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PubMed1998

Adding wheat middlings, microbial phytase, and citric acid to corn-soybean meal diets for growing pigs may replace inorganic phosphorus supplementation.

Three experiments were conducted with 96 growing Landrace x Yorkshire x Duroc crossbreds to determine the collective effectiveness of cereal phytase from wheat middlings, microbial phytase, and citric acid in improving phytate-P bioavailability in corn-soy diets. In Exp. 1, 40 gilts (7 wk old) were fed five diets for 8 wk. Diets 1, 2, and 3 were low-P, corn-soybean meal diets (CSB) + 0, .1, or .2% inorganic P (Pi) as calcium phosphate, respectively. Diet 4 was a similar corn-soy diet that included 15% wheat middlings (461 cereal phytase U/kg). Diet 5 was the CSB + microbial phytase (1,200 U/kg; Natuphos, BASF, Mount Olive, NJ). In Exp. 2, 16 barrows (8 wk old) were fed two diets for 6 wk. Diet 1 was the same as Diet 3 of Exp. 1 (.2% Pi). Diet 2 was Diet 4 of Exp. 1 + microbial phytase (300 U/kg). In Exp. 3, 40 barrows and gilts (6 wk old) were fed four diets for 6 wk. Diets 1 and 2 were the same as those in Exp. 2. Diet 3 was Diet 2 of Exp. 2 + 1.5% citric acid. Diet 4 was similar to Diet 3 but contained 10 instead of 15% wheat middlings. In Exp. 1, pigs fed the low-P, CSB (Diet 1) had lower (P < .05) ADG, ADFI, plasma Pi concentration, bone strength, and mobility score than pigs of the other four treatments. Measurements for pigs fed the 15% wheat middlings diet were not significantly different from those of pigs fed the CSB + .1% Pi or microbial phytase. In Exp. 2, ADG (P=.06) during wk 1 to 3 and gain:feed ratio (P < .02) and plasma Pi concentration (P < .005) during all weeks favored pigs fed the CSB + .2% Pi compared with the other diet including 15% wheat middlings. In Exp. 3, identical ADG during all weeks and similar plasma Pi concentrations at wk 4 and 6 were observed between pigs fed the two citric acid diets (Diets 3 and 4) and the CSB + .2% Pi (Diet 1). Pigs fed Diet 4 (10% wheat middlings) had even higher (P < .02) gain:feed ratio during wk 1 to 3 than those fed Diet 1. It seems feasible to completely replace calcium phosphate with 10 to 15% wheat middlings, 300 U microbial phytase/ kg, and 1.5% citric acid in the corn-soy diets for growing pigs.

6-Phytase↗

PubMed2000

Effects of base ingredient in cooked molasses blocks on intake and digestion of prairie hay by beef steers.

Twelve steers (332 kg) were used in three simultaneous 4 x 3 incomplete Latin squares to evaluate effects of beet molasses (BEET), cane molasses (CANE), or concentrated separator by-product (CSB) as base ingredients in cooked molasses blocks on intake and digestion of prairie hay and ruminal characteristics. All steers had ad libitum access to prairie hay (5.9% CP and 69.4% NDF; DM basis). The four experimental treatments included a control (no supplement) and three cooked molasses blocks, based on BEET, CANE, or CSB, fed daily at .125% of BW (.42 kg/d as-fed, .13 kg/d CP). Forage OM, NDF, and N intakes; digestible OM, NDF, and N intakes; and total tract OM and N digestibilities (percentage of intake) were greater (P < .05) for steers fed cooked molasses blocks than for control steers. Total tract OM digestibility was greater (P < or = .06) for steers fed BEET blocks (54.0%) than for those fed CSB (52.1%) or CANE blocks (52.2%). Digestion of NDF was greatest (P < .05) for steers fed BEET blocks (51.9%) and tended to be greater (P < .07) for steers fed CANE (49.3%) or CSB blocks (49.3%) than for control steers (46.9%). Ruminal ammonia concentrations were greater (P < .05) for steers fed cooked molasses blocks (.89 mM) than for control steers (.21 mM); this was primarily due to increases to 4.6 mM at 2 h postfeeding for steers fed blocks. Concentrations of total VFA in ruminal fluid were greater (P < .05) for steers fed BEET (92.7 mM) and CSB (88.1 mM) blocks than for control steers (80.3 mM), whereas concentrations for steers fed CANE blocks were intermediate (85.4 mM). Steers supplemented with cooked molasses blocks had greater molar percentages of butyrate than did control steers, particularly shortly after feeding. In summary, supplementation with cooked molasses blocks increased forage intake and digestion. The three base ingredients elicited similar responses, although steers fed BEET had slightly greater OM and NDF digestibilities than those fed CANE or CSB.

