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Biomedical subjects

D M Parham

Publications and source records attributed to D M Parham.

At least 145 records · Page 8Linked to original sources

Malignant rhabdoid tumor: a highly malignant childhood tumor with minimal karyotypic changes.

Malignant rhabdoid tumors (MRT) are rare; thus very few cytogenetic studies of this type of tumor have been performed. We report the results of cytogenetic studies of 10 MRTs from various anatomic primary sites. Six cases had normal diploid karyotypes with no detectable rearrangements or aneuploidy except for occasional tetraploid cells. In 4 of these cases the tumor phenotype was verified by electron microscopic studies. In a seventh case only normal cells were identified in short-term culture, but a del(13)(q14) appeared after 4 months in culture. A soft tissue MRT contained a translocation, t(8;15)(q12;p11), and a liver MRT contained a del(3)(q21) or t(3;?)(q21;?). The single case of a primary brain MRT had monosomy 22 with deletion of part of the remaining chromosome 22. Our findings indicate that visible chromosomal rearrangements occur in fewer than half of MRTs. When combined with other reported series, our study indicates that monosomy 22 is a non-random chromosomal abnormality in primary MRT of the brain.

Brain Neoplasms↗

Childhood chondrosarcoma: MR imaging with gadolinium-DTPA.

The radiologic, CT, MR, and histological features of a case of chondrosarcoma of the femur presenting in childhood are reported. This case emphasizes the use of correlative imaging in establishing the diagnosis as well as the value of MR supplemented by Gadolinium-DTPA enhancement in disclosing abundant necrosis within the tumor.

Child↗

Expression of CD15 antigen in urinary bladder transitional cell carcinoma.

The biopsy specimens of 91 patients between the ages of 38 and 94 with transitional cell carcinoma of the bladder were retrospectively reviewed to determine if the expression of CD15 antigen detected by a monoclonal antibody MC2 was correlated with prognosis. Expression was variable, ranging from strong expression of the antigen by only the superficial cells in well differentiated papillary lesions to weak expression by most cells in solid or invasive tumours. In the invasive component there was a correlation between MC2 expression and tumour type, suggesting that the cell surface carbohydrate detected by MC2 may have a role in cell adhesion. There was no correlation between staining and survival. It is concluded that tumour type, grade, and stage remain the best prognostic indicators of urothelial tumours.

Adult↗

Use of MR imaging to assess results of chemotherapy for Ewing sarcoma.

MR imaging was used to monitor the results of initial chemotherapy of primary Ewing sarcoma of bone. The signal intensities of the soft-tissue and marrow components of the tumor were evaluated on T2-weighted images obtained in 10 patients (nine with responsive tumors) at presentation and during and immediately after completion of two cycles of chemotherapy. MR evidence of marrow and soft-tissue involvement was seen in all tumors at presentation. After treatment, the bone-marrow component of the nine drug-sensitive tumors showed an increase in signal intensity that in eight cases became comparable to that of water. Changes in signal intensity of the soft-tissue component were variable, consisting of increases in two of the responsive lesions, no change in three, a decrease in two, and complete resolution of the soft-tissue mass in two. There was no increase in signal intensity of either the bone-marrow or the soft-tissue component of the single nonresponsive tumor. All of the responsive tumors showed advanced healing, and abundant bony sclerosis was apparent on CT. Bone-marrow examinations, performed in seven of the nine patients with responsive lesions, disclosed no evidence of tumor in four. Two patients had residual extramedullary tumor; the nonresponsive lesion contained sheets of tumor cells. The increase in marrow signal intensity on T2-weighted images was associated with replacement of marrow elements by a loose, hypocellular myxoid matrix containing modest amounts of collagen, consistent with response to chemotherapy and eradication of disease. Therefore, an increase in the T2-weighted signal intensity of the bone-marrow component of Ewing sarcoma of bone reflected a favorable response to chemotherapy. MR signal changes, however, were not predictive of resolution of malignant disease within adjacent soft tissue.

