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BACKGROUND: Recent molecular studies of the RHD gene have revealed that Del individuals retain a grossly intact RHD gene or have a portion of RHD in their genomes. No Del phenotype has yet been shown to induce a primary or secondary alloanti-D immunization, however. CASE REPORT: A 67-year-old D- Japanese woman with a history of allosensitization from transfusion of D+ red blood cells (RBCs) was negative for anti-D at admission. After she received RBCs from 19 apparently D- donors, she developed anti-D with an 8-fold titer. The titer of anti-D increased further to 128-fold after transfusions of cross-match-compatible D- negative RBCs from 40 donors over the next 2 years. Two of 59 donors were found to be RHD gene-positive and antigen D- with a Del phenotype, that is, RHD(K409K). CONCLUSION: This is the first case in which RBCs having the Del phenotype induced a secondary alloanti-D immunization. A D- donor with the RHD(K409K) allele was associated with the development of anti-D. Adverse episodes or evidence of hemolysis was not observed after the transfusion of RHD(K409K) RBCs. Further clinical evidence is needed to reveal whether the Del phenotype has a clinically relevant potential for anti-D immunization. [ABSTRACT FROM AUTHOR]

It is well-known that FK506 strongly inhibits cytokine production by T cells in vitro. However, less evidence is available from in vivo studies of ocular allergy. To study the anti-inflammatory effect of FK506 eye drops on late and delayed-type responses in several animal models of ocular allergy. Rats and guinea-pigs were sensitized with egg albumin (EA) in adjuvant and later challenged by topical EA application to their eyes to examine the late response. Biopsy specimens of conjunctiva were stained with haematoxylin–eosin or stained for T cells and eosinophils. In addition, rats, rabbits and guinea-pigs were sensitized with complete Freund's adjuvant and later challenged by injecting purified protein derivatives for the delayed-type response. Bulbar conjunctival oedema and hyperaemia were graded by score in rabbits, and Evans blue (EB) extravasation was measured in rats and guinea-pigs. FK506 (0.01–1%) and steroid (0.1%) eye drops were instilled in the eyes of animals several times, before and after challenge. FK506 eye drops inhibited T cell and eosinophil infiltration in the late response and EB extravasation in the delayed-type response in rats. Also, they inhibited conjunctival oedema, hyperaemia and ocular mucus in the delayed-type response in rabbits. These effects were similar to those of steroid eye drops (betamethasone sodium phosphate, fluorometholone). FK506 eye drops also inhibited inflammatory cell infiltration, the loss of conjunctival epithelium and decrease of goblet cells in the late response as well as EB extravasation in the delayed-type response in guineapigs, a steroid-resistant species. FK506 eye drops inhibit late and delayed-type responses in animal models of ocular allergy. [ABSTRACT FROM AUTHOR]

OBJECTIVE:&EMSP;:To compare the morphology of the masseter muscle in patients with mandibular prognathism with that of normal subjects. Methods: Three-dimensional X-ray computed tomography (CT) was performed on 69 patients with mandibular prognathism and compared with 91 normal subjects. The angle of the muscle direction in relation to the Frankfurt horizontal plane and the area and the ratio of length of the short to long axes (s/l ratio) on the section perpendicular to the muscle direction were measured. Results: The mean angle, area and s/l ratio in patients with mandibular prognathism was 76.6° (s.d. 4.4°), 318.3 mm2 (s.d. 77.2 mm2) and 0.312 (s.d. 0.049), respectively. Those of the normal subjects were 65.1° (s.d. 4.4°), 368.3 mm2 (s.d. 97.2 mm2) and 0.393 (s.d. 0.054), respectively. The angle was significantly larger, and the area and s/l ratio were significantly smaller than those of normal subjects (P<0.001). Conclusion: The morphology of the masseter muscle in mandibular prognathism is significantly different from that of normal subjects. Our results may be helpful in evaluating the results of orthognathic surgery. [ABSTRACT FROM AUTHOR]

Objective: To examine the possible correlation between the stage of internal derangement and the antero-posterior length of the disk in relation to the length of the articular eminence. Study design: Twenty asymptomatic volunteers with normal joints and 120 patients with TMJ dysfunction underwent MR imaging. The A-P length of the disk in relation to the length of the articular eminence (D/E ratio) was measured. Results: The D/E ratio was 0.95 in the asymptomatic volunteers, 0.83 in patients with disk displacement with reduction, 0.74 in those with disk displacement without reduction and 0.57 in the patients with disk displacement and osteoarthritis. The relationship between the D/E ratio and the stage of internal derangement was statistically significant (P < 0.01). Conclusion: The D/E ratio decreases with advancing internal derangement. We suggest that it is a reliable numerical method for staging the degree of the internal derangement. [ABSTRACT FROM AUTHOR]

