The gene encoding LERK-7 (EPLG7, Epl7), a ligand for the Eph-related receptor tyrosine kinases, maps to human chromosome 5 at band q21 and to mouse chromosome 17

The human uterine glandular epithelium undergoes a sequence of well characterized changes during the menstrual cycle that presumably play an important role in preparation for blastocyst implantation. The aim of this study was to measure objectively glandular volume over the entire menstrual cycle and compare the results with eight different clinical superovulation or hormone replacement therapy (HRT) subject groups. Endometrial biopsies were taken from control normal menstrual cycle subjects (n = 96), and eight other smaller groups of women who had received different in-vitro fertilization (IVF) related treatments. The total area of glandular epithelium was objectively measured from routine histological slides using computerized image analysis. Control menstrual cycle results showed a significantly greater gland area in the early secretory stage of the cycle than at any time between the early proliferative through to the mid-late proliferative stages (P < 0.05). IVF patients receiving clomiphene citrate and human menopausal gonadotrophin had a significantly smaller glandular area than those in the control groups at equivalent stages of the menstrual cycle. The use of progesterone supplementation removed this significant difference. Patients on the ?Flare' regime had the highest gland area, although this was not significantly different from controls. Buserelin down-regulation gave a gland area that was closest to the normal cycle controls. The three HRT groups showed high variability in gland volume between patients. The results from this study demonstrate that superovulation can cause significant alterations in endometrial gland volume, but that these do not necessarily preclude implantation.     

The genetic locus for free sialic acid storage disease maps to the long arm of chromosome 6

Salla disease (SD), or adult-type free sialic acid storage disease, is an autosomal recessive lysosomal storage disorder characterized by impaired transport of free sialic acid across the lysosomal membrane and severe psychomotor retardation. Random linkage analysis of a sample of 27 Finnish families allowed us to localize the SD locus to the long arm of chromosome 6. The highest lod score of 8.95 was obtained with a microsatellite marker of locus D6S286 at theta = .00. Evidence for linkage disequilibrium was observed between the SD locus and the alleles of three closely linked markers, suggesting that the length of the critical region for the SD locus is in the order of 190 kb.     

The prognostic significance of deletion of the long arm of chromosome 20 in myeloid disorders

OBJECTIVE: The effect of cigarette smoking on gallbladder (GB) emptying and refilling after a fatty meal was examined in 10 healthy volunteers (four women and six men, mean age 27.6 yr). METHODS: On three different days, the subjects underwent in randomized order: a control test without smoking (C), or they smoked two cigarettes during the early (0-20 min; S0-20), or late (20-40 min; S20-40) phase of the meal-induced GB emptying. GB volumes were measured ultrasonographically before the meal and at 10, 20, 30, 40, 60, 90, 120, 150, and 180 min postprandially. Two-way ANOVA was applied for statistical assessment of the results. RESULTS: The fasted GB volumes amounted to 15.7 +/- 1.8 cm3 (C), 15.0 +/- 1.7 cm3 (S0-20), and 18.4 +/- 2.3 cm3 (S20-40), F2;18 = 1.524, NS. Maximum GB emptying was observed until 60 min after the meal, with a nadir of the GB volume amounting to 7.3 +/- 1.3 cm3 (C), 6.6 +/- 1.2 cm3 (S0-20), and 7.1 +/- 1.1 cm3 (S20-40). No significant difference was found between the stimuli tested when absolute GB volumes were considered: F2;180 = 2.725, NS. Analysis of the GB emptying-refilling curves normalized for the fasted GB volume revealed that a significant inhibitory effect was produced by smoking two cigarettes during the late phase of GB emptying on the subsequent GB refilling: F2;162 = 11.066, p < 0.001 for the whole curve, and F2;72 = 7.126, p < 0.005 for the refilling phase. A significant contrast was found next between S20-40 and the control day (p < 0.001 whole curve; p < 0.005 refilling phase only), as well as between S20-40 and S0-20 (p < 0.001 whole curve; p < 0.025 refilling phase only). CONCLUSION: We conclude that smoking two cigarettes does not disturb the fatty meal-induced GB contraction in healthy humans. Subsequent GB refilling is delayed if smoking takes place during the late phase of the postprandial GB contraction.     

