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Biomedical subjects

J J Butler

Publications and source records attributed to J J Butler.

At least 19 recordsLinked to original sources
PubMed2000

Response of engineered cartilage tissue to biochemical agents as studied by proton magnetic resonance microscopy.

OBJECTIVE: To test the hypothesis that magnetic resonance imaging (MRI) results correlate with the biochemical composition of cartilage matrix and can therefore be used to evaluate natural tissue development and the effects of biologic interventions. METHODS: Chondrocytes harvested from day-16 chick embryo sterna were inoculated into an MRI-compatible hollow-fiber bioreactor. The tissue that formed over a period of 2-4 weeks was studied biochemically, histologically, and with MRI. Besides natural development, the response of the tissue to administration of retinoic acid, interleukin-1beta (IL-1beta), and daily dosing with ascorbic acid was studied. RESULTS: Tissue wet and dry weight, glycosaminoglycan (GAG) content, and collagen content all increased with development time, while tissue hydration decreased. The administration of retinoic acid resulted in a significant reduction in tissue wet weight, proteoglycan content, and cell number and an increase in hydration as compared with controls. Daily dosing with ascorbic acid increased tissue collagen content significantly compared with controls, while the administration of IL-1beta resulted in increased proteoglycan content. The water proton longitudinal and transverse relaxation rates correlated well with GAG and collagen concentrations of the matrix as well as with tissue hydration. In contrast, the magnetization transfer value for the tissue correlated only with total collagen. Finally, the self-diffusion coefficient of water correlated with tissue hydration. CONCLUSION: Parameters derived from MR images obtained noninvasively can be used to quantitatively assess the composition of cartilage tissue generated in a bioreactor. We conclude that MRI is a promising modality for the assessment of certain biochemical properties of cartilage in a wide variety of settings.

Animals↗
PubMed1999

Murine TRAIL (TNF-related apoptosis inducing ligand) expression induced by T cell activation is blocked by rapamycin, cyclosporin A, and inhibitors of phosphatidylinositol 3-kinase, protein kinase C, and protein tyrosine kinases: evidence for TRAIL induction via the T cell receptor signaling pathway.

TRAIL (TNF-related apoptosis inducing ligand), like other members of the TNF family of proteins, is able to induce apoptosis in sensitive target cells. Recently, cell-surface TRAIL has been shown to be expressed by activated human and mouse T lymphocytes, raising the possibility that TRAIL might be involved in T cell-mediated cytotoxicity and/or immune regulation. In the present study we show by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis that activated, but not resting, mouse T cells express abundant TRAIL mRNA. TRAIL transcripts were detectable within 4 h of T cell activation. A panel of pharmacologic inhibitors was used to investigate the signal transduction pathways involved in TRAIL gene induction following T lymphocyte activation. TRAIL gene expression was sensitive to the src-like protein tyrosine kinase (PTK) inhibitor herbimycin A, as well as the more general PTK inhibitor genistein, suggesting the involvement of a src family PTK. The PKC inhibitors staurosporine and calphostin C, and the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294002, also prevented TRAIL mRNA transcription by activated T cells, indicating a role for PKC and PI3-K. In addition, TRAIL induction was inhibited by cyclosporin A, implicating the Ca(2+)/calmodulin-dependent protein phosphatase calcineurin. TRAIL expression was also blocked by rapamycin, which inhibits p70 S6 kinase involved in CD28 and interleukin (IL)-2 receptor signaling. However, TRAIL mRNA expression was not induced by IL-2, suggesting that TRAIL gene induction is not coupled to the IL-2 receptor. Data obtained by RT-PCR were confirmed at the protein level by immunoblotting with TRAIL-specific antibody. We conclude that TRAIL gene induction is initiated through a T cell receptor-associated signaling pathway similar to that responsible for the expression of cytokine genes such as IL-2.

Animals↗
PubMed1998

Hodgkin's disease: correlation of clinical characteristics with probabilities for negative lymphangiogram vs. negative laparotomy findings in patients with Stage I supradiaphragmatic presentations vs. those in patients with Stage II.

