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PubMed1999

Induction of Fos-like-immunoreactivity in the central extended amygdala by antidepressant drugs.

The induction of the early gene c-fos was evaluated through Fos immunohistochemistry in areas belonging to the extended amygdala after acute administration of two antidepressants, citalopram and imipramine. Both citalopram and imipramine at the dose of 5 and 20 mg/kg, respectively, induced Fos-like immunoreactivity (FLI) in the central amygdaloid nucleus, lateral division of the bed nucleus of the stria terminalis (BSTL), and interstitial nucleus of the posterior limb of the anterior commissure (IPAC). The shell of the nucleus accumbens, which forms a continuum with the central extended amygdala, showed a decrease of FLI after administration of either citalopram or imipramine. The mechanism of action and the brain areas affected by antidepressants are still a matter of debate. By showing that the central extended amygdala is a common site of action for two different antidepressant types, these results provide new insight into the mechanism of action of antidepressants.

Adrenergic Uptake Inhibitors↗

PubMed1997

Extended lifespan and immortalization of human fibroblasts induced by X-ray irradiation.

The induction of immortalization of human fibroblasts by carcinogens is a very rare process. Hybrids between immortal cells and normal fibroblasts senesce, indicating that immortal cells must lose one or more senescence genes for immortalization. To examine the possible involvement of multiple gene alterations in extended lifespan or immortalization of normal human fibroblasts, normal human fibroblasts (WHE-7 cells) and skin fibroblasts (MDAH 087 cells) derived from a Li-Fraumeni syndrome patient with a mutated p53 allele were periodically irradiated with x rays. All six unirradiated control MDAH 087 cell cultures ceased growing by 37 population doublings (PD) and senesced. In contrast, one of six MDAH 087 cultures irradiated one to three times with x rays (2 or 4 Gy at 2 Gy/min) grew continuously for over 450 PD, indicating that the cells were immortal. All 12 WHE-7 cell cultures that were irradiated under the same conditions and all 20 unirradiated control WHE-7 cultures did not become immortal. Single-stranded DNA conformation analysis and DNA sequencing revealed that no additional mutations were induced by x-ray irradiation in exons 2-10 of the p53 gene of the immortal cells (LCS-4X2 cells) and that loss of the wild-type p53 gene was necessary but not sufficient for immortalization. Karyotypic analysis and chromosome painting analysis demonstrated that a high percentage (more than 98%) of LCS-4X2 cells had lost chromosome 6. Irradiation of WHE-7 cells nine times with x rays (2 Gy at 2 Gy/min) extended the cells' lifespans but did not immortalize them. These cells (X9 cells) exhibited a nonrandom karyotypic alteration, monosomy 6, that was confirmed by loss of heterozygosity for a polymorphic dinucleotide repeat sequence on chromosome 6. DNA analysis showed that X9 cells had no mutations in exons 2-10 of the p53 gene. DNA fingerprint analysis with a multi-locus probe detected DNA rearrangements in LCS-4X2 cells and X9 cells, indicating that both cells could have mutations at a gene or genes other than the p53 gene. The results are consistent with our previous findings that cells with a mutation in one gene involved in cellular senescence (i.e., the p53 gene in Li-Fraumeni fibroblasts) are prone to immortalization. Furthermore, we conclude that immortalization of normal human fibroblasts is a multistep process involving loss or inactivation of multiple genes, such as p53 and a gene on chromosome 6. Loss of a gene on chromosome 6 without p53 alterations extends cellular lifespan without immortalizing the cells.

Adult↗

PubMedDate not supplied

Extended tropism of an adenoviral vector does not circumvent the maturation-dependent transducibility of mouse skeletal muscle.