Adolescent↗

The Evi-1 zinc finger myeloid transforming gene is normally expressed in the kidney and in developing oocytes.

Activation of the Evi-1 zinc finger gene is commonly associated with the transformation of murine leukemias and is involved in some cases of human AML involving rearrangements at chromosome 3q25. To determine the normal function of the gene, we have looked for expression in a variety of cell lines and tissues. The predominant sites of expression of the gene are in the kidney and ovary. In the kidney, expression is localized to the renal tubules in the corticomedullary junction. In the ovary, high levels of the Evi-1 protein are found in the cytoplasm of developing oocytes. The latter result suggests a potential role for the Evi-1 gene product in early oocyte development.

Animals↗

Is renal salvage feasible in unilateral Wilms' tumor? Proposed computed tomographic criteria and their relation to surgicopathologic findings.

The ability of computed tomographic (CT) criteria to predict the potential for resection with renal salvage in unilateral Wilms' tumor was evaluated retrospectively in 10 children given preoperative treatment for initially inoperable disease. Criteria were (a) tumor involving only one pole and occupying less than one-third of the kidney, (b) functioning kidney, (c) no invasion of collecting system or renal vein, and (d) clear margins between tumor, kidney, and surrounding structures. Review of preoperative CT scans correctly predicted nonsalvageability (as assessed by surgicopathologic findings) in seven cases. Sufficient pathologic data were lacking to confirm positive CT predictors in one case. One patient was rated resectable with salvage on surgicopathologic review, but not by CT criteria, and in one case, a prediction could not be made. The potential for renal salvage may be greater in samples with smaller initial tumor size, and addition of other imaging modalities might enhance the accuracy of prediction. Further studies are needed to assess the feasibility of prospective trials evaluating the risks and benefits of partial nephrectomy in unilateral Wilms' tumor.

Adolescent↗

Expression of the 5.1 H11 antigen, a fetal muscle surface antigen, in normal and neoplastic tissue.

The monoclonal antibody 5.1 H11 recognizes an antigen on human fetal muscle and on rhabdomyosarcoma cell lines and xenografts that has been shown to be homologous to the neural cell adhesion molecule. To evaluate its range of expression, we used immunoperoxidase staining of fresh frozen-tissue sections to determine monoclonal antibody 5.1 H11 reactivity in normal and neoplastic tissue. Among normal tissue specimens, intense antibody staining was seen in brain and peripheral nerve, and weaker staining in ganglionic elements of colon. In addition to 26 of 29 rhabdomyosarcoma specimens, 5.1 H11 antibody showed reactivity to 9 of 10 Wilms' tumors, 6 of 6 neural tumors, and 4 of 4 gliomas, and with single specimens of ectomesenchymoma, clear-cell sarcoma of kidney, undifferentiated sarcoma of liver, ovarian fibroma, and neurofibroma. We conclude that the monoclonal antibody 5.1 H11 recognizes an antigen present not only on fetal muscle but on normal brain and nerve as well. In addition to rhabdomyosarcoma, a variety of other tumors, most of which have been previously shown to express neural cell adhesion molecule, also appear to express the antigen recognized by 5.1 H11. Our results thus offer additional confirmatory evidence that an epitope of neural cell adhesion molecule is the antigen for 5.1 H11.

Antibodies, Monoclonal↗

Myogenic regulatory protein (MyoD1) expression in childhood solid tumors: diagnostic utility in rhabdomyosarcoma.

