Close linkage of three merozoite surface protein genes on chromosome 2 of Plasmodium falciparum

Actin the main component of the cellular microfilament network, is present in human respiratory syncytial virus (HRSV) purified virions, as an internal component. This fact and the results of immunoprecipitation studies indicate that during HRSV infection in HEp-2 cells there are interactions between cellular actin and viral components, that can promote a transitory increase in the polymerization of synthetized actin, mainly of the beta isotype. This increased actin polymerization can be related with the formation of cytoplasmic extensions, that contain beta actin and viral particles observed in the HRSV infected HEp-2 cells. The formation of these structures may indicate that HRSV has developed an actin-based motility system similar to that described for other viral and bacterial systems.     

Molecular cloning and chromosomal mapping of olfactory receptor genes expressed in the male germ line: evidence for their wide distribution in the human genome

PURPOSE: The authors evaluated the effectiveness of ultrasound biomicroscopy to determine the condition of the ciliary body during perioperative examinations of patients with atopic dermatitis and retinal detachment. METHODS: The authors compared two groups of patients with atopic dermatitis and retinal detachment. Parameters included patient age, gender, eye, cataract, type and location of breaks, macular involvement, detachment of the ciliary epithelium, and preoperative and postoperative best-corrected visual acuities. Group 1 included six patients (nine eyes) who were examined before surgery and after surgery using ultrasound biomicroscopy, with which the authors also measured the maximum height of the detachment of the ciliary epithelium. Group 2 included 10 patients (13 eyes) who did not undergo ultrasound biomicroscopy. RESULTS: In group 1, ultrasound biomicroscopy showed ciliary epithelium detachment in all eyes before surgery and in eight of nine eyes after successful retinal reattachment. The height of the ciliary detachment, however, decreased dramatically after surgery. Although almost all the parameters between groups 1 and 2 were similar, the authors observed a significant difference in the incidence of preoperative diagnosis of ciliary detachment (P = 0.023). CONCLUSION: Ultrasound biomicroscopy is beneficial in detecting detachment of the ciliary epithelium. The residual shallow detachment that remains after successful surgery suggests the fragility of the ciliary body.     

Comparative mapping of 9 human chromosome 22q loci in the laboratory mouse

We present a comparative map of genes on human chromosome 22q and homologous loci in the mouse genome. Gene order in humans was established using a panel of somatic cell hybrids. Genetic maps spanning homologous segments on three mouse chromosomes were generated using an interspecific backcross. The conserved linkage between human chromosome 22 and mouse chromosome 16 includes two closely linked loci, Comt and IgI-1. The second conserved linkage involves human chromosome 22 and mouse chromosome 11 and contains two genetically and physically linked loci, Lif and Nfh. Finally, conserved synteny involving mouse chromosome 15 and human chromosome 22 spans 30 cM and contains five loci (Acr, Bzrp, Dia-1, Il2rb and Pdgfb). Loci within this conserved synteny have been sublocalized to different portions of human chromosome 22. The order of genes on mouse chromosome 15 and human chromosome 22 provides further evidence for chromosomal rearrangements within the conserved synteny that have occurred since the divergence of lineages leading to mice and humans.     

Synteny mapping of four genes from the short arm of human chromosome 19 to bovine chromosome 7

Four genes on the short arm of human chromosome 19 (HSA 19p) were assigned to bovine chromosome 7 (BTA 7) using a bovine x rodent somatic hybrid cell panel. These four genes were cartilage oligomeric matrix protein (COMP), lymphoblastic leukemia derived sequence 1 (LYL1), lysosomal alpha-mannosidase (MANB), and RAS oncogene family member RAB3A. Bovine sequence tagged sites were developed for the four genes and used for screening a bovine x rodent somatic cell panel. All four genes were mapped to bovine synteny group U22 (BTA 7) with a correlation coefficient of 0.901-1.000. This study confirms that the centromeric region of BTA 7 is conserved with HSA 19p.     