BACKGROUND: Efficient adenoviral gene delivery to mature skeletal muscle has been hindered by different factors. The low levels of adenoviral attachment receptor (CAR) that have been reported in this tissue may be a limiting factor. Therefore, adenoviral transduction of mature muscle may be improved by extending the tropism of the adenoviral vectors to attachment receptors that are highly expressed in mature myofibers. In this study, we have investigated whether an extended tropism adenoviral vector which additionally attaches to the broadly expressed heparan-containing receptors (AdPK) can bypass the maturation-dependent adenoviral transducibility of mouse skeletal muscle. METHODS: The adenoviral vector AdPK carrying the LacZ gene was evaluated as a gene delivery vehicle in mouse skeletal muscle at different maturities in vitro and in vivo. The viral transduction efficiencies were determined by histochemical and ONPG analysis of the beta-galactosidase activity level. RESULTS: Higher transduction efficiencies were detected in immature muscle from normal mice, and in mature muscle from merosin-deficient dy/dy mice (carrying myofibers with an impaired extracellular matrix) and dystrophin-deficient mdx mice (showing a high level of myoblast activity) when compared to mature muscle from normal mice. CONCLUSION: Despite the enhanced attachment characteristics, the extended tropism adenoviral vector is, similarly to the wild-type adenoviral vector in previous studies, still hindered by both a protective extracellular matrix and the diminished myoblast-mediation in mature muscle.

Adenoviridae↗

PubMed1976

Lymphosarcoma. A comparison of extended to conservative chemotherapy.

Sixty-three patients with Stage III and IV lymphocytic lymphoma were randomized for induction treatment between a single course of nitrogen mustard and a 14-day course of prednisone (conservative therapy) or sequential rotation of BCNU, nitrogen mustard and cytoxan with intermittent vincristine and prednisone for 6 months (extended therapy). Maintenance therapy by an oral alkylating agent (cytoxan or chlorambucil) with or without prednisone was given. Complete remission occurred in 75% of the conservative and 77% of the extended therapy group. The median duration of remission was similar, and greater than 27 months in both groups, and there was no difference in survival. At 1 year 80% of patients with no prior chemotherapy were in remission vs. 47% of patients with prior chemotherapy (p less than .01). No significant advantage for extended chemotherapy was found. The addition of vincristine was not helpful in induction and prednisone during maintenance did not improve the duration of remission or survival.

Adult↗

PubMed1990

Extended-field radiation therapy for carcinoma of the cervix.

The survival of cervical carcinoma patients with paraaortic/high common iliac nodal metastases was evaluated by retrospective chart review during a 13-year interval. Thirty-three patients with cervical carcinoma and surgically documented nodal metastases received primary, extended-field radiation therapy. Overall 2-year and 5-year actuarial survival rates after diagnosis were 37% and 31%, respectively. Survival was analyzed in terms of the variables patient age, clinical stage, tumor histologic type, the presence of enlarged paraaortic/high common iliac lymph nodes, the extent of nodal involvement (microscopic versus macroscopic), the presence of intraperitoneal disease, and whether intracavitary brachytherapy was administered. The use of intracavitary radiation therapy was associated with improved local control and survival (P = 0.017). None of the other variables were statistically related to patient survival. Twenty-two of the patients died of cervical cancer and five are surviving without evidence of cancer. Four patients died of intercurrent disease. Two patients developed bowel-related radiation complications; both patients received chemotherapy concurrent with the radiation therapy. One of the two patients died of radiation enteritis. The use of extended-field radiation therapy does benefit a small group of patients and may result in extended patient survival.

Adenocarcinoma↗

PubMed1991

Cancer incidence among asbestos-exposed chemical industry workers: an extended observation period.

A previous study on the incidence of cancer in a cohort of 286 asbestos-exposed electrochemical industry workers observed from 1953 through 1980 has been extended with another 8 years of follow-up. The incidence of cancer was derived from the Cancer Registry of Norway, and the expected figures were calculated by a life table method. During the extended follow-up period from 1981 through 1988, among the cohort members there were 12 new cancer cases versus 14.2 expected (SIR 85, 95% CI 44-158). In a lightly exposed sub-cohort, the extended follow-up revealed 4 cases of lung cancer or pleural mesothelioma (ICD, 7th revision 162-163) versus 1.6 cases expected (SIR 256, 95% CI71-654). In a heavily exposed sub-cohort, the corresponding figures were 3 and 0.5 (SIR 588, 95% CI 118-1,725).

Asbestos↗

PubMed1984

A combined scanning electron microscopy and immunofluorescence study demonstrating that the odontoblast process extends to the dentinoenamel junction in human teeth.