PURPOSE: At a time both when late complications and second malignancies have become a growing concern and when staging laparotomy has been largely abandoned and comparative studies for staging Hodgkin's disease by state of the art computed tomography (CT) vs. lymphangiography have revealed minimal differences in results for these procedures, our purpose for undertaking this study was twofold. Our initial reason was to determine and compare probabilities for negative abdominal findings for patients with Stage I presentations with those for patients with Stage II as determined by lymphangiography and subsequently by laparotomy for those patients who had negative lymphangiograms. Our second reason, being an extension of the first, was to create a resource that can be used in conjunction with other information for arriving at appropriate treatment decisions including giving either more or particularly less than standard institutional therapy and especially with respect to the abdomen. METHODS AND MATERIALS: Data on 714 patients with prelymphangiogram Stage I-II upper torso presentations of Hodgkin's disease were entered prospectively in our database between 1968 and 1987. Twenty-eight with lymphocyte predominant disease, who had both negative lymphangiogram and negative laparotomy findings and 17 with questionable diagnoses of lymphocyte-depleted or unclassified disease were excluded from subsequent analyses of 669 patients with nodular sclerosis (NS) and mixed cellularity (MC) diagnoses. RESULTS: Stage I: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms and nodular sclerosis histology, whereas negative laparotomy findings correlated strongly with a combination of no constitutional symptoms and female sex. Predicted probabilities depended on the ratios of favorable to unfavorable characteristics. Stage II: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms, nodular sclerosis histology, age <40 years, and <4 involved sites, whereas negative laparotomy findings correlated strongly with a combination of <4 involved sites and mediastinal disease. Predicted probabilities again depended on the ratios of favorable to unfavorable characteristics. CONCLUSION: This study demonstrated that probabilities for negative abdominal findings for patients with supradiaphragmatic presentations of NS and MC Hodgkin's disease depended on: 1) whether the disease presented as Stage I or as Stage II; 2) whether staging was limited to a lymphangiogram or whether it included a laparotomy; and 3) or whether the clinical features associated with the presenting stage and methods of staging were favorable or unfavorable.

Abdomen↗
PubMed1998

Cartilage formation in a hollow fiber bioreactor studied by proton magnetic resonance microscopy.

The ideal in vitro system for investigating the regulation of cartilage formation and maintenance would allow for three-dimensional tissue growth, a wide range of biochemical interventions, and non-destructive evaluation. We have developed a hollow fiber bioreactor (HFBR) system which meets these criteria. After injection with embryonic chick sternal chondrocytes, neocartilage is elaborated around the hollow fibers, reaching a thickness of up to a millimeter after four weeks of growth. This process was monitored over time with nuclear magnetic resonance (NMR) microimaging and correlative biochemical and histologic analyses. Tissue volume and cellularity increased greatly during development. This was accompanied by changes in magnetic resonance properties consistent with increased macromolecular content. Further, tissue heterogeneity, observed as regional variations in cell size in histologic sections, was also observed in quantitative NMR images.

Animals↗
PubMed1994

Nasopharyngeal lymphoid tissue masses in patients with human immunodeficiency virus-1. Histologic findings and clinical correlation.

BACKGROUND: Although the histologic changes in lymph nodes in patients infected with the human immunodeficiency virus-1 (HIV-1) are well described, the histology and resulting clinical symptoms of hyperplastic nasopharyngeal lymphoid tissue (NPLT) in these patients are not widely known, particularly to pathologists and oncologists. METHODS: Nine patients with HIV-1 presented with a nasopharyngeal mass, nasal stuffiness, nasal bleeding, hearing loss, and cervical lymphadenopathy in various combinations. Tonsillar tissue was biopsied or removed from all nine. RESULTS: The tonsillar tissue showed a spectrum of the changes of reactive lymphoid hyperplasia. CONCLUSIONS: Clinicians and pathologists must be aware of the spectrum of histologic changes and clinical features relating to biopsies from NPLT to interpret the changes correctly and to avoid a misdiagnosis of malignant lymphoma.

Adult↗
PubMed1992

Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: clinical, pathologic, immunophenotypic, and molecular analysis.

