KiSS-1 is a promising candidate tumor-suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS-1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS-1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS-1 expression by using the median as the cutoff value of KiSS-1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS-1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS-1-expressing tumors had a significantly worse overall and disease-free survival. In multivariate analysis, KiSS-1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS-1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention.

Congenital malformations such as neural tube defects and a kinky or waved vertebral column were observed at higher incidence in embryos from nonobese diabetic (NOD) female mice with overt diabetes (NOD-D; 40.3%, P less than 0.005) or without overt diabetes (NOD-N; 8.4%, P less than 0.05) than in control Institute of Cancer Research (ICR) mouse embryos (1%) at day 13 of gestation. In vivo and in vitro preimplantation development of NOD-N, NOD-D, and ICR embryos did not differ in rate of development, size, or morphology. Embryos cultured from one-cell to early blastocyst stage were mutually transferred to uterine horns of pseudopregnant females between NOD-D and ICR mice and examined at day 13 of gestation. There were significant decreases in ratios of implantation and of viable embryos in ICR embryos transferred to NOD-D recipients (52%, P less than 0.001 and 14%, P less than 0.001, respectively) compared with those ratios in ICR embryos transferred to ICR uteri (79.2 and 56.2%) or those in NOD-D embryos transferred to ICR uteri (70.3 and 33.1%). Furthermore, 18 of 45 viable ICR embryos transferred to NOD-D dams had malformations, whereas there were no malformations in 73 viable ICR embryos transferred to ICR recipients, suggesting deleterious effects of maternal diabetic environment to embryos. On the other hand, 8 of 58 viable NOD-D embryos that were cultured in vitro and transferred to ICR uteri had malformations such as neural tube defects.(ABSTRACT TRUNCATED AT 250 WORDS)

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These craniofacial features, especially the ear anomalies and facial asymmetry indicate that the Hfm transgenic mouse represents a useful model for the HFM-microtia spectrum. In particular, it supports the hypothesis that at least a proportion of HFM anomalies has a genetic causation mediated via mesenchymal disruptions and possibly embryonic hemorrhages.

Exencephaly has been induced in mouse embryos by chlorambucil (CA), a cytotoxic agent. To understand the course of development of this malformation, open neural tube defects in CA‐treated mice were examined using light and scanning electron microscopes (SEM). CA was given to the pregnant mice on day 7.4 of gestation. Embryos were removed and fixed on gestational days 9.3–9.4, 9.7–9.8 and 10.4, and compared to control embryos from untreated mice. By gestational day 9.4, all control embryos had closed neural tubes, except for the posterior neuropores, and well developed brain vesicles. By contrast, in the experimental embryos the frequencies of open neural tube were 26/33 (78.8%), 32/ 40 (80.0%) and 23/66 (34.8%) on each day examined, respectively. Open neural tube defects were classified into six patterns according to the location and magnitude of the open area. The patterns of open neural tube on day 9.7–9.8 were diverse; however, in almost all cases on day 10.4 the open neural tube appeared in a region from the caudal forebrain to the rostral hindbrain. It was evident that an unusual pattern of closure of the neural tube was involved in forming the cranial neural tube. The present study shows that failure of closure of the cranial neural tube in the CA‐treated mouse embryos can be defined as a primary neural tube defect (NTD), which can be, in part, repaired by unusual closure of the neural tube. At high magnifications of SEM, the neuroectodermal surfaces of the 9.0‐day affected embryos often had a number of slender processes projecting from the neuroepithelial cells. “Ruffles” and “blebs” at the lateral edges of the neural folds were observed in both control and affected embryos.

ABSTRACT. Monoclonal antibodies against human plasminogen activator urokinase have been produced. A G62 hybridoma-producing antibody (IgG) was purified on a DEAE-cellulose column, and it proved useful for the measurement, identification and purification of antigens that had approximate molecular weights of 55-and 33-Kdaltons.For immunochemical measurements and purification, a competitive enzymelinked immunosorbent assay (ELISA) and affinity chromatography using antibody-immobilized Sepharose 4B were developed. The ELISA has sensitivity to 20 p mole antigen molecules. The binding capacity of the antigen on the affinity column was evaluated on SDS-polyacrylamide slab gels as well as by fibrin autography and ELISA. Results showed that there was quantitative purification with no loss of enzyme activity in the one-step procedure.Western blotting and affinity binding showed antigenic bands with apparent molecular weights of 55-and 33-Kdaltons. Because the 55-Kdalton form contains 33-and 22-Kdalton components connected by a disulfide bond, the epitope domain is present on the 33-Kdalton chain.Using this antibody, we examined human kidney sections by direct immunofluorescence to locate the antigen. It was found in epithelial cells of convoluted segments, in glomerulus cells and in capillary endothelial cells, evidence that renal tubular cells synthesize the antigen which then is secreted in urine.

Objective Our comprehension of hemifacial microsomia (HFM) has been hindered by its diverse phenotype and unclear etiopathogenesis. The conventional view has been that HFM's facial defects result from embryonic hemorrhages in the region of the first and second branchial arches. A more recent model based on a transgenic mutation of a locus termed Hfm (B1 to B3 on chromosome 10) appears to provide an insight into HFM causation. This study investigated the validity of this model by examining the Hfm craniofacial phenotype and histological development of the embryonic head (E13.5 to 17.5). Results The results confirmed that although the loss-of-function mutation was transmitted in an autosomal dominant manner, the penetrance rate was significantly reduced and only Hfm heterozygotes were viable. The observations here extend the Hfm phenotype beyond microtia and jaw asymmetry to include structural and positional anomalies affecting the external auditory meatus, middle ear, cranial base, maxilla, and pharyngeal structures. Temporo-mandibular joint (TMJ) development and palatal shelf fusion were also affected in a small number of cases. In addition, some Hfmembryos displayed a novel finding: transposition of the developing inner ear between the tubotympanic recess and cranial base. Conclusions These craniofacial features, especially the ear anomalies and facial asymmetry indicate that the Hfm transgenic mouse represents a useful model for the HFM-microtia spectrum. In particular, it supports the hypothesis that at least a proportion of HFM anomalies has a genetic causation mediated via mesenchymal disruptions and possibly embryonic hemorrhages.