Tissue-specific renin-angiotensin system in pulmonary lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM), a multisystem disease found in middle-aged women, is characterized by cystic lung destruction and abdominal tumors (e.g., angiomyolipomas, lymphangioleimyomas), resulting from proliferation of abnormal-appearing, smooth muscle-like cells (LAM cells).

Explant pathology study of decellularized carotid artery vascular grafts.

The purpose of this study was to evaluate the morphologic findings in small-diameter freeze-dried decellularized carotid artery grafts implanted in goats as carotid artery interposition grafts for 6-7 months. Unimplanted decellularized carotid artery grafts did not contain intact cells; however, remnants of smooth muscle cells were present in the media. The extracellular matrix was well preserved.

Angiotensin II AT(1) and AT(2) receptors contribute to maintain basal adrenomedullary norepinephrine synthesis and tyrosine hydroxylase transcription.

Angiotensin II (Ang II) AT(1) receptors have been proposed to mediate the Ang II-dependent and the stress-stimulated adrenomedullary catecholamine synthesis and release. However, in this tissue, most of the Ang II receptors are of the AT(2) type. We asked the question whether AT(1) and AT(2) receptors regulate basal catecholamine synthesis.

Matrix metalloproteinases and their tissue inhibitors in the lesions of cardiac and pulmonary sarcoidosis: an immunohistochemical study.

The pathogenesis of the tissue damage and fibrosis in sarcoidosis is poorly understood. The matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) must be considered in this regard, because they control the lysis of connective tissue components. Immunohistochemical studies (peroxidase and dual labeling for confocal microscopy) of reactivity for MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, and the 4 membrane-type-MMPs were made on tissues from patients with cardiac (n = 4) and pulmonary (n = 5) sarcoidosis.

Immunohistochemical study of endothelin-1 and matrix metalloproteinases in plexogenic pulmonary arteriopathy.

The matrix metalloproteinases (MMPs) and endothelin-1, a potent vasoconstrictor and mitogen for smooth muscle cells, have been shown to be involved in the pathogenesis of various vascular disorders. However, the expression of endothelin-1 and the activation of MMPs have not been fully evaluated in plexogenic pulmonary arteriopathy (PPA). Immunohistochemical and confocal microscopic studies were conducted to evaluate the reactivity of lung tissue from six patients with pulmonary hypertension for alpha-smooth muscle actin (alpha-SMA), desmin, vimentin, factor VIII, endothelin-1, various types of MMPs (MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9), membrane type-MMPs (MT-MMPs), tissue inhibitors of MMPs (TIMPs), and type IV collagen.

Expression of human telomerase reverse transcriptase in lymphangioleiomyomatosis.

Telomerase synthesizes nucleotide hexameric repeats (telomeres) at the ends of chromosomes, replacing base sequences that are lost from these sites during each mitotic cycle and protecting these ends against the action of exonucleases and ligases. Therefore, telomerase is essential for maintaining cellular replication. To evaluate the role of telomerase in the proliferation of abnormal smooth muscle cells (lymphangioleiomyomatosis [LAM] cells) in LAM, we performed immunostaining and in situ hybridization studies to identify telomerase protein and messenger RNA (mRNA), respectively, in pulmonary (n = 18) and extrapulmonary (n = 4) lesions from 22 women with LAM (14 untreated and 8 treated with progesterone or tamoxifen).

Critical role of NADPH oxidase-derived reactive oxygen species in generating Ca2+ oscillations in human aortic endothelial cells stimulated by histamine.

There is increasing evidence that intracellular reactive oxygen species (ROS) play a role in cell signaling and that the NADPH oxidase is a major source of ROS in endothelial cells. At low concentrations, agonist stimulation of membrane receptors generates intracellular ROS and repetitive oscillations of intracellular Ca(2+) concentration ([Ca(2+)](i)) in human endothelial cells. The present study was performed to examine whether ROS are important in the generation or maintenance of [Ca(2+)](i) oscillations in human aortic endothelial cells (HAEC) stimulated by histamine.

The etiology of oculocutaneous albinism (OCA) type II: the pink protein modulates the processing and transport of tyrosinase.

