Twinning rate in spontaneous abortions.

An unselected series of spontaneous abortions and their mothers were karyotyped with Q-bands to obtain a frequency of twin conceptions lost during the first trimester. Among 661 spontaneous abortions, 15 twin pairs were identified including two sets of conjoined twins. Analysis of Q-band variants permitted the exclusion of cases with two cell lines that could be attributed to maternal contamination or mosaicism. The twinning rate among spontaneous abortions was 1/44 compared with 1/103 live births and stillbirths in the Ontario population. If Weinberg's differential method is applied to these data, the frequency would be as high as 1/30 under the assumption that the incidence of monozygotic twins among abortions is the same as that for live births.     

MEMBRANE-COATING GRANULES OF KERATINIZING EPITHELIA

The purpose of this study has been to obtain information on the development of the envelop of horny cells that resists the action of keratinolytic agents. Toward this end the epidermis, oral mucosa, and tongue epithelium of various vertebrates, as well as the isolated envelopes of horny cells, were examined by electron microscopy. It was found that small cytoplasmic granules (1,000 to 5,000 A) that develop within differentiating epithelial cells move toward the cell periphery, and after fusion with the plasma membrane, empty their contents into the intercellular spaces. The content of the granules spreads over the cell surfaces, and subsequently a thickened and coated cell envelope is formed that resists the action of keratinolytic agent. The membrane-coating granule is regarded as a specific differentiation product of the keratinizing epithelium. It contains numerous inner membranes and is assumed to engage in synthetic activities such as, perhaps, the formation of polysaccharides.     

Fragile-X syndrome: Unique genetics of the heritable unstable element

The fragile site at Xq27.3 is an unstable microsatellite repeat, p(CCG)n. In fragile-X syndrome pedigrees, this sequence exhibits variable amplification, the length of which correlates with fragile-site expression. There is a direct relationship between increased p(CCG)n copy number and propensity for instability: individuals having large amplifications exhibit somatic variation due to increased instability. The instability of the p(CCG)n repeat, when transmitted through affected pedigrees, explains the unusual segregation patterns of fragile-X phenotype, referred to as the Sherman paradox. All individuals of fragile-X genotype were found (where testing was possible) to have a parent with amplified p(CCG)n repeat, indicating that few, if any, cases of fragile-X syndrome are not familial.     

Refined genetic localization for central core disease

Central core disease (CCO) is an autosomal dominant myopathy clinically distinct from malignant hyperthermia (MHS). In a large kindred in which the gene for CCO is segregating, two-point linkage analysis gave a maximum lod score, between the central core disease locus (CCO) and the ryanodine receptor locus (RYR1), of 11.8, with no recombination. Mutation within RYR1 is responsible for MHS, and RYR1 is also a candidate locus for CCO. A combination of physical mapping using a radiation-induced human-hamster hybrid panel and of multipoint linkage analysis using the Centre d'Etude du Polymorphisme Humain families established the marker order and sex-average map distances (in centimorgans) on the background map as D19S75–(5.2)–D19S9–(3.4)–D19S191–(2.2)–RYR1–(1.7)–D19S190–(1.6)-D19S47–(2.0)–CYP2B. Recombination was observed between CCO and the markers flanking RYR1. These linkage data are consistent with the hypothesis that CCO and RYR1 are allelic. The most likely position for CCO is near RYR1, with a multipoint lod score of 11.4, in 19q13.1 between D19S191 and D19S190, within the same interval as MHS (RYR1).     

Four familial translocations ascertained through spontaneous abortions

Summary In a study of 514 spontaneous abortions, 194 were found to have a chromosome anomaly. Of these, 4 (2.1%) were unbalanced translocations. Three of the translocations were Robertsonian (13q14q) and one was reciprocal. Each translocation was ascertained independently and each was associated with a balanced rearrangement in a carrier parent.     

Chromosome analysis on 930 consecutive newborn children using quinacrine fluorescent banding technique

Summary Chromosome analysing using quinacrine fluorescence was performed on 930 consecutive newborn infants. The total incidence of major chromosome aberrations including numerical changes of the sex chromosomes, and structural changes of autosomes, was 0.54%. Incidences of XYY (0.4%) and XXY (0.2%) were relatively higher as compared to other studies. About 0.75% of the newborn infants were found to have a variable bright fluorescent band located on the proximal area of the short arm (p11) rather than on the proximal long arm (q11) of chromosome No. 3. Attempts were also made to record the variable fluorescent regions on 7 autosomes and the Y chromosome.     

Immunohistochemistry in the evaluation of neovascularization in tumor xenografts

Angiogenesis, or neovascularization, is known to play an important role in the neoplastic progression leading to metastasis. CD31 or Factor VIII-related antigen (F VIII RAg) immunohistochemistry is widely used in experimental studies for quantifying tumor neovascularization in immunocompromised animal models implanted with transformed human cell lines. Quantification, however, can be affected by variations in the methodology used to measure vascularization including antibody selection, antigen retrieval (AR) pretreatment, and evaluation techniques. To examine this further, we investigated the microvessel density (MVD) and the intensity of microvascular staining among five different human tumor xenografts and a mouse syngeneic tumor using anti-CD31 and F VIII RAg immunohistochemical staining. Different AR methods also were evaluated. Maximal retrieval of CD31 was achieved using 0.5 M Tris (pH 10) buffer, while maximum retrieval of F VIII RAg was achieved using 0.05% pepsin treatment of tissue sections. For each optimized retrieval condition, anti-CD31 highlighted small vessels better than F VIII RAg. Furthermore, the MVD of CD31 was significantly greater than that of F VIII RAg decorated vessels (p<0.001). The choice of antibody and AR method has a significant affect on immunohistochemical findings when studying angiogenesis. One also must use caution when comparing studies in the literature that use different techniques and reagents.     

Phase locking in integrate-and-fire models with refractory periods and modulation

It is known [8, 11, 16, 26] that phase locking can entrain frequency information when the leaky integrate-and-fire (IF) model of a neuron is forced by a periodic function. We show that this is still the case when the IF model is made more biologically realistic. We incorporate into our model spike dependent threshold modulation and refractory periods. Consecutive firing times from this model and their respective interspike intervals are related by an annulus map. We prove a general theorem concerning orientation reversing annulus twist homeomorphisms, which shows that our map admits a unique rotation number. This implies, in particular, that chaotic behaviour is not possible in our model and phase locking is predicted.This research was partially supported by NSF EIA-BITS grant 426411This research was partially supported by the Summer Undergraduate Research Program sponsored by IGERT grant NSF-DGE 9972824 and the Undergraduate Scholars Program at MSU-BozemanAcknowledgement The authors would like to thank Marcy Barge for discussions of prime ends and Sherry Heis for formatting the diagrams.     

Gene structure and expression study of the SEDL gene for spondyloepiphyseal dysplasia tarda

Spondyloepiphyseal dysplasia tarda (SEDL) is an X-linked recessive disorder of endochondral bone formation caused by mutations in the SEDL gene. Here we present the structural analysis and subcellular localization of human SEDL. The SEDL gene is composed of six exons and spans a genomic region of approximately 20 kb in Xp22. It contains four Alu sequences in its 3' UTR and an alternatively spliced MER20 sequence in its 5' UTR (exon 2). Complex alternative splicing was detected for exon 4. Altogether seven SEDL pseudogenes were detected in the human genome: SEDLP1, a transcribed retropseudogene (or retro-xaptonuon) on chromosome 19q13.4 with potential to encode a protein identical to that of the SEDL gene; SEDLP2, another retropseudogene (not transcribed) on chromosome 8; and five truncated pseudogenes, SEDLP3-SEDLP7, on chromosome Yq11.23. Based on the knowledge of the yeast SEDL ortholog we speculated that the SEDL protein may participate along the ER-to-Golgi transport compartments. To test this hypothesis we performed transient transfection studies with tagged recombinant mammalian SEDL proteins in Cos-7 cells. The tagged SEDL proteins localized to perinuclear structures that partly overlapped with the intermediate ER-Golgi compartment (ERGIC; or vesicular tubular complex, VTC). Two human SEDL mutations (157-158delAT and C271T(STOP)) introduced into SEDL FLAG and GFP constructs led to the misplacement of the SEDL protein primarily to the cell nucleus and partially to the cytoplasm. Based on these experiments we suggest that the COOH end of the SEDL protein might be responsible for proper targeting of SEDL along the ER-Golgi membrane compartments (including Golgi and ERGIC/VTC).