Changes in the molecular sieve of glomerular basement membrane in rats with aminonucleoside nephrosis.

Isolated and purified glomerular basement membranes (GBM) of normal and aminonucleoside (PAN) nephrosis rats were observed by electron microscopy after negative staining. Although GBM of normal rats appeared as a molecular sieve with uniform pores, GBM of nephrotic rats showed enlargement and elongation of the pores. For an average of fifty pores, the long dimension was 40.4+/-10.7 A and the short dimension 13.8+/-3.6 A in nephrosis whereas the long dimension was 12.3+/-2.5 A and the short dimension 8.4+/-1.0 A in normal rats. Changes in the pores in GBM were thought to result in increased permeability of serum protein and hence proteinuria

Ultrastructure of rat renal tubular basement membrane--meshwork structure demonstration by negative staining.

The tubular basement membrane (TBM) (i.e. tubular basal lamina) of rat kidney was shown to be a fine meshwork by electron microscopy after negative staining. Strands of the meshwork formed a regular three dimensional lattice work. The pores of the meshwork were polygonal. There were two main pore sizes: one approximately 30 A in diameter, the other 42--60 A. In view of our previous observation that glomerular and alveolar basement membranes were made up fine meshwork, it is quite possible that the basement membranes of other organs are also made up such fine meshwork.</p

Detection of DR antigen on leukemic cells from a patient suffering from adult T-cell leukemia and progressive systemic sclerosis.

This report concerns an unusual case of adult T cell leukemia (ATL) complicated with progressive systemic sclerosis (PSS). The surface markers of peripheral blood mononuclear cells (PBM) and lymph node cells, both of which mainly consisted of leukemic cells, were examined. The effect of these cells on the pokeweed mitogen (PWM)-induced IgG synthesis by normal PBM also was studied. The leukemic cells formed rosettes with sheep red blood cells (SRBC; E) and expressed T cell antigen, Leu-1, and DR antigen. The detection of cell surface antigens was carried out by employing monoclonal antibodies against these antigens. We diagnosed this case as DR positive ATL. In terms of the immunoregulatory function of these leukemic cells, the co-culture experiments showed that these cells had some suppressive effect on the PWM-induced IgG production by allogeneic normal PBM.</p

DataSheet1_Physalin H, physalin B, and isophysalin B suppress the quorum-sensing function of Staphylococcus aureus by binding to AgrA.PDF

The virulence of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), depends on the expression of toxins and virulence factors controlled by the quorum-sensing (QS) system, encoded on the virulence accessory gene regulator (agr) locus. The aim of this study was to identify a phytochemical that inhibits Agr-QS function and to elucidate its mechanism. We screened 577 compounds and identified physalin H, physalin B, and isophysalin B—–phytochemicals belonging to physalins found in plants of the Solanaceae family—–as novel Agr-QS modulators. Biological analyses and in vitro protein–DNA binding assays suggested that these physalins suppress gene expression related to the Agr-QS system by inhibiting binding of the key response regulator AgrA to the agr promoters, reducing the function of hemolytic toxins downstream of these genes in MRSA. Furthermore, although physalin F suppressed gene expression in the Agr-QS system, its anti-hemolytic activity was lower than that of physalins H, B, and isophysalin B. Conversely, five physalins isolated from the same plant with the ability to suppress Agr-QS did not reduce bacterial Agr-QS activity but inhibited AgrA binding to DNA in vitro. A docking simulation revealed that physalin interacts with the DNA-binding site of AgrA in three docking states. The carbonyl oxygens at C-1 and C-18 of physalins, which can suppress Agr-QS, were directed to residues N201 and R198 of AgrA, respectively, whereas these carbonyl oxygens of physalins, without Agr-QS suppression activity, were oriented in different directions. Next, 100-ns molecular dynamics simulations revealed that the hydrogen bond formed between the carbonyl oxygen at C-15 of physalins and L186 of AgrA functions as an anchor, sustaining the interaction between the carbonyl oxygen at C-1 of physalins and N201 of AgrA. Thus, these results suggest that physalin H, physalin B, and isophysalin B inhibit the interaction of AgrA with the agr promoters by binding to the DNA-binding site of AgrA, suppressing the Agr-QS function of S. aureus. Physalins that suppress the Agr-QS function are proposed as potential lead compounds in the anti-virulence strategy for MRSA infections.</p

Escalated Maximum Dose in the Planning Target Volume Improves Local Control in Stereotactic Body Radiation Therapy for T1-2 Lung Cancer

Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. The purpose of this study was to investigate the optimal dose distribution and prognostic factors for local control (LC) after SBRT for lung cancer. A total of 104 lung tumors from 100 patients who underwent SBRT using various treatment regimens were analyzed. Dose distributions were corrected to the biologically effective dose (BED). Clinical and dosimetric factors were tested for association with LC after SBRT. The median follow-up time was 23.8 months (range, 3.4–109.8 months) after SBRT. The 1- and 3-year LC rates were 95.7% and 87.7%, respectively. In univariate and multivariate analyses, pathologically confirmed squamous cell carcinoma (SQ), T2 tumor stage, and a Dmax 10) were associated with worse LC. The LC rate was significantly lower in SQ than in non-SQ among tumors that received a Dmax 10) (p = 0.016). However, there were no significant differences in LC rate between SQ and non-SQ among tumors receiving a Dmax ≥ 125 Gy (BED10) (p = 0.198). To conclude, SQ, T2 stage, and a Dmax 10) were associated with poorer LC. LC may be improved by a higher Dmax of the planning target volume