Staphylococcal toxic shock syndrome toxin 1-induced tumor necrosis factor alpha and interleukin-1 beta secretion by human peripheral blood monocytes and T lymphocytes is differentially suppressed by protein kinase inhibitors.

The signal transduction pathways by which staphylococcal toxic shock syndrome toxin 1 (TSST-1) induces tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion were examined with various protein kinase inhibitors. TNF-alpha secretion by normal human monocytes and T cells in response to TSST-1 was suppressed by inhibitors of protein kinase C (H7) and tyrosine kinases (genistein). In contrast, the secretion of IL-1 beta was blocked by a cyclic AMP- and cyclic GMP-dependent kinase inhibitor (HA1004) as well as by H7 and genistein. These results suggest that the secretion of TNF-alpha and IL-1 beta may be differentially regulated by TSST-1 and that protein kinases play an important role in mediating cytokine responses to the toxin.     

Changes of interleukin expression correlate with Helicobacter pylori infection and lymph node metastases in gastric carcinoma.

Helicobacter pylori (HP) infection induces expression of IL-8 and IL-10 in benign gastric epithelium. This study compared the expression of cytokines in CD4+ and CD8+ lymphocyte subsets of peripheral blood lymphocytes (PBL), benign mucosal lymphocytes (ML), and tumor infiltrative lymphocytes (TIL) as well as in the benign and malignant epithelial cells of the same patient, with respect to the presence of HP infection, lymph node metastases, and tumor histologic type. The mRNA of the cytokines was measured by a semiquantitative RT-PCR method. The levels were ranked and compared using the Wilcoxon sign-ranked test. Compared with CD8+ ML, the CD8+ TIL expresses higher levels of IL-6 and IL-8 but lower level of IL-4 in patients with lymph node metastases. In patients with HP infection, expression of IL-8 and IL-10 was higher in the gastric carcinoma cells than in the benign epithelial cells while expression of IL-6 and IL-8 were higher in CD8+ TIL than CD8+ ML. Overexpression of IL-8 in HP associated gastric carcinomas suggested that they might have arisen from HP-infected epithelial cells.     

Clear cell chondrosarcoma: case report and ultrastructural study

A case of clear cell chondrosarcoma in a Chinese patient is described. The clear cells showed strongly positive S-100 protein immunoreactivity. Ultrastructurally 2 types of chondroid cells were demonstrated. One type appeared more primitive with abundant electron-lucent cytoplasm and sparse organelles. The other type of cell was more differentiated with presence of microvilli and numerous dilated cisternae of endoplasmic reticulum. Previous ultrastructural studies on these lesions were reviewed and compared with the present findings.     

Allelic loss of chromosome 6q in gastric carcinoma.

Loss of the long arm of chromosome 6 (6q) has frequently been reported in gastric carcinoma, and most gastric cancer patients have evidence of intestinal metaplasia in the stomach. However, the relationship between loss of chromosome 6q and intestinal metaplasia has not been studied. In the first part of the study, we define the critical deletion region of chromosome 6q using loss of heterozygosity technique (LOH). Seventeen microsatellite markers were used to detect loss of heterozygosity (LOH) in 37 microdissected gastric tumors. We also examined intestinal metaplasia (IM) foci of the stomach in the same cancer patient (17 cases). Losses on chromosome 6q were detected in high frequency (51%) by LOH. Two distinct regions of common allelic loss were identified: one centered on the marker D6S300 (at 6q16.1) and the second on D6S446 (at 6q27), with LOH frequency of 36% and 31.3%, respectively. The deletions fall into 2 discrete regions, suggesting the existence of at least 2 tumor suppressor genes in 6q. The losses at 6q27 were confirmed by fluorescence in situ hybridization study (FISH). In the cases with LOH in the tumor, no LOH were detected in the autologous IM areas, but losses were detected by FISH. In some cases, these genetic changes may be acquired in the transition from normal gastric mucosa to intestinal metaplasia.     

Multisystem obstruction with cholestasis, pigmentary retinopathy, and cleft palate: a new syndrome?

A number of systemic abnormalities associated with cholestasis have been reported in the literature. This paper describes two unrelated patients with cholestasis and an unusual constellation of abnormalities including cleft palate/lip, hydronephrosis/hydroureter, retinal pigmentation, and intestinal septum.     

Microradiography with an x-ray image magnifier: application to dental hard tissue

The superior spatial resolution obtained with parallel-beam microradiography over conventional contact microradiography has allowed us to image microstructural features of dental hard tissue not previously reported. Our efforts to extend these techniques to provide a real-time capability for viewing in situ demineralization and remineralization effects, at and below the 1-micron level, have resulted in an instrument with several novel and unique features. Using a synchrotron radiation source of x rays and diffraction image magnification, we are now able to change magnification at will (x-ray zoom lens). In addition, the energy range over which the instrument operates gives one considerable flexibility in optimizing image contrast. The techniques of parallel-beam microradiography, and diffraction image magnification are applicable to problems in many other areas of science. Using examples within dental research, the uniqueness and versatility of these new techniques are discussed.     

Rapid and complete donor chimerism after unrelated mismatched cord blood transplantation in 5 children with beta-thalassemia major.

Hematopoietic stem cell transplantation is currently the only curative therapy for beta-thalassemia major. However, <30% of patients have unaffected HLA-identical siblings to serve as donors. We investigated the feasibility of using umbilical cord blood transplants from unrelated HLA mismatched donors and a myeloablative preparative regimen that did not involve total body irradiation. Between October 2003 and November 2004, 5 children with beta-thalassemia major received busulfan, cyclophosphamide, and antithymocyte globulin before cord blood transplantation (median dose, 8.8 x 10(7) cells per kilogram of body weight) from unrelated donors (1 or 2 of 6 HLA antigens were mismatched) and were then evaluated for engraftment, adverse effects, and treatment outcome. The median times to neutrophil engraftment, red blood cell transfusion independence, and platelet engraftment were 12, 34, and 46 days after transplantation, respectively. All patients showed grade II or III acute graft-versus-host disease; none developed extensive chronic graft-versus-host disease until the date of last contact. All patients were alive at a median follow-up of 303 days after transplantation, with complete donor chimerism and transfusion independence. These results are encouraging and clearly show the feasibility of unrelated mismatched umbilical cord blood transplantation in the treatment of children with beta-thalassemia major.     

Intravenous regional analgesia with a forearm tourniquet

Lidocaine 0.5 per cent in a dose of 2 mg X kg-1 was used for intravenous regional analgesia with the tourniquet cuff placed over the forearm. The level of tourniquet cuff pressure employed was the arterial "occlusion pressure" plus 50 mmHg. In 48 normotensive patients successful analgesia was achieved; in seven hypertensive patients, four were pain-free, but the other three required more lidocaine to achieve adequate analgesia. No toxic symptoms and signs were observed. Measurement of serum lidocaine concentrations in 12 patients confirmed the safety of the technique, although small leakage of lidocaine past the inflated forearm tourniquet was detected in some patients.     

Application of Moment Analysis to Nonlinear Drug Disposition Described by the Michaelis–Menten Equation

An equation for the mean residence time (MRT) of drug in the body is derived for the system where drug is injected intravenously into a one-compartment model and eliminated by a single, capacity-limited process. This MRT is a complex function of dose, volume, V _m, and K _m but degenerates into the classical volume/clearance expression under limiting low-dose conditions (K _m C ₀). The equation was validated by comparison of the MRT obtained by direct calculation versus numerical area estimation for simulated data. The equation may be useful analytically in the estimation of the fundamental Michaelis–Menten parameters, V _m and K _m, from experimental data.