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Biomedical subjects

V B Reddy

Publications and source records attributed to V B Reddy.

At least 37 records · Page 2Linked to original sources

Humoral (antibody-mediated) rejection in lung transplantation.

To confirm the existence and characterize the pathologic features of humoral (antibody-mediated) lung rejection, we prospectively studied 55 lung transplant recipients (24 male [44%] and 31 female [56%], age range 14 to 69 years [mean 45]). The time between transplantation and biopsy ranged from 2 to 1546 days (mean 274). We performed direct immunofluorescence with C3, immunoglobulin M, and immunoglobulin G antibodies on frozen sections of 106 transbronchial biopsies and one wedge biopsy and compared the results with 13 explanted lungs, one donor lung, and two controls. The histologic diagnoses of these 107 biopsies included acute cellular rejection (62, 58% [minimal 23, mild 33, moderate 5, and severe 1]), chronic rejection (eight, 7%), chronic vascular rejection (two, 2%), acute vasculitis (five, 5%), cytomegalovirus pneumonitis (two, 2%), acute pneumonia (two, 2%), acute organizing pneumonia (two, 2%), diffuse alveolar damage (one, 1%), no evidence of rejection or infection (30, 28%), lipoid pneumonia (one, 1%), and inadequate for histologic diagnosis (one, 1%). Eighty-nine of 106 (84%) transbronchial biopsies, the wedge biopsy, and control lungs were satisfactory for direct immunofluorescence, because each contained alveolate lung parenchyma and arterioles or venules. There was no demonstrable immunofluorescence in the wall of the blood vessels or in the lung parenchyma in any case. We conclude that (1) transbronchial biopsies and wedge biopsies provide adequate material to evaluate humoral rejection, and (2) in spite of the large population studied, the satisfactory material obtained, and the wide range of histologic diagnoses, we could not demonstrate the occurrence of humoral rejection in the lung.

Adolescent↗

Catalytic properties and structural components of lysyl oxidase.

Key aspects of the biosynthesis and catalytic specificity of lysyl oxidase (LO) have been explored. Oxidation of peptidyl lysine in synthetic oligopeptides is markedly sensitive to the presence of vicinal dicarboxylic ami/no acid residues. Optimal activity is obtained with the -Glu-Lys- sequence within a polyglycine 11-mer, whereas the -Lys-Glu- sequence is much less efficiently oxidized. The -Asp-Glu-Lys- sequence is a very poor substrate, although this sequence is oxidized in type I collagen fibrils. These results are considered in the light of a model requiring collagen to be assembled as fibrils prior to oxidation by LO. An in vitro system for the expression of catalytically active LO has been devised. Deletion or inclusion of the cDNA coding for the propeptide region in the expressed construct results in apparently identical, catalytically active enzyme products, indicating the lack of essentiality of this region for active enzyme production. These effects are considered with respect to the conservation of the amino acid sequence of LO produced by different species.

Amino Acid Sequence↗

Expression of lysyl oxidase from cDNA constructs in mammalian cells: the propeptide region is not essential to the folding and secretion of the functional enzyme.

Rat aortic lysyl oxidase cDNA was expressed under a metallothionein promoter in Chinese hamster ovary cells using a dihydrofolate reductase selection marker. One methotrexate-resistant cell line, LOD-06, generated by transfecting with full-length cDNA, yielded lysyl oxidase proteins consistent with the 50 kDa proenzyme and a 29 kDa mature catalyst. A second cell line, LOD32-2, was generated by transfection with a truncated cDNA lacking sequences which code for the bulk of the propeptide region. Both cell lines secreted apparently identical, 29 kDa forms of mature lysyl oxidase each of which catalyzed the deamination of human recombinant tropoelastin and alkylamines, consistent with the known specificity of lysyl oxidase. The secreted enzyme forms were inhibited by chemical inhibitors of lysyl oxidase activity, including beta-aminopropionitrile, phenylhydrazine, ethylenediamine, alpha, alpha'-dipyridyl, and diethyldithiocarbamate. Sensitivity to these agents is consistent with the presence of copper and carbonyl cofactors in the expressed enzymes, characteristic of lysyl oxidase from connective tissues. These results indicate the lack of essentiality of the deleted proprotein sequence for the proper folding, generation of catalytic function, and secretion of lysyl oxidase.

