2; R1 = (CH2)23-CH3; R2 = (CH2)14-CH3 or (CH2)16-CH3. Alkyl-acyl substitutions in the glycerol backbone showed considerable heterogeneity. These three glycolipids belong to a relatively new class of compounds and may represent sequential steps in the biosynthesis of glycosyl-phosphatidylinositols which anchor proteins or other glycoconjugates to Leishmania cell membranes.

Animals↗
PubMed1989

Inhibitory effects on protein kinase C activity by lipophosphoglycan fragments and glycosylphosphatidylinositol antigens of the protozoan parasite Leishmania.

Fragments of the lipophosphoglycan of Leishmania donovani were generated by phospholipase C digestion and mild acid hydrolysis. The fragments were purified and examined for inhibitory activity on protein kinase C isolated from rat brains. On a molar basis, the 1-O-alkylglycerol portion of LPG exhibited the most inhibitory activity, whereas the carbohydrate domain was not as effective. In addition, several glycolipid antigens from L. major, which contain short carbohydrate chains attached to phosphatidylinositol, were also efficient inhibitors of the enzyme. These results are consistent with the hypothesis that protein kinase C may be a key target for the parasites to overcome within host macrophages.

Animals↗
PubMed1989

Fatty acyl coupled catalase.

Bovine liver catalase (hydrogen-peroxide:hydrogen peroxide oxidoreductase, EC 1.11.1.6) was derivatized by 9"(10")-[4'-(2-(4,6-dichloro-1,3,5-triazinyl) oxy)butoxy] stearic acid and the fatty acyl-coated enzyme was separated from native catalase and excess reagent by hydroxyapatite chromatography. The derivatization of catalase resulted in coupling the long-chain fatty acyl residues to lysine, histidine and arginine, while other amino acids remained essentially unaffected. The fatty acyl-coated enzyme was water soluble at pH greater than 7.0 but became octanol and ether soluble at pH less than 6.5. The derivatized enzyme retained 50-80% of the catalatic- and peroxidative-specific activities. The free carboxyl function of the coupled long-chain fattyl acyl residues could serve as substrate for ATP-dependent CoA-thioesterification catalyzed by the rat liver microsomal long-chain fatty acyl-CoA synthase.

Acylation↗
PubMed1989

Evidence for a phosphatidylinositol anchor in glycolipid antigens of Leishmania major.

The structure of the membrane anchor of three Leishmania major surface antigenic glycolipids was analyzed. Phosphatidylinositol-specific phospholipase C treatment and nitrous acid deamination indicated the presence of a phosphatidylinositol anchor linked to the glycan through a non-N-acetylated hexosamine. An ester linkage on the C-2 of glycerol was revealed by phospholipase A2 hydrolysis. This fatty acyl substitution was not found on the phosphatidylinositol anchor of the Leishmania lipophosphoglycan.

Animals↗
PubMed1989

Adjuvant chemotherapy for osteosarcoma.

From this review of chemotherapy trials, several observations can be made. Osteosarcoma is a complex disease involving multiple histologies, each with a different prognosis. Prognostic factors that have been shown to be important include anatomic location of the primary tumor, stage at presentation (patients with metastatic or local recurrent disease fair far worse than those with primary disease), age at onset (children fair worse than the teenager with osteosarcoma), and location within the extremity (patients with more distal tumors fairing better than patients with more proximal tumors). There is convincing evidence for the efficacy of chemotherapeutic agents such as methotrexate in high doses (at least 8 g/m2 for adults, 12 g/m2 for children), Adriamycin, and cisplatin. The combination of Adriamycin and cisplatin appears to be more beneficial relative to either one of these agents alone. The efficacy of the combination of BCD as a triple-drug regimen, although useful in several different trials, has not been convincingly shown. Finally, from several of the recent randomized trials, it appears, that chemotherapeutic regimens containing an Adriamycin and cisplatin combination appear to be superior to those that do not include this combination. However, these observations are made from a historical perspective and have not been conclusively proven by randomized prospective investigations. The observations concerning the natural history of the disease and the activity of various chemotherapeutic agents suggest certain clinical practice algorithms. Essential staging procedures would include a bone scan looking for multifocal or metastatic disease, and CT scans of the chest looking for metastases to the lung. From all studies, it is apparent that surgery is mandatory for the primary tumor and should be an integral portion of all treatment methods. Chemotherapy should be considered for all patients with osteosarcoma, and the essential drugs in the regimen appear at present to minimally include high-dose methotrexate, Adriamycin, and cisplatin. It would also appear from several of these reports that not only is the adjuvant use of these chemotherapeutic agents indicated, but that the preoperative use of these agents has had significant advantages. The neoadjuvant chemotherapy begins the essential systemic chemotherapy at a very early stage, allows histologic assessment of treatment effect, permits altering drug regimens postoperative, and in many reported trials has allowed less than amputative surgery (limb salvage) to be performed. Finally, close follow-up of patients with osteosarcoma has therapeutic value.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Leishmania major: glycolipid antigens recognized by immune human sera.

