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Biomedical subjects

R S Larson

Publications and source records attributed to R S Larson.

At least 19 recordsLinked to original sources
PubMed1999

Rarity of genomic instability in pathogenesis of systemic anaplastic large cell lymphoma (ALCL) in immunocompetent patients.

Microsatellite instability (MSI) is a recently described type of genetic alteration resulting from defects in the DNA mismatch repair genes that appears to play an integral role in neoplastic transformation. MSI has been described in a wide variety of malignancies; however, data regarding the role of MSI in the pathogenesis of non-Hodgkin's lymphoma (NHL) are limited. MSI appears to be important in some T-cell lymphomas, including ALCL arising in immunocompromised patients. In addition, MSI has recently been identified in CD30+ cutaneous lymphoproliferative processes and lymphoblastic lymphoma. In this study, we have analyzed five well-characterized cases of systemic T-cell ALCL arising in immunocompetent patients for the presence of MSI. Genomic DNA isolated from paired normal and tumor tissue was analyzed at seven microsatellite loci by polymerase chain reaction. We were unable to identify MSI or loss of heterozygosity (LOH) in our cases, suggesting that abnormalities in the DNA mismatch repair system do not play a major role in the pathogenesis of most systemic ALCL. Our data provide additional molecular evidence that the various subgroups of lymphoma with ALCL morphology are biologically distinct processes.

Adolescent↗
PubMed1998

Local reinvention of the CDC HIV prevention community planning initiative.

The Centers for Disease Control and Prevention (CDC), in coordination with 65 states, cities, and territories, implemented HIV prevention community planning beginning in 1994. This large scale innovation in public health planning has involved tens of thousands of professionals and community residents. Though a single case study, Michigan provides a strong test of the implementation of this national prevention planning model because of the state's decentralized approach to HIV prevention community planning involving several hundred residents. A decentralized approach to community planning promises to maximize participation and the sharing of leadership as well as obstacles to community planning. Here, the CDC Guidance for community planning is contrasted with empirical observation of implementation in Michigan. We conclude that the high expectations for a decentralized approach to HIV prevention community planning can be best achieved when a distinction is drawn between information-seeking tasks and decision-making tasks. We recommend that information-seeking tasks be centrally coordinated, and that decision-making tasks be decentralized, to most fully achieve the potential of HIV prevention community planning.

Centers for Disease Control and Prevention, U.S.↗
PubMed1997

Retinoic acid induces aggregation of the acute promyelocytic leukemia cell line NB-4 by utilization of LFA-1 and ICAM-2.

All-trans retinoic acid (tRA) is a potent differentiation agent that is effective therapy for acute promyelocytic leukemia (APL). However, 5% to 25% of patients develop retinoic acid syndrome, a potentially life-threatening complication in which the pathogenesis relates to adhesive alterations of APL cells. Therefore, we investigated the relationship between tRA-induced differentiation and the adhesive properties of APL cells. After confirming differentiation-related morphological changes of NB-4 cells in response to tRA, we showed that homotypic aggregation of NB-4 cells grown in tRA for 72 hours is dose-dependent with a median effective dose of approximately 50 nmol/L. Maximal aggregation occurred at mean and peak therapeutic serum concentrations (100 and 1,000 nmol/L, respectively). Aggregation also increased with the length of tRA exposure over 168 hours. Aggregation was inhibited by neutralizing antibodies against LFA-1 and ICAM-2. Notably, antibodies directed against VLA-4, other beta2 integrins (Mac-1 and p150), or other potential LFA-1 counterstructures that were expressed on the cell surface (ICAM-1 and ICAM-3) did not block aggregation. Aggregation occurred with similar kinetics regardless of the presence of phorbol ester or the "activating" monoclonal antibody (MoAb) KIM 185, suggesting that the avidity of LFA-1 is not modulated on NB-4 cells in a manner similar to other leukocytes. Consistent with the prompt clinical effectiveness of methyl prednisolone sodium succinate (MPSS) in retinoic acid syndrome, MPSS rapidly inhibited homotypic aggregation in a dose-dependent manner. Thus, tRA alters the adhesive properties of APL cells by inducing the expression of high-avidity beta2 integrins, aggregation is inhibited by LFA-1 and ICAM-2 MoAb, and tRA effects are rapidly reversible by MPSS. Taken together, our findings provide a clinically relevant system for study of LFA-1/ICAM-2 interaction and suggest a mechanism in part for retinoic acid syndrome and the effectiveness of MPSS in ameliorating retinoic acid syndrome.

Antibodies, Monoclonal↗
PubMed1997

Potent growth inhibitory activity of zidovudine on cultured human breast cancer cells and rat mammary tumors.

Originally designed as an antitumor agent, zidovudine (AZT) has exhibited only marginal tumor growth inhibitory activity. Recently, three abstracts have described positive clinical outcomes for a small number of patients with advanced breast cancer treated with weekly infusions of either methotrexate or cisplatin and AZT. Consequently, we conducted a preclinical study of the anti-breast cancer and anti-mammary tumor activity of AZT. Here we have demonstrated that AZT, alone, has a preferential in vitro and in vivo effect on breast and mammary cancer cells. It is 1000 times as potent as an inhibitor of the in vitro growth of the human breast cancer cell line MCF-7 (IC50 = 10 +/- 5 nM) than of the growth of the T-cell leukemia cell line CEM (IC50 = 14 +/- 2 microM). A novel mechanism for this preferential effect on growth is indicated by the 3-4-fold increase in production of phosphorylated AZT (mono-, di-, and triphosphate) in MCF-7 relative to CEM. We extended these in vitro observations to in vivo studies in rats and found that AZT is a potent in vivo inhibitor of the growth of methylnitrosourea-induced rat mammary tumors without any apparent toxic effects on internal organs. These preclinical results demonstrate, for the first time, that AZT has significant anti-breast cancer activity and strongly suggest that the clinical usefulness of this drug is worthy of investigation.

Animals↗
PubMed1997

The spectrum of multiple myeloma: diagnostic and biological implications.

Myeloma is a common and well-studied hematopoietic neoplasm with an impressive spectrum of clinical, laboratory, and histological findings. To enhance our understanding of the diversity of myeloma, including its earliest forms, the clinical and pathological findings in 145 cases of myeloma were documented and analyzed. Our analysis indicated that myeloma has at least two distinct subtypes: one presenting with bone lesions and a nodular growth pattern and the other presenting with anemia and an infiltrative growth pattern. The relationship of these two forms to plasma cell biology is not clear, although both types appear to arise in the marrow. The criteria used in this study identified 85% of cases overall, with a range of 70% to 100%, depending on clinical presentation. Immunoperoxidase studies are required to establish the diagnosis in patients with early marrow involvement. Myeloma in younger patients appears to be clinically and pathologically similar to myeloma in older patients. Factors such as dysplasia, immunoglobulin type, or leukemic phase were evenly distributed among clinical presentations and did not apparently identify clinicopathological subtypes of myeloma.

Adult↗
PubMed1996

Microsatellite analysis of posttransplant lymphoproliferative disorders: determination of donor/recipient origin and identification of putative lymphomagenic mechanism.

The genetic mechanisms that give rise to posttransplant lymphoproliferative disorders (PTLDs) are not well established, yet previous studies have focused or) the role of immunosuppression and EBV infection. We investigated whether microsatellite analysis could: (a) determine the recipient/donor origin of the tumor; and (b) document novel genetic alterations in PTLDs, i.e., microsatellite instability. We characterized seven cases of PTLD (five B-cell and two T-cell non-Hodgkin's lymphomas) in which donor allograft tissue, normal recipient tissue, and tissue from the PTLDs were available. In each case, six microsatellite loci were analyzed. Five cases were of host origin (three B-cell and two T-cell lymphomas). The two cases of donor origin were B-cell lymphomas. Multiple loci showed microsatellite instability in two cases of host-derived T-cell non-Hodgkin's lymphomas (28% of PTLDs). These findings show that microsatellite analysis may be used to determine the host or donor origin of PTLDs and suggest for the first time that defective DNA mismatch repair may be an underlying genetic mechanism of lymphomagenesis in some cases of PTLD.

Adult↗
PubMed1995

The Ivemark syndrome: prenatal diagnosis of an uncommon cystic renal lesion with heterogeneous associations.

Renal dysplasia has been reported in association with a number of anatomical abnormalities, including pancreatic dysgenesis and hepatic anomalies. The combination of renal, hepatic, and pancreatic dysplasia (RHPD), also known as Ivemark syndrome, is rare and uniformly fatal. We report here the gross and histological findings in 4 cases of combined RHPD, 2 of which were detected by prenatal ultrasonography. Evaluation of these 4 and the other 20 reported cases shows that combined RHPD has considerable variability in the histological findings and in organ involvement. In addition, nearly half were associated with anomalies in other organ systems, and 11 of the 24 were familial. In this study, ultrasonographic and histological abnormalities were seen as early as 18.5 weeks gestation in 1 case.

Abnormalities, Multiple↗
PubMed1995

Diffuse microscopic angiodysplasia--a previously unreported variant of angiodysplasia. Report of a case.