Isolation of human chromosome 21-specific cosmids and their uses in mapping of cosmid contigs on chromosomal subregions

Seven well-trained male long-distance runners were studied during a 100-km road race. Hematologic parameters, plasma electrolytes, glucose, lactate, urea, and creatinine content in plasma and the activity of the enzymes gamma-glutamyltransferase and creatinine kinase were determined before and after the race. A slight increase in hematocrit was found after the race, although the red blood cell count and hemoglobin concentration remained unchanged. Further, a significant rise in the number of white blood cells, lymphocytes, and neutrophils was found after the race. Postrun concentrations of plasma sodium and potassium increased significantly from 142 +/- 7 to 161 +/- 7 mmol.L-1, and from 4.22 +/- 0.37 to 5.15 +/- 0.46 mmol.L-1 (p < 0.05), respectively. Plasma concentrations of lactate (1.29 +/- 0.31 vs. 3.57 +/- 1.22 mmol.L-1), urea (6.09 +/- 1.0 vs. 8.35 +/- 1.35 mmol.L-1), creatinine (73.4 +/- 3.5 vs. 117.6 +/- 19.4 mumol.L-1), plasma creatine kinase (91.1 +/- 25.1 vs. 2843 +/- 2341 IU.L-1), and gamma-glutamyltransferase (20.28 +/- 1.88 vs. 24.14 +/- 4.09 IU .L-1) increased significantly (p < 0.05) after the run. It was concluded that during ultralong-distance races, acute renal dysfunction and muscle damage could contribute to the observed hypernatremia and hyperkalemia.     

Molecular linkage of the human alpha 1-antitrypsin and corticosteroid-binding globulin genes on chromosome 14q32.1

The genes encoding alpha 1-antitrypsin (alpha 1AT; gene symbol PI) and corticosteroid-binding globulin (CBG) are part of a cluster of structurally related serine protease inhibitor (serpin) genes on human Chromosome (Chr) 14q32.1. This cluster also includes the genes encoding alpha 1-antichymotrypsin (AACT) and protein C inhibitor (PCI), as well as an alpha 1-antitrypsin-related sequence (ATR; gene symbol PIL). In this report we present a detailed restriction map of a 110-kb region of genomic DNA that includes the alpha 1AT, ATR, and CBG genes. Gene order in this interval is tel-alpha 1AT-ATR-CBG-cen, and all three genes are transcribed in a distal-to-proximal orientation. Within the gene cluster, ATR is approximately 12 kb downstream of alpha 1AT, and CBG is about 57 kb downstream of alpha 1AT. Repetitive DNA sequences have been mapped throughout the interval, and several new restriction site polymorphisms in the region are described.     

Structure and chromosomal mapping of the mouse P2X3 gene

Since arthritis induced by Mycobacterium products (adjuvant) in rats is considered to be immunologically driven, the objective of the present study was to determine if the immunosuppressor drug cyclosporin could affect hindpaw edema and joint hyperalgesia simultaneously. Female Holtzman rats (140-170 g) presented hyperalgesia and edema on the 8th and 12th day following adjuvant injection. Daily systemic (oral or intramuscular) administration of cyclosporin (0.5-5.0 mg kg (-1) day (-1)) or dexamethasone (0.01-0.1 mg kg (-1) day (-1)) for 15 days starting on day zero dose-dependently inhibited the hindpaw edema and hyperalgesia in arthritic rats. However, hyperalgesia but not edema could be detected two days after cyclosporin withdrawal. We concluded that a) the continuous presence of cyclosporin is essential to reduce the development of joint hyperalgesia and that b) different mechanisms underlie the appearance of hyperalgesia and edema in this model. The intracerebroventricular (i.c.v.) administration of 5-50-fold smaller doses of cyclosporin (1.5-150 micrograms/day) or dexamethasone (15 micrograms/day) also reduced the arthritic hindpaw edema and hyperalgesia. Peripheral blood from animals injected with effective systemic cyclosporin doses showed detectable levels of the drug, whereas peripheral blood from those injected with i.c.v. cyclosporin did not, as measured by specific RIA. Our results indicate that cyclosporin administered by the central route is as effective as by the systemic route to reduce joint hyperalgesia and hindpaw edema in arthritic rats. The antiarthritic effect induced by low doses of cyclosporin in the central nervous system (CNS) could be explored to avoid it often associated systemic side effects during chronic therapy. However, the mechanism(s) involved in the antiarthritic response to cyclosporin in the CNS remain to be elucidated.     

Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens including DNA, ribosomal P, Ro (SS-A), La (SS-B), and the spliceosome. Etiology is suspected to involve genetic and environmental factors. Evidence of genetic involvement includes: associations with HLA-DR3, HLA-DR2, Fcgamma receptors (FcgammaR) IIA and IIIA, and hereditary complement component deficiencies, as well as familial aggregation, monozygotic twin concordance >20%, lambdas > 10, purported linkage at 1q41-42, and inbred mouse strains that consistently develop lupus. We have completed a genome scan in 94 extended multiplex pedigrees by using model-based linkage analysis. Potential [log10 of the odds for linkage (lod) > 2.0] SLE loci have been identified at chromosomes 1q41, 1q23, and 11q14-23 in African-Americans; 14q11, 4p15, 11q25, 2q32, 19q13, 6q26-27, and 12p12-11 in European-Americans; and 1q23, 13q32, 20q13, and 1q31 in all pedigrees combined. An effect for the FcgammaRIIA candidate polymorphism) at 1q23 (lod = 3.37 in African-Americans) is syntenic with linkage in a murine model of lupus. Sib-pair and multipoint nonparametric analyses also support linkage (P < 0.05) at nine loci detected by using two-point lod score analysis (lod > 2.0). Our results are consistent with the presumed complexity of genetic susceptibility to SLE and illustrate racial origin is likely to influence the specific nature of these genetic effects.     

