A dominantly inherited malformation syndrome with short stature,upper limb anomaly,minor craniofacial anomalies,and absence of TBX5 mutations: Report of a Thai family

We report on a Thai family with dominantly inherited malformation syndrome with upper limb anomalies, short stature, quadricuspid aortic valve, and minor craniofacial anomalies. The affected individuals comprised a mildly affected mother, a moderately affected daughter, and a most severely affected son. The daughter and son had short stature. The craniofacial abnormalities comprised frontal bossing, hypoplastic nasal bones, depressed nasal bridge, and broad nasal alae. The upper limb defects varies among the patients, ranging from radial ray defects in the mother through radial and ulnar ray defects with unilateral humeral hypoplasia in the daughter to radial ray defects with severe oligodactyly and bilateral humeral hypoplasia in the son. All patients in this family had hypoplasia of the shoulder girdle and resembled what is observed in many families with Holt‐Oram syndrome. Moreover, the son showed quadricuspid aortic valve with mild aortic regurgitation. However, the present family did not show any mutation of the TBX5 gene, a disease‐causing gene of Holt‐Oram syndrome. The present family deserves further investigation on other genes that play a role in the development of the upper limbs, particularly of radial rays. © 2002 Wiley‐Liss, Inc.     

Meaning in measurement of bone mineral content as preoperative evaluation of aged patients

Recently, mean span of life has been prolonged, and extensive operations are performed on aged patients. However, there are cases which have a difference between their chronological and actual ages. Bone mineral content (BMC) decreases with age and the decrease in BMC might suggest deterioration of immunological competence as observed in osteoporosis. Whether BMC can be an index for evaluation of geriatric patients' actual age from the aspect of immunological competence was investigated. Subjects were 54 cases aged more than 60. Twenty-one healthy young males and females were enrolled as the control group. Quantitative CT is used for assessment of BMC. The value obtained by dividing BMC by the standard BMC of the same age and sex, was defined as BMC index. BMC indices of normal BMC group were more than 0.8 and those of decreased BMC group were less than 0.8. Some immunological markers were investigated. Lymphocyte subset OKT3+ was reduced and juvenile lymphocytes expressed by OKT6+ and OKT3+-(OKT4+ + OKT8+) increased (corrected). Increased in juvenile lymphocyte and decrease in lymphocyte blast transformation and competence of generating interleukin 2 were observed in decreased BMC group. BMC is useful as preoperative evaluation for geriatric operative cases and patients of BMC index below 0.8 need to be paid attention to postoperative infection.     

Escherichia coli tryptophan repressor binds multiple sites within the aroH and trp operators

DNase I footprinting and methylation protection studies have been used to analyze the binding of Escherichia coli Trp repressor to the trpR, aroH, and trp operators. The methylation protection assay shows that Trp repressor binds in two successive major grooves of the trpR operator, three successive major grooves of the aroH operator, and four successive major grooves of the trp operator. The simplest model that explains the difference in Trp repressor interaction at the three operators is that the aroH and trp operators are composed of multiple, helically stacked binding sites. When viewed in three dimensions, each site is positioned on a different face of the DNA, and together process up the surface of the DNA helix. Analysis of a deletion derivative of the trp operator supports this model.     

Clonorchiasis complicated with duodenal papillary cancer in a visitor from China]

It is well known that long-term infection with Clonorchis sinensis often causes bile duct cancer, usually. It occurs in the intrahepatic bile duct. We encountered a rare case of clonorchiasis complicated with duodenal papillary cancer. The patient was a woman from China. Although clonorchiasis is rarely found in Japan, the promotion of international exchange may increase the number of visitors from endemic areas. Thus we must pay sufficient attention to this disease. Also, we reported that the microplate ELISA technique was useful in the diagnosis of clonorchiasis with high accuracy in this case.     

