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Biomedical subjects

R Benjamin

Publications and source records attributed to R Benjamin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effects of apolipoprotein E genotype on cortical neuropathology in senile dementia of the Lewy body and Alzheimer's disease.

Apolipoprotein E (APO E) genotypes were determined in a UK population of neuropathologically confirmed control cases, and in cases of Lewy body dementia (SDLT) and late onset Alzheimer's disease (AD). APO E epsilon 4 allele frequency was significantly elevated in both SDLT and AD groups with a concomitant reduction in the APO E epsilon 3 allele frequency. The epsilon 2 allele frequency in the AD group was only 25% of the control population, though because of the relatively small sample size this reduction was not significant; the epsilon 2 allele frequency in the SDLT group was normal. No significant association was found between senile plaque density and neurofibrillary tangle density in the neocortex and APO E allele dose in either SDLT or AD. Although the possession of APO E epsilon 4 is associated with an increased risk of developing SDLT and AD, actual APO E genotype does not appear to affect the burden of pathology.

Alleles↗
PubMed1995

Rhabdomyosarcoma of the nose and paranasal sinuses in adults and children.

OBJECTIVE: To determine the biologic behavior, risk factors for recurrence, and influence of multimodality therapy on outcome for children and adults with rhabdomyosarcoma of the nose and paranasal sinuses. DESIGN: Retrospective review of medical records. PATIENTS: During a 36-year period 37 patients (median age, 23.0 years) with histologically confirmed rhabdomyosarcoma of the nose and paranasal sinuses were treated for cure. Median follow-up was 28 months (range, 1 to 260 months). Histologic subtypes included embryonal, 16; alveolar, 15; mixed, 1; and unclassified, 5. Cervical metastases were present in 38%. Patients were treated with surgery, 4; radiotherapy, 3; chemotherapy, 3; surgery and radiotherapy, 1; surgery and chemotherapy, 1; chemotherapy and radiotherapy, 24; and chemotherapy, radiotherapy, and surgery, 1. RESULTS: The overall 5-year survival was 44%. For patients treated with chemotherapy and radiotherapy or chemotherapy, radiotherapy, and surgery, the 5-year survival was 60%, compared with 19% for patients treated with the other forms of therapy. Factors associated with poorer survival were adult onset of disease, alveolar histology, and treatment with systemic chemotherapy for less than 1 year. Patients receiving chemotherapy for greater than 1 year had a 5-year survival of 82%, compared with 71% for those with less than 1 year of treatment. Improved survival was associated with a lower incidence of distant metastasis. CONCLUSIONS: A combination of chemotherapy and radiotherapy may provide the best means of obtaining local-regional control for rhabdomyosarcoma arising in the nose and paranasal sinuses. The risk of regional disease is high, requiring comprehensive radiotherapy to the neck in addition to the primary site. Surgical resection should be reserved for patients with residual disease after chemotherapy and radiotherapy. Administration of chemotherapy for more than 1 year is associated with improved survival because of a decreased incidence of metastatic disease.

Adolescent↗
PubMed1995

A therapy group for mothers with dissociative disorders.

This paper describes the evolution of a therapy group for mothers with dissociative disorders. Although the group is for survivors of childhood trauma, its focus is on the present dilemmas of child rearing rather than on past traumas. It uses mothering as a common bond to improve parenting and interpersonal skills and to propel forward each member's individual therapy. The article summarizes the relevant literature, provides a rationale for such a group, and discusses the issues of cotherapy, combined therapy, group process, transference, countertransference, and thematic material.

Adult↗
PubMed1994

The gene family of EF-hand calcium-binding proteins from the flagellum of Trypanosoma brucei.