Amino Acid Sequence↗

Cell proliferation markers in predicting metastases in malignant melanoma.

It is often difficult to predict the outcome of melanoma in patients with Clark level III-IV disease. We sought to identify markers of cell proliferation which may be useful in predicting prognosis. Patients with Clark's level III-IV malignant melanoma who had no local recurrences or metastases were matched with patients of comparable level and thickness who did experience recurrences of metastases. Cell proliferation markers p53, proliferating cell nuclear antigen (PCNA), and Ki-67 were assessed by immunohistochemistry. DNA ploidy was determined by flow cytometry. There was no difference in the expression of p53, PCNA, and Ki-67 between patients with metastases and patients without metastases. However, patients with metastases were more likely to have an aneuploid tumor cell population than were patients without metastases (p < 0.03). Expression of cell proliferation markers do not appear to help predict prognosis in advanced level melanoma; however, aneuploidy may be associated with a greater probability of metastasis.

Adolescent↗

Cytologic patterns of metastatic thymoma: diagnosis by fine-needle aspiration biopsy.

Thymomas are the most frequent primary tumors of the anterior mediastinum. These lesions are slow growing and can be locally invasive, but extrathoracic metastases are rare, occurring in less than 2% of cases. Fine-needle aspiration biopsy (FNAB) may be helpful in making the diagnosis of metastatic thymoma, with or without a clinical history of primary mediastinal thymoma. We report three cases of metastatic thymoma diagnosed by FNAB. Each case illustrates a distinctive cytologic pattern. While two of the patients had a history of histologically confirmed thymoma 11 and 13 years previously, a third patient presented with an enlarged supraclavicular lymph node and pulmonary nodules, and no prior diagnosis of thymoma. These cases demonstrate that based on distinctive cytologic patterns and features, a diagnosis of metastatic thymoma can be made with FNAB. Ancillary studies will often confirm the diagnosis.

Aged↗

Prognostic significance of DNA ploidy in male breast carcinoma. A retrospective analysis of 32 cases.

BACKGROUND: DNA aneuploidy has been prognostically significant in female breast carcinoma of low stage, but its value in male breast carcinoma remains undetermined. METHODS: Flow cytometric DNA analyses were performed retrospectively on paraffin-embedded tissue from 32 men with breast carcinoma (mean follow-up time, 5.97 years [standard deviation +/- 4.63]; range, 1 to 18 years). RESULTS: Multivariate discriminant function analysis showed only tumor size less than 2 cm to be independently predictive of better disease-free survival (P less than 0.05). DNA ploidy (aneuploid, 25 patients; diploid, 7 patients) and lymph node status (positive, 22 patients; negative, 10 patients) were not predictive of survival, regardless of tumor size. CONCLUSIONS: The authors concluded that DNA ploidy may not significantly predict survival in male breast carcinoma.

Adult↗

Dermatomyofibroma. A benign cutaneous, plaque-like proliferation of fibroblasts and myofibroblasts in young adults.

