Sepsis-induced SOCS-3 expression is immunologically restricted to phagocytes

We have shown that immune cells from septic mice exhibit a suppressed response to exogenous stimuli in vitro. The suppressors of the cytokine signaling (SOCS) family are proteins that block intracellular signaling and can be induced by inflammatory mediators. Therefore, we hypothesized that SOCS-3 is up-regulated in immune cells in response to a septic challenge induced by cecal ligation and puncture (CLP). Mice were subjected to CLP or sham-CLP, and 2-48 h later, the blood, thymus, spleen, lung, and peritoneal leukocytes were harvested and examined. SOCS-3 was undetectable in thymocytes or blood leukocytes. In contrast, SOCS-3 was up-regulated in the spleen, lung, and peritoneal leukocytes in a time-dependent manner. Further examination revealed that only the macrophages and neutrophils expressed SOCS-3. These data suggest that cytokines and bacterial toxins present during sepsis have the ability to suppress the cytokine and/or lipopolysaccharide response and the function of immune cells by up-regulating SOCS-3.     

Triple synchronous neoplasms in one kidney: report of a case and review of the literature

We report the case of a patient with three synchronous but histologically different primary renal tumors that were all in the same kidney. Two tumors were different subtypes of renal cell carcinoma (RCC), and the third was a variant form of angiomyolipoma. The patient was a 62-year-old man who was receiving antihypertensive drugs and came to our hospital for a regular check-up. Ultrasonography performed during the visit revealed a left renal mass, but the patient had no related symptoms. Subsequent computed tomography revealed two round, high-density masses, one in the mid-portion and the other in the lower pole of the left kidney, and multiple cysts in the right kidney and the liver. The mass in the mid-portion measured 3.3 x 3.0 x 2.8 cm, and the mass in the lower pole measured 1.7 x 1.1 x 0.9 cm. A left radical nephrectomy was performed. On gross examination, an additional ovoid nodule (0.6 cm in the greatest dimension) was found in the lower pole. Microscopically, the largest tumor consisted of a broad alveolar arrangement of large round cells with abundant eosinophilic or clear cytoplasm, distinct cell borders, and perinuclear halos, features consistent with chromophobe RCC. The smallest tumor was a conventional (clear-cell) RCC. The third tumor was composed solely of atypical epithelioid cells with prominent nucleoli and yellowish-brown to black pigments. The tumor cells were positive for melanin (Fontana-Masson stain), the melanoma marker HMB45, vimentin, smooth-muscle actin, and the macrophage marker CD68 and were negative for cytokeratin. This tumor was considered a pigmented epithelioid type of angiomyolipoma. The histologic, histochemical, and immunohistochemical features in this case confirmed the presence of three synchronous primary tumors, a chromophobe and a clear-cell type RCC and a pigmented epithelioid angiomyolipoma, all of which were in the same kidney. This case is the first of its type reported in the literature.     

Amoeboid Microglial Cells and not Astrocytes Synthesize TNF-alpha in Swiss Mouse Brain Cell Cultures

The role of tumour necrosis factor (TNF-alpha) in brain physiology and pathology has been the focus of several studies. However, the source of this lymphokine in the central nervous system and the regulation of its synthesis is still poorly understood. We have therefore used purified astrocytes and brain macrophages in culture to compare the abilities of these two cell types to synthesize TNF-alpha and its mRNA. We find that, in the Swiss mouse, no significant TNF activity or TNF-alpha mRNA are produced by astrocytes, even following activation with lipopolysaccharides (LPS). On the other hand, purified microglial cells express a cytotoxic activity able to kill TNF-sensitive LM cells. Part of this activity is released into the culture medium and part remains bound to the membrane after mild paraformaldehyde treatment, demonstrating the existence in the culture of the soluble and membrane-bound forms of TNF activity. The fact that amoeboid microglial cells, and not astrocytes, are the actual source of TNF in brain cultures was further demonstrated by Northern blot analysis and in situ hybridization using a TNF-alpha specific oligonucleotide probe. The definition of the cell type which, in the CNS, is responsible for TNF synthesis will allow the regulation of this lymphokine to be analysed and opens the way for a better understanding of the interactions between amoeboid microglial cells and the other cell types which make up the nervous system.     

Identification of residues linked to the slow-->fast transition of thrombin.

