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Biomedical subjects

D Spencer

Publications and source records attributed to D Spencer.

At least 73 records · Page 4Linked to original sources
PubMed1994

Radiation therapy for non-AIDS associated (classic and endemic African) and epidemic Kaposi's sarcoma.

PURPOSE: A retrospective analysis of patients with non-AIDS and AIDS-related Kaposi's sarcoma, who were treated with radiation therapy. METHODS AND MATERIALS: Between 1978 and 1992, 56 patients with one of the three major types (classical, endemic, epidemic) of Kaposi's sarcoma received radiation therapy as their sole treatment modality. Extent of fields, daily fractionation, and total dose were applied on a clinical basis. These lesions received superficial x-ray therapy, Co-60 teletherapy, or 6-8 MeV electron beams. Field sizes depended on extent of the lesion. Total dose administration ranged from 8-12 Gy in one exposure, or a total of 24-30 Gy fractionated over 2-3 weeks. RESULTS: The majority of patients responded to radiation therapy. Symptomatic relief was achieved in 80-100% of patients irrespective of the type of Kaposi's sarcoma, treatment modality, or schedule. Side effects were tolerable in all but three patients with epidemic type Kaposi's sarcoma, who developed severe mucositis. CONCLUSION: Radiotherapy is the most useful mode of palliative treatment for all forms of Kaposi's sarcoma in southern African patients.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Malignant lymphoma with primary cardiac manifestations: a case report.

This case report describes a 29-year-old black patient presenting with right heart failure secondary to massive lymphomatous cardiac involvement. Additional sites of involvement included mesenteric lymph nodes and the small bowel. Malignant lymphoma with primary cardiac manifestations is very rare and follows an aggressive course. The importance of early diagnosis and commencement of immediate therapy is emphasized.

Adult↗
PubMed1994

Development of a non-selecting, non-perturbing method to study human brain tumor cell invasion in murine brain.

The infiltrative nature of glial and some meningeal neoplasms is responsible for the failure of surgical removal and high recurrence rate of these tumors. Modeling of this process in vitro and in vivo will lead to a better understanding of the pathophysiology of this process and identify targets for novel therapy directed towards this phenotype. We present the results of the development and refinement of two model systems of tumor invasion: one in vitro barrier assay using the basement membrane extract Matrigel, and one in vivo where molecular detection of tumor cells allows single cell discrimination by in situ hybridization histochemistry. These techniques have strong correlations which validate their utility as measures of nervous system tumor invasion.

Animals↗
PubMed1994

Classical Kaposi's sarcoma in Caucasians in Africa--experience at the Johannesburg Hospital (1978-1992).

The data are scant concerning classical Kaposi's sarcoma (CKS) among the Caucasian population of Africa. A description of the clinical features of 15 such patients, treated and followed up at the Johannesburg General Hospital over a 14-year period (1978-1992) is presented. All patients were negative for the human immunodeficiency virus. After a mean follow-up of 50 months (range: 7-168 months), 2 patients are alive with absent or minimal disease; 1 patient is alive with stable disease and 1 has active disease involving his extremities. Three patients were lost to follow-up but had minimal or no disease when last seen. Five patients died of unrelated causes but also had minimal or no disease at their last visit. One patient died of sepsis related to active KS. Only two patients died of progressive KS. No alterations in humoral or cellular immunity were demonstrated in 2 patients with persistent disease. Four (27%) patients developed lymphoproliferative disorders including non-Hodgkin's lymphoma, Waldenström's macroglobulinemia, Hodgkin's disease and Castleman's disease (angiofollicular lymph node hyperplasia) preceding or following the diagnosis of CKS. These data confirm the indolent nature and good outcome of the classical form of Kaposi's sarcoma among Caucasians in the southern African region. The marked association between CKS and lymphoproliferative disorders warrants a long-term awareness and continued monitoring for these complications.

Adult↗
PubMed1994

Lymphoproliferative malignancies in association with endemic African Kaposi's sarcoma.

The association of classical Kaposi's sarcoma with lymphoproliferative disorders is well known. However, far less is known about lymphoproliferative malignancies in endemic African Kaposi's sarcoma. A review of 47 patients with the endemic type of Kapos's sarcoma treated at the Johannesburg Teaching Hospital Complex between 1980 and 1992 revealed four patients (8.5 pc) in whom Kaposi's sarcoma was associated with a malignant lymphoma. Possible pathogenetic mechanisms are suggested and the current literature is reviewed.