PURPOSE: The entity of diffuse microscopic angiodysplasia is described, and a patient with severe gastrointestinal hemorrhage because of this submucosal source of bleeding is reported. METHOD: Case records of a patient with severe gastrointestinal hemorrhage were reviewed, and histologic findings were compared with colonoscopic and operative findings. The patient received 51 units of packed red blood cells over 3.5 months and remained undiagnosed, despite an exhaustive evaluation, until autopsy. RESULTS: Ectatic veins, venules, and capillaries were present within the submucosa in virtually every section of the small and large intestine examined (79 of 86 sections). Histologic evidence of bleeding from these submucosal vessels was identified in three sites (colon, jejunum, and ileum). The absence of endoscopically visible lesions was explained by findings that vessels did not traverse the muscularis mucosa and that mucosal depth was normal. This case of diffuse microscopic angiodysplasia, therefore, represents a unique variant, because the vascular findings were so diffuse and the mucosa remained histologically and endoscopically uninvolved, despite severe bleeding. CONCLUSION: Gastrointestinal bleeding from angiodysplasia is generally assumed to arise from endoscopically recognizable vascular ectasia within the mucosa. Thus, this case helps provide an explanation for some cases in which occult or massive bleeding is assumed to be secondary to angiodysplasia, even when endoscopic verification is not possible. Recognition of this disease process may require segmental resection or deep biopsy of endoscopically normal intestine.

Aged↗
PubMed1995

CD4 predicts nonlymphocytic lineage in acute leukemia. Insights from analysis of 125 cases using two-color flow cytometry.

The classification of acute leukemia into lymphoid or nonlymphoid is of critical therapeutic importance. Two-color flow cytometric analysis has emerged as a valuable addition to morphology and cytochemistry for the distinction of acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL). By careful selection of monoclonal antibody (mAb) combinations, diagnostic accuracy, and cost effectiveness may be enhanced compared to flow cytometry using one-color analysis. The sensitivity and specificity of a mAb panel were assessed in the determination of nonlymphocytic lineage in acute leukemia. One hundred twenty-five consecutive cases of acute leukemia were analyzed in which Wright's-stained smears, cytochemical stains, and immunophenotyping studies had been performed. The antibody panel included the nonlymphoid markers CD13, CD33, CD14, and CD4 in combination with CD2, as well as a broad panel of lymphoid and nonlineage specific markers. Of the 125 cases of acute leukemia studied, 85 cases (68%) were nonlymphocytic and 32 cases (26%) were lymphocytic (28 cases B cell, 4 cases T cell). CD13 and CD33 were very sensitive in the detection of ANLL, being expressed on 94% and 93% of ANLL cases, respectively. Sixty-five percent of cases of ANLL were CD4+ (CD2-). However, CD4+ (CD2-) had a much higher specificity (91%) for ANLL than CD13 (75%) or CD33 (84%), which were expressed in a significant number of ALL. When leukemic cells were positive for CD4 (CD2-) and either CD13 or CD33, specificity and positive predictive value (PPV) for ANLL rose to 96% and 98%, respectively. The combination of CD4 positivity with either CD13 or CD33 has higher specificity and PPV than the traditional positivity for both CD13 and CD33 (specificity 89%, PPV 96%). Careful analysis of the sensitivity, specificity, and predictive values of mAbs using this method has also allowed us to establish a more cost-effective and diagnostically relevant mAb panel. Our studies show that CD4 is underappreciated as a very specific and moderately sensitive marker for ANLL.

Antibodies, Monoclonal↗
PubMed1995

Use of fluorescence in situ hybridization (FISH) in the diagnosis of DiGeorge sequence and related diseases.

The proximal portion of human chromosome 22q has been implicated in the pathogenesis of a clinically diverse group of conditions including DiGeorge sequence (DGS), velocardiofacial syndrome, and CHARGE association as well as isolated conotruncal heart anomalies. Frequently, overlap in the clinical presentation of these syndromes occurs and, recently, the presence of microdeletions on chromosome 22q11.2 with varying frequencies has been demonstrated in these syndromes. Using fluorescence in situ hybridization (FISH), we assessed 20 consecutive patients who were cytogenetically and clinically evaluated for a suspected syndrome that could be due to a microdeletion of chromosome 22q11.2. After cytogenetic testing and full clinical evaluation, we compared the results by FISH with the final clinical diagnosis and karyotype results. We found that microdeletions of 22q11.2 were detected in three of the five patients who were evaluated for DGS. The three cases with microdeletions appeared clinically to have DGS while the two negative cases were more atypical. High-resolution banding techniques did not detect a microdeletion in any of the cases; however, one of the 20 patients had a translocation between chromosomes 13 and 22. This patient also had a microdeletion of 22q11.2 detected by FISH and clinical features of DGS. None of the patients who were evaluated for disorders related to DGS showed microdeletions. We conclude that FISH is a useful, easily applied technique for the diagnosis of 22q11.2 microdeletion syndromes, particularly DGS. This test may also be useful in genetic counseling and in both prenatal and postnatal diagnoses.

