A subset of breast invasive ductal carcinoma with distinctive cytomorphology,aggressive clinical behavior,and unique immunologic profiles

BACKGROUND: Invasive ductal carcinoma of the breast is a heterogeneous collection of divergent types of carcinomas. Some subtypes have been characterized by histologic observations. This study describes a distinctive subset recognized through cytomorphologic examination of breast carcinoma specimens obtained by fine-needle aspiration biopsies (FNAB). Identification of this subset is established further by analyses of its clinical and immunologic characteristics. METHODS: One hundred patients underwent FNAB and were diagnosed with breast ductal carcinoma. These diagnoses were followed by surgical resections and histologic evaluation of tumors. Immunohistochemical analyses of estrogen receptor, progesterone receptor, Her2/neu, p53 protein, and Ki-67 were performed. Patient's age, race, and family history of breast carcinoma were obtained. The objective of the study is to identify a cytomorphologically distinctive, clinically relevant, subset of breast carcinomas. RESULTS: A subset carcinoma was recognized by cytomorphologic examination of Pap-stained FNAB slides. This subset consisted of seven patients with a median age of 37 years. At the time of surgical resection, all patients had axillary lymph node metastases. Six of seven patients had distant metastases. Immunohistochemical studies revealed that all tumors are positive for p53 protein and negative for estrogen and progesterone receptors. CONCLUSION: This study presented a unique subset of breast ductal carcinomas that involved young patients and had aggressive growth behavior. These tumors expressed p53 protein but not estrogen and progesterone receptors.     

Langerhans cells histiocytosis in one family

Histiocytosis of Langerhans cells (class 1 histiocytosis) includes a range of clinical manifestations that have been described as bone eosinophilic granuloma, Hand-Schüller-Christian syndrome, and Letterer-Siwe diseases. This syndrome represents a spectrum of severity and prognosis of some underlying disorder which is usually sporadic. This report describes three cases in one family, who developed the disease a few years after their brother was found to be suffering from histiocytosis. All 3 patients had the same clinical manifestations: hyperthermia, eczematic rash, and swelling in skull, hand, and foot. X rays showed lytic areas in the skull and metacarp of fourth finger. Serology for EBV infection was negative. Infiltration of abnormal Langerhans cells histiocytes were demonstrated in bone biopsies. These patients were given chemotherapy. Case 1 (brother) died 1 year after chemotherapy, case 2 (girl) was given chemotherapy without success. She was given T-cell suppressor (cyclosporine), which induced remission, and case 3 was given chemotherapy, which was successful.     

T-cell proliferative responses following sepsis in neonatal rats

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment of animals with COX-2 inhibitor also significantly prevented the sepsis-associated mortality in neonates. In conclusion, the present study demonstrated T-cell suppression during neonatal sepsis is accompanied by a decrease in IL-2 production. Such suppressions were ameliorated with COX-2 inhibitor suggesting a role for PGE2 in the suppressed T-cell-mediated immune function in neonatal sepsis.     

Synthesis and in vitro antibacterial evaluation of N-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-yl] piperazinyl quinolones

A series of N-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-yl]piperazinyl quinolones (7a-c) were synthesized and evaluated for in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria. The antibacterial data revealed that compounds 7a-c had strong and better activity against tested Gram-positive organisms than the reference quinolones such as ciprofloxacin, norfloxacin and enoxacin. However, all three compounds were nearly inactive against Gram-negative bacteria. Compound 7a (ciprofloxacin analogue) was the most active compound against Gram-positive bacteria (MIC=0.008-0.015 mug mL(-1)).     

Production and characterization of monoclonal antibodies with specificity for human HLA-G isoforms

Production of monoclonal antibodies to HLA-G, a nonpolymorphic antigen of non-classical HLA class I, is of basic and clinical importance. In the present study, monoclonal antibodies were prepared which recognize different membrane bound and soluble isoforms of HLA-G, following immunization of BALB/c mice with a synthetic peptide. Use of this peptide (23 residues), which is present in the alpha1 domain of HLA-G, was previously demonstrated to provide antibodies useful for recognition of HLA-G isoforms in human placenta. Antibody-producing hybridomas were screened by an indirect one-step ELISA method. A clone designated 5E6H7, secreted antibodies useful in immunostaining studies involving both surface HLA-G of placental tissues and soluble forms of this antigen in human sera. In addition, unreactivity of this antibody with human lymphocytes and sections of normal human skin was observed by immunofluorescence microscopy, thus demonstrating its specificity for HLA-G.