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Biomedical subjects

D Rubin

Publications and source records attributed to D Rubin.

At least 19 recordsLinked to original sources
PubMed1997

Murine isograft studies of gut immunity: recirculation and homing of mononuclear cells.

BACKGROUND & AIMS: Recirculation of lymphocytes requires appropriate signals on the lymphocytes as well as the vascular endothelium. The aim of this report was to study the expression of the mucosal addressin required for Peyer's patch-selective lymphocyte homing during ontogeny of the murine intestine and investigate the role of this addressin in recirculation of mononuclear cells. METHODS: Immunohistochemistry and murine intestinal isografts were used in which the small intestine from neonatal mice is implanted subcutaneously in mice with severe combined immunodeficiency disease. RESULTS: Expression of the mucosal addressin cell adhesion molecule 1 during murine intestinal ontogeny was detected from embryonic day 15 in developing gut and in adult Peyer's patches and lamina propria. Isografted intestine developed normally; it was not exposed to luminal contents but expressed the mucosal addressin cell adhesion molecule 1. Mononuclear cells recirculated to native and isografted intestine and recirculation was inhibited by monoclonal antibody to mucosal addressin in a regionally specific manner with greatest inhibition in the distal intestine. CONCLUSIONS: The mucosal vascular addressin is expressed early in ontogeny and can be detected in lamina propria in addition to Peyer's patches of the gut. The isograft not only developed into a morphologically normal intestine but also expressed differentiation antigens required for normal lymphoid homing to gut without exposure to luminal contents or lymphocytes.

Animals↗
PubMed1997

Modification of in vivo and in vitro TNF-alpha, IL-1, and IL-6 secretion by circulating monocytes during hyperbaric oxygen treatment in patients with perianal Crohn's disease.

Treatment of perianal inflammatory lesions in Crohn's disease (CD) is unsatisfactory and novel treatment modalities are pursued. We have recently reported a good clinical effect of hyperbaric oxygen (HBO) treatment in perianal CD. In the present study, seven patients with perianal CD were subjected to daily sessions of HBO in a multiplace hyperbaric chamber. Each patient received a total of 20 sessions during a time period of 1 month, and IL-1, IL-6, and TNF-alpha measurements were done several times during the initial sessions and after completing therapy. Pretreatment cytokine levels were elevated in patients compared to age-matched 10 normal controls. During the first 7 days of treatment, IL-1, IL-6, and TNF-alpha levels in supernatants of LPS-stimulated monocytes derived from patients' peripheral blood were decreased compared to pretreatment levels. Parallel measurements of serum IL-1 levels revealed an initial elevation and thereafter decreased levels, which remained low throughout the first week of HBO treatment. After completion of therapy, cytokine levels increased to pretreatment values. We conclude that alterations in secretion of IL-1, IL-6, and TNF-alpha may be related to the good clinical effect of HBO treatment in CD patients with perianal disease.

Adult↗
PubMed1997

Decreased sensitivity to insulin-like growth factor I in Turner's syndrome: a study of monocytes and T lymphocytes.

Turner's syndrome is characterized, amongst other things, by growth retardation with high serum levels of insulin-like growth factor 1 (IGF-I) in relation to growth, by a tendency to autoimmune disease and by insulin resistance with hyperlipidaemia. Assuming a role for IGF-I subresponsiveness in the last two features, the present study was designed to evaluate in patients with Turner's syndrome their monocyte/macrophage response to growth hormone (GH) and to IGF-I with respect to low-density lipoprotein (LDL) degradation and to the monocyte-dependent lymphocyte proliferation. Nineteen patients with Turner's syndrome and puberty-matched control subjects were studied. Monocytes were isolated from the blood of the patients and the control group, and cultured to develop into macrophages. The cells were then incubated with 125I-labelled LDL (25 micrograms of protein mL-1) in the absence or presence of 50 ng mL-1 IGF-I or GH, and cellular lipoprotein degradation was determined. GH and IGF-I effects on T-cell proliferation were measured in autologous mixed lymphocyte reaction Monocytes/macrophages degradation of LDL was lower in Turner's syndrome patients than in control subjects (P < 0.05). IGF-I stimulated LDL degradation by 42 +/- 8% in the control subjects and by only 16 +/- 7% in Turner's syndrome patients (P < 0.05). Control lymphocyte proliferation in AMLR was significantly augmented by 50-100 ng mL-1 GH or IGF-I. Lymphocytes derived from peripheral blood of Turner's syndrome patients remained almost unaffected by either GH or IGF-I. Measurement of IL-2 secretion by purified blastoid T lymphocytes-I. revealed a significant augmentation by 100 ng mL-1 GH and by 50-100 ng mL-1 IGF-I in control subjects, and almost no response in Turner's0 ng syndrome. Turner's syndrome is associated with decreased sensitivity of peripheral blood mononuclear cells to GH and to IGF-I, as is evident by the reduction in LDL degradation, monocyte-stimulated T-lymphocyte proliferation and IL-2 secretion by blastoid T cells.