The extent of the odontoblast cell process has been the subject of controversy for many years. Using SEM we have examined the extent and morphology of the process on dentine surfaces of human teeth which were partially demineralized and collagenase digested. Third molars were extracted and split; the dentine surface was demineralized, digested by bacterial collagenase, fixed with glutaraldehyde, postfixed in osmium tetroxide, and prepared for SEM investigation. The SEM study revealed the presence of many processlike structures which extended from the odontoblast cell bodies up to the dentinoenamel junction (DEJ). These processes demonstrated lateral and terminal branching and some of them terminated in distended spheres. We have also applied an immunofluorescence technique at the light microscope level to these exposed dentinal surfaces to localize the intracellular microtubules. For this, a second series of third molars was processed in the same manner as for the SEM up to the fixation stage. Teeth were then fixed in periodate-lysine-paraformaldehyde, postfixed in -20 degrees C acetone, and then incubated with affinity-purified rabbit antitubulin antibodies, followed by fluorescein-conjugated goat antirabbit IgGs. Intratubular immunofluorescence labelling for tubulin was evident from the odontoblast cell bodies up to the DEJ. The presence of the tubulin-containing structures extending to the DEJ supports the hypothesis that the structures observed with the SEM are odontoblast processes and that the odontoblast processes do extend to the DEJ.

Adult↗

PubMed1990

The effect of ethnicity on major histocompatibility complex complement allotypes and extended haplotypes in patients with systemic lupus erythematosus.

Previous studies of patients with systemic lupus erythematosus (SLE) have shown an increased frequency of certain major histocompatibility complex (MHC) markers, including HLA-DR2, DR3, and C4AQ0 (C4A-null), in Caucasian patients. However, most of these studies were of randomly selected, unrelated patients; families were not included, and haplotypes were not determined. In order to define more accurately the possible role of MHC genes in lupus susceptibility, HLA-A, B, C, and DR, as well as BF, C2, C4A, C4B, and GLO, markers were determined in 62 Caucasian patients of known ethnic background, and in the members of their families. The distributions of extended haplotypes (fixed combinations of HLA-B, DR, and complotype alleles), fragments thereof, and individual alleles were determined in SLE patients and controls. The MHC distributions in all patients were compared with haplotypes in a normal Caucasian population. There were no statistically significant differences between the frequencies of any MHC marker, fragment, or extended haplotype in the patients compared with the controls. The patients were categorized into 2 groups of European ancestry (English/Irish; other Europeans), and each group was compared with a group of ethnically matched controls. There was a statistically significantly increased frequency of the alleles C4AQ0 and DR3 and the complotype SC01 in SLE patients of English/Irish descent as compared with ethnically matched controls. The increase in C4AQ0 and DR3 could be accounted for by the fact that they were part of the extended haplotype [HLA-B8;SC01;DR3] and/or its fragment (SC01;DR3). No increase in any MHC marker was observed in the other patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement System Proteins↗

PubMed2003

Risk factors for perioperative morbidity and mortality after extended hepatectomy for hepatocellular carcinoma.

BACKGROUND: Extended hepatectomy with resection of more than four segments is a high-risk operation, especially in patients with hepatocellular carcinoma (HCC) associated with chronic liver disease. This study evaluated the risk factors for morbidity and mortality following extended hepatectomy for HCC. METHODS: Preoperative and intraoperative variables of 155 patients who underwent extended hepatectomy for HCC were analysed to identify risk factors for postoperative morbidity and mortality. RESULTS: The overall morbidity rate was 55.5 per cent (n = 86). Most morbidity was due to ascites or pleural effusion. Significant life-threatening complications occurred in 20.0 per cent (n = 31). The perioperative mortality rate was 8.4 per cent (n = 13). Multivariate analysis found that portal clamping (P = 0.023) and perioperative blood transfusion (P < 0.001) were risk factors for morbidity, whereas perioperative blood transfusion (P < 0.001) was the only risk factor for significant morbidity. Co-morbid illness (P = 0.019) and perioperative blood transfusion (P = 0.004) were risk factors for perioperative mortality. CONCLUSION: Meticulous operative techniques to minimize blood loss and transfusion, while avoiding a prolonged Pringle manoeuvre, may help reduce postoperative morbidity. Avoidance of perioperative blood transfusion and careful preoperative selection of patients in terms of overall physiological status are important measures to reduce the postoperative mortality rate.