We report nine examples of a distinct cutaneous plaque-like proliferation of fibroblasts and myofibroblasts. Eight of nine lesions were located in or around the shoulder, including axilla and upper arm. There was a predominance of women to men of 8:1. The lesions measured from 1 to 2 cm in greatest diameter. All patients were young adults (mean age 29.8 yr). All lesions involved the reticular dermis in a plaque-like fashion and extended to the upper part of the subcutaneous septa in seven cases. The lesions consisted of a proliferation of very uniform slender spindle-shaped cells arranged as well-defined elongated and intersecting fascicles with a predominantly parallel arrangement to the skin surface. There was no evidence of cytologic atypia and mitotic figures were infrequent. The spindle-shaped cells were separated by thin collagen fibers. Elastic fibers were preserved and some of them appeared thicker than normal. All adnexal structures were spared. Immunohistochemistry revealed that the cells stained positively for vimentin and muscle actin, but lacked smooth-muscle specific actin, desmin, and S-100 protein. Some dermal dendrocytes stained positively for Factor XIIIa, but the spindle-shaped cells were negative. Electron microscopy studies revealed a mixture of fibroblasts, myofibroblasts, and undifferentiated mesenchymal cells. All lesions were treated by conservative excision; follow-up information revealed no evidence of recurrence. We name this distinct lesion dermatomyofibroma. To the best of our knowledge, this entity has not been previously described in the literature.

Adult↗

Lectin histochemistry of sex cord-stromal tumors and small cell carcinoma of the ovaries.

Binding sites of peanut agglutinin (PNA), Ulex europaeus (UEA-1), concanavalin A (Con A), and wheat germ agglutinin (WGA) were localized in 10 granulosa cell tumors, 10 Sertoli-Leydig cell tumors, 4 theca cell tumors, and 5 small cell carcinomas. Con A and WGA reacted positively with the majority of the studied neoplasms. PNA and UEA-1 were persistently negative in the sex cord-stromal tumors (SCST) but showed focal positivity in small cell carcinomas. Negative reactions of SCST with PNA and UEA-1 may serve for differentiation between them and common epithelial tumors that are usually PNA and UEA-1 positive.

Binding Sites↗

Unusual benign fibrous and fibrohistiocytic tumors of the skin.

This article reviews recently reported unusual benign fibrous and fibrohistiocytic tumors of the skin. Some of these lesions are variants of common and well-known entities. Because some of these variants have cytologic atypia, they could be confused with malignant neoplasms.

Fibroma↗

A synthetic DNA encoding a modified human urokinase resistant to inhibition by serum plasminogen activator inhibitor.

Using DNA synthesis technology we constructed two synthetic DNAs, designated syn-uPA-DNA and mut-uPA-DNA. Syn-uPA-DNA contains the complete coding sequence of human presecretion form of single-chain u-PA. Mut-uPA-DNA was derived from syn-uPA-DNA by deleting 18 base pairs coding for amino acids Arg179-Ser184. Each synthetic DNA was inserted into a bovine papilloma viral genome-based expression vector to obtain expression in mouse cells. The results indicate that both syn-uPA and mut-uPA proteins are secreted predominantly in single-chain form. The single-chain form of both enzymes can be completely converted to two-chain form by treatment with plasmin. Both enzymes are as active as natural urokinase (std-uPA) isolated from urine. Analysis of enzymatic activity indicates that under conditions where syn-uPA and std-uPA are completely inhibited by endothelial-type plasminogen activator inhibitor (PAI-1), mut-uPA retains 90% activity. In identical experiments with placental-type PAI (PAI-2), mut-uPA retains 80% activity. Syn-uPA is capable of forming a approximately 100-kDa complex with PAI, whereas mut-uPA can not. PAI-treated mut-uPA has kinetic properties similar to untreated syn-uPA or std-uPA. Overall, the data indicate that amino acids Arg179-Ser184 function at least in part as a binding site for PAI. Resistance to PAI inhibition may increase the potency of mut-uPA as a thrombolytic agent.

Amino Acid Sequence↗

Lectin binding to common epithelial tumors of the ovaries.

Binding sites of peanut agglutinin (PNA), Ulex europaeus (UEA-1), wheat germ agglutinin, concanavalin A, and Ricinus communis were localized in 46 common epithelial ovarian tumors. Binding pattern of serous cystadenomas showed significant similarity with the pattern seen in the epithelium of fallopian tubes. Lectin affinity of endometriosis and endometrioid tumors was similar to normal endometrium in secretory phase. Binding pattern of clear cell carcinomas was similar to gestational endometrium, with PNA and UEA-1 showing strong affinity. This pattern is in contrast to clear cell carcinomas of the kidney, that do not bind PNA and UEA-1. Mucinous cystadenomas exhibited binding patterns identical with cervical epithelium. Malignant counterparts of the described tumors were characterized by the partial loss of lectin binding and uneven distribution of the binding reaction.