Oculocutaneous albinism (OCA) is caused by reduced or deficient melanin pigmentation in the skin, hair, and eyes. OCA has different phenotypes resulting from mutations in distinct pigmentation genes involved in melanogenesis. OCA type 2 (OCA2), the most common form of OCA, is an autosomal recessive disorder caused by mutations in the P gene, the function(s) of which is controversial.

The doxorubicin cardioprotective agent dexrazoxane (ICRF-187) induces endopolyploidy in rat neonatal myocytes through inhibition of DNA topoisomerase II.

Dexrazoxane (ICRF-187), which is clinically used to reduce doxorubicin-induced cardiotoxicity, is also a potent catalytic inhibitor of DNA topoisomerase II. In this study we showed that dexrazoxane inhibited the division of neonatal rat ventricular myocytes in culture, and resulted in nuclear multilobulation (demonstrated by three-dimensional reconstruction of confocal images) and marked increases in nuclear size and DNA ploidy levels (as shown by flow cytometry). It was concluded that dexrazoxane interfered with cell division in cardiac myocytes by virtue of its ability to inhibit topoisomerase II.

SK&F 95654-induced acute cardiovascular toxicity in Sprague-Dawley rats--histopathologic, electron microscopic, and immunohistochemical studies.

The characteristics and pathogenesis of the cardiovascular toxicity induced by the type III selective phosphodiesterase inhibitor SK&F 95654 were examined in 2 studies. Sprague-Dawley rats received either a single sc injection of 50, 100, or 200 mg/kg SK&F 95654 and were euthanized at 24 hours after administration of the drug (Study 1), or were given a single subcutaneous (sc) injection of 100 mg/kg SK&F 95654 and euthanized at 1, 2, 4, 6, 8,12, 24 hours, or 2 weeks after treatment (Study 2). Control rats received either DMSO or saline.

Expression of telomerase reverse transcriptase (TERT) in malignant mesotheliomas.

To evaluate the usefulness of determinations of telomerase activity for distinguishing malignant from benign mesothelial lesions, immunohistochemical (using a rabbit polyclonal antibody and the peroxidase method; n = 68) and in situ hybridization (using sense and antisense oligonucleotide probes; n = 46) studies were made on malignant mesotheliomas (epithelioid, 39; sarcomatoid, 18, including 2 of the desmoplastic type; and biphasic, 11) and 19 benign mesothelial lesions (benign mesothelial hyperplasia, 3; and reactive pleuritis, 16). In addition, biochemical studies of telomerase activity were made in 9 of the malignant mesotheliomas. Telomerase activity was detected histochemically in all but one of the malignant mesotheliomas, but only in one (pleuritis) of the benign lesions, in which it was present only in activated lymphocytes.

Expression of matrix metalloproteinases in invasive pulmonary adenocarcinoma with bronchioloalveolar component and atypical adenomatous hyperplasia.

To investigate the association between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and the clinicopathological features in lepidic and invasive components of adenocarcinoma of the lung, we performed immunostaining for type IV collagen, various MMPs, and TIMPs in 27 cases of invasive adenocarcinomas and 5 cases of atypical adenomatous hyperplasia of alveolar epithelial cells (AAH). Mean extent of lepidic growth was 61% and the survival was significantly better in cases with 50% or more lepidic component. The preservation of type IV collagen in lepidic areas correlated inversely with lymphatic or vascular invasion (P = 0.

Influence of alpha-melanocyte-stimulating hormone and ultraviolet radiation on the transfer of melanosomes to keratinocytes.

The epidermal melanin unit in human skin is composed of melanocytes and keratinocytes. Melanocytes, located in the basal layer of the epidermis, manufacture melanin-loaded organelles called melanosomes. Through their dendritic processes, melanocytes distribute melanosomes to neighboring keratinocytes, where their presence confers to the skin its characteristic color and photoprotective properties.

The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin- and mitoxantrone-induced cardiotoxicity.

Purpose: To compare the protective effect of dexrazoxane (DRZ) against cardiotoxicity induced by doxorubicin (DXR) and mitoxantrone (MTX).

Methods: Adult male spontaneously hypertensive rats (SHR) were treated with 1 mg/kg DXR (i.v.

Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages.