Functional evidence for involvement of multiple putative tumor suppressor genes on the short arm of chromosome 3 in human oral squamous cell carcinogenesis

The authors present their experience at the Centre for the surgical treatment of morbid obesity at Milano University where since 1974, 603 obese patients underwent surgery: 312 jejuno-ileal bypass (JIB), 70 bilio-intestinal bypass (BIB), 102 horizontal gastroplasties (HGP), 44 silastic ring vertical gastroplasties (SRVGP) and 75 adjustable silastic gastric banding (ASGB). Average follow-up for these procedures is 16, 6, 11, 4 years and 24 months respectively. Weight loss is satisfactory in all cases even though the percentages vary in the different procedures. The most serious complications (severe hepatic failure, oxalic interstitial nephritis, persisting malabsorption) occurred in patients submitted to JIB. The best clinical outcome with the lowest complications rate was obtained with BIB compared to other intestinal bypasses. The most frequent complication observed in patients submitted to gastroplasties was incoercible vomiting while the most severe complications were diffuse peritonitis, secondary to gastric perforation, and peripheric neuropathy. Our experience confirms that surgical treatment of morbid obesity refractory to medical therapy is today a safe and effective treatment. BIB has still a role in super-obese young patients (BMI over 50) refusing dietary restriction lifetime. The gastric procedures, especially laparoscopic ASGB, seem to be the best option. The excellent outcome of bariatric surgery can be obtained only in specialized centers where various specialists work together.     

Physical and linkage mapping of the gene for the alpha3 chain of type IX collagen, COL9A3, to human chromosome 20q13.3

Type IX collagen is a minor cartilage component which associates with mixed fibrils of types II/XI collagen. We have determined the precise physical and genetic locations for the gene encoding the alpha3 chain of type IX collagen, COL9A3. Utilizing fluorescence in situ hybridization, radiation hybrid mapping, and multipoint linkage analysis, we have mapped COL9A3 to human chromosome 20q13.3, 13 cM telomeric to D20S173.     

Genetic linkage of chromosomal tetracycline resistance and pigmentation to a purine auxotrophic marker and the isoleucine-valine-leucine structural genes in Staphylococcus aureus

Three tetracycline resistance determinants (tmn-3106, tmn-3110, and tmn-3511) reported by Asheshov (1975) to be chromosomal in Staphylococcus aureus have been linked by transformation to a purine auxotrophic marker (pur-110), a cluster of eight genes involved in the biosynthesis of isoleucine, valine, and leucine (the ilv-leu region), a marker (ilvR10) that may be involved in the regulation of the ilv-leu region, and a gene involved in pigmentation (pig-131). The linkage group thus defined is tmn-3106-pur-110-ilvR10-(ilv-leu)-pig-131. The orientation of the ilv-leu region relative to ilvR10 and pig-131 was not determined. The tmn-3106, tmn-3110, and tmn-3511 determinants exhibit the same linkage relationships to the other markers. It is concluded that this linkage group represents a portion of the chromosome of S. aureus.     

Comparative mapping of Xp22 genes in hominoids--evolutionary linear instability of their Y homologues

The extracellular matrix is now recognized as a biologically active and dynamic composition of structural, adhesive, and counteradhesive fibrous proteins embedded in a hydrated ground substance of glycosaminoglycans and proteoglycans. The ability of resident cells to detect small differences in the specific combination, concentration and distribution of matrix components suggests that perturbation of the homeostatic matrix can lead to remodelling following angioplasty. Recent studies reviewed herein have focused on how alterations of the relative composition of matrix components ultimately leads to changes in cell growth, behaviour and differentiation, all of which can significantly contribute to remodelling of the vascular wall following injury. These cell-matrix interactions may provide novel therapeutic targets in the prevention of unfavourable remodelling that leads to restenosis.     