Transcripts for the muscle regulatory gene MyoD1 are expressed during normal skeletal muscle myogenesis and in rhabdomyosarcomas but not in other tissues or in soft-tissue sarcomas. Here we report the distribution of MyoD1 protein, determined by reactivity with anti-MyoD1 polyclonal sera in normal tissues, rhabdomyosarcoma cell lines, and in a variety of pediatric solid tumors. The distribution of MyoD1 protein was highly restricted in normal tissues and was detected only in fetal skeletal muscle and more faintly in adult skeletal muscle. All six human rhabdomyosarcoma cell lines analyzed expressed MyoD1 mRNA transcripts as well as immunoreactive protein. The immunohistochemical expression of MyoD1 protein was then examined in 49 surgical specimens from a variety of pediatric solid tumors. Each of 16 rhabdomyosarcoma specimens was positive for MyoD1, including four that did not express the intermediate filament protein desmin. Two of five specimens originally designated sarcoma type indeterminate (STI) and two of three specimens originally designated extraosseous Ewing's sarcoma (EOE) were positive for MyoD1, suggesting commitment to myogenic differentiation. Three of eight Wilms' tumors, which also expressed desmin and had clearly evident myogenic elements, also were positive for MyoD1. Tumors that failed to express MyoD1 protein included neuroblastoma, primitive neuroectodermal tumor, non-Hodgkins lymphoma, embryonal sarcoma of the liver, malignant fibrous histiocytoma, malignant rhabdoid tumor, and Ewing's sarcoma of the bone. These results indicate that expression of MyoD1 protein is highly restricted in normal human tissues and that expression of this gene product in malignant tissue may be diagnostic for rhabdomyosarcoma. Furthermore MyoD1 staining may be a valuable adjunct in the classification of pediatric soft-tissue sarcomas.

Child↗

Peripheral primitive neuroectodermal tumor (peripheral neuroepithelioma) in children. A review of the St. Jude experience and controversies in diagnosis and management.

All patients diagnosed with primitive neuroectodermal tumor (PNET) and extraosseous Ewing's sarcoma in one institution between 1962 and 1987 were reviewed. Of the 26 cases studied, 16 had been diagnosed originally as PNETs, seven tumors were rediagnosed as PNET or EOE by histologic review, and three tumors had an original diagnosis of extraosseous Ewing's sarcoma. To determine whether these diagnoses determine a group of tumors with unique biologic behavior and identifiable pathologic characteristics, clinical and treatment response data were compiled, and electron microscopic and immunohistochemical studies were done for those patients with adequate samples. With combined modality therapy, this group achieved a substantially shorter disease control interval than patients with disseminated osseous Ewing's sarcoma or disseminated neuroblastoma--10.8 months versus 17 months and 16 months, respectively. The pattern of relapse and distant spread also differed among these tumor types. Immunohistochemical studies (for example, neuron-specific enolase and beta 2 microglobulin) were helpful in confirming the diagnosis but were not definitive in themselves. Tentative diagnostic criteria are proposed for use in studies designed to provide further information on the nature and treatment of PNET. Some of the controversies regarding diagnosis are discussed. The authors propose a uniform approach to treatment of extraosseous Ewing's sarcoma and PNET in order to try to clarify their relation.

Adolescent↗

Immunohistochemical expression of neuron-specific enolase and Leu 7 in Ewing's sarcoma of bone.

Neural features have been documented in a series of small round cell tumors of bone, previously classified as Ewing's sarcoma of bone (ESB), using light microscopic, ultrastructural, immunohistochemical, and in vitro techniques. To date, correlation of the presence of these features in ESB with clinical outcome has not been performed. The authors investigated the clinical relevance of positivity to antibodies against neuron-specific enolase (NSE) and Leu 7 (HNK 1) using the avidin-biotin complex technique in 40 cases of ESB seen at St. Jude (Memphis, TN) during the period 1968 to 1986. Twenty-three cases (58%) were positive for NSE and/or Leu 7. The median disease-free survival of patients with localized tumors and NSE and/or Leu 7 positivity was 3.8 years compared to a median disease-free survival of 1.6 years for those without these markers and localized disease. Using the log-rank test, a statistically significant difference was shown in these two groups of patients (P = 0.049). The authors conclude that in this relatively small series ESB commonly expresses NSE and/or Leu 7 and that the presence of these markers is of no prognostic significance overall, but that in patients with localized ESB the presence of NSE and/or Leu 7 by immunostaining may be a favorable prognostic indicator.