Adolescent↗
PubMed1996

Tumor angiogenesis in primary and metastatic colorectal cancers.

PURPOSE: Angiogenesis is needed to sustain growth of both primary and metastatic lesions; however, comparisons in microvessel density between a primary tumor and its metastases have not been widely performed. We studied microvessel density in primary colorectal cancers and their liver metastases. METHODS: Sections from 32 primary lesions and 53 hepatic metastases were immunostained with a monoclonal antibody for von Willebrand's factor, an endothelial cell marker. Blood vessels were quantified under x 100 magnification using both conventional light microscopy and computer-assisted image analysis. Primary and metastatic angiogenesis scores (AS), i.e., vessel counts, were analyzed with respect to tumor size, hepatic multicentricity, synchronicity, resectability, and patient survival. Using computer-assisted calculations, the same analyses were performed using blood vessel to tumor surface area ratios, vessel wall thickness, and intensity of immunostaining. RESULTS: Angiogenesis scores were significantly lower in metastatic lesions compared with their primary tumors (P < 0.0001). Primary AS did not correlate with metastatic tumor size, resectability, multicentricity, or patient survival. Metastatic AS strongly predicted patient survival (P < 0.0009) but with a negative coefficient, i.e., higher scores were associated with improved survival. Metastatic AS were higher in resectable than in nonresectable metastases and in solitary than in multiple metastases; however, these trends were not statistically significant. Metachronous liver lesions had significantly higher angiogenesis scores than synchronous metastases (P < 0.04). Similar trends were seen using computer-assisted image analysis. CONCLUSIONS: These results indicate that in presence of an established metastasis, there is a weak angiogenic relationship between a primary tumor and its metastasis. Heterogeneity in metastatic lesions cannot be explained solely by studying angiogenesis in primary tumors. Microvessel density in a primary tumor may not be useful as an independent prognostic indicator in late stages of disease. In such cases, assessment of microvessel density in a metastatic tumor whenever possible may be an indicator of prognosis.

Biomarkers, Tumor↗
PubMed1996

Solitary fibrous tumor of the lacrimal gland fossa.

BACKGROUND: Solitary fibrous tumors are rare spindle cell neoplasms that most commonly arise in the pleura. Recently, solitary fibrous tumors of the orbital soft tissues have been described. The authors report the first case of solitary fibrous tumor arising in the lacrimal gland fossa and discuss features that may distinguish solitary fibrous tumor from other lacrimal fossa lesions. METHODS: A left lacrimal gland fossa tumor was excised via lateral orbitotomy from a 76-year-old man and analyzed by light microscopy. Immunohistochemical studies were performed using antibodies to CD34, vimentin, epithelial membrane antigen, cytokeratins AE1-3 and Cam5.2, S-100 protein, and actin. RESULTS: The histopathologic features of the tumor were typical of solitary fibrous tumor. A well-circumscribed, variably cellular proliferation of bland spindle cells displayed both "patternless" and storiform growth patterns. Immunohistochemical studies showed that the tumor cells expressed vimentin and CD34 but did not express epithelial membrane antigen, cytokeratins, S-100 protein, or actin. The patient is free of tumor recurrence after 1 year of follow-up. CONCLUSION: The authors report the first case of solitary fibrous tumor arising in the lacrimal gland fossa. The clinical presentation of this tumor was similar to that of pleomorphic adenoma (benign mixed tumor) of the lacrimal gland; fortunately, the treatment for both of these lacrimal gland fossa neoplasms is en bloc excision. The histopathologic appearance of solitary fibrous tumor is varied, and immunohistochemical analysis may help in distinguishing solitary fibrous tumor from other lacrimal fossa lesions. Careful follow-up of patients with solitary fibrous tumor is important because recurrence may present years after excision of the primary tumor.