Adolescent↗

PubMed2007

Extended abdominoperineal resection with gluteus maximus flap reconstruction of the pelvic floor for rectal cancer.

BACKGROUND: Intraoperative tumour perforation, positive tumour margins, wound complications and local recurrence are frequent difficulties with conventional abdominoperineal resection (APR) for rectal cancer. An alternative technique is the extended posterior perineal approach with gluteus maximus flap reconstruction of the pelvic floor. The aim of this study was to report the technique and early experience of extended APR in a select cohort of patients. METHODS: The principles of operation are that the mesorectum is not dissected off the levator muscles, the perineal dissection is done in the prone position and the levator muscles are resected en bloc with the anus and lower rectum. The perineal defect is reconstructed with a gluteus maximus flap. Between 2001 and 2005, 28 patients with low rectal cancer were treated accordingly at the Karolinska Hospital. RESULTS: Two patients had ypT0 tumours, 20 ypT3 and six ypT4 tumours. Bowel perforation occurred in one, the circumferential resection margin (CRM) was positive in two, and four patients had local perineal wound complications. Two patients developed local recurrence after a median follow-up of 16 months. CONCLUSION: The extended posterior perineal approach with gluteus maximus flap reconstruction in APR has a low risk of bowel perforation, CRM involvement and local perineal wound complications. The rate of local recurrence may be lower than with conventional APR.

Aged↗

PubMed1994

Initial experience with an extendable and reusable probe balloon-on-a-wire dilatation catheter in multivessel coronary angioplasty.

The "probe" balloon-on-a-wire device is an excellent balloon catheter for traversing very tight stenoses. Extending the probe by transecting its proximal inflation hub and then linking it to an extension wire has further enhanced its utility, as a wire exchange can then be performed without loosing wire access across a dilated lesion. We now report a previously undescribed technique for reconstituting and reusing an extended probe. The probe is initially transected at its proximal end. It is then extended by connecting a "Linx" wire into the open central lumen of the probe's hypotube. An over-the-wire balloon dilatation system is then substituted, via a wire exchange using a probing catheter, for final definitive dilatation. The probe is then reconstituted in the following manner. The inflation hub of the probe is recreated by modifying a standard USCI Tuohy-Borst Y adaptor and attaching this to the transected probe hypotube. It is subsequently used for dilating other stenotic arteries during multivessel angioplasty. The utility of this method was demonstrated in 5 consecutive cases. All cases underwent successful dilatations. There were no complications. This initial experience would suggest that the probe can be reused quite safely and effectively.

Adult↗

PubMed1993

Smooth muscle myosin subfragment-1 is a kinetic analogue for heavy meromyosin in the extended conformation.

The 10S-->6S (Flexed-->Extended) transition in smooth muscle myosin is related to increased ATPase activity, but there is controversy over whether the analogous 9S-->7S transition in HMM is also associated with ATPase activity. We therefore studied the association of ionic strength, phosphorylation, and ATPase activity for HMM as compared to S1 which has no apparent flexed conformation. In addition, we performed both steady state and single turnover analyses, to control for artifacts due to multiple subfragment populations that might skew steady state results. At low ionic strength where myosin and HMM are in the flexed conformation, HMM had a near zero ATPase activity while S-1 had a high ATPase rate (0.07 s-1). At 400 mM ionic strength, where both myosin and HMM are in the extended conformation, S1 and HMM had the same ATPase rate (0.04 s-1). Phosphorylation did not affect S1 significantly, but shifted the HMM curve to higher rates at lower ionic strengths. Both steady state and single turnover experiments gave the same results, indicating that steady state results were not skewed by multiple subfragment populations. These data indicate that HMM has a conformation-ATPase relation similar to that observed with myosin. Furthermore, these findings suggest that the S1 ATPase rate corresponds to that of HMM in the extended conformation.