The goals of this study were to evaluate the response to treatment in chronic lymphocytic leukemia (CLL) according to clinical, pathologic, immunophenotypic, and molecular features, as well as to address the clinical significance of each finding. One hundred fifty-nine CLL patients with either advanced Rai stage III or IV (81 patients) or progressive Rai stage 0 to II (78 patients) were treated with fludarabine (30 mg/m2/d intravenously every day for 5 days) plus prednisone (30 mg/m2/d orally daily for 5 days). Thirty-six patients were previously untreated. The response rates were 12% complete response (CR), 30% nodular complete response (nCR), and 18% partial response (PR). In all patients who achieved a complete response (both CR and nCR) less than 30% of nucleated cells were lymphocytes on marrow aspirate differential analysis; however, nCR patients had residual nodular and/or interstitial lymphocyte involvement on marrow biopsy examination. There was no evidence of leukemic infiltration on marrow biopsy examination in CR patients. With a median follow-up of 35 months, comparison of time to progression in the CR and nCR groups at 2 years showed a projected 87% versus 55% progression-free survival (P less than .03). Residual disease assessment by flow cytometry using simultaneous dual-color staining on blood and marrow lymphocytes was also performed on each patient. Residual disease was determined by the expression of CD5 on B lymphocytes and the monoclonality of surface light-chain expression. After six courses of fludarabine plus prednisone, no residual disease was detected by flow cytometry in 89% of the CRs, 51% of the nCRs, and 19% of the PRs. Clinical residual disease in PR patients with no residual disease detectable by flow cytometry was limited to lymph-adenopathy. Time to progression at 2 years was longer in CR and nCR patients having no residual disease detected by flow cytometry (84% v 39% 2-year progression-free survival, P less than .001). Posttreatment lg gene rearrangement analysis using JH, J kappa, and C lambda probes demonstrated no rearranged bands and a return to the germline configuration in five of seven CRs and two of eight nCRs studied. The molecular studies were concordant with the dual-parameter immunophenotype results and none of the patients who reverted to a germline DNA pattern after treatment have experienced relapse. The absence of detectable minimal residual disease by bone marrow biopsy, dual-color flow cytometry, and lg gene rearrangement analysis is achieveable in CLL with fludarabine and is predictive of the response duration.

Adult↗
PubMed1992

The histologic diagnosis of Hodgkin's disease.

Histologic criteria for the diagnosis of Hodgkin's disease are being modified, primarily as a result of phenotypic analysis. It seems likely that non-Hodgkin's lymphomas have been diagnosed as mixed-cellularity and lymphocytic-depletion Hodgkin's disease on the basis of previously accepted histologic criteria. As a result, phenotypic studies are indicated in all examples of lymphocytic-depletion Hodgkin's disease and in those cases of mixed-cellularity Hodgkin's disease in which the histologic findings are unusual. The effects of genotypic analysis on histologic criteria remain to be elucidated.

Diagnosis, Differential↗
PubMed1992

Progressive transformation of germinal centers: comparison of 23 pediatric patients to the adult population.

Approximately 10% of enlarged lymph nodes showing reactive follicular hyperplasia (RFH) will contain one or more progressively transformed germinal centers (PTGC). Comparison of 23 patients 16 yr old and younger (the pediatric group) of age to the adult population (greater than 16 yr old) indicates that most of the patients in each category present with a solitary asymptomatic enlarged lymph node (63% each group), usually cervical, and, while there may be recurrent lymphadenopathy showing RFH with PTGC (RFH/PTGC), evolution to Hodgkin's disease (HD) or other lymphomas is rare. Cases of PTGC unassociated with HD comprise the largest group: 70% (16/23 patients) of pediatric group; 60% (52/87 patients) of adult group. Five pediatric patients (22%) had antecedent HD (four males with lymphocytic predominance-nodular, NL&H HD; one female with nodular sclerosis, NSHD); this group is too small for comparison with adults. One patient (4%) subsequently developed NL&H HD; one patient had concurrent PTGC in the lymphoid rim surrounding NL&H HD. The 23 pediatric patients ranged from 4 to 16 yr (median 11, mean 11.3) with a male predominance (18 M, 5 F) similar to the adult population. Three differences occur comparing PTGC patients without associated HD from the two age groups. The less than or equal to 16 age group has a higher recurrence rate of PTGC (50 versus 23%); two or more biopsies showing PTGC after the initial biopsy was common, 19 versus 0%; and, morphologically, the pediatric cases unassociated with HD more often contain epithelioid histiocytic clusters (44 versus 0%), which may rim the PTGC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse.

From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years.