Aged↗
PubMed1995

Regional expression of murine intestinal immune cells in normal and isografted intestine.

The spatial organization and differentiation of the gut immune system was studied using immunohistochemistry from Embryonic Day 15 until adulthood. Leukocyte common antigen-positive cells were detected first, followed by macrophages, B, and then T lymphocytes increasing in number and intensity of staining until adulthood. The adult mouse displays regional localization of gut immune cells with highest expression in proximal intestine, decreasing distally to ileum with the fewest cells present in colon. The role of intestinal contents, bone marrow, and thymus on maturation of the gut immune system during development was studied using an isograft model: small intestine from neonatal mice were implanted subcutaneously into SCID mice and developed into morphologically normal intestine. Injected syngeneic mononuclear cells recirculated to the isografted intestine and SCID host intestine with the same regional expression as normal adult. This model is useful to define the mechanisms that establish and maintain cellular and regional differentiation of the normal gut immune system.

Animals↗
PubMed1995

Role of the Entamoeba histolytica cysteine proteinase in amebic liver abscess formation in severe combined immunodeficient mice.

Evidence from in vitro studies suggest that the Entamoeba histolytica cysteine proteinase plays a role in the tissue lysis and cytopathic effects seen in invasive amebiasis. We used affinity-purified antibodies against a recombinant E. histolytica cysteine proteinase to demonstrate that the proteinase is present extracellularly in amebic liver abscesses in mice with severe combined immunodeficiency (SCID mice). Treatment of E. histolytica trophozoites with specific cysteine proteinase inhibitor E-64 blocked or greatly reduced liver abscess formation at 48 h in SCID mice. Our study suggests an important role for a functional cysteine proteinase in amebic liver abscess formation.

Animals↗
PubMed1994

Monitoring skeletal cancer metastases with the bone isoenzyme of tissue unspecific alkaline phosphatase.

The efficacy of bone alkaline phosphatase (ALP) isoenzyme measurement using lectin precipitation in confirming metastatic bone lesions was compared with total ALP and osteocalcin assay in serum. Sixty-five patients with cancer and metastases to bone (n = 44), liver (n = 15) or lymph nodes (n = 6) as well as 33 healthy adults were studied. Assay of bone ALP is as sensitive but more specific than assay of total ALP in the identification of bone metastases. On the other hand, bone ALP did not correlate with osteocalcin, as is the case in other bone diseases. In the serial monitoring of nine patients with skeletal metastases, bone ALP correlated well with the presence of pain and the progression or regression of metastatic spread.

Adult↗
PubMed1994

Troponin T as a marker of ischemic myocardial injury.

