Receptors for Treponema pallidum attachment to the surface and matrix proteins of cultured human dermal microvascular endothelial cells

Pathogenicity of Treponema pallidum may depend upon the binding of Treponema pallidum to matrix proteins, especially to fibronectin. Infectious organism or cell to matrix interactions are mediated by a family of adhesion molecule receptors known as integrins. Once in the host, the pathogenic Treponema pallidumdum adheres to the vascular endothelium and readily penetrates surrounding tissues. Fibronectin plays an important role in the mediation of the attachment of Treponema pallidum to host cells, including endothelial cells. We found that the binding of Treponema pallidum to human dermal microvascular endothelial cells and to a glass surface coated with fibronectin is inhibited by the presence of arginine-glycine- aspartic acid (RGD), and analysis of the surface receptor revealed an antigenic similarity to an integrin molecule, namely alpha5. This ability to adhere to host endothelium and fibronectin is quite unique to T. pallidum among the treponemes, and may be a key pathogenic factor.     

PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted,but Functional in Patients with COVID-19

1. Download : Download high-res image (218KB)
2. Download : Download full-size image

     

Efficient correction for CT image artifacts caused by objects extending outside the scan field of view

The purpose of this paper is to develop a method of eliminating CT image artifacts generated by objects extending outside the scan field of view, such as obese or inadequately positioned patients. CT projection data are measured only within the scan field of view and thus are abruptly discontinuous at the projection boundaries if the scanned object extends outside the scan field of view. This data discontinuity causes an artifact that consists of a bright peripheral band that obscures objects near the boundary of the scan field of view. An adaptive mathematical extrapolation scheme with low computational expense was applied to reduce the data discontinuity prior to convolution in a filtered backprojection reconstruction. Despite extended projection length, the convolution length was not increased and thus the reconstruction time was not affected. Raw projection data from ten patients whose bodies extended beyond the scan field of view were reconstructed using a conventional method and our extended reconstruction method. Limitations of the algorithm are investigated and extensions for further improvement are discussed. The images reconstructed by conventional filtered backprojection demonstrated peripheral bright-band artifacts near the boundary of the scan field of view. Images reconstructed with our technique were free of such artifacts and clearly showed the anatomy at the periphery of the scan field of view with correct attenuation values. We conclude that bright-band artifacts generated by obese patients whose bodies extend beyond the scan field of view were eliminated with our reconstruction method, which reduces boundary data discontinuity. The algorithm can be generalized to objects with inhomogeneous peripheral density and to true "Region of Interest Reconstruction" from truncated projections.     

Thymocyte-thymocyte interaction for efficient positive selection and maturation of CD4 T cells

Despite numerous reports on MHC class II expression by T cells from a wide spectrum of mammalian species including humans, the biological relevance of this phenomenon has never been tested with appropriately designed animal models. To address this issue, we developed mouse models in which immature thymocytes are the only positively selecting antigen-presenting cells in the thymus. In these mice, CD4+ T cells were generated with the appropriate maturation phenotype and showed a diverse repertoire of TCR Vbetas. The CD4+ T cells were functionally competent, mediating effective allogeneic responses that involved polyclonal TCR Vbetas. These results suggest that the thymocyte-thymocyte (T-T) interaction operates as an independent pathway for CD4+ T cell selection in the thymi of species with MHC II-positive thymocytes. This T-T interaction appears to be the basis for the generation of donor MHC-restricted CD4+ T cells in xenogeneic hosts.     