Extraction of whole promastigotes with a mixture of hexane-isopropanol yielded two carbohydrate-lipid fractions immunologically active against immune sera from patients with cutaneous leishmaniasis (CL): CLF-1 and CLF-2. Thin layer chromatography (TLC) separated both fractions into eight bands labeled A-H. Four of these bands, Rf 0.19, 0.25, 0.39 and 0.48 (A, B, C and E, respectively) were recognized by antibody from patients with CL in a solid phase radioimmunoassay. Antigens were also detected by autoradiography after immunoblotting of TLC. Compound A could be labeled biosynthetically with [3H]oleic acid, [14C]galactose, [14C]mannose, [14C]glucose and [32P]phosphate. B incorporated [14C]galactose, [14C]mannose, [14C]glucose and [14C]myo-inositol. C was labeled with [14C]galactose and [14C]mannose, while E incorporated [14C]glucose, [14C]mannose, [3H]oleic acid and [14C]myoinositol. Two antigens (A and B) could be also labeled on the surface of living promastigotes using galactose oxidase and [3H]sodium borohydride. Experimental data showed that CLF-1 and CLF-2, both carbohydrate-containing fractions, had different chromatographic patterns from excreted factor (EF), a polysaccharide antigen from Leishmania. The present study characterizes glycolipid molecules from L. major promastigotes, able to stimulate the immune system from patients with CL.

Animals↗
PubMed1988

Persistence of human leishmanial antibodies in an endemic area of visceral leishmaniasis in El Agamy, Egypt.

In an endemic area of visceral leishmaniasis (VL), individuals with leishmanial antibodies that reacted in the radioimmunoassay (RIA) were retested to determine duration of leishmanial antibody retention. One fourth of adults retained antibodies for at least 10 months. At least 2/3 of asymptomatic children retained leishmanial antibodies for 5 to 7 months after detection. 2/3 of children treated for VL retained leishmanial antibodies for 5 to 7 months after treatment, while 1/3 retained antibodies for over a year. These data modify conclusions that can be drawn from a single serosurvey. Since leishmanial RIA antibodies can persist in humans for at least two transmission seasons, incidence estimates require serial serosurveys.

Adult↗
PubMed1988

Cell-mediated responses and protection elicited by a carbohydrate-lipid-containing fraction extracted from Leishmania major promastigotes.

Carbohydrate-lipid-containing fractions (CLF) extracted from Leishmania major promastigotes and recognized by sera from immune but not from normal human donors were evaluated for their capacity to elicit cell-mediated responses. It was found that one of these fractions, CLF-1, stimulated the in vitro response of lymphocytes from immune but not from normal human donors. A similarly extracted fraction from L. donovani parasites also elicited an in vitro response by cells from donors immune to L. major. The response was mediated by antigen-presenting cells, and specific Leu 3+ Leu 2- T cells from a human T-cell line responded to the antigen. In vivo, the CLF-1 elicited delayed-type hypersensitivity (DTH) response in L. major-immunized C3H mice, which was comparable to the DTH response elicited by freeze-thawed and sonicated L. major promastigotes. C3H mice were vaccinated with CLF-1 prior to challenge with live L. major promastigotes. Mice vaccinated with CLF-1-containing liposomes showed a significant degree of protection to challenge. These results suggest that the carbohydrate-lipid-containing fraction described here may represent a functional antigenic entity from Leishmania parasites.