Actins↗

PubMed1992

Genetic control of nonresponsiveness to hepatitis B virus vaccine by an extended HLA haplotype.

We previously reported evidence for a statistical association between the serologically determined HLA-Bw54, DR4 and DRw53 alleles and the non-immune responsiveness to hepatitis B virus surface antigen (HBsAg) in the Japanese population. To identify the locus and allele within the HLA region associated with the nonresponsiveness to HBsAg, serological HLA typing, DNA typing of HLA-DQ and DP alleles using amplified HLA genes and sequence-specific oligonucleotide probes, and restriction fragment length polymorphism (RFLP) analysis of the fourth component of complement (C4) genes were performed in healthy unrelated Japanese vaccinees who were immunized subcutaneously three times with plasma-derived HBsAg vaccine. In nonresponders to HBsAg, the frequencies of HLA-Bw54 cross-reactive epitope group (CREG); (Bw54, Bw55, Bw56 and other Bw22), C4 RFLP (6.5 kb + 12.0 kb), DR4, DRw53 and DQw4 (DQA1*0301-DQB1*0401) were increased and the frequencies of HLA-DR1, DRw6 and DQw1 were decreased as compared with those in healthy unrelated controls. Further analysis revealed that the coexistence of HLA-Bw54CREG and DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) was associated with the nonresponder group, whereas, donors positive for exclusively either Bw54 CREG or DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) were not associated with the nonresponder group. Because there is a strong linkage disequilibrium between HLA-Bw54CREG, C4 RFLP (6.5 kb + 12.0 kb) and HLA-DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) in the Japanese population, the extended HLA-Bw54CREG-C4 RFLP (6.5 kb + 12.0 kb)-DR4-DR-w53-DQw4 (DQA1*0301-DQB1*0401) haplotype may well control nonimmune responsiveness to HBsAg. This extended HLA haplotype controls nonresponsiveness as a dominant genetic trait because all ten heterozygotes and two of three probable homozygotes of this extended HLA haplotype were nonresponders.

Adult↗

PubMed2006

Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive cerebral white matter disorder in children. This disease is histopathologically characterized by myelin splitting and intramyelinic vacuole formation. MLC is caused by mutations in the gene MLC1, which encodes a novel protein, MLC1. Since the first report, 50 mutations in this gene have been found. Mutations occur throughout the entire coding region and include all different types: 11 splice-site mutations; one nonsense mutation; 24 missense mutations; and 14 deletions and insertions. Until now, six polymorphisms within the coding sequence of MLC1 had been reported. In about 20% of the patients with a typical clinical and MRI picture, no mutations in the MLC1 gene are found. Several of the families, in which no mutations are found, also do not show linkage with the MLC1 locus, which suggests a second gene involved in MLC. The absence of mutations may also be the consequence of performing standard mutation analysis that can miss heterozygous deletions, mutations in the promoter, 3' and 5' untranslated regions (UTRs), and intron mutations, which may influence the amino acid composition of the end product. In this work we describe 13 novel mutations, including those found with extended mutation analysis on MLC patients. This study shows that extended mutation analysis is a valuable tool to identify at least some of the missing mutations. Therefore, we suggest extended mutation analysis for the MLC1 gene, if no mutations are found during standard analysis.

Base Sequence↗

PubMed2004

IL1RAPL1 is associated with mental retardation in patients with complex glycerol kinase deficiency who have deletions extending telomeric of DAX1.

IL1RAPL1 (interleukin-1 receptor accessory protein-like, gene 1) has recently been shown to be mutated in patients with X-linked mental retardation. Clinical experience has suggested that patients with the contiguous gene syndrome, complex glycerol kinase deficiency (cGKD), will have mental retardation (MR) if they have deletions extending from the GK gene into the DMD gene and/or involving a significant extension telomeric from DAX1. We examined cell lines from patients with cGKD whose clinical features would be informative and would allow us to determine if IL1RAPL1 deletions can help to explain the MR in patients with deletions extending telomeric from DAX1. Our results showed that nearly all patients with deletions involving DAX1, but not DMD, had MR if IL1RAPL1 was deleted. If ILIRAPLI and DMD were intact, the patients with DAX1 deletions only rarely had normal development. Deletions in DNA from patients with cGKD who exhibited MR and had normal IL1RAPL1 all involved the GK and DMD genes. Our data are consistent with the association of IL1RAPL1 gene deletion and MR in the majority of patients with cGKD and deletions extending telomeric from DAX1.

Adrenal Glands↗

PubMed1984

The limited host range of an Agrobacterium tumefaciens strain extended by a cytokinin gene from a wide host range T-region.

The host range of Agrobacterium tumefaciens strain LBA649 (pTiAg57) is limited to grapevine and a few other plant species. Its host range was extended through the introduction of the T-region from the wide host range octopine plasmid pTiAch5. In contrast, R prime plasmids harboring the entire wide host range virulence region were unable to achieve this effect. Via site-directed mutagenesis a search was performed to identify the T-DNA genes which were responsible for the observed host range extension. Inactivation of one of the onc-genes (the cyt gene) was found to abolish the capacity of the T-region to extend the host range of LBA649. Therefore, we cloned the cyt gene into a disarmed T-region plant vector and used it in complementation studies with pTiAg57 via the binary vector strategy. We show that the mere presence of the cyt gene from a wide host range Ti plasmid is sufficient to extend the host range of LBA649 to certain plants. We conclude that the limited host range of LBA649 is not caused by a lack of recognition of plants but is mainly due to the absence or inactivity of a cyt gene in the T-region of pTiAg57.

Journal Article↗

PubMed1985

The arrangement of H5 molecules in extended and condensed chicken erythrocyte chromatin.

Chemical cross-linking with dithiobis(succinimidyl propionate) has been used to investigate the relative disposition of neighbouring H5 (H1) molecules in chicken erythrocyte chromatin in the extended (nucleosome filament) and condensed (300 A filament) states; in this chromatin H5 and H1 are interspersed along the nucleosome filament, rather than segregated into blocks, as shown by the nature of the cross-linked dimers and their relative amounts. Detailed analysis of the cross-linked H5 homopolymers from extended chromatin and condensed nuclear chromatin indicates which domains of H5 are in contact (or close proximity) in the two states. Two results suggest a polar, head-to-tail arrangement of H5 molecules along the nucleosome filament. This arrangement persists when chromatin adopts higher-order structure but in the folded state neighbouring basic C-terminal domains, in particular, are more closely juxtaposed than they are in extended chromatin.

Animals↗

PubMed1996

Influence of food on the oral bioavailability of loratadine and pseudoephedrine from extended-release tablets in healthy volunteers.

The effect of a high-fat breakfast on the bioavailability of the components of an extended-release tablet containing 10 mg loratadine in the immediate-release coating and 240 mg pseudoephedrine sulfate in the extended-release core was studied in 24 healthy male volunteers in a single-dose, two-way crossover study. The drug was administered after a 10-hour overnight fast or within 5 minutes of consuming a standardized high-fat breakfast. Serial blood samples were collected over a 48-hour period, and plasma was analyzed for loratadine and its active metabolite descarboethoxyloratadine (DCL), and pseudoephedrine. For pseudoephedrine, maximum concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUCzero-infinity) were similar after both treatments, indicating no relevant food effect on the bioavailability of pseudoephedrine. Also, the absorption profiles of pseudoephedrine (from Wagner-Nelson analysis) were similar for the fed and fasted treatments, indicating no apparent differences in absorption. Plasma concentration-time profiles and values for Cmax and AUCzero-infinity of DCL were similar for the two treatments, indicating no relevant food effect on the pharmacokinetics of DCL. In contrast, for loratadine, administration with food resulted in a significantly increased mean Cmax (53%) and AUC from time zero to the final quantifiable sample (AUCif) (76%). However, the resultant Cmax and AUC of loratadine under fed conditions were well below those previously obtained at steady-state after multiple-dose administration of loratadine (40 mg/day) that were shown to be safe and well-tolerated in several clinical studies. The effect of food on the bioavailability and pharmacokinetic profiles of the components of a combination loratadine/pseudoephedrine extended-release tablet is not likely to be clinically significant.

Adult↗