The expression of midkine (MK) in lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats was examined. The animals were administered 2000 p.p.m. of BHP in their drinking water for 12 weeks, then maintained without further treatment until being killed 20-28 weeks after the beginning of the experiment. MK mRNA expression of adenocarcinomas and squamous cell carcinomas assessed by means of the reverse transcriptase-polymerase chain reaction and northern blot analysis was significantly higher than in rat embryonic tissues (positive controls) and contrasted strongly with the lack in normal lungs. MK protein was detected immunohistochemically in 58.3% of alveolar hyperplasias, 92.3% of adenomas and 100% of adenocarcinomas and squamous cell carcinomas. The extent of staining significantly increased along with malignant progression in adenomatous (pre-)neoplastic lesions and tended to become more pronounced with malignant progression in squamous lesions. The results suggest that MK may play some essential roles in the development and progression of lung tumors induced by BHP in rats. [ABSTRACT FROM PUBLISHER]

Monitoring the transduction efficiency is of paramount importance in gene therapy. To monitor adenovirus-mediated wild-type p53 gene transfer, we have used a quantitative assay which tests the ability of human p53 to activate transcription in yeast. Selective amplification of cellular and viral p53 transcripts followed by quantitative assessment of mutant p53 content with the assay permits measurement of the wild-type p53 transduction efficiency into SF-188, U251MG and HUG31 glioblastoma cells. One reverse transcription primer tracks the wild-type/mutant ratio of endogenous p53 mRNA (P2), and the other the wild-type/mutant ratio of both endogenous and exogenous p53 mRNA (P1). Following infection of cell lines homozygous for mutant p53, the apparent transduction efficiency calculated (τ0 = [P1 - P2]/[1 + P2]) correlated with the level of p21 expression. Transduction efficiency in heterozygous wild-type/mutant HUG31 cells increased linearly with multiplicity of infection (MOI) for τ0 values between 0.5 and 5.9, and admixture of normal cell-derived RNA produced only a modest reduction in τ0 value, in keeping with theoretical predictions. These results suggest that the yeast p53 functional assay may be a useful tool for monitoring p53 gene therapy. [ABSTRACT FROM AUTHOR]

Apoptosis, a mechanism for removal of genetically damaged cells and for maintenance of desired size of cell populations, has been implicated in tumor development. Previously, we defined polymorphic loci for susceptibility to apoptosis of thymocytes Rapop1, Rapop2, and Rapop3 on mouse Chromosomes 16, 9, and 3, respectively, using recombinant congenic CcS/Dem strains, each of which contains a random set of 12.5% STS/A genome in the genetic background of BALB/cHeA. The STS/A alleles at these loci confer lower susceptibility to radiation-induced apoptosis of thymocytes than the BALB/cHeA. In the present study, we tested susceptibility of colon crypt cells to radiationinduced apoptosis. In contrast to apoptosis in thymus, the STS/A mice were more susceptible to apoptosis in colon than the BALB/ cHeA. Among the CcS/Dem strains, CcS-4, CcS-7, and CcS-16 were more susceptible to apoptosis in colon than the BALB/cHeA; in thymus, the CcS-7 mice are less susceptible, and the CcS-4 and CcS-16 are not different from the BALB/cHeA. Thus, individual CcS/Dem strains showed different apoptosis susceptibility in the two organs. Analysis of (CcS-7 × BALB/cHeA)F2 hybrids revealed linkage of susceptibility to radiation-induced apoptosis of colon crypt cells to two loci on Chrs 9 and 16, to which Rapop2 and Rapop1 are mapped. The STS/A allele at the locus on chromosome 9 results in high susceptibility to apoptosis of colon crypt cells in mice homozygous for the BALB/cHeA allele at the locus on Chr 16. Although these two loci may be identical to Rapop1 and Rapop2, they affect apoptosis in colon in a way different from that in thymus. [ABSTRACT FROM AUTHOR]

We investigated the relationship between regenerating renal tubular epithelial cells and myofibroblast development in chronic progressive nephropathy (CPN) of aged male F344 rats. We used established criteria to classify disease in rats with CPN as grade 1 (n=9), grade 2 (n=10), grade 3 (n=7) and grade 4 (n=4). Five young rats served as controls (grade 0). The ratio of fibrotic tissues per unit area, assessed in collagen type III-immunostained sections by morphometric analysis, increased significantly with advancing grade of CPN. Vimentin-expressing, regenerating renal tubules were found from grade 1 and continued to increase in number up to grade 3, decreasing slightly, however, in grade 4. Similar kinetics were seen for the number of alpha-smooth muscle actin-positive myofibroblasts, and there was a significant correlation between the number of regenerating renal tubules and myofibroblast development (correlation coefficient=0.83, P<0.01). The myofibroblasts developed in close association with the fibrotic areas seen in grades 1-4; the cells also reacted to desmin or vimentin, indicating the activated state. Immunohistochemistry for platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-beta revealed that vimentin-positive renal tubules were positive for PDGF-BB, but negative for TGF-beta, and that interstitial reactive cells showed no positive reactions for both factors. The present studies on rat CPN showed that regenerating renal tubules may be a major source of a fibrogenic growth factor, PDGF-BB, and that the PDGF-BB might induce the development of fibrogenic cells, myofibroblasts, culminating in progressive interstitial fibrosis. [ABSTRACT FROM AUTHOR]