A study was undertaken to evaluate the clinical relevance of serum troponin T (TnT) as a marker of ischemic myocardial injury, using a new automated enzyme immunoassay. The reference range for serum TnT was established by measuring serum TnT concentrations in blood obtained from 262 healthy subjects. The serum concentration of TnT was compared to serum creatine kinase activity, creatine kinase MB (mass and activity), myoglobin concentration, and lactate dehydrogenase activity: in 77 patients with myocardial infarction (55 received thrombolytic treatment); in 32 patients with unstable angina; in 30 patients with nonischemic heart diseases; and in 40 patients with skeletal muscle injuries. Our findings showed that: a) 99% of healthy blood donors had TnT concentrations < 0.10 micrograms/L; b) the test had a high clinical efficiency in the diagnosis of acute myocardial infarction, with a sensitivity of 1.0 and a specificity of 0.88 at a decision level of 0.20 micrograms/L; c) serum TnT had a later peak value (8-38 h), but a wider diagnostic window (> 126 h) than the traditional markers considered in the study; d) serum TnT had an excellent sensitivity in the detection of microinfarctions in patients with unstable angina pectoris; e) the release patterns of serum TnT were qualitatively different in perfused versus nonperfused patients. Peak serum TnT values and time to peak values were statistically different (p = 0.0336 and p = 0.0001) in reperfused and nonreperfused AMI patients, respectively; f) a ratio of serum TnT at 16 h to serum TnT at 32 h after chest pain > 1 provided a good indication of reperfusion in thrombolytic treatment (94% efficiency).

Adult↗
PubMed1994

CD20+ T-cell lymphoma. Neoplastic transformation of a normal T-cell subset.

CD20 is a 35-kDa protein that is expressed early in B-cell ontogeny and is lost during terminal B-cell differentiation into plasma cells. It is thought to be B-cell-specific. However, the CD20 antigen, detected by the monoclonal antibody L26, has been reported in some cases of T-cell lymphoma. This report describes a case of a malignant lymphoma coexpressing T-cell-lineage antigens and CD20 and characterization of a CD20+ T-cell population in the peripheral blood of healthy donors. The tumor cells were pleomorphic medium-sized cells that expressed a range of T-cell-specific antigens, including CD2, CD3, CD4, CD5, CD6, CD7, and beta F1. In addition, the tumor cells expressed CD20 on frozen (B1) and paraffin sections (L-26). Stains for other pan-B cell antigens, including CD19 and CD22, and immunoglobulin light and heavy chains were negative. To determine whether this unusual coexpression of T-cell-lineage antigens and CD20 represented aberrant antigen expression or neoplastic transformation of an unusual normal T-cell subset, the authors examined specimens of peripheral blood lymphocytes from healthy donors for evidence of a CD20+ T-cell population by using three-color immunofluorescence analysis by flow cytometry. Two distinct populations of CD20+ cells were observed in peripheral blood. One expressed bright CD20 (6.6% to 23.7%, mean 14.47% of peripheral blood lymphocytes) and other B-cell associated antigens, whereas the other expressed dim CD20 (.94% to 11.90%, mean 3.50% of peripheral blood lymphocytes) and coexpressed CD3. Approximately two thirds (52.8% to 82.3%, mean 64.1%) of the dim CD20 cells were CD8+ and one third (19.2% to 74.1%, mean 37.5) CD4+. These cells also expressed CD5 and the alpha-beta chain of the T-cell receptor and lacked CD19 and CD22. These results indicate that CD20 is expressed on some normal peripheral blood T cells. CD20 expression by T-cell lymphomas may represent neoplastic transformation of a normal subset of CD20+ T cells rather than aberrant antigen expression by neoplastic cells. The nature of the CD20 antigen on T cells and the function of the normal population remain to be determined.

Aged↗
PubMed1994

Richter's transformation of chronic lymphocytic leukemia with Hodgkin's-like cells is associated with Epstein-Barr virus infection.

The appearance of a high-grade lymphoma in the setting of B-cell chronic lymphocytic leukemia (CLL) is termed Richter's syndrome. Usually the high-grade component is a monomorphous, large cell lymphoma, but occasionally the high-grade component takes the form of Hodgkin's disease or a Hodgkin's-like lymphoma. Although Richter's syndrome is thought to represent clonal evolution of the underlying B-cell neoplasm in most cases, such a progression is difficult to explain when the high-grade component is Hodgkin's disease. We report two cases of Richter's syndrome in which the large cells had a morphology consistent with Reed-Sternberg cells and were found in a background of CLL. The large cells in both cases expressed the CD15 and CD30 antigens in a pattern characteristic of Reed-Sternberg cells, and the large cells in one case also expressed monotypic cytoplasmic immunoglobulin of the same type as that expressed by the underlying CLL. In both cases, Southern blot analysis of DNA from lymph nodes that contained both CLL and the Hodgkin's-like component showed single immunoglobulin gene rearrangements. Using the polymerase chain reaction, we found Epstein-Barr virus DNA in lymph nodes from both cases, and in peripheral blood lymphoid cells from one case 4 yr before the onset of Richter's syndrome. Immunoperoxidase staining showed expression of EBV latent membrane protein only in the Reed-Sternberg-like cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Expression of CA 15.3 protein in the cyst contents distinguishes benign from malignant pancreatic mucinous cystic neoplasms.