Isolation and chromosomal mapping of a mouse homolog of the Batten disease gene CLN3

We describe the isolation and chromosomal mapping of a mouse homolog of the Batten disease gene, CLN3. Like its human counterpart, the mouse cDNA contains an open reading frame of 1314 bp encoding a predicted protein product of 438 amino acids. The mouse and human coding regions are 82 and 85% identical at the nucleic acid and amino acid levels, respectively. The mouse gene maps to distal Chromosome 7, in a region containing genes whose homologs are on human chromosome 16p12, where CLN3 maps. Isolation of a mouse CLN3 homolog will facilitate the creation of a mouse model of Batten disease.     

Gene-based anchoring of the rat genetic linkage and cytogenetic maps: new regional localizations, orientation of the linkage groups, and insights into mammalian chromosome evolution

In order to generate anchor points connecting the rat cytogenetic and genetic maps, the cytogenetic position of 62 rat markers (including 55 genes) already localized genetically was determined by fluorescence in situ hybridization. Whenever possible, markers located near one end of the linkage groups were included. These new localizations allowed us to unambiguously orient the 20 autosomal and the X chromosome linkage groups. The position of the centromere in the linkage map could also be determined in the case of several metacentric chromosomes. In addition, the regional localization of 15 other rat genes was determined. These new data bring useful information with respect to comparative mapping with the mouse and the human and to mammalian evolution. They illustrate, for instance, that groups of genes can remain syntenic during mammalian evolution while being subjected to intrachromosomal rearrangements in some lineages (synteny is conserved while gene order is not). This analysis also disclosed cases of synteny conservation in one the two rodent species and the human, while the synteny is split in the other rodent species: such configurations are likely examples of lineage-specific interchromosomal rearrangements associated with speciation.     

Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization

The region of human chromosome 22q11 is prone to rearrangements. The resulting chromosomal abnormalities are involved in Velo-cardio-facial and DiGeorge syndromes (VCFS and DGS) (deletions), "cat eye" syndrome (duplications), and certain types of tumors (translocations). As a prelude to the development of mouse models for VCFS/DGS by generating targeted deletions in the mouse genome, we examined the organization of genes from human chromosome 22q11 in the mouse. Using genetic linkage analysis and detailed physical mapping, we show that genes from a relatively small region of human 22q11 are distributed on three mouse chromosomes (MMU6, MMU10, and MMU16). Furthermore, although the region corresponding to about 2.5 megabases of the VCFS/DGS critical region is located on mouse chromosome 16, the relative organization of the region is quite different from that in humans. Our results show that the instability of the 22q11 region is not restricted to humans but may have been present throughout evolution. The results also underscore the importance of detailed comparative mapping of genes in mice and humans as a prerequisite for the development of mouse models of human diseases involving chromosomal rearrangements.     

Re-expression of RAG-1 and RAG-2 genes and evidence for secondary rearrangements in human germinal center B lymphocytes

V(D)J recombination occurs in immature B cells within primary lymphoid organs. However, recent evidence demonstrated that the recombination activating genes RAG-1 and RAG-2 can also be expressed in murine germinal centers (GC) where they can mediate secondary rearrangements. This finding raises a number of interesting questions, the most important of which is what is the physiological role, if any, of secondary immunoglobulin (Ig) gene rearrangements. In the present report, we provide evidence that human GC B cells that have lost surface immunoglobulin re-express RAG-1 and RAG-2, suggesting that they may be able to undergo Ig rearrangement. Furthermore, we describe two mature B cell clones in which secondary rearrangements have possibly occurred, resulting in light chain replacement. The two clones carry both kappa and lambda light chains productively rearranged, but fail to express the x chain on the cell surface due to a stop codon acquired by somatic mutation. Interestingly, the analysis of the extent of somatic mutations accumulated by the two light chains might suggest that the lambda chain could have been acquired through a secondary rearrangement. Taken together, these data suggest that secondary Ig gene rearrangements leading to replacement may occur in human GC and may contribute to the peripheral B cell repertoire.     

Deletion mapping and linkage analysis provide strong indication for the involvement of the human chromosome region 8p12-p22 in breast carcinogenesis

We have identified a high frequency of loss of heterozygosity (LOH) on the human chromosome region 8p12-p22 in a panel of microdissected familial (86% LOH) and sporadic (74% LOH) breast tumours. The two most frequently deleted regions were defined around marker D8S133 and in a broader centromeric region bounded by markers D8S137 and D8S339. We cannot unequivocally characterize the 8p12-p22 loss as an early or a late event in breast carcinogenesis. In parallel, we have performed linkage analysis in four German breast cancer families. A location score greater than 13.67 corresponding to a LOD score of 2.97 at the marker D8S137 has been obtained. Our results considerably strengthen the evidence for a breast cancer susceptibility gene(s) located on the short arm of the chromosome region at 8p12-p22.