Adolescent↗

Identification of octadeca-9,11-dienoic acid and its significance in the diagnosis of cervical intraepithelial neoplasia.

In 1987 it was claimed using high performance liquid chromatography (HPLC) that the molar ratio of octadeca-9,11-dienoic acid to its parent linoleic acid (18:2 (9,12)) was raised in malignant and premalignant conditions of the cervix. In this study based on a gas chromatographic procedure which prevents autoxidation and avoids the detection limitations of HPLC, we have shown that assay of these fatty acids has no role to play in the assessment of cervical neoplasia.

Carcinoma, Squamous Cell↗

Extrarenal Wilms' tumor.

The extrarenal location of Wilms' tumor is extremely rare. These tumors can arise from other neoplasms, generally teratomas, or they can present without any associated teratomatous elements. We encountered only 19 well-documented cases of isolated extrarenal nephroblastoma, and we describe three previously unreported patients with this disease. Two of the three children presented also with horseshoe kidneys, an association that may have clinical and embryologic significance. The presence of tumor cephalad to a horseshoe kidney is easier to explain when we consider that they originate from primitive mesodermal tissue, probably mesonephric rests, and not from metanephric remnants. Also, this association should alert physicians to the possible diagnosis of extrarenal nephroblastoma in patients with a retroperitoneal mass and horseshoe kidneys. These patients should be treated according to the same protocols as those for patients with intrarenal Wilms' tumor.

Child↗

A retrospective study of breast carcinoma: causes of death and pattern of metastases.

Autopsy reports and clinical request forms between March 1973 and September 1986 were reviewed for patients with a clinical history of breast carcinoma. During this period 85 cases were identified. The causes of death and metastatic pattern of the breast carcinoma were recorded. Only 25 (29%) of these patients died as a direct consequence of this disease. Of the 85 cases in total, 28 were thought clinically to have died as a result of breast carcinoma but autopsy confirmed these findings in only 21 (75%).

Adult↗

Unusual chronic maculopapular rash associated with human immunodeficiency virus infection.

A 21-year-old black man with sickle cell disease who has received blood transfusions for 11 years because of recurrent stroke has had a decline in numbers of circulating lymphocytes and T4 cells over the past four years. Two and a half years ago persistent generalized lymphadenopathy developed, associated with a positive test for human immunodeficiency virus (HIV) antibody. For the past seven months he has had a pruritic maculopapular rash, primarily on the extensor surfaces of the extremities. Multiple skin biopsies revealed only nonspecific perivascular infiltrates of mononuclear cells. This rash appears to be an unusual manifestation of HIV infection, and may be an indicator of impending AIDS.

Adult↗

Breast carcinoma cellularity and its relation to oestrogen receptor content.

The cellularity of 104 primary breast carcinomata was determined by semiautomated image analysis to allow the relation between cellularity and oestrogen receptor content values to be assessed. The oestrogen receptor content of tumours detected by a steroid binding assay showed no correlation with cellularity, although a possible weak negative correlation was observed between tumour cellularity and oestrogen receptor content detected by enzyme immunoassay. It is concluded that there is no single direct correlation between tumour cellularity and oestrogen receptor content.

Adult↗

Critical evaluation of monoclonal antibody staining in breast carcinoma.

The immunoperoxidase staining of 84 primary invasive breast carcinomas with four monoclonal antibodies (BRST-1, HMFG1, EMA, B72.3) was evaluated by semiquantitative light microscopical examination and quantitative image analysis. Major differences in the staining of the tumours for each of the monoclonal antibodies was observed. Correlation between monoclonal antibody staining and patient age, survival, histological grade, tumour diameter and cellularity was also carried out. This showed a significant association between histological grade and staining with BRST-1 and EMA.

Antibodies, Monoclonal↗