Animal Feed↗

PubMed2001

Soybean hulls as a primary ingredient in forage-free diets for limit-fed growing cattle.

In Exp. 1, 300 heifers (260 kg initial BW) were used to compare growth performance of cattle fed forage-free diets containing predominantly soybean hulls with that of cattle receiving roughage- and corn-based diets and to determine whether cattle fed soybean hull-based diets would respond to supplementation with methionine hydroxy analogue (MHA), lipid-coated betaine, or concentrated separator by-product (CSB; a source of betaine). Treatments included 1) a roughage-based diet fed at 2.75% of BW, 2) a corn-based diet fed at 1.5% of BW, 3) a corn-based diet fed at 2.25% of BW, 4) a soybean hull-based diet fed at 1.5% of BW (SH1.5), 5) a soybean hull-based diet fed at 2.25% of BW (SH2.25), 6) SH1.5 top-dressed with 11.4 g/d Alimet (10 g/d MHA), 7) SH2.25 top-dressed with 11.4 g/d Alimet, 8) SH2.25 top-dressed with 7 g/d of a lipid-coated betaine product (4.2 g/d betaine), and 9) SH2.25 top-dressed with 250 g/d CSB (15.5 g/d betaine). Supplemental MHA, betaine, and CSB did not change DMI, ADG, or gain:feed ratio for cattle fed soybean hulls. Heifers fed soybean hull-based diets gained 29% slower (P < 0.05) and had 27% lower gain:feed ratios than heifers fed the corn-based diets. Cattle fed soybean hull-based diets had gains that were lower (P < 0.05) than those of cattle fed the roughage-based diets, but gain:feed ratios were similar because cattle were fed less of the soybean hull-based diets. Roughage-fed cattle had similar gains but 25% lower (P < 0.05) gain:feed ratios than cattle fed the corn-based diets. In Exp. 2, degradation by ruminal microbes of betaine in anhydrous betaine, betaine-HCl, feed-grade betaine, lipid-coated betaine, and CSB was evaluated in vitro using ruminal inocula collected from steers fed a high-grain or high-roughage diet. The roughage diet led to less betaine disappearance than the grain diet. More betaine was degraded from CSB than from other sources, perhaps because sugars provided by CSB stimulated fermentation, but no large differences occurred among the other four sources. Betaine from all sources was extensively degraded, although some betaine may escape ruminal degradation.

Animal Feed↗

PubMed2004

Effect of soybean variety and processing on growth performance of young chicks and pigs.

The objective of this study was to determine whether soybeans without the Kunitz trypsin inhibitor and lectins could be fed effectively to young chicks and pigs. Specifically, we compared the growth performance of chicks and pigs fed diets containing modified soybeans: Kunitz trypsin inhibitor-free (KF), lectin-free (LF), lectin and Kunitz trypsin inhibitor-free (LFKF), conventional soybeans (CSB), and commercially obtained, dehulled, solvent-extracted soybean meal (SBM). A 7-d chick experiment was conducted to evaluate the nutritional value of CSB, KF, LF, LFKF, and SBM. The experiment was conducted as a completely randomized design, with four replicates, five treatments, and six male chicks per pen (n = 120). The five treatments consisted of 23% CP dextrose-soybean-based diets containing KF, LF, LFKF, CSB, or SBM as the source of dietary protein. A 28-d pig experiment was conducted to evaluate the nutritional value of CSB, LF, LFKF, and SBM. Pens of four pigs were assigned randomly to a control, corn-SBM, or one of six corn-soybean diets containing raw or extruded soybean varieties as a 2 x 3 factorial arrangement of treatments in a randomized complete block design with five blocks per treatment (n = 140). Chicks fed diets containing any of the raw soybean varieties gained less weight (P < 0.05) than chicks fed SBM (22.81 g/d for SBM vs. 14.17 g/d for the raw soybeans combined). Among the raw soybean treatments, there was a greater effect on growth performance (P < 0.05) by removing both lectins and Kunitz trypsin inhibitor (ADG of 16.56 g for LFKF) than by removing each antinutritional factor separately (ADG of 14.38 and 14.11 g for KF and LF, respectively). Pig growth performance was different (P < 0.001) for SBM (ADG of 409 g) and all the varieties when extruded (ADG of 450 g for CSB, 417 g for LF, and 408 g for LFKF) compared with the raw soybean treatments (ADG of 101 g for CSB, 165 g for LF, and 266 g for LFKF). Among the raw soybean treatments, growth performance improved (P = 0.003) as the antinutritional factor, lectin, was removed from the soybean and improved further (P = 0.045) when both lectins and Kunitz trypsin inhibitor were removed. The growth-inhibiting effect of feeding modified soybeans to young animals was more detrimental for pigs than for chicks in our experiments. Soybeans without the Kunitz trypsin inhibitor and lectins cannot be fed successfully to young chicks and pigs without heating.