Residues energetically linked to the allosteric transition of thrombin from its anticoagulant slow form to the procoagulant fast form have been identified by site-directed mutagenesis. The energetics of recognition by the two forms of the enzyme were probed by using a synthetic chromogenic substrate, fibrinogen, and hirudin. The thrombin residues E39, W60d, E192, D221, and D222 are linked to the slow-->fast transition and are part of an "allosteric core" through which events originating at the Na+ binding loop propagate to other regions of the enzyme. The thrombin residues Y76, W96, W148, and R173 lie at the periphery of the allosteric core, affect recognition of fibrinogen and hirudin to the same extent in both forms, and are not linked to the slow-->fast transition.     

Clear cell sarcoma of kidney in an adolescent and in young adults: a report of four cases with ultrastructural, immunohistochemical, and DNA flow cytometric analysis

Clear cell sarcoma of the kidney is a distinct, highly malignant pediatric neoplasm. Its occurrence in adults is extremely rare and the subject of isolated case reports. We present a series of four cases (three males and one female) identified in an adolescent and in young adults (16, 18, 20, and 25 years) with flank mass (three cases), hematuria (two cases), flank pain (two cases), and hypertension (one case). Three patients had stage III disease and one had stage I disease (National Wilms' Tumor Study staging system). All tumors had predominantly or exclusively the classic histology of a monotonous proliferation of uniform small round cells with evenly distributed fine chromatin, although focal microcyst formation (two cases) and spindled architecture (one case) (variant patterns) were also noted. Therapy in all cases consisted of surgery and chemotherapy with or without radiation. Follow-up data (29-202 months) showed distant metastases in all four cases, including the lung (four cases), bone (two cases), and the liver (two cases). Three patients died of disease at 29, 59, and 63 months (mean, 50.3 months), and one patient is alive with no evidence of disease at 202 months. Ultrastructural features included scattered primitive junctions, short and irregular cytoplasmic extensions, and scant to a moderate amount of mitochondria. Immunohistochemical study (three cases) showed immunoreactivity with vimentin (two cases) and no reaction with cytokeratin, epithelial membrane antigen, S-100 protein, or desmin. Flow cytometric analysis showed diploid DNA content in three primary tumors and tetraploidy in one metastatic tumor. The proliferative activity (S-phase fraction) was low to intermediate (mean, 9.8%). Our data suggest that clear cell sarcoma of the kidney in the young adult age group resembles its pediatric counterpart in ultrastructural and immunohistochemical characteristics, proclivity for skeletal and visceral metastasis, DNA diploid status with relatively low S-phase, and aggressive clinical course. Clear cell sarcoma of the kidney in adult patients, although rare, must be differentiated from sarcomatoid carcinoma, sarcomas, and round cell tumors because of its unique characteristics in comparison to other renal neoplasms.     

Increased risk of salivary gland tumors after low-dose irradiation

Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow-up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.     

Adsorption of Heavy Metals Ions from Mining Metallurgical Tailings Leachate Using a Shell-Based Adsorbent: Characterization,Kinetics and Isotherm Studies

This study defines the optimal parameters that allow the use of waste mollusk shells (WS) to remove heavy metals from three mining and metallurgical leachates. First, the influence of parameters such as pH, contact time, initial metal concentration, adsorbent dose and the presence of co-ions in Cu²⁺, Cd²⁺, Zn²⁺ and Ni²⁺ adsorption was investigated in synthetic solutions. Metal uptake was found to be dependent on the initial pH of the solution, the removal rate increasing with the increase in pH, showing the highest affinity at pH 5–6. The removal efficiency at lower concentrations was greater than at higher values. The competitive adsorption results on bimetallic solutions showed that the adsorption capacity of the sorbent was restricted by the presence of other ions and suppressed the uptake of heavy metals compared to the single adsorption. Cu²⁺ was the metal that most inhibited the removal of Cd²⁺, Zn²⁺ and Ni²⁺. The Langmuir isotherm provided the best fit to the experimental data for Cu²⁺, Cd²⁺ and Zn²⁺ and the Freundlich isotherm, for Ni²⁺. The data showed that the maximum adsorption capacity a_max for Zn²⁺, Cd²⁺ and Cu²⁺, was 526.32 mg g⁻¹, 555.56 mg g⁻¹ and 769.23 mg g⁻¹, respectively. Sorption kinetics data best fit the pseudo-second-order kinetic model. The results obtained in the tests with three mining and metallurgical leachates showed that WS were effective in simultaneously removing several heavy metals ions such as Cu, Ni, Zn, Cd, Ni, As and Se.