Adenocarcinoma↗

Global and molecular hemostatic markers in acute myeloid leukemia.

Patients with acute myeloid leukemia have multiple hemostatic and thrombotic complications, which may or may not result from disseminated intravascular coagulation. Previous studies incorporating routine coagulation analyses failed to detect any clinically useful information in most of these patients. In this study, the first comprehensive evaluation of the various aspects of the hemostatic system in a population of patients with acute myeloid leukemia was performed. Eighteen patients (23-71 years of age) were studied at either diagnosis or relapse. Hemostatic studies were performed at onset and on days 3, 7, and 30 after initiation of therapy. The bone marrow blast counts ranged from 8% to 98%; prothrombin time and activated partial thromboplastin time showed only minor prolongations in a few of these patients. However, in all patients measurement of platelet-associated markers revealed elevated platelet factor 4 and thromboxane B2 and normal 6-keto-prostaglandin F1 alpha levels. Fibrinolytic markers showed an increase in D-dimer and tissue plasminogen activator and a decrease in alpha 2-antiplasmin levels. Plasminogen, plasminogen activator inhibitor, and fibrinogen levels were normal. Coagulation markers demonstrated a decrease in protein C and antithrombin III levels and an elevation of the thrombin-antithrombin complex. The pretreatment values for all hemostatic markers studied were similar to the values obtained on days 3, 7, and 30 during treatment. This investigation demonstrated a subclinical activation of the components of the hemostatic system possibly leading to a hypercoagulable state. Although only six patients (33%) experienced hemorrhagic complications, the risk of bleeding and/or thrombosis was strongly evident in all patients. The significance of finding abnormal levels of specific molecular markers of hemostasis will be established in the future application of such markers in clinical evaluations of leukemic patients known to be at risk for coagulation disorders.

Acute Disease↗

Synchronous adenocarcinomas of jejunum and cecum following transverse colon carcinoma. A case study.

A case of synchronous primary adenocarcinomas of the small and large bowel in a patient previously treated by transverse colectomy for cancerous polyps is presented. These new primaries were incidental findings during surgery for suspected recurrence of colonic carcinoma. Primary tumors of the small bowel are rare, and the diagnosis of primary adenocarcinoma of small bowel in the presence of primary adenocarcinoma of large bowel requires a high degree of suspicion and may well modify the prognostic outcome if detected early.

Adenocarcinoma↗

Inflammatory myopathy and acquired immunodeficiency syndrome.

A 33-year-old black woman with advanced acquired immunodeficiency syndrome (AIDS) presented with rapidly progressive muscle weakness and serologic and radiologic evidence of central nervous system Toxoplasma infection. Muscle biopsy revealed an inflammatory infiltrate predominantly composed of macrophages and T suppressor/cytotoxic cells. Human immunodeficiency virus major core protein (p24) was also detected in macrophages and damaged muscle cells around the inflammatory infiltrates. The patient improved clinically with glucocorticoid therapy for polymyositis and pyrimethamine and clindamycin therapy for toxoplasmosis.

Acquired Immunodeficiency Syndrome↗

Plasma cell granuloma of the heart.

A case of plasma cell granuloma arising in the free ventricular wall and involving the coronary arteries of a 10-month-old female infant is presented. Morphologic characteristics were comparable with those of plasma cell granulomas arising elsewhere. The histologic, immunohistochemical, and ultrastructural observations, and in particular the quiescent clinical course of the disease and its control with anti-inflammatory medication, favor a nonneoplastic nature of the lesion. This report documents the presence of an intracardiac plasma cell granuloma for the second time in the medical literature.

Coronary Vessels↗