The flagellum of Trypanosoma brucei contains calmodulin, and a separate family of antigenically related EF-hand calcium-binding proteins which we call calflagins. The following study evaluates the structure and genomic organization of the calflagin family. Genomic Southern blots indicated that multiple copies of calflagin genes occurred in T. brucei, and that all of these copies were contained in a single 23 kb XhoI-XhoI fragment on chromosomes 15 and 16 mRNAs of 1.2 and 1.6 kb were identified in bloodstream and procyclic life-cycle stages. Genomic fragments of 2.5 and 1.7 kb were cloned that encoded calflagin sequences. The calflagin genes were arranged tandemly along the genomic fragments. Three new members of the calflagin family were sequenced from a cDNA clone and the two genomic clones. Two unrelated families of 3' flanking sequences were downstream from the calflagin genes. An open reading frame that was unrelated to any calflagin sequence was at the 5' end of the 2.5 kb genomic fragment. The deduced amino acid sequences of the genomic clones (called Tb-24 and Tb-1.7g) were similar to the previously described Tb-17. Each encoded an approximately 24 kDa protein which contained three EF-hand calcium-binding motifs and one degenerate EF-hand motif. The cDNA encoded a protein (called Tb-44A) which was approximately twice as large as the other calflagins. The large size resulted from a nearly direct repeat of 186 amino acids. In general, variability among the T. brucei calflagins was greater than observed for related proteins from Trypanosoma cruzi. We demonstrate that this variability resulted from amino acid substitutions at the N-terminus, C-terminal extensions, and duplication of internal segments.

Amino Acid Sequence↗
PubMed1994

Mechanism of the anti-tumour effect of biochemotherapy in melanoma: preliminary results.

During the conduct of a biochemotherapy trial in which cisplatin, vinblastine and dacarbazine (CVD) were administered concurrently with interleukin-2 (IL-2) plus interferon-alpha 2a (IFN-alpha 2a) (biochemotherapy) in advanced melanoma, we performed a series of laboratory studies in an attempt to understand better the mechanism of anti-tumour effect of the regimen. We initially hypothesized that CVD enhanced the anti-tumour effect of the biotherapy. However, in the first 10 patients studied, of whom eight were responders, we observed no lymphokine-associated killer cell (LAK) and minimal natural killer (NK) cell activities. This prompted us to change our initial hypothesis. Based on the work of others which showed a marked synergism between IL-1 alpha and cisplatin, apparently mediated by H2O2 derived from tumour-infiltrating macrophages, we reasoned that the biotherapy could enhance the cytotoxicity of the CVD regimen. To evaluate macrophage function, we measured serum neopterin levels in eight responders and seven non-responders. An increase of six or more times above baseline levels was observed in seven out of eight responders but in only two of seven non-responders (P = 0.041). We also examined the level of DNA inter-strand cross-link in peripheral blood mononuclear cells in four responders and four responders, as a means to evaluate the DNA repair process. A DNA cross-link index > or = 0.75 was observed in all four responders but only in one non-responder (P = 0.14). Our preliminary results suggest that concurrent biochemotherapy may exert its predominant anti-tumour effect by direct cytotoxicity and that macrophages may be involved in this process.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Optimization of methods to achieve mRNA-mediated transfection of tumor cells in vitro and in vivo employing cationic liposome vectors.

Direct in vivo transfection of tumor nodules in situ via liposome-DNA complexes has been employed as a strategy to accomplish antitumor immunization. To circumvent the potential safety hazards associated with systemic localization of delivered DNA, the utility of mRNA transcript-mediated gene delivery was explored. Capped, polyadenylated mRNA transcripts encoding the firefly luciferase and Escherichia coli lacZ reporter genes were derived by in vitro transcription. Transfection of the human breast cancer cell line MDA-MB-435 in vitro was accomplished employing cationic liposome-mRNA complexes. Evaluation of a panel of cationic liposome preparations demonstrated significant differences in the capacity of the various preparations to accomplish mRNA-mediated transfection. Quantitative evaluation of in vitro transfection demonstrated that target cells could be transfected at a high level of efficiency. The mRNA liposome-complexes were evaluated for in vivo transfection of tumor nodules in human xenografts in athymic nude mice. It could be demonstrated the liposome-mRNA complexes were comparable in efficacy to liposome-DNA complexes in accomplishing in situ tumor transfection. Thus, mRNA may be considered as an alternative to plasmid DNA as a gene transfer vector for genetic immunopotentiation applications.