Monoclonal Antibody Specific for TIRC7 Induces Donor-specific Anergy and Prevents Rejection of Cardiac Allografts in Mice

T cell immune response c-DNA (TIRC7) is up-regulated during the early stages of T-cell activation in response to alloantigens. In this study, we analyzed the effects of newly developed monoclonal antibodies (mAb) against TIRC7 in acute cardiac allograft rejection. Fully vascularized heterotopic allogeneic heart transplantation was performed in mice across a full-mismatch barrier (C57Bl/10 into CBA). Recipients received seven injections (day 0-7) of a novel anti-TIRC7 mAb or remained untreated. Graft survival, histology and ex vivo lymphocyte functions were tested. Targeting of TIRC7 with an anti-TIRC7 mAb diminishes lymphocyte infiltration into grafts resulting in delay of morphological graft damage and prolongation of allograft survival. The lymphocytes from anti-TIRC7 mAb-treated animals exhibit hypo-responsiveness without evidence of lymphocyte depletion against the donor allo-antigens. Proliferation and expression of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were down-regulated while interleukin-4 (IL-4) and IL-10 expression were spared. Moreover, anti-TIRC7 mAb enhanced up-regulation of CTLA-4 expression but suppressed up-regulation of CD25 on stimulated lymphocytes in vitro and in vivo. Ligation of TIRC7 has important effects on the regulation of co-stimulatory signaling pathways associated with suppressing of T-cell activation. Targeting of TIRC7 may therefore provide a novel therapeutic approach for modulating T cell immune responses during organ transplantation.     

Successful Repair of the Right Atrial Isomerism, Double Outlet Right Ventricle, Cornmon Atrioventricular Canal, Pulmonary Stenosis, and Total Anomalous Pulmonary Venous Connection

A 6-year-old boy was successfully operated on for double outlet ventricle, common atrioventricular canal with severe valvular regurgitation, right atrial Isomerism, L-loop ventricles, total anomalous pulmonary venous connection, and pulmonary stenosis with hypoplastic left pulmonary artery. The Interventricular rerouting from the left ventricle to the ascending aorta was performed with a spiral patch, the lnteratrlal switching was performed by a Mustard patch, the common atrioventricular orifice was partitioned and valve repair was performed, and an 18-mm valved conduit was inserted between the right ventricle and the pulmonary artery. Although the patient had a small residual ventricular septal defect and pulmonary stenosls, the patient Is alive and well.     

K-Ras gene status and expression of Ras/mitogen-activated protein kinase (MAPK) signaling molecules in ameloblastomas

BACKGROUND: To clarify the roles of rat sarcoma (Ras)/mitogen-activated protein kinase (MAPK) signaling pathway in oncogenesis and cytodifferentiation of odontogenic tumors, K-Ras gene status and expression of Ras, Raf1, MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK)1, and ERK1/2 proteins were analyzed in ameloblastomas as well as in tooth germs. METHODS: Paraffin sections of 10 tooth germs and 46 benign and 6 malignant ameloblastomas were examined immunohistochemically for the expression of K-Ras, Raf1, MEK1, and ERK1/2. Frozen tissue samples of 22 benign ameloblastomas and 1 malignant (metastasizing) ameloblastoma were analyzed by direct DNA sequencing to detect K-Ras gene alteration. RESULTS: Immunohistochemical reactivity for K-Ras, Raf1, MEK1, and ERK1/2 was detected in both normal and neoplastic odontogenic epithelium, and these molecules were reactive chiefly with odontogenic epithelial cells neighboring the basement membrane. Plexiform ameloblastomas showed slightly stronger expression of these Ras/MAPK signaling molecules than follicular ameloblastomas. Keratinizing cells and granular cells showed decreased reactivity for the signaling molecules. Basal cell ameloblastomas showed slightly stronger reactivity for the signaling molecules than did the other subtypes. K-Ras immunoreactivity in malignant ameloblastomas was lower than that in dental lamina of tooth germs. Direct DNA sequencing showed a GGT to GCT point mutation at codon 12 of K-Ras gene in one ameloblastoma. Conclusion: Expression of K-Ras, Raf1, MEK1, and ERK1/2 in tooth germs and ameloblastomas suggests that Ras/MAPK signaling pathway functions to regulate cell proliferation and differentiation in both normal and neoplastic odontogenic epithelium. K-Ras gene status implied that K-Ras mutations might play a minor role in oncogenesis of odontogenic epithelium.