Animals↗
PubMed1988

Dot-ELISA, a potential immunoassay for the detection of Plasmodium falciparum antibodies.

The dot enzyme-linked immunosorbent assay (dot-ELISA) was compared to the indirect immunofluorescent assay (IIFA) and radioimmunoassay (RIA) for the detection of malaria antibodies. Of 281 sera tested by dot-ELISA, 220 were from Ethiopia, 11 from the Sudan, and 50 from Egypt. A close correlation between the dot-ELISA and RIA results was observed in 92% of the 220 Ethiopian cases. Of the remainder, 6% gave positive RIA and negative dot-ELISA results, and 2% gave positive dot-ELISA and negative RIA results. Antibody titres determined by dot-ELISA and RIA were positively correlated in 10 of the 11 Sudanese cases tested by direct microscopical examination. The eleventh case was positive by dot-ELISA at 1:1000 dilution, but negative by RIA and direct examination. With the 50 Egyptian sera, the dot-ELISA results showed close correspondence to the IIFA results, but the dot-ELISA was 20-40 fold more sensitive than the IIFA. To test specificity, 62 samples from patients with 11 different diseases and conditions were examined by dot-ELISA. No malaria antibodies were detected in any of these or in sera from healthy controls. Dot-ELISA is a potentially useful method for sero-epidemiological studies of malaria.

Animals↗
PubMed1988

Rhabdomyosarcoma of the trachea.

A 12-year-old girl was admitted on two occasions to our department because of severe dyspnoea, necessitating emergency tracheostomy. On the second admission, a lateral neck X-ray demonstrated a globular tumour which was found to be an embryonal rhabdomyosarcoma. The patient received post-operative radiation therapy followed by two years of continued chemotherapy. She is now five years post diagnosis and requiring no further therapy for about three years and her condition remains in remission.

Child↗
PubMed1988

The epidemiology of human visceral leishmaniasis in El Agamy (Alexandria Governorate), Egypt: serosurvey and case/control study.

In Alexandria Governorate, Egypt, 27 cases of visceral leishmaniasis (VL) were detected from 1982-1985 through active and passive case detection. Twenty-two were located in El Agamy, a resort town of 50,000 residents located 15 km west of the City of Alexandria. To describe the disease focus, eight areas of 100-200 households in El Agamy were mapped and censused. All individuals were examined clinically, and blood was obtained by finger stick to measure leishmanial antibodies by radioimmune assay. Two case/control studies were carried out in the mapped areas. In one study, case households were more often found near open garbage containers than were control households. In a second case/control study, houses with cases of VL or seropositive individuals were found more likely to face open areas. These results demonstrate that characteristics of houses which could increase exposure to reservoir hosts can be associated with VL or leishmanial seropositivity. This suggests that control programmes should improve garbage disposal and should focus on houses located in peripheral areas of the community.

Adolescent↗
PubMed1988

Immunosuppressive medication associated with leishmanial antibodies in adults residing in an endemic focus of infantile visceral leishmaniasis--a case/control study.

In a focus of infantile visceral leishmaniasis in Al Agamy (Alexandria), Egypt, adults were found by radioimmune assay to have leishmanial antibodies. This finding was unexpected, and an explanation was sought. Seropositive adults and age- and sex-matched seronegative controls were interviewed to ascertain possible predisposing risk factors. Ten of 16 seropositive individuals were taking corticosteroids compared to one of 22 seronegative individuals (P = 0.0002). Two seropositive individuals (one woman and one man) were taking phenylbutazone, and two women were taking female sex hormones. The association between immunosuppressive medication and leishmanial seropositivity suggests that acquired changes in host population immunocompetence may significantly alter age-specific seroprevalence of leishmanial antibodies.

Adult↗