BACKGROUND: Inflammatory pseudocysts, serous cystadenomas, and mucinous cystic tumors comprise most cystic lesions of the pancreas. The mucinous tumors include mucinous cystic neoplasms, which are benign on histologic examination but have the potential for malignant transformation, and mucinous cystadenocarcinomas. Accurate preoperative classification of pancreatic cysts with clinical and radiologic criteria is often impossible, and as a result many cystic tumors are inappropriately treated as pseudocysts. Analysis of percutaneous needle-aspirated cyst fluid for tumor markers, enzymes, viscosity, and cytologic study has been proposed as a useful modality to distinguish mucinous from nonmucinous cystic lesions. However, no reliable cyst fluid parameter distinguishes benign from malignant mucinous tumors. METHODS: The concentration of the tumor marker CA 15-3 was measured by immunoassay in cyst fluid from six pseudocysts, five serous cystadenomas, three mucinous cystic neoplasms, and six mucinous cystadenocarcinomas. RESULTS: The concentration of CA 15-3 in the cyst fluid of mucinous cystadenocarcinomas was higher (mean, 178 units/ml; range, 40 to 392) than that of mucinous cystic neoplasms (mean, 4.7 units/ml; range, 0 to 14), serous cystadenomas (mean, 9.2 units/ml; range, 0 to 32), and pseudocysts (mean, 15.3 units/ml; range, 0 to 66). An upper cutoff value of 30 units/ml distinguished mucinous cystic neoplasms from mucinous cystadenocarcinomas with 100% sensitivity and 100% specificity (p = 0.01). CONCLUSIONS: Production of CA 15-3 appears to coincide with malignant transformation in pancreatic mucinous cystic neoplasms. We conclude that measurement of CA 15-3 levels in the cyst fluid is useful in the differentiation of benign from malignant pancreatic mucinous cysts.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

In vivo modulation of natural killer cell activity by tamoxifen in patients with bilateral primary breast cancer.

Natural killer (NK) cell activity, the autologous mixed lymphocyte reaction (AMLR) and proportions of T cell subpopulations (CD3+/CD4+ and CD3+/CD8+) and NK cells (CD16+) were studied in 21 patients with bilateral primary breast cancer (BBC), 10 patients with single-breast cancer (SBC) and 20 healthy controls. All patients studied had no evidence of disease and had been off radiotherapy and/or chemotherapy for at least 1 year. Ten patients with BBC were also treated with tamoxifen. Patients with SBC had NK cell activity, AMLR responses and T cell subpopulations that were comparable to those of normal controls. In patients with BBC, a significant (P < 0.01) increase in NK activity compared to that in normal controls (42 +/- 13% versus 21 +/- 10%, effector-to-target cell ratio, 25:1) and a significant (P < 0.05) decrease in CD4+ T cell proportions (30 +/- 15% versus 49 +/- 13%) and absolute numbers (472 +/- 82/mm3 versus 953 +/- 131/mm3) were found. However, the proliferative response of BBC patients' T lymphocytes in AMLR was in the range of the normal controls. Lymphocytes derived from 10 BBC patients treated with tamoxifen exhibited NK cell activity that was comparable to that of normal controls and patients with SBC, and was significantly (P < 0.01) reduced compared to the pretreatment period. BBC patients who received tamoxifen also show a reduction in the proportion of CD4+ T cells and in AMLR proliferative responses, which decreased compared to levels in normal controls. Taken together, these results indicate that long-term tamoxifen treatment modulates immune responses in BBC patients.

