Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria?

Apoptosis is an essential physiological process for the selective elimination of cells, which is involved in a variety of biological events. The Bcl-2 family is the best characterized protein family involved in the regulation of apoptotic cell death, consisting of anti-apoptotic and pro-apoptotic members. The anti-apoptotic members of this family, such as Bcl-2 and Bcl-x_L, prevent apoptosis either by sequestering proforms of death-driving cysteine proteases called caspases (a complex called the apoptosome) or by preventing the release of mitochondrial apoptogenic factors such as cytochrome c and AIF (apoptosis-inducing factor) into the cytoplasm. After entering the cytoplasm, cytochrome c and AIF directly activate caspases that cleave a set of cellular proteins to cause apoptotic changes. In contrast, pro-apoptotic members of this family, such as Bax and Bak, trigger the release of caspases from death antagonists via heterodimerization and also by inducing the release of mitochondrial apoptogenic factors into the cytoplasm via acting on mitochondrial permeability transition pore, thereby leading to caspase activation. Thus, the Bcl-2 family of proteins acts as a critical life–death decision point within the common pathway of apoptosis.     

Glomerular injury induced by cationic 70-kD staphylococcal protein; specific immune response is not involved in early phase in rats

A highly cationic staphylococcal protein (designated p70, MW 70 kD, pI>10) belongs to the groups of bacterial proteins that can bind immunoglobulin without specific antigen–antibody recognition; heparin inhibition tests indicated a charge interaction. This study evaluated the nephritogenicity of p70, which has affinity for the glomerular basement membrane (GBM), and the influence of various mediator systems on the induction of glomerulonephritis by p70. The left kidneys of intact rats, rats given cobra venom factor (complement-depleted), or rats given anti-adhesion molecules (ICAM-1 and LFA-1a) were perfused with p70. Proteinuria started within 24 h and persisted at day 5. Intraglomerular infiltration of cells was seen as early as 15 min, peaking at day 1. Deposits of rat IgG and C3 were seen in a subendothelial location 15 min after p70 perfusion in the left kidney and were found in a predominantly subepithelial location from 1 day onwards. Complement depletion and blockade of adhesion molecules suppressed proteinuria from day 2 onwards; these manipulations also prevented the recruitment of infiltrating cells and partially hindered the transfer of IgG across the GBM and the accumulation of IgG in the subepithelial region. In the non-perfused right kidneys, deposits of IgG and C3 were comparable to those in the left kidneys, suggesting that p70–IgG complexes formed in the circulation may also contribute to the deposits in the GBM. Heparin inhibition tests indicated an electrostatic interaction between p70 and immunoglobulin. Complement and inflammatory mediator systems (granulocytes, monocytes/macrophages, and/or lymphocytes) were required to provoke glomerular injury. p70 might play a role in acute glomerulonephritis following Staphylococcus aureus infection. © 1998 John Wiley & Sons, Ltd.     

An autopsy case of congenital complete heart block in a newly born of a mother with systemic lupus erythematosus

Summary An autopsy case of congenital atrioventricular (AV) heart block is described. A newborn infant of a mother with systemic lupus erythematosus died 10 h after birth. Autopsy revealed hematoxylin bodies in the AV node, central fibrous body, and fibrous annulus of the heart. Also, immunoglobulin G (IgG) localization in the hematoxylin bodies was demonstrated by an immunoperoxidase technique. It is suggested that IgG or immune complexes crossed the placenta and that the immune deposition directly injured the cardiac conduction system, causing AV block.     

Richter's syndrome presenting as a nasal lymphoma

Richter's syndrome (RS) is a high-grade large cell lymphoma arising in patients with B-cell chronic lymphocytic leukemia (CLL). The prognosis of RS is very poor and the development of RS is a serious complication of CLL. We present a case of a patient with a 4-year history of B-cell CLL who developed diffuse large B-cell nasal lymphoma. The patient exhibited good response to chemotherapy and irradiation and achieved complete remission. Five months later, the patient suffered leptomeningeal involvement and has been treated with repeated intrathecal chemotherapy. Leukemic cells of the patient expressed CD13. CD13+ CLLs have been reported to have an unfavorable prognosis and this case may support the view.     