Adolescent↗
PubMed1991

Clinical implications of nodal reactive follicular hyperplasia in the elderly patient with enlarged lymph nodes.

In older persons, the humoral immune response, as reflected morphologically by proliferation and expansion of germinal centers, is relatively subdued in comparison with the florid reactive follicular hyperplasia (RFH) which may be observed in younger age groups. The presence of RFH in lymph node biopsies in patients 60 yr or older, which we have regarded with concern since 1972, appears to represent an imbalance of the immune system, in some patients, on the background of which predominantly non-Hodgkin's malignant lymphoma (NHL) may be present or will develop. Fifty-eight patients 60 yr old or more who presented with enlarged lymph nodes exhibiting inappropriate RFH for age were identified during the interval from 1969 to 1989. An apparent etiology was initially identified for the reactive follicular hyperplasia in only 12 cases: five with documented rheumatoid arthritis; one each with a history of trauma, positive monospot test, and combination of thrombophlebitis and fungal skin infection, and two each with elevated Epstein-Barr virus (EBV) titers and human immunodeficiency virus type 1 (HIV-1) seropositivity. While most were alive or died of nonlymphomatous causes and one was lost to follow-up, 18 (31%) patients either had concurrent lymphoma or subsequently developed diffuse NHL. There were ten diffuse interfollicular (I-Foll) lymphomas (six concurrent), two diffuse mixed cell lymphomas (DMCL), one diffuse large cell lymphoma (DLCL), one diffuse immunoblastic sarcoma (DIBS), two diffuse small noncleaved cell lymphomas (DSNCL), one unclassified NHL, and only one Hodgkin's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1990

Stimulation of myelopoiesis in chronic lymphocytic leukemia and in other lymphoproliferative disorders by recombinant human granulocyte-macrophage colony-stimulating factor.

In an attempt to stimulate granulopoiesis, we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to 11 patients with lymphoproliferative disorders. Ten patients had neutropenia, six of whom had severe neutropenia (less than 500 neutrophils), including two with agranulocytosis. GM-CSF (60-250 micrograms/m2/day) was administered by continuous intravenous infusion daily for 14 days at 2-week intervals. Significant increases in white blood cell counts (1.3-to 11.7-fold) and neutrophils (1.7- to more than 29-fold) were seen in 10 of 11 patients, including one patient with agranulocytosis. Eosinophils (3.9- to greater than 65-fold) and monocytes (1.3- to 5-fold) increased as well. In contrast, no significant increases were seen in total lymphocytes or in different phenotypic subsets of lymphocytes during treatment. The overall proportion of myeloid and lymphoid elements in bone marrow remained stable. These results indicate that GM-CSF is effective in stimulating myelopoiesis in neutropenic states associated with lymphoproliferative disorders. Further studies will be necessary to determine whether the correction of neutropenia ultimately translates into clinical benefit.

Bone Marrow↗
PubMed1990

Differentiation of T-cell lymphoma from Hodgkin's disease. Mitotic rate and S-phase analysis.

Flow cytometric DNA and proliferative compartment (S + G2M) analysis was performed on lymph nodes from 37 patients with Hodgkin's disease (HD) and on 16 lymph nodes plus 6 extranodal biopsies from 22 patients with peripheral T-cell lymphomas (PTCLs). The mitotic rate per 20 high-power fields (HPFs) was also determined for each case. The PTCLs showed significantly higher proliferative activity than the HD cases, as evidenced by a mean S + G2M of 12.0% versus 5.0% for HD and a median mitotic rate of 27 versus 5 mitoses per 20 HPFs in the HD cases. Because morphologic distinction, particularly of mixed cellularity HD (HDMC), from the diffuse small cleaved cell (DSCCL) or mixed cell (DMCL) pattern of PTCL may at times be difficult, these subgroups were compared separately. The 2 cases of DSCCL plus 12 of DMCL yielded a higher proportion of S-phase cells than the 9 HDMC cases with S + G2M means of 9.9% versus 3.3% and a higher mitotic rate, median 21 versus 7 per 20 HPFs. These findings suggest that S-phase determination and mitotic rate provide additional parameters in discriminating PTCL from HD in the most histologically similar cases.

Adolescent↗
PubMed1990

The value of immunophenotyping on paraffin sections in the identification of T-cell rich B-cell large-cell lymphomas: lineage confirmed by JH rearrangement.

Immunophenotyping of lymphomas using paraffin-embedded lymphoid tissue, not previously distorted by frozen section, is useful in identifying the large neoplastic B cells that may be in the minority in T-cell rich B-cell lymphoma (TCRBCL). Even in cases in which frozen tissue sections are available, the improved morphology in unfrozen sections allows the proper classification of these lymphomas as large cell and identifies their B-cell lineage, which is important for clinical therapeutic studies. Seven cases initially believed to be diffuse mixed cell lymphoma of possible peripheral T-cell lineage showed the large cells to be immunoreactive with L-26 (pan B-cell marker) with the majority of smaller lymphocytes immunoreactive for UCHL-1 and Leu-22 (pan T-cell markers). K/lambda immunostaining on frozen sections was equivocal. In these cases, the diagnosis of large-cell lymphoma of B-cell lineage was confirmed by detection of immunoglobulin heavy- (all seven cases) and light- (six of seven cases) chain gene rearrangements, with germ-line configuration of the T-cell receptor beta-chain gene (all cases). Some cases of TCRBCL may not show detectable rearrangement of the immunoglobulin genes because of the low concentration of neoplastic cells in the samples submitted. The presence of rearrangements in these seven cases, however, supports the diagnosis of TCRBCL based on paraffin immunophenotyping when frozen tissue is not available or when molecular studies are not feasible. Although these seven cases are classified as large-cell lymphoma, an intermediate-grade lymphoma, the influence of the reactive T-cell population on the clinical behavior will require follow-up studies.

Adult↗
PubMed1990

Lymphoreticular disease masquerading as or associated with an inguinal or femoral hernia.

Twelve patients (eight men and four women) had previously undiagnosed lymphoreticular disease associated with or simulating an inguinal (nine) or femoral (three) hernia. The disease was present on the left side in eight. Four patients (three women and one man) did not have an actual hernia. Two of these women had a preoperative diagnosis of femoral hernia. Seven of the patients, including all of the women, had non-Hodgkin's lymphoma (three diffuse large cell, two follicular mixed cell and two follicular small cleaved cell) and one patient had lymphocytic predominance (nodular lymphocytic and histiocytic) Hodgkin's disease. No stage predominated. Inguinal lymph nodes from two patients showed, histologically, Kaposi's sarcoma and type I human immunodeficiency virus (HIV) associated disease. Each patient was homosexual and HIV seropositive. Changes suggestive of viral cause were present in the lymph node of one patient. The enlarged lymph nodes of the 12th patient showed stellate suppurative granulomas containing cat-scratch bacilli demonstrated by Warthin-Starry stain. Because of the special processing needs for lymphoreticular diseases and potential for misdiagnosis, surgeons, clinicians and pathologists should be aware of the spectrum of lymphoreticular processes occurring in lymph nodes associated with or masquerading as a hernia, particularly in women.

Adult↗
PubMed1989

Angiosarcoma arising in an irradiated breast. A case report and review of the literature.

The authors discuss an angiosarcoma that developed in a 50-year-old woman's breast 10 years after she underwent conventional postoperative irradiation with cobalt 60 teletherapy. Although angiosarcoma developing in a lymphedematous arm after radical mastectomy is a well-known phenomenon, and several cases of angiosarcoma are known to have occurred in the chest wall after mastectomy with or without irradiation, only one other case of angiosarcoma in an irradiated breast has been reported. The possible role of therapeutic irradiation in inducing this malignancy is discussed.

Breast Neoplasms↗
PubMed1989

Unexpected splenic nodules in leukemic patients.

We reviewed a series of five splenectomy specimens from patients with various leukemias (three cases of chronic myelocytic leukemia, one case of acute myelocytic leukemia, and one case of hairy cell leukemia). In addition to diffuse red pulp disease, we unexpectedly encountered nodules grossly in each of the specimens. These represented sea blue histiocytosis (one case), focal hairy cell leukemia (one case), localized blast transformation (one case), and concentrated foci of treated leukemia (two cases), with a prominence of immature granulocytic precursors on a background of trilineage hyperplasia. These cases are reported because they are unusual and because they furnish interesting correlates of gross and microscopic anatomy.

Adult↗