Breast Neoplasms↗
PubMed1993

An open trial of cefoperazone plus sulbactam for the treatment of fever in cancer patients.

Cancer patients received cefoperazone plus sulbactam for 673 febrile episodes presumed to be caused by infection. Overall, 415 (76%) of the 545 evaluable episodes responded. There were 213 responses (84%) amongst the 254 fevers of unknown origin and 202 responses (69%) amongst the 291 documented infections. Fifty-one (61%) of the 83 episodes pneumonia and 74 (64%) of the 115 episodes of bacteraemia responded. Only 39 (58%) of the 67 infections caused by Gram-positive bacteria responded compared with 55 (86%) of 64 Gram-negative infections which included seven of eight caused by Pseudomonas aeruginosa. Eighteen (67%) of 27 polymicrobial infections responded to the regimen. Response rates were significantly lower amongst the 125 patients whose neutrophil counts decreased during therapy than amongst the 158 patients whose neutrophil counts increased. Adverse events which were possibly or probably related to antibiotic therapy were observed during 73 of the episodes; the most commonly reported side-effects were diarrhoea and skin rash. Six patients developed a coagulopathy without haemorrhage and two experienced anaphylactic reactions. In this open trial cefoperazone plus sulbactam proved to be an effective regimen for initial therapy of fever in cancer patients. It should be combined with a glycopeptide in those institutions where infections caused by methicillin-resistant staphylococci are frequently encountered.

Adolescent↗
PubMed1992

Unique histological changes in lung metastases of osteosarcoma patients following therapy with liposomal muramyl tripeptide (CGP 19835A lipid).

We have recently begun a phase II trial in patients with osteosarcoma who developed pulmonary metastases during adjuvant chemotherapy or who presented with pulmonary metastases that persisted despite chemotherapy. Eligible patients were rendered free of visible disease by surgery. Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE, CGP 19835A lipid) (2 mg/m2) was infused twice weekly for 3 months. In five patients, a single tumor nodule recurred within 6 weeks after completion of therapy. These lesions were resected and submitted for pathological examination. Tissue specimens obtained after therapy were compared to those obtained before therapy. All the patients showed a histological change in the characteristics of the pulmonary tumors. In three patients, peripheral fibrosis surrounded the tumor and inflammatory cell infiltration and neovascularization were present. This is in contrast to central necrosis, with viable peripheral tumor cells and no inflammatory response observed in lesions resected following chemotherapy. In a fourth case, evidence of early fibrotic changes was found. This and the fifth case showed a change in malignant characteristics, from high grade before liposomal therapy to low grade after therapy. The present study provides evidence for a biological effect of liposomal MTP-PE.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

HLA-B27 and disease: a consequence of inadvertent antigen presentation?

The close association of HLA-B27 with arthritic conditions has led to the suggestion that these diseases are mediated by cytotoxic T lymphocytes that recognize self-peptides presented by HLA-B27 molecules. The further association with enteric bacterial infections suggests that bacterial antigens may prime the CTL that later crossreacts on self. Bacterial infections do not usually generate CTL responses. We speculate here that unusual properties of HLA-B27 molecules may predispose to such responses. Thus, HLA-B27-related disease may be an unfortunate consequence of the generation of a suitable, self-mimicking HLA-B27-binding peptide by certain bacteria, plus an unusual propensity for the HLA-B27 molecule to bind and present such peptides.

Arthritis↗
PubMed1991

Mood variability in adolescents: a study of depressed, nondepressed and comorbid patients.

In a study to examine the variability of mood in psychiatrically disturbed adolescents, 30 inpatients aged 13-17 reported on current depressive symptoms three times a day for seven consecutive days, using a set of visual analog scales (the Adolescent Mood Scale: AMS) to record DSM-IIIR and other depressive symptoms. Ten of the patients had no depressive diagnosis; 11 had both a depressive and an 'externalizing' diagnosis (mainly conduct disorders and substance abuse disorders), and nine had depressive diagnoses but no externalizing disorder. Variability was defined in terms of (1) range of AMS scores; (2) amount of change from one test point to the next; (3) rhythmicity, measured by the autocorrelation function across 21 test points. All three groups had high levels of depressive symptoms throughout the week. On all measures of severity of depression, the depressed girls were more depressed than the depressed boys, irrespective of comorbidity. Measures of variability, however, showed no effect of sex, but comorbid patients were more likely to have a wide range of mood scores, and reported a 45% greater amount of mood change. Only five subjects had a significant lag1 autocorrelation function, and there was no indication of diurnal rhythmicity. Implications for research and diagnosis are discussed.