The 42 amino acid form of beta amyloid (Abeta42) plays a pivotal role in neurotoxicity and the activation of mononuclear phagocytes in Alzheimer's disease (AD). Our recent study revealed that FPRL1, a G-protein-coupled receptor, mediates the chemotactic and activating effect of Abeta42 on mononuclear phagocytes (monocytes and microglia), suggesting that FPRL1 may be involved in the proinflammatory responses in AD. We investigated the role of FPRL1 in cellular uptake and the subsequent fibrillar formation of Abeta42 by using fluorescence confocal microscopy.

Lymphangioleiomyomatosis: CT of diurnal variation of lymphangioleiomyomas.

Purpose: To evaluate the imaging and clinical features of lymphangioleiomyomas and to describe the phenomenon of diurnal variation in the size of lymphangioleiomyomas in patients with lymphangioleiomyomatosis.

Materials And Methods: One hundred twenty-eight patients with lymphangioleiomyomatosis underwent chest and abdominopelvic computed tomography (CT). Thirteen patients underwent CT in the morning and afternoon of the same day to assess diurnal variation in lymphangioleiomyoma size.

Oculocutaneous albinism types 1 and 3 are ER retention diseases: mutation of tyrosinase or Tyrp1 can affect the processing of both mutant and wild-type proteins.

Various types of oculocutaneous albinism (OCA) are associated with reduced pigmentation in the skin, hair, and eyes that results from mutations in genes involved in melanin synthesis. Immortal mouse melanocyte lines (melan-a, melan-b, and melan-c) provide opportune models with which to investigate the etiology of two different types of OCA (types I and III), which arise from mutations in Tyr and Tyrp1, respectively. We compared intracellular processing, sorting, and degradation of tyrosinase and Tyrp1, and the effects on their catalytic function and melanin synthesis, in these wild-type and mutant melanocytes.

Reversible airflow obstruction, proliferation of abnormal smooth muscle cells, and impairment of gas exchange as predictors of outcome in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare disease, occurring in women, characterized by cystic degeneration of the lungs, abdominal tumors, and proliferation of abnormal smooth muscle cells. Lung function abnormalities consist of impairment of the diffusion capacity (DL(CO)) and airflow obstruction. The objective of this study was to correlate the functional impairment with histologic measures of disease severity to identify predictors of disease outcome.

Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions.

Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well known. Some years ago, we generated peptide-specific antibodies to murine melanosomal proteins that proved to be instrumental in elucidating melanocyte development and differentiation in mice, but cross-reactivity of those antibodies with the corresponding human proteins often was weak or absent.

A model for melanosome biogenesis based on the purification and analysis of early melanosomes.

Melanosome biogenesis and function were studied after purification of early stage melanosomes and characterization of specific proteins sorted to that organelle. Melanosomes were isolated from highly pigmented human MNT1 melanoma cells after disruption and initial separation by sucrose density gradient centrifugation. Low-density sucrose fractions were found by electron microscopy to be enriched in stage I and stage II melanosomes, and these fractions were further separated and purified by free flow electrophoresis.

Distribution and mRNA expression of insulin-like growth factor system in pulmonary lymphangioleiomyomatosis.

Background: Insulin-like growth factors (IGF-1 and IGF-2), the IGF-1 receptor (IGF-1R), and IGF-binding proteins (IGFBPs) are involved in normal pulmonary development and in the pathogenesis of smooth muscle cell tumors.

Methods: To evaluate the role of the IGF system in lymphangioleiomyomatosis (LAM), we used immunohistochemical and in situ hybridization techniques to characterize the expression of IGF-1, IGF-2, IGF-1R, and IGFBP-2, -4, -5, and -6 in lung tissue from 18 LAM patients.

Results: IGF-1, ICGF-2, IGF-1R, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6 were expressed by LAM cells.

Association of lymphangioleiomyomatosis (LAM) with endosalpingiosis in the retroperitoneal lymph nodes: report of two cases.

We report 2 patients in whom pulmonary lymphangioleiomyomatosis (LAM) affected the retroperitoneal lymph nodes and was associated with endosalpingiosis. These lesions were large, encapsulated masses with multiple cysts containing chylous fluid. Both were characterized by proliferating LAM cells that formed fascicles separated by slit-like channels.