Animal Feed↗

PubMed2006

A double-blind study of citalopram versus placebo in the treatment of compulsive sexual behaviors in gay and bisexual men.

OBJECTIVE: Compulsive sexual behavior (CSB) is a condition characterized by loss of control over sexual behavior and repeated negative consequences, including unsafe sex. Selective serotonin reuptake inhibitors have been found to reduce CSB symptomatology in open-label trials. The objective of this study was to conduct a preliminary double-blind, placebo-controlled evaluation of the efficacy, acceptability, and tolerability of citalopram in the treatment of CSB. METHOD: Twenty-eight men who have sex with men who met the threshold for CSB on the basis of existing validated measures participated in a 12-week, double-blind trial of citalopram 20 to 60 mg/day to evaluate its effects on CSB symptoms. The primary efficacy measure was the Yale-Brown Obsessive Compulsive Scale-Compulsive Sexual Behavior. The study was conducted from June 2002 to April 2004. RESULTS: Significant treatment effects were obtained for sexual desire/drive (p < .05) and frequency of masturbation (p < .01) and pornography use (p < .05). Both groups reduced sexual risk, but did not differ significantly. CONCLUSIONS: This study provides partial support for the effectiveness of citalopram for reducing symptoms of CSB in this population. Larger-scale trials are recommended to determine the public health benefits of this treatment.

Adult↗

PubMed1991

Temporal specificity in cross-modal transfer of the rabbit nictitating membrane response.

Two experiments examine cross-modal transfer of response features specific to the interstimulus interval (ISI) between a conditioned stimulus (CS) and an unconditioned stimulus. Rabbits were given initial training with a stimulus (CSA) in one modality (e.g., tone) at a designated ISI (e.g., 600 ms). Training was then shifted to a new stimulus (CSB) in another modality (e.g., light) at a new ISI (e.g., 400 ms). The timing of early conditioned responses (CRs) to CSB reflected the ISI of CSA. Ultimately, CRs to CSB shifted to a temporal location conforming to the ISI of CSB. When the ISI of CSB was shorter than that of CSA, CRs to CSA also shifted to a locus conforming to the ISI of CSB. The present results confirmed previous findings that training in one CS modality accelerates CR acquisition to a CS in another modality. The findings are compared with the transfer of response patterns in instrumental learning sets and are discussed regarding their implications for theories of cross-modal transfer.

Animals↗

PubMed1999

Natural history of composite sequential bypass: ten years' experience.

