A gene (ETM) for essential tremor maps to chromosome 2p22-p25

We report the results of linkage analysis in a large American family of Czech descent with dominantly inherited "pure" essential tremor (ET) and genetic anticipation. Genetic loci on chromosome 2p22-p25 establish linkage to this region with a maximum LOD score (Zmax) = 5.92 for the locus, D2S272. Obligate recombinant events place the ETM gene in a 15-cM candidate interval between the genetic loci D2S168 and D2S224. Repeat expansion detection analysis suggests that expanded CAG trinucleotide sequences are associated with ET. These findings will facilitate the search for an ETM gene and may further our understanding of the human motor system.     

Localization of the gene encoding the alpha subunit of human interleukin-5 receptor (IL5RA) to chromosome region 3p24-3p26

The chromosomal location of the human gene for the alpha subunit of interleukin-5 receptor (IL5RA) has been determined. The human IL5RA gene was localized to the short arm of chromosome 3 by Southern blot analysis of DNA from a panel of mouse-human hybrid somatic cell lines. The IL5RA gene has been further localized to human chromosome region 3p24-3p26 by in situ hybridization of a molecularly cloned IL5RA cDNA fragment to metaphase chromosomes. The results suggest that the IL5RA locus is unlinked to other members of the hematopoietic receptor family. Assignment of the IL5RA gene to chromosome 3 at bands p26-p24 raises the possibility that it may be altered by certain nonrandom chromosomal abnormalities arising in human hematopoietic malignancies and solid tumors.     

Mapping of the interleukin 5 receptor gene to human chromosome 3 p25-p26 and to mouse chromosome 6 close to the Raf-1 locus with polymorphic tandem repeat sequences

Simple-sequence tandem repeat sequences in the 3' UTR of interleukin 5 (IL5)-receptor gene of human and mouse are polymorphic in their length among humans and different strains of mice. In 20 different human Epstein-Barr virus (EBV)-transformed cell lines, six alleles of IL5R could be distinguished. In the mouse, three different alleles are found. With the human-specific IL5R tandem repeat marker in human-rodent somatic cell hybrids, the IL5R gene was mapped to human Chromosome (Chr) 3 p25-p26. With the mouse-specific IL5R tandem repeat sequence in recombinant inbred strains of mice, the Il5r gene was mapped to the distal part of mouse Chr 6 close to the Raf-1 locus.     

Mapping of the gene encoding the regulatory subunit RII alpha of cAMP-dependent protein kinase (locus PRKAR2A) to human chromosome region 3p21.3-p21.2

We isolated by the differential display technique a novel gene that was expressed abundantly in adipose and female-specific tissues. The cDNA contained an open reading frame of 2097 nucleotides encoding a 699-amino-acid peptide. The predicted protein showed homology to several known extracellular matrix (ECM) proteins such as proteoglycan, keratocan, and decorin. Moreover, the amino acid sequence contained several possible functional domains that would participate in protein-protein interactions, including an RGD sequence, a von Willebrand factor domain (VWFC), and a leucine-rich repeat. These findings suggest that this novel protein functions in cell-cell and/or cell-ECM recognition processes. Northern blot analysis revealed expression predominantly in adipose tissue as well as female-specific organs such as mammary gland, ovary, and uterus among 20 human adult tissues examined. We assigned the gene to chromosome 9q22.3 by means of fluorescence in situ hybridization.     

Radiation hybrid mapping of the human MN/CA9 locus to chromosome band 9p12-p13

A previously healthy 12-year-old Japanese girl developed meningoencephalitis due to Cryptococcus neoformans. During the course of her illness she suffered persistent high fever, severe pancytopenia, hypercytokinemia and liver dysfunction. Laboratory findings, including results of a bone marrow examination, strongly indicated complication by haemophagocytic syndrome (HPS). The preceding cryptococcal infection was thought to be a cause of the HPS because no other viral or bacterial infection could be confirmed. The girl died of acute respiratory failure during the progressive course of HPS. This may be the first reported case of HPS due to cryptococcal infection in an otherwise healthy child.     

Molecular cloning and mapping of a human cDNA (SC5DL) encoding a protein homologous to fungal sterol-C5-desaturase

OBJECTIVE: To study the effective materials in the immune response and the humoral immunity in graft rejective reaction in the host after penetrating keratoplasty (PKP). METHODS: PK was performed on 2 groups of monkeys with a 5.5 mm button in a 5.0 mm bed. The heterogroup (human to monkey) had 4 monkeys, and homo-group (monkey to monkey) also 4. Nelken's method was modified. Two kinds of antigens, corneal endothelial and stromal antigens, had been made the first time. Enzyme linked immunosorbent assay (ELISA) was used to detect the anti-corneal endothelial antibody (ACEAb) in the serum and aqueous humor of the host. RESULTS: After PKP, the anti-corneal stromal antibody did not increase obviously, while the increase of ACEAb was distinct. CONCLUSION: Humoral immune response can occur in the host after PK, and the effective material is ACEAb.     

Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25

Sialolithiasis with obstruction of major salivary gland ducts can lead to clinical tumefaction related to cystic dilatation. In addition to mucus accumulation, these pseudoneoplasms feature hyperplasia and squamous metaplasia of the ductal lining epithelium, with varying degrees of inflammation. The authors report five examples of this lesion aspirated from two males and three females ranging in age from 45 to 80 years (median 65 years). Three were in the submaxillary gland, and two were in the parotid. In three cases, stone fragments were identified, and diagnoses of sialolithiasis were rendered; two of these patients underwent surgical excision. The remaining two cases showed prominent foam cells and metaplastic squamous cells in a mucoid background that mimicked low grade mucoepidermoid carcinoma. Stone fragments were not identified and a differential diagnoses of sialolithiasis versus low grade mucoepidermoid carcinoma were suggested. Surgical excision revealed sialolithiasis in both instances. When stone fragments are identified in aspirated material, these cases pose little diagnostic difficulty. However, when this material is not present, epithelial changes and mucus accumulation may be difficult to distinguish from low grade mucoepidermoid carcinoma. Cautious interpretation is suggested in this setting.     

Assignment of the gene encoding the limbic system-associated membrane protein (LAMP) to mouse chromosome 16B5 and human chromosome 3q13.2-q21

Both insulin and muscle contraction stimulate glucose transport activity. However, contraction stimulation does not involve the insulin signalling intermediate phosphatidylinositol 3-kinase (PI 3-kinase). Protein kinase B (PKB) has recently been identified as a direct downstream target of PI 3-kinase in the insulin signalling pathway. We have examined here whether the two stimuli share PKB as a convergent step in separate signalling pathways. Insulin stimulates both glucose transport, GLUT4 cell-surface content and PKB activity (by 4-6-fold above basal) in a wortmannin-sensitive manner in in vitro incubated rat soleus muscles. By contrast, muscle contraction, which stimulates glucose transport and the cell surface content of GLUT4 by 3-fold above basal levels, had no effect on PKB activity. These data demonstrate that PKB is not a mediator of contraction-induced glucose transport and GLUT4 translocation.     

Mapping of human DNA-binding nuclear protein (NP220) to chromosome band 2p13.1-p13.2 and its relation to matrin 3

Human NP220 (hNP220) is a novel DNA-binding nuclear protein, which has an arginine/serine-rich motif and polypyrimidine tract-binding motif, and NP220s and matrin 3 are thought to form a novel family of nuclear proteins. We have determined a chromosomal localization of the cDNA encoding human NP220 to 2p13.1-p13.2 by using fluorescence in situ hybridization. Human matrin 3 cDNA was mapped to chromosomes 1p13.1-p21.1 and 5q31.3, demonstrating that these novel nuclear proteins with similar functions are on different chromosomes.     

Sequence and chromosome assignment to 11p13-p12 of human RAG genes

The recombination-activating genes RAG-1 and RAG-2 are required for V(D)J DNA rearrangements at loci for immunoglobulin and T cell receptor genes. We isolated the human RAG-2 gene and determined its nucleotide sequence. Mapping analysis of RAG-1 and RAG-2 genes on human chromosomes by fluorescence in situ hybridization indicated that the genes are located on chromosome 11p13-p12. RAG-1 and RAG-2 do not seem to be linked to any of the primary immunodeficiencies for which defective genes have already been mapped.     

Refined mapping of the psoriasin gene S100A7 to chromosome 1cen-q21

Psoriasin is a low molecular weight protein of the S100 family, which is highly upregulated in psoriatic epidermis, and whose function is related to skin inflammatory responses. We have applied a cDNA probe from the corresponding psoriasin gene S100A7 in a refined localisation analysis. S100A7 was mapped physically by human/rodent somatic cell hybrid analysis, and more precisely genetically by multilocus linkage analysis of 40 CEPH (Centre d'Etude du Polymorphisme Humain) families. The resulting 12-point linkage map was supported by odds of at least 1000:1, where S100A7 could be placed with a multipoint lodscore of 27.4 in an approximately 7-cM interval. The order of the 12 loci was as follows (with the best estimates of recombination frequencies given in between): AMY2B-0.091-D1S73(0.039)-D1S11(-0.053)-D1S189(-0 .017)-D1S1252 (-0.017)-D1S13(-0.078)-D1Z5(-0.051)-S100A7(-0.022)- MUC1(-0.026)-SPTA1 (-0.066)-ATP1A2(-0.014)-APOA2. Furthermore, from this map S100A7 could be assigned to the regional position of chromosome 1cen-q21. The linkage information presented should be of great value in association and linkage studies of diseases where psoriasin, or some of the several other very closely linked and functionally related genes, are seen as candidate genes, e.g. in psoriasis.     

The protein kinase N (PKN) gene PRKCL1/Prkcl1 maps to human chromosome 19p12-p13.1 and mouse chromosome 8 with close linkage to the myodystrophy (myd) mutation

OBJECTIVE: This study was performed to evaluate the frequency of postdeglutitive aspiration in lateral hypopharyngeal pouches and to correlate postdeglutitive aspiration to pouch size and dynamics. MATERIALS AND METHODS: Two radiologists retrospectively analyzed 325 videofluorography examinations of patients swallowing. The 325 patients were 22-81 years old, 173 men and 152 women. Patients who had undergone surgery of the hypopharynx were excluded from the study. All pouches found on videofluorography were classified into grade I, II, or III. Because iodinated contrast agent had been used initially, patients who had no or minimal aspiration underwent a second imaging examination using high-density barium. RESULTS: Of the 325 patients, 118 had lateral hypopharyngeal pouches: 77 bilateral and 41 unilateral. Postdeglutitive aspiration was diagnosed in 14 (56%) of the 25 grade III pouches and in two (3%) ot the 58 grade II pouches. Aspiration was not seen in any of the 112 grade I pouches. CONCLUSION: The prevalence of postdeglutitive aspiration is high in patients who have grade III pouches. To date, no appropriate conservative treatment has been described; however, in severe cases surgery is warranted.