A gene essential to brain growth and development maps to the distal arm of rat chromosome 12

Studies were undertaken to determine the stability of nitrobenzodiazepines and their 7-amino metabolites in water and blood. At 22 degrees C nitrazepam and clonazepam were stable in sterile fresh blood containing preservative over 28 days, whereas 25% of flunitrazepam was degraded. At 37 degrees C all three drugs were substantially lost over 9 h (29-51%). There was only a small loss observed for the 7-amino metabolites and no substantial amounts of parent drug and 7-amino metabolite were degraded in water under these conditions. In the absence of preservative substantial amounts (25-50%) of parent drugs were lost in fresh blood over 10 days at 22 degrees C. In bacterially-contaminated postmortem blood all three drugs were completely degraded over 8 h at 22 degrees C with almost all drug completely converted to the respective 7-amino metabolite. These metabolites were also partially degraded (10-20%) over 45 h at 22 degrees C. All 3 nitrobenzodiazepines were stable in blood stored for up to 24 months at -20 degrees C, or 4 degrees C over 10 months. Their respective 7-amino metabolites were, however, relatively unstable at -20 degrees C with a significant loss (29%) after 2 months. At 4 degrees C a 21% loss occurred after 1 month. Freeze/thawing was found not to affect the concentration of nitrobenzodiazepine and 7-amino metabolites. These results show that the nitrobenzodiazepines and their metabolites are unstable chemically and metabolically in blood. We advise that blood collected for the purpose of nitrobenzodiazepine determinations should be preserved with sodium fluoride, stored at -20 degrees C and assayed as soon as practicable, preferably within a week of collection.     

The gene encoding protein-tyrosine phosphatase RPTP epsilon (PTPRE) is assigned to human chromosome 10q26

In suspected Horner's syndrome, cocaine eye drops are applied to verify the diagnosis. Subsequent application of hydroxyamphetamine or pholedrine eye drops allows localization of the site of the interruption in the oculosympathetic pathway. In the present study the influence of cocaine on subsequent pholedrine testing was examined. Cocaine 5% and pholedrine 5% eye drops were applied to eight (72-h interval only six) normal volunteers with light-colored irides. The ages of the subjects ranged from 23 to 40 years. Eye drops were applied to the same eye at varying intervals of up to 72 h, with the cocaine being given between 8:30 and 9:30 a.m. Pupil diameters were recorded by means of a frame-grabber card in a personal computer and were subsequently measured before and at 50-60 min after each drug application in 1.7 cd/m2 ambient light. In the absence of pretreatment with cocaine, pholedrine changed the mean pupil diameter from 6.89 to 8.57 mm. At 12 h after cocaine pretreatment the pupil remained dilated. Pholedrine dilated the pupil further, from 7.69 to 8.61 mm. When cocaine was given 24 h before pholedrine, the pupil dilated from 6.75 to 8.25 mm; at 48 h after cocaine application, pholedrine dilated the pupil from 6.14 to 8.20 mm; and at 72 h after cocaine pretreatment, pholedrine dilated the pupil from 5.74 to 8.00 mm. As compared with the mean diameter of the untreated contralateral pupil, the pholedrine-induced dilation amounted to 2.32 mm in the absence of cocaine pretreatment, 1.04 mm at 12 h after cocaine application, 1.29 mm at 24 h after cocaine administration, 1.89 mm at 48 h after cocaine pretreatment, and 2.18 mm at 72 h after cocaine application. The residual cocaine effect interfered with the mean pupil dilation produced by pholedrin for at least 48 h. To ensure that the sensitivity of the pholedrine test is maximal, the examiner should delay its use for more than 48 h after the cocaine test.     

The gene for death agonist BID maps to the region of human 22q11.2 duplicated in cat eye syndrome chromosomes and to mouse chromosome 6

Cat eye syndrome (CES) is associated with a duplication of a segment of human chromosome 22q11.2. Only one gene, ATP6E, has been previously mapped to this duplicated region. We now report the mapping of the human homologue of the apoptotic agonist Bid to human chromosome 22 near locus D22S57 in the CES region. Dosage analysis demonstrated that BID is located just distal to the CES region critical for the majority of malformations associated with the syndrome (CESCR), as previously defined by a single patient with an unusual supernumerary chromosome. However, BID remains a good candidate for involvement in CES-related mental impairment, and its overexpression may subtly add to the phenotype of CES patients. Our mapping of murine Bid confirms that the synteny of the CESCR and the 22q11 deletion syndrome critical region immediately telomeric on human chromosome 22 is not conserved in mice. Bid and adjacent gene Atp6e were found to map to mousechromosome 6, while the region homologous to the DGSCR is known to map to mouse chromosome 16.     

Human somatostatin receptor genes: localization of SSTR5 to human chromosome 20p11.2

The gene encoding the somatostatin receptor subtype designated as SSTR5 was mapped to human chromosome 20p11.2 by using fluorescence in situ hybridization to metaphase chromosomes. Fluorescence in situ hybridization using a probe for SSTR5 in combination with probes for neuroendocrine convertase-2 (NEC2), thrombomodulin (THBD), and brain glycogen phosphorylase (PYGB) established a physical order for these loci of 20pter-NEC2-SSTR5-THBD-PYGB-cen.     