Adult↗
PubMed1994

Lymphoproliferative disorders in non-AIDS-associated Kaposi's sarcoma. The Johannesburg Hospital experience, 1980-1992.

The association of the non-AIDS-related, classic form of Kaposi's sarcoma (KS) with secondary malignancies, especially lymphoproliferative disorders, has frequently been noted. However, in endemic African-type KS, such an association has been reported only rarely. A review of 62 non-AIDS-related cases of KS treated and followed up at Johannesburg General Hospital between 1980 and 1992 revealed 8 patients (13%) in whom KS was associated with malignant lymphoproliferative disorders. The prevalence of secondary lymphoproliferative disorders was not significantly different among patients with classic KS (3/15; 20%) when compared with those who had African KS (4/47; 8%). In both forms of KS subtle disturbances of immunity have been described which may play a role in the pathogenesis of secondary lymphoproliferative disorders, although the factors responsible and the pathogenetic mechanisms involved in malignant lymphoid transformation in these patients have not been fully elucidated.

Adult↗
PubMed1994

Biology of disease and clinical aspects of AIDS-associated lymphoma: a review.

AIDS-related lymphoma was not apparent until 1985, when a statistically significant increase in the frequency of lymphoma had occurred. Over 50% are high-grade lymphoma, either immunoblastic or small, noncleaved cells (Burkitt's-like lymphoma), with involvement of extranodal sites such as the central nervous system (> one-third of patients), gastrointestinal tract, skin and bone marrow. Optimal therapy for AIDS-associated lymphoma has not yet been defined. Using intensive chemotherapy protocols, high response rates, albeit of brief duration, have been demonstrated. The majority of patients succumbed to intercurrent opportunistic infections. Poor prognosis has been particularly noted in debilitated patients, patients with a CD4 cell count of < 200/dl, bone marrow and brain involvement and a history of AIDS before diagnosing the lymphoma. New strategies in the management of patients with AIDS-lymphoma should include cytotoxic therapy, antiretroviral therapy, anti-pneumocystic Carini pneumonia, prophylaxis of CNS spread and marrow protective therapy (haematopoietic growth factors).

AIDS-Related Opportunistic Infections↗
PubMed1994

AIDS-related Kaposi's sarcoma: a review.

Infection with the human immunodeficiency virus (HIV) is the primary cause of AIDS and related disorders. Infection with HIV results in diminished cellular immunity, propensity to opportunistic infections, and an increased incidence of certain neoplasms. Kaposi's sarcoma (KS) is the most common neoplasm in persons infected with HIV. This epidemic, or HIV-related KS, usually follows an aggressive course with involvement of skin, lymph nodes, and internal organs. Normally, the disease has a progressive clinical course despite being responsive to radio- or chemotherapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Kaposi's sarcoma in renal transplant recipients. Experience at Johannesburg Hospital, 1966-1989.

Between August 1966 and December 1989, 989 renal transplant recipients were followed up at the Renal Transplant Unit of Johannesburg Hospital. Seventy-five (7%) patients developed a total of 95 malignancies of which 5 (6%) were Kaposi's sarcoma. All patients received immunosuppressive agents; steroids, azathioprine and/or cyclosporin A. Clinical presentations included both limited skin involvement (1 patient) and disseminated forms of the disease: necrotic oral lesions (1 patient); disseminated skin involvement and lung metastases (1 patient); and widespread skin lesions with lymphadenopathy (2 patients). Four patients responded with complete tumour regression at all sites upon withdrawal of the immunosuppressive drugs. One patient suffered disease progression, and immunosuppression was continued, albeit at reduced dosages. These cases illustrate a relatively rare complication of immunosuppressive therapy. However, complete withdrawal of immunosuppressive drugs may result in sustained complete regression, despite the presence of advanced KS.

Adult↗
PubMed1993

Radiation therapy in endemic (African) Kaposi's sarcoma.

PURPOSE: Evaluating the role of radiation therapy in the treatment of the endemic, African variant of Kaposi's sarcoma. A retrospective analysis. METHODS AND MATERIALS: Between 1978 and 1990, 28 symptomatic African patients with the African Human Immunodeficiency Virus negative type of Kaposi's sarcoma were referred to the Johannesburg General Hospital. Following staging, all patients were treated with radiation therapy. Doses ranged between 8-10 Gy (single fraction) or 14-24 Gy fractionated over 1-3 weeks. RESULTS: Complete and partial regression of cutaneous lesions was achieved in 9 (32%) and 15 (54%) patients, retrospectively. A complete/near-complete alleviation of symptoms was achieved in all patients. Response rate and duration of response was not influenced by age, radiation modality or schedule. Side effects were minimal. CONCLUSION: Our study emphasizes the high radiosensitivity of the endemic, African type of Kaposi's sarcoma, indicating its usefulness as the treatment of choice for this disease.