BACKGROUND: We previously reported 48-month patency rates of composite sequential bypass (CSB) approaching 60%. Yet, extended patency and limb salvage rates are unknown. HYPOTHESIS: Long-term patency and limb salvage rates of CSB are affected by sex, bypass configuration, and warfarin therapy. DESIGN: Medical records of all patients who underwent CSB during a 10-year period were retrospectively reviewed. SETTING: A referral center for the Chicago, Ill, region. PATIENTS: One hundred consecutive patients (mean age, 68.8 years; 57% were men and 49% had diabetes) undergoing 102 CSBs for limb salvage (ulcer, 43%; rest pain, 39%; and gangrene, 18%) from January 1986 to January 1996 were identified. INTERVENTIONS: Warfarin was used after surgery by 72% of patients and aspirin was used by the remainder of them. MAIN OUTCOME MEASURES: Life table primary patency and limb salvage rates were compared for sex, diabetes mellitus status, location of distal prosthetic anastomosis (above knee vs. below knee), and anticoagulation drug therapy (warfarin sodium vs aspirin) with log-rank statistics. RESULTS: Primary patency of CSB was 56% at 24 months, 29% at 48 months, and 20% at 84 months (SE <10%; mean follow-up, 19.6 months [range, 1.0-110.0 months]). Limb salvage rates were 64% at 24 months, 30% at 48 months, and 23% at 84 months (SE <10%); 66% and 90% of patients had failed grafts requiring amputation by 3 months and 1 year, respectively. CONCLUSIONS: Composite sequential bypass for limb salvage provides reasonable 2-year patency. However, patency rates steadily declined from year 2 to year 5. After CSB failure, limb salvage rates are poor, with 90% of patients progressing to amputation within 1 year.

Adult↗

PubMed1988

Death of the subcallosal glial sling is correlated with formation of the cavum septi pellucidi.

In this study we have examined the developmental fate of a population of cells that is located beneath the rostral corpus callosum during the perinatal period. These cells form a distinct slinglike structure along the geographically defined corticoseptal boundary (CSB) and may play a role in guiding callosal axons across the midline. The sling is a transient structure present in fetal and neonatal animals but not in adults. Here we show that the CSB cells die and that this debris is removed by macrophages. The sequence of cell degeneration in the CSB is highly stereotyped and follows a spatiotemporal pattern that is correlated with fusion of the cerebral hemispheres and subsequent growth across the midline of the callosal axons. The subcallosal location of the resorbing CSB is found in the exact place in which a fluid-filled cavity (the cavum septi pellucidi) is transiently found during the perinatal period. The tight temporal and spatial correlation between callosal axon decussation, degeneration of the CSB, and cavum septi formation suggests that these three phenomena may be causally related.

Aging↗

PubMed2007

Long-term consumption of fermented soybean-derived Chungkookjang enhances insulinotropic action unlike soybeans in 90% pancreatectomized diabetic rats.

BACKGROUND: We previously reported that Chungkookjang (CKJ), fermented unsalted soybeans, exhibited better anti-diabetic action than cooked soybeans (CSB) in vitro, but its effectiveness and mechanism have not been studied in vivo. AIM OF THE STUDY: We investigated whether CKJ modulated insulin resistance, insulin secretion, and pancreatic beta-cell growth and survival in 90% pancreatectomized (Px) diabetic rats. METHODS: The Px rats weighing 201 +/- 12 g were divided into four groups and fed for 8 weeks with a CSB diet, a CKJ diet, a casein diet, or a casein diet plus rosiglitazone (20 mg/kg body weight/day). With the exception of protein sources and contents of isoflavonoid aglycones and glycosides, the composition of the diets was made identical by adding soybean oil and cellulose to a casein diet. At the end of the experimental periods, hyperglycemic clamp was performed in conscious, unstressed and overnight fasted Px rats to measure insulin secretion capacity. Insulin/IGF-1 signaling was measured by immunoblotting in isolated islets from the treated rats, and beta-cell mass, proliferation and apoptosis were also determined by immunohistochemistry. RESULTS: After 8-week administration, CSB did not modulate glucose-stimulated insulin secretion, but surprisingly, CKJ enhanced insulin secretion. In addition, CKJ potentiated insulin/IGF-1 signaling in islets via the induction of insulin receptor substrate-2 expression, leading to increasing pancreatic duodenal homeobox-1, insulin promoter transcription factor. In parallel with the enhancement of the signaling, CKJ elevated pancreatic beta-cell hyperplasia by increasing its proliferation and decreasing apoptosis, whereas CSB did not. CONCLUSION: Based on these results, the fermentation of soybeans predominantly with Bacillus subtilis generated isoflavonoid aglycones and small peptides, which improved insulinotropic action in islets of type 2 diabetic rats. Overall, the anti-diabetic action of CKJ was superior to CSB in type 2 diabetic rats.

Animals↗

PubMed2003

Surgical treatment of coronary subclavian steal syndrome with carotid subclavian bypass.