Adolescent↗
PubMed1990

Guilt by association: HLA-B27 and ankylosing spondylitis.

The remarkable association between HLA-B27 and ankylosing spondylitis (AS) remains an enigma. While previous reviews have discussed the controversies surrounding the involvement of bacteria in the etiology of this disease and the sequence variability between subtypes of HLA-B27, concepts of disease mechanism remain ill-defined. In this article Richard Benjamin and Peter Parham synthesize new data on the structure and function of HLA class I molecules into possible mechanisms that might underly the pathogenesis of AS.

Amino Acid Sequence↗
PubMed1989

A prospective evaluation of a triple-drug regimen containing cisplatin, vinblastine, and dacarbazine (CVD) for metastatic melanoma.

Based on the independent activity of cisplatin, vinblastine, and dimethyl-triazeno-imidazole-carboxamide (DTIC) (CVD), a combination of these agents was used in the treatment of patients with advanced melanoma. Vinblastine was used in a dose of 1.6 mg/m2/d for 5 days, DTIC was used in a dose of 800 mg/m2 intravenously (IV) on day 1, and cisplatin was used in a dose of 20 mg/m2/d for 4 days starting on day 2 of chemotherapy. The courses of chemotherapy were repeated at 3-week intervals. All patients were premedicated with antiemetics, and IV hydration was used before cisplatin. Fifty-two consecutive patients were registered and 50 were evaluable for response. Two patients achieved a complete response (CR) and 18 patients had a partial response (PR) for an overall response rate of 40% (95% confidence interval, 27% to 55%). The median duration of response was 9 months and the median survival time of the responders was 12 months. The overall median survival time of patients treated on this protocol was 9 months. The treatment was associated with significant toxicity consisting of nausea, vomiting, diarrhea, and partial hair loss. Additionally, neutropenia with a median nadir granulocyte count of 500/microliters was observed, and significant anemia required blood transfusions in a majority of the patients after three to four courses of chemotherapy. The dose-limiting toxicity was peripheral neuropathy which required discontinuation of cisplatin after six to eight courses of chemotherapy. We believe that this triple-drug regimen has significant activity that appears to be superior to the single-agent activity of these drugs, both in terms of increased response rate and duration of response.

Adult↗
PubMed1989

Induction of classical transplantation tolerance in the adult.

Transplantation tolerance across histoincompatibilities in multiple non-H-2 minors (B10.BR into CBA/Ca) and "minor" plus H-2D (B10.A into CBA/Ca) antigens has been achieved successfully by combined adult bone marrow transplantation and treatment with CD4 and CD8 mAbs. The tolerant state was confirmed by permanent acceptance of donor strain skin grafts, and in vitro unresponsiveness to donor cells. Tolerance was associated with partial donor chimerism to various degrees. Tolerance to minor transplantation antigens induced in this manner was restricted to recipient-type MHC. The possibility was raised that tolerance resulted, at least in part, from clonal anergy rather than deletion.

Animals↗
PubMed1989

Sensitivity and specificity of pooled versus individual sera in a human immunodeficiency virus antibody prevalence study.

We evaluated the efficacy of testing pooled versus individual sera for the detection of human immunodeficiency virus antibody. A total of 5,000 individual specimens and 500 pools of 10 specimens each were assayed by an enzyme-linked immunosorbent assay. There was complete agreement in human immunodeficiency virus enzyme-linked immunosorbent assay reactivity for pooled versus individual specimens. An estimated savings of 60 to 80% (labor and supplies) can be realized dependent upon pooling and assay format.

Cost-Benefit Analysis↗