HIV Seronegativity↗
PubMed1993

The role of viral enhancer "core" motif-related sequences in regulating T cell receptor-gamma and -delta gene expression.

T cells express clonally distributed alpha beta or gamma delta Ag receptor heterodimers. Transcriptional enhancers for the genes of all four subunits are active in both gamma delta and alpha beta T cells, but are less active or inactive in other cells. Conserved sequence motifs are present in all four enhancers, suggesting that common transcription factors regulate TCR gene expression. One of these motifs in the gamma 3 site of the TCR-gamma enhancer is similar to motifs found in several other lymphoid-specific and viral enhancers. This conserved "core" sequence is present in the enhancers of Moloney and SL3-3 murine leukemia viruses, important for transcription in T cells and in determining disease specificity. Here we characterize the gamma 3 site of the gamma enhancer and a corresponding homologous site, delta E3, of the TCR-delta enhancer. Our results suggest that the core site is critical for activity of the 200-bp gamma enhancer fragment and of the gamma 3 and delta E3 sites. Furthermore, we identify a nuclear factor in human T cell lines that specifically binds the core region in these and several other core-containing enhancers. This factor may be identical to or related to a purified bovine nuclear core binding factor that binds the core region of the Moloney murine leukemia virus enhancer, gamma 3 and delta E3 sites, suggesting that similar proteins regulate the TCR-gamma, delta and Moloney murine leukemia virus enhancers. Other sequences in the gamma 3 site upstream of the core sequence are also critical for activity in T cells, suggesting that at least two different factors are required for functional activity of the gamma 3 site.

Animals↗
PubMed1992

Vicilin with carboxy-terminal KDEL is retained in the endoplasmic reticulum and accumulates to high levels in the leaves of transgenic plants.

Gene constructs were designed to test the effect of the endoplasmic reticulum (ER)-targeting signal, KDEL, on the level of accumulation of a foreign protein in transgenic plants. The gene for the pea seed protein vicilin was modified by the addition of a sequence coding for this tetrapeptide at its carboxyl terminus. The altered gene was placed under the control of a CaMV 35S promoter and its expression in the leaves of both tobacco and lucerne (alfalfa) was compared with that of an equivalent vicilin construct lacking the KDEL-coding sequence. The presence of the ER-targeting signal led to a greatly enhanced accumulation of the heterologous protein. In lucerne and tobacco leaves, the level of vicilin-KDEL protein was 20 and 100 times greater than that of the unmodified vicilin, respectively. These differences in expression level could not be explained by corresponding differences in the steady-state levels or the translatability of the mRNAs. However, when the stability of vicilin and vicilin-KDEL proteins was compared in their respective transgenic hosts, unmodified vicilin was found to be degraded with a half-life of 4.5 h while vicilin-KDEL was much more stable with a half-life of more than 48 h. Immunogold labelling of leaf tissues from transgenic lucerne and tobacco showed the presence of vicilin associated with large aggregates within the ER lumen of vicilin-KDEL plants. No such aggregates were detected in transgenic plants expressing wild-type vicilin. It is concluded that the carboxy-terminal KDEL caused the retention of the modified vicilin in the ER, and that this retention led to the increased stability and higher level of accumulation of vicilin-KDEL in leaves of transgenic plants.

Amino Acid Sequence↗
PubMed1991

Spinal arteriovenous malformation.

The authors discuss a patient with a large (15 x 10 x 12 cm), bony soft tissue intradural arteriovenous malformation (AVM) who presented with a 20-year history of back pain. Plain radiographs revealed a destructive lesion. Magnetic resonance imaging showed serpentine vascular structures within the thecal sac and lytic bone lesions with multiple level involvement. A Craig needle biopsy by the referring physician, as well as an open biopsy by the authors, caused severe bleeding. There was no evidence of neoplasm. Selective spinal angiography demonstrated a metameric juvenile type AVM whose intradural component was fed by the artery of Adamkiewicz. Because the patient had no neurological deficit on presentation, the options of embolization and then surgery were considered too risky. The patient is being followed conservatively.

Adult↗