Coronary subclavian steal syndrome (CSS) results from proximal subclavian artery occlusive disease causing reversal of flow in an internal mammary artery used as conduit for coronary artery bypass leading to myocardial ischemia. Although percutaneous transluminal angioplasty and stent (PTAS) for subclavian lesions has been successful, it is not always feasible. In this study, the results of carotid subclavian bypass (CSB) for symptomatic CSS due to subclavian occlusion and stenosis not amenable to PTAS were analyzed. The records of patients undergoing CSB for CSS between 1991 and 2001 were reviewed. Patients with lesions not amenable to angioplasty or stent were selected for CSB. Degree of preoperative myocardial ischemia was stratified according to New York Heart Association classification. Graft patency was analyzed by life-table methods. Our results showed that CSB for treatment of symptomatic CSS can be performed safely with excellent mid-term durability. In the setting of proximal subclavian artery disease not amenable to PTAS, CSB provides an acceptable means of treatment for symptomatic CSS.

Aged↗

PubMed1991

Electron microscopic demonstration of glucocorticoid recognition sites on isolated rat hepatocytes.

Ultrastructural evidence is presented for the presence of membrane-bound glucocorticoid recognition and binding sites. Corticosterone was derivatized at 3 different positions and coupled covalently to bovine serum albumin (BSA). All three derivatives competed for binding of [3H]corticosterone by isolated rat hepatocytes. The most effective competitor, corticosterone-succinate-BSA (CSB), was adsorbed onto colloidal gold particles (CSB-gold, 17 +/- 3 nm dia). When isolated rat hepatocytes or mouse pituitary tumor cells (AtT 20) are incubated with CSB-gold, specific binding in the microvilli-rich region of these cells is seen. This binding of CSB-gold is reduced by about 50% in the presence of unlabelled CSB or corticosterone.

Animals↗

PubMed2005

Transcription-coupled repair: impact on UV-induced mutagenesis in cultured rodent cells and mouse skin tumors.

UV-induced cyclobutane pyrimidine dimers (CPDs) are removed with accelerated speed from the transcribed strand of expressed genes in cultured mammalian cells by a process called transcription-coupled repair (TCR). It has been previously shown that this phenomenon has consequences for the molecular nature of the mutations induced by UV-light. Here, we review these data and show that TCR has not only a clear impact on UV-induced mutations in cultured mammalian cells but also on genes involved in tumor formation in the skin of UV-exposed mice. Mutations observed in the p53 gene in UV-induced squamous cell carcinoma are predominantly found at sites of dipyrimidines in the non-transcribed strand. In contrast, in UVC-irradiated Csb(-/-) Chinese hamster cells and in UVB-induced tumors in the Csb(-/-) mouse, almost all mutations are at positions of dipyrimidine sites in the transcribed strand of the mutated gene. Csb(-/-) mice appear to be susceptible to UVB-induced skin cancer in contrast to the human CSB patients. We speculate that the UVB-induced cancer susceptibility of Csb(-/-) mice is related to the absence of TCR as well as to a lack of a compensating global genome repair system for CPDs in mice.

Animals↗

PubMed1990

Molecular analysis of an acatalasemic mouse mutant.

The Csb acatalasemia mouse mutant differentially expresses reduced levels of catalase activity in a tissue specific manner. In order to pinpoint the molecular lesion that imparts the acatalasemia phenotype in Csb mice we have utilized the polymerase chain reaction technique to isolate catalase cDNA clones from control and Csb mouse strains. Sequence analyses of these cDNA clones have revealed a single nucleotide difference within the coding region of catalase between control and Csb mice. This nucleotide transversion (G----T) is located in the third position of amino acid 11 in the catalase monomer. In control mouse strains glutamine (CAG) is encoded at amino acid 11, while in Csb mice this codon (CAT) encodes histidine. This amino acid is located within a region that forms the first major alpha-helix in the amino-terminal arm of the catalase subunit and, as such, may render the catalase molecule unstable under certain physiological conditions.

Amino Acid Sequence↗

PubMedDate not supplied

Psychiatric comorbidity and compulsive/impulsive traits in compulsive sexual behavior.

In recent years there has been an increase in identifying and treating a clinical syndrome that has been given many different names, including compulsive sexual behavior (CSB). The purpose of this study was to determine the prevalence of psychiatric disorders in a sample of individuals with CSB, as evaluated by a structured psychiatric interview. A secondary focus of this research was to determine if individuals with CSB exhibit obsessive-compulsive characteristics or exhibit impulