Synthesis and preliminary pharmacological assessment of novel gamma-hydroxybutyric acid derivatives

Synthesis and properties of new N-substituted amides of alpha-(1,1-ethylenedioxy)-ethyl-gamma-hydroxybutyric acid are described. The compounds were obtained by aminolysis of 3-(1,1-ethylenedioxy)-ethyltetra-hydrofuran-2-on with primary alkylarylamines. Preliminary pharmacological assessment revealed that the compounds exert weaker influence on the central nervous system than the reference gamma-hydroxybutyric acid. Three of the novel compounds offered some protection against pentetrazole-induced tonic seizures in mice.     

Aspiration biopsy of the breast tumors. Analysis of diagnostically difficult cases.

In this paper the authors described those of the breast fine needle aspirates which were difficult for interpretation e.g. clear-cut differentiation between benign and malignant character of the lesion could not be made. There were 40 such cases (1.96%) out of 2332 breast tumors biopsied between 1987-1989. In the cases that proved to be malignant on histology the authors described cytological features which speak in favour of malignancy. In the group of smears which proved to be benign on histology the authors described the features that imitate atypia and should not be misdiagnosed as malignant. The described criteria may be of some help in cytological diagnosis of breast masses.     

Fine‐needle aspiration cytology of subcutaneous toxoplasmosis: A case report

Toxoplasmosis is a common opportunistic infection in patients with AIDS in whom it typically presents as encephalitis, pneumonia, lymphadenitis, and myocarditis. Skin involvement is very rare and, to our best knowledge, Toxoplasma gondii forming a subcutaneous mass has not been reported. Here, we report the findings of an interesting case of subcutaneous toxoplasmosis with the cytological appearance of an inflammatory fibrovascular lesion in a HIV‐positive patient and discuss the differential diagnosis. Diagn. Cytopathol. 2010;38:716–720. © 2009 Wiley‐Liss, Inc.     

Synthesis and preliminary pharmacological screening of some 8-substituted methylxanthines

Methods of synthesis, chemical properties and results of preliminary pharmacological screening for 8-amino substituted derivatives of caffeine (1-3) and 7,8-disubstituted derivatives of 8-aminotheophylline (8-12) have been described. The compounds show weak sedative and antidepressive activity and some of them (2, 10, 12) also small antinociceptive effect.     

Tibial fractures with infrapopliteal arterial injuries

Tibial fractures with associated infrapopliteal arterial injuries have been inadequately documented in the literature. Eighteen patients with these injuries were admitted to Boston City Hospital during a 10-year period. Three patients required below-knee amputation, and two of these had ischemic intervals of greater than 8 h before vascular treatment. Six patients had delayed diagnoses of arterial injuries, but none required amputation. There were 15 open and three closed tibial fractures. Nine fractures were badly comminuted. Eight of the 14 viable limbs had delayed unions, but only one was associated with local vascular insufficiency. Five patients had complaints attributed to vascular insufficiency without clinical findings. Our conclusion is that the limb with an infrapopliteal arterial insult combined with a tibial fracture can survive with patency of only the anterior tibial or posterior tibial artery. Poor clinical results correlate with the severity of bony injury and not with the particular arterial injury. The incidence of below-knee amputation can best be related to delay in vascular treatment.     

Low molecular weight analogs of trolox with potent antioxidant activity in vitro and in vivo

Alpha-tocopherol and its water-soluble derivative, Trolox, are capable of terminating free radical chain reactions and limiting reperfusion-induced cell damage. In the present study, we have quantitated the effects of two relatively potent analogs of alpha-tocopherol/Trolox, WIN 62079 and U-78517F, which attenuated exogenously generated free radical damage in cultured cells and reperfusion injury in vivo. In a cultured rat renal tubular epithelial cell line (NRK-52E), millimolar concentrations of ascorbate or the combination of Trolox plus ascorbate reduced cellular damage (quantitated as lactate dehydrogenase [LDH] release) induced by radicals generated by hypoxanthine/xanthine oxidase. In contrast, WIN 62079 and U-78517F attenuated damage at micromolar concentrations. Similarly, intravenous administration of WIN 62079 (three hourly doses of 3 mg/kg) and U-78517F (10 mg/kg infused over 5 min) reduced reperfusion-induced myocardial damage in rabbit coronary-occulded hearts: Trolox (three hourly doses of 100 mg/kg) was less potent and required ascorbate (three hourly doses of 150 mg/kg) as a cofactor. These data demonstrate that is feasible to design potent, water-soluble analogs of Trolox which are efficacious against free radical-mediated cell death and which do not require ascorbate as a cofactor. Moreover, since U-78517F and WIN 62079 are two to three orders of magnitude more potent than Trolox, and since they contain different amino side chains, these data further support the concept that side chain modifications of the chromane ring nucleus of alpha-tocopherol derivatives significantly affect activity, possibly by providing additional activity or by enhancing availability to the cellular site of action. © 1992 Wiley-Liss, Inc.     

Shedding of the guinea pig peritoneal macrophage Fc gamma receptor. Effect on apparent association constant and on the number of IgG-binding sites on the cells

During our studies on the structure and properties of guinea pig peritoneal macrophage Fc gamma receptor we observed that these cells spontaneously release an IgG-binding material into supernatant. Although the shedding was accompanied by a decrease in IgG-binding ability of macrophages, the number of IgG-binding sites/cell before and after shedding was similar. However, macrophages after the shedding interacted with IgG with a lower apparent association constant, Ka. Therefore, we assume that the decrease of IgG-binding ability of cells was an effect of decrease in value of Ka. Experiments with protein synthesis inhibitors showed that the shed receptor is replaced by "de novo" synthesized receptor molecules.     

Differential diagnosis of malignant lymphomas and related disorders by specific pattern of expression of immunophenotypic markers revealed by multiparameter flow cytometry (Review)

The introduction of monoclonal antibodies (mAbs) for cell immunophenotyping and use of flow cytometry with the progressively improving software for multivariate analyses have revolutionized the diagnosis and influenced the classification of hematologic neoplasms. In this review we focus on the practical application of flow cytometry in the diagnosis and classification of malignant lymphomas and related lymphoproliferative disorders with special emphasis on differential diagnosis. A general approach to the utilization of flow cytometry (FC) in hematopathology with an algorithm to diagnose the most common neoplasms is presented. We discuss precursor B-cell neoplasms, mature B-cell neoplasms (SLL/CLL, mantle cell lymphoma, marginal zone lymphoma, hairy cell leukemia, diffuse large B-cell lymphoma, plasma cell dyscrasias and lymphomas with plasmacytic differentiation), precursor T-lymphoblastic leukemia and mature (peripheral) T-cell neoplasms, including T-SLL/PLL, anaplastic cell lymphomas and large granular cell leukemia/lymphoma. The text is accompanied by characteristic FC scatterplots of the discussed entities.     

Colonic adenomas with extramedullary myeloid tumor (granulocytic sarcoma).

Extramedullary myeloid tumor (EMT) is an accumulation of malignant immature cells of the granulocytic series that is usually green in appearance due to the presence of myeloperoxidase. These invasive and destructive tumors occur most commonly in the skull and surrounding tissues, lymph nodes, skin and soft tissues. Regardless of the site, EMTs are difficult to recognize and may be easily overlooked or diagnosed as malignant lymphoma. EMTs may precede the diagnosis of a chronic myeloproliferative disorder or acute myeloid leukemia, may present coincident with the hematologic diagnosis, or may herald a relapse after therapy. An accurate diagnosis of EMT is of great clinical importance in the ongoing management of hematologic malignancies. We report here two unusual cases of EMT of the colon, which infiltrated adenomatous polyps. We conclude that increased cellularity within the lamina propria of polyps and mucosal surfaces in general should be carefully examined.