Abnormalities, Multiple↗
PubMed1993

Primary mucoepidermoid carcinoma of the thyroid: diagnosis by fine-needle aspiration biopsy.

Fine-needle aspiration biopsy (FNAB) has been recognized as a safe and reliable procedure in the evaluation of thyroid nodules. We herein report a case of a low-grade mucoepidermoid carcinoma of the thyroid that was diagnosed with this technique. Examination of an intra-operative FNAB showed cohesive clusters of polygonal squamoid cells with distinct cellular borders, uniform round nuclei, distinct nucleoli, and homogeneous amphophilic to cyanophilic cytoplasm. Focal keratin "pearl" formation was apparent, along with extracellular, lightly basophilic mucin deposits mantled by squamoid cells. These cytologic features are characteristic of low-grade mucoepidermoid carcinoma, as seen in other anatomic sites. This impression was confirmed by examination of paraffin sections. Previous reports have indicated that mucoepidermoid thyroid carcinoma is an indolent, locally recurring lesion. However, in spite of low-grade histology in our case, the neoplasm presented with distant metastases to bones, pleura, and lung.

Biopsy, Needle↗
PubMed1990

The leukocyte integrin LFA-1 reconstituted by cDNA transfection in a nonhematopoietic cell line is functionally active and not transiently regulated.

The functional activity of lymphocyte function-associated antigen 1 (LFA-1) on leukocytes can be regulated by T-cell receptor (TCR) stimulation and pharmacologic agents. It was of interest to determine if functionally active LFA-1 could be reconstituted on a nonhematopoietic, LFA-1-negative cell line. We report the expression of LFA-1 and diethylaminoethyl (DEAE) Mac-1 alpha beta heterodimers on the cell surface of a fibroblastoid cell line, COS, by DEAE dextran cotransfection of the alpha and beta subunit cDNAs. Immunoprecipitation studies demonstrated that the alpha and beta subunit was expressed in heterodimers. The alpha or beta subunit was expressed at lower levels after transfection with the alpha or beta subunit cDNA alone. Cotransfection of the alpha and beta subunit cDNAs, but not transfection of alpha or beta alone, was sufficient to reconstitute intercellular adhesion molecule-1 (ICAM-1) binding activity. Consistent with this observation, LFA-1 on the fibroblastoid cells possesses the activation epitope defined by the L16 monoclonal antibody (mAb). This epitope marks the conversion of LFA-1 from the low to high avidity state on peripheral blood T lymphocytes (PBLs) and is constitutively present on activated cell lines. In contrast to LFA-1 on leukocytes, the functional activity of LFA-1 on fibroblastoid cells was not influenced by phorbol ester treatment. Furthermore, the use of agents that interfere with intracellular signaling, a protein kinase C inhibitor, cAMP analogue, or the combination of a phosphodiesterase inhibitor and adenyl cyclase activator, did not affect the binding of COS cells expressing LFA-1 to purified ICAM-1.

Alkaloids↗
PubMed1989

Retinal detachment after neodymium:YAG laser posterior capsulotomy.

We reviewed the records of 397 patients who had undergone Nd:YAG laser posterior capsulotomy between July 1983 and August 1988. Of the 366 eyes that had been followed up for three months or more, 13 (3.6%) developed a retinal detachment after capsulotomy; of these 13 detachments, 11 (84.6%) occurred within the first year. The combination of male gender with axial myopia (greater than or equal to 25.00 mm), a history of lattice degeneration, or a history of retinal detachment in the fellow eye was a significant risk factor for the development of retinal detachment after YAG capsulotomy.

Cataract Extraction↗
PubMed1989

Neodymium:YAG laser zonulysis for treatment of lens subluxation.

Nine eyes with lens subluxation in seven patients (6 patients with Marfan's syndrome, 1 with idiopathic lens subluxation) were treated by neodymium:YAG (Nd:YAG) laser zonulysis. The procedure uses an Nd:YAG laser to lyse the zonules to obtain a clear aphakic visual axis. Pretreatment best-corrected visual acuity was 20/60 or worse in eight eyes (6 eyes less than or equal to 20/200). Movement of the crystalline lens was achieved after zonulysis in all cases (100%), and a clear aphakic visual axis, sufficient to maintain aphakic correction without diplopia or glare, was obtained in eight eyes (88.9%). The procedure was combined with optical iridotomy in three cases (33.3%). Five cases (55.6%) required more than one zonulysis treatment. Visual acuity improved two or more Snellen lines in all but one eye (7 eyes greater than or equal to 20/60). Four cases had complications which included: increased intraocular pressure (IOP), mild iritis, recurrent migration of the lens into the visual axis, and crystalline lens damage. The final two complications necessitated eventual surgical removal of the lens. These results suggest that Nd:YAG laser zonulysis may be of benefit as an alternative treatment modality for selected patients with lens subluxation.

Adult↗