Alterations in extracellular matrix components in transplant glomerulopathy

The distribution pattern of extracellular matrix (ECM) components in transplant glomerulopathy was studied in relation to light microscopic features, actin expression of mesangial cells, and intraglomerular inflammatory cells. Nine cases of mild (group I) and nine cases of severe (group II) transplant glomerulopathy were stained with antisera against fibronectin (FN), tenascin (TN), collagen types III and IV, smooth muscle actin, CD45RO, CD68, and Ki-67 antigen. The composition of ECM was similar in the two groups. The expanded mesangium was diffusely stained by type-IV collagen, FN and TN, and focally and weakly stained by type-III collagen and smooth muscle actin. Type-IV collagen was linearly stained along the capillary walls, imparting a double-contour feature, whereas FN and TN showed granular staining along the capillary walls. CD68 positive cells were increased in severe transplant glomerulopathy, but this increase was not related to ECM deposition. These findings suggest that increased glomerular deposition of normal and abnormal ECM components participate in the evolution of transplant glomerulopathy. Received: 5 October 1999 / Accepted: 17 January 2000     

High-performance liquid chromatographic determination of trimebutine and its major metabolite, N-monodesmethyl trimebutine, in rat and human plasma

A rapid, selective and very sensitive ion-pairing reversed-phase HPLC method was developed for the simultaneous determination of trimebutine (TMB) and its major metabolite, N-monodesmethyltrimebutine (NDTMB), in rat and human plasma. Heptanesulfonate was employed as the ion-pairing agent and verapamil was used as the internal standard. The method involved the extraction with a n-hexane-isopropylalcohol (IPA) mixture (99:1, v/v) followed by back-extraction into 0.1 M hydrochloric acid and evaporation to dryness. HPLC analysis was carried out using a 4-microm particle size, C18-bonded silica column and water-sodium acetate-heptanesulfonate-acetonitrile as the mobile phase and UV detection at 267 nm. The chromatograms showed good resolution and sensitivity and no interference of plasma. The mean recoveries for human plasma were 95.4+/-3.1% for TMB and 89.4+/-4.1% for NDTMB. The detection limits of TMB and its metabolite, NDTMB, in human plasma were 1 and 5 ng/ml, respectively. The calibration curves were linear over the concentration range 10-5000 ng/ml for TMB and 25-25000 ng/ml for NDTMB with correlation coefficients greater than 0.999 and with within-day or between-day coefficients of variation not exceeding 9.4%. This assay procedure was applied to the study of metabolite pharmacokinetics of TMB in rat and the human.     

Age-related changes in gene expression patterns of matrix metalloproteinases and their collagenous substrates in mandibular condylar cartilage in rats

Matrix metalloproteinases (MMPs) have been implicated in physiological cartilage matrix remodelling as well as in pathological and invasive extracellular matrix remodelling of tissue. Age-related changes in the gene expression patterns of MMPs in mandibular condylar cartilages (MCCs) were analysed. We examined the gene expression patterns of Mmp-8 and -13 and their substrates, Col1a1, Col2a1 and Col10a1, in MCC of growing and ageing rats. Temporomandibular joints of male Wistar rats aged 4, 8, 16 and 32 weeks were subjected to in situ hybridization analysis. Histologically, MMCs showed characteristics of growth plate cartilage at ages 4 and 8 weeks, and more closely resembled articular cartilage thereafter. Mmp-8 was expressed in the cells in all cartilaginous cell layers at ages 4 and 8 weeks, and then was localized only in the mature cells at ages 16 and 32 weeks. Whereas Mmp-13 expression was limited to the lowermost hypertrophic chondrocytes in the growth stage, mature chondrocytes instead of hypertrophic chondrocytes expressed Mmp-13 in adult non-hypertrophic MCC. Because Mmp-8 and -13 expression overlapped with Col2a1 and Col10a1, chondrocytes could play a pivotal role in degradation as well as production of the cartilaginous matrix in MCC.     