Mechanism of taxane neurotoxicity

The two taxanes (paclitaxel and docetaxel) are widely employed in standard antineoplastic practice. Although these agents are now well established, some toxic side effects have been reported. Toxicity of these agents includes bone marrow suppression (principally neutropenia), hypersensitivity reactions, cutaneous reactions, edema and neurotoxicity. The most prominent neurotoxicity is a sensory neuropathy. Controlling neuropathy is crucial for maintaining the quality of life of patients because it is usually persistent and hard to manage. The precise mechanism for taxane-induced neuropathy is still unknown. The taxanes are known to promote aggregation of intracellular microtubules. Abnormal aggregation of microtubules in the neuronal cells may cause this neuropathy. In addition, the taxanes have been suggested to have intrinsic toxicity and directly injure the cells. A better understanding of the mechanism for this neuropathy may improve the quality of life of patients who undergo taxane antineoplastic therapy.     

Gastrointestinal stromal tumor of the stomach mimicking adrenal tumor: a case report

A gastrointestinal stromal tumor of the stomach mimicking an adrenal tumor in a 67-year-old woman is reported. The patient sought medical attention for left flank pain in December 2001. A spherical calcification was evident in the left hypochondrium in an abdominal radiography, and computed tomography revealed a mass 8 cm in diameter at the upper pole of the left kidney. She then was admitted to our hospital. Physical examination and laboratory screening showed hypertension, diabetes mellitus and slight hemoconcentration. Endocrine examination showed normal serum adrenal hormone concentrations. Magnetic resonance imaging again demonstrated the mass, which showed enhancement along its margins after intravenous contrast administration. With a preoperative diagnosis of adrenal tumor, we performed total resection. The pediculated tumor, arising from the stomach, showed c-kit immunohistochemical staining permitting a histopathological diagnosis of gastrointestinal stromal tumor.     

Generation of free radicals and/or active oxygen by light or laser irradiation of hydrogen peroxide or sodium hypochlorite

Generation of free radical and/or active oxygen by light or laser irradiation of hydrogen peroxide (H2O2) or sodium hypochlorite (NaClO), which have been used for tooth whitening or root canal irrigation, was investigated using electron spin resonance spectroscopy combined with a spin-trapping technique. When H2O2 was exposed to light or laser radiation, the amount of hydroxyl radical generated changed according to the concentration of H2O2 and irradiation time. The amount of 5,5-dimethyl-1-pyrrolidone-(2)-oxyl-(1) (DMPO-X) also changed in accordance with irradiation time. The amounts of hydroxyl radical generated from H2O2 after irradiation were in the order: plasma lamp > halogen lamp > He-Ne laser > Yellow He-Ne laser. On the other hand, the amounts of DMPO-X generated from NaClO after irradiation were in the order: plasma lamp > Yellow He-Ne laser > halogen lamp > He-Ne laser.     

Ultrastructural localization of aminopeptidase A/angiotensinase and placental leucine aminopeptidase/oxytocinase in chorionic villi of human placenta

AIMS: Membrane-bound aminopeptidases in human placenta are thought to be involved in maintaining homeostasis during pregnancy by metabolizing bioactive peptides such as oxytocin and angiotensin at the interface between the fetus and mother. Because determining the precise localization of these enzymes is required to support this notion, we investigated the ultrastructural localization of two principal enzymes, aminopeptidase A (APA; EC 3.4.11.7)/angiotensinase and placental leucine aminopeptidase (P-LAP; EC 3.4.11.3)/oxytocinase in human first trimester and full-term placenta. METHODS: Immunohistochemical analysis using anti-P-LAP and anti-APA antibodies was performed on ultrathin frozen sections of fixed human placental villi. RESULTS: Transmission immunoelectron microscopy revealed that both enzymes were expressed on the surface of apical microvilli of syncytiotrophoblast cells and, to a lesser extent, on the basal infoldings. The location of the two enzymes did not vary between the first trimester and full-term placenta sections, while the staining intensities were slightly enhanced in full-term villi. CONCLUSIONS: Our observation that P-LAP and APA are present on the microvilli, which is a site of interaction between the mother and fetus, suggests possible involvement of these enzymes in cleaving peptide hormones from the fetus and mother in order to regulate bioactivity.     

A 7-year-old boy with mycoplasmal infection requiring extracorporeal membrane oxygenation

A 7-year-old boy with Down syndrome developed severe acute respiratory distress syndrome after a respiratory infection with Mycoplasma pneumoniae with an unusually high agglutination titre (1:10240). Initially, mechanical ventilation and nitric oxide inhalation were used, but these did not improve the alveolar-arterial oxygen gradient. Extracorporeal membrane oxygenation for 152 h improved the lung condition. CONCLUSION: our case suggests that Mycoplasma pneumoniae should be considered as an aetiological agent in acute respiratory distress syndrome. Extracorporeal membrane oxygenation might have a valuable role in the management.