Adult↗
PubMed1993

Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus.

A recent outbreak of multiresistant strains of Acinetobacter calcoaceticus biotype anitratus was observed mostly, but not exclusively, in the surgical intensive care unit in our hospital. Disk diffusion and microdilution susceptibility studies demonstrated resistance to imipenem, all aminoglycosides, and all individual beta-lactam antibiotics. Only ampicillin plus sulbactam, cefoperazone plus sulbactam, and polymyxin produced zone sizes and MICs in the susceptible ranges. Determination of MICs and MBCs demonstrated that sulbactam was the antimicrobial agent responsible for the killing of these organisms. Nine of 10 patients who were infected with imipenem-resistant Acinetobacter strains and received ampicillin plus sulbactam for > 3 days improved clinically, and in many cases organisms were eradicated from the site of isolation.

Acinetobacter Infections↗
PubMed1992

Ricin and lentil lectin-affinity chromatography reveals oligosaccharide heterogeneity of thyrotropin secreted by 12 human pituitary tumors.

Some patients with thyrotropin (TSH)-producing pituitary tumors are more hyperthyroid than others despite similar TSH levels in serum, suggesting that qualitatively different TSH molecules with differing bioactivities may be secreted by different tumors. We used ricin and lentil lectin-affinity chromatography to test whether the TSH oligosaccharides varied among 12 patients with TSH-producing tumors. We found that each tumor secreted heterogeneous isoforms of TSH that differed in their extents of exposed galactose (Gal) residues, and their degrees of sialylation and core fucosylation. These biochemical parameters also varied markedly for TSH secreted by different tumors. Isoforms appeared to reflect poor sialyltransferase activity in two tumors and efficient sialyltransferase in the remainder. TSH secreted by tumors was more fucosylated than TSH secreted by control euthyroid persons. There was an inverse relationship between the sialylation and fucosylation of tumor TSH. No simple relationship between TSH oligosaccharide structures and bioactivity was evident, although mixtures of isoforms having the least and most sialylated TSH seemed to be the most bioactive clinically. In three patients from whom serum and medium TSH were both available, TSH in serum was more sialylated than TSH secreted by the tumor in vitro, perhaps reflecting slow clearance of sialylated isoforms from the circulation. Core fucosylation of serum TSH was less than that of medium TSH. These data prove that human tumors secrete TSH with heterogeneous oligosaccharide structures.

Adult↗
PubMed1992

Structures of high-mannose and complex oligosaccharides of mouse TSH and free alpha-subunits after in vitro incubation of thyrotropic tissue with TRH.

To determine whether incubation of mouse thyrotropic tissue with TRH in vitro influenced the oligosaccharide structure of TSH, thyrotropic tumor tissue or pituitary tissue was incubated in vitro with [3H]mannose or with [35S]sulfate and [3H]methionine, in the absence or presence of TRH for times up to 24 h. [3H]mannose-labeled oligosaccharides from intracellular TSH and free alpha-subunits were analyzed by paper chromatography, and were predominantly Man9GlcNAc and Man8GlcNAc units both in the absence and presence of TRH. The [35S]sulfate/[3H]methionine ratio in secreted molecules was greater for TSH than for free alpha-subunits; within TSH heterodimers the ratio was greater for beta-subunits than alpha-subunits. The [35S]/[3H] ratio was not altered in TSH or free alpha-subunits by TRH. Analyses of [3H]mannose-labeled charged oligosaccharides by HPLC anion-exchange chromatography revealed similar types of oligosaccharides present on TSH subunits and free alpha-subunits (having one or two sulfate residues, one or two sialic acid residues, or both a sulfate and a sialic acid residue). These charged oligosaccharides occurred in different proportions on TSH subunits compared to free alpha-subunits, and also differed depending on whether the tissue source was tumorous or nontumorous. The proportions of oligosaccharide unit types were not altered by TRH. Thus, while this study provided information concerning the high-mannose and complex oligosaccharides of mouse TSH, there was no evidence that short incubations of tissues with TRH in vitro caused modulation of TSH oligosaccharide structures.

Animals↗