Different modifying responses of capsaicin in a wide-spectrum initiation model of F344 rat

The modifying potential of capsaicin (CAP) on lesion development was examined in a rat multiorgan carcinogenesis model. Groups 1 and 2 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, ip, single dose at commencement), N-methylnitrosourea (MNU) (20 mg/kg, ip, 4 doses at days 2, 5, 8, and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Group 3 received vehicles without carcinogens during the initiation period. Group 4 served as the untreated control. After this initiating procedure, Groups 2 and 3 were administered a diet containing 0.01% CAP. All surviving animals were killed 20 weeks after the beginning of the experiment and the target organs examined histopathologically. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with CAP. CAP treatment significantly decreased the incidence of adenoma of the lung but increased the incidence of papillary or nodular (PN) hyperplasia of the urinary bladder. The tumor incidence of other organs, such as the kidney and thyroid, was not significantly different from the corresponding controls. These results demonstrated that concurrent treatment with CAP not only can inhibit carcinogenesis but can also enhance it depending on the organ. Thus, this wide-spectrum initiation model could be used to confirm organ-specific modification potential and, in addition, demonstrate different modifying effects of CAP on liver, lung, and bladder carcinogenesis.     

Endocrinology: Randomized trial of misoprostol and cervagem in combination with a reduced dose of mifepristone for induction of abortion

Mifepristone (600 mg) in combination with a prostaglandin hasbeen demonstrated to be a safe, acceptable alternative to vacuumaspiration for induction of abortion in the first 9 weeks ofpregnancy. However, the efficacy and side-effects of differentprostaglandins used in combination with mifepristone have notbeen assessed in a randomized trial. In this study, 800 womenseeking an abortion at gestational age 63 days amenorrhoea wererandomized to receive either 0.5 mg gemeprost by vaginal pessary(group I) or 600 µg misoprostol (group II) by mouth –48h after taking 200 mg mifepristone by mouth. The side-effectsand number of complete abortions were used as measures of efficacy.There was no significant difference in the rate of completeabortion between group I [96.7%; 95% confidence interval (CI)94.9–98.5%, n = 391] and group II (94.6%; 95% CI 92.3–96.9,n = 386). It was not possible to assess the outcome with certaintyin the remaining 23 women. However, there were significantlymore ongoing pregnancies in the women who received misoprostolthan in those who received gemeprost (nine versus one, P <0.01) and in eight of these 10 women the gestation was >49days. Fewer women in group II required analgesia than in groupI (48 versus 60%, P < 0.001) although the number requestingopiate was similar in each group (6.9 versus 5.2%, P > 0.4).The incidence of nausea and vomiting after misoprostol (47.8and 21.9% respectively) was higher (P < 0.001) than aftergemeprost (33.9 and 12% respectively). The incidence of infectionand heavy bleeding was low in both groups (<2%) and onlyone woman required blood transfusion. We conclude that the recommendeddose of mifepristone and gemeprost can be reduced without impairingclinical efficacy in pregnancies up to 63 days amenorrhoea.Misoprostol is a safe alternative prostaglandin but has a higherincidence of ongoing pregnancies especially at gestation after49 days amenorrhoea.     

Small-sized acute subdural hematoma: operate or not.

A retrospective study of 90 cases of small-sized (less than 3 mm on the printed CT film) acute (within 24 hours) subdural hematoma (SASDH) is presented. From March 1985 to December 1986, the SASDH were immediately operated on (operation rate: 86.0%). From January 1988 to December 1989, we attempted to treat them conservatively (operation rate: 49.1%). The patient population for this study consisted of 38 surgically-treated patients in the first period (Group I), 26 surgically-treated patients in the second period (Group IIs), and 26 conservatively-treated patients in the second period (Group IIc). We compared the clinical features, radiologic findings, and outcome of these 3 groups. The clinical features of Group I, including age, sex, Glasgow Coma Scale (GCS) score on admission, pupillary status on arrival, and interval from injury to the CT, did not differ significantly from those of Group II (P greater than 0.01). The only difference was the timing of the operation. In Group I, 20 patients (52.6%) received an operation within 4 hours, while in Group IIs, only 7 patients (26.9%) underwent surgery within 4 hours (P less than 0.05). The radiologic findings of Group I, including the thickness and volume of the hematoma, the degree of midline shift, and the frequency of skull fracture, also did not differ from those of Group II (P greater than 0.1). However, the outcome of Group II strikingly differed from that of Group I. The mortality rate was 76.3% in Group I, while it was 44.2% in Group II (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)