Evidence for two distinct tumor-suppressor gene loci on the long arm of chromosome 11 in human oral cancer

Loss of heterozygosity (LOH) on human chromosome 11 has been reported in a variety of human cancers. To search for the existence of tumor-suppressor gene(s) associated with oral squamous cell carcinoma (SCC) on chromosome 11, we have performed high-resolution deletion mapping in 31 patients with oral SCC using 22 microsatellite markers for this chromosomal region. LOH was observed in 14 of 25 cases (56.0%) that were informative with at least one locus. Most allelic deletions detected in our study were specific to the long arm of the chromosome. Furthermore, the data presented here show 2 distinct, commonly deleted regions. The first region, with frequent LOH, was restricted between markers DIIS939 and DIIS924 separated by 3 centimorgans (cM) on chromosome 11q23. The second region of common deletion was identified between markers DIIS912 and DIIS910, separated by 7 cM at 11q25. Our results suggest that at least 2 tumor-suppressor genes involved in the development of oral SCC are present on the long arm of chromosome 11.     

Independent amplification and frequent co-amplification of three nonsyntenic regions on the long arm of chromosome 20 in human breast cancer

DNA amplification at 20q13.2 is common in breast cancer, correlates with poor prognosis, and may reflect location of an important oncogene. Recently, other regions along 20q were also found to undergo amplification. Here, amplification levels and patterns of co-amplification were analyzed by interphase fluorescence in situ hybridization at 14 loci along 20q in 146 uncultured breast carcinomas and 14 cell lines. Three regions were independently amplified in uncultured tumors: RMC20C001 region at 20q13.2 (highly amplified in 9.6% of the cases), PTPN1 region 3 Mb proximal (6.2%), and AIB3 region at 20q11 (6.2%). Co-amplifications involving two or three of these regions were seen in 11 of the 19 highly amplified tumors. The results suggest that three distinct nonsyntenic regions along 20q may be important and that complex chromosomal rearrangements underlie their frequent co-amplification in breast cancer.     

A NotI restriction map of the entire long arm of human chromosome 21

A variety of maps of the human genome have been constructed, including cloned DNA maps. We have isolated 40 of the 42 NotI sites that exist on the long arm of human chromosome 21, as NotI linking clones and constructed a complete NotI restriction map spanning the entire region. This map, which provides the most reliable ordering and distance estimation in the region from a pericentromeric locus to the terminus, demonstrates the usefulness of linking clone mapping for analysing human chromosomes.     

A new Graves disease-susceptibility locus maps to chromosome 20q11.2. International Consortium for the Genetics of Autoimmune Thyroid Disease

The autoimmune thyroid diseases (AITDs) include two related disorders, Graves disease (GD) and Hashimoto thyroiditis, in which perturbations of immune regulation result in an immune attack on the thyroid gland. The AITDs are multifactorial and develop in genetically susceptible individuals. However, the genes responsible for this susceptibility remain unknown. Recently, we initiated a whole-genome linkage study of patients with AITD, in order to identify their susceptibility genes. We studied a data set of 53 multiplex, multigenerational AITD families (323 individuals), using highly polymorphic and densely spaced microsatellite markers (intermarker distance <10 cM). Linkage analysis was performed by use of two-point and multipoint parametric methods (classic LOD-score analysis). While studying chromosome 20, we found a locus on chromosome 20q11.2 that was strongly linked to GD. A maximum two-point LOD score of 3.2 was obtained at marker D20S195, assuming a recessive mode of inheritance and a penetrance of.3. The maximum nonparametric LOD score was 2.4 (P=.00043); this score also was obtained at marker D20S195. Multipoint linkage analysis yielded a maximum LOD score of 3.5 for a 6-cM interval between markers D20S195 and D20S107. There was no evidence for heterogeneity in our sample. In our view, these results indicate strong evidence for linkage and suggest the presence of a major GD-susceptibility gene on chromosome 20q11.2.     

Ophthalmic findings with partial trisomy (duplication) of the long arm of chromosome 7

BACKGROUND: The sensitivity of diagnostic imaging of processes in the parotid gland has been increased by improved spatial resolution, yet specificity remains unchanged. The purpose of this study was to determine whether the low-flow color duplex technique alters the specificity of B-mode ultrasonography. PATIENTS AND METHODS: Forty-one patients with tumors of the parotid gland were examined by color duplex echography as well as histologically. Twenty-eight of the 41 patients had benign tumors and 13 had malignant disease. In 17 of 41 patients, color duplex ultrasonography failed to detect any vascularization within the tumor. Histopathological examination showed that 3 of these 17 tumors were malignant and 14 of 17 were benign. Intranodal vascularization was detected in 24 cases. Ten of these patients were found to have malignant tumors of the parotid gland; 14 had benign parotid tumors. RESULTS: Our present findings show that marked intratumoral vascularization especially appears in malignant tumors. In contrast to lymph nodes, the location and texture of intranodal blood vessels do not provide information about the nature of the neoplasm. CONCLUSIONS: Low flow duplex ultrasonography does not increase the specificity of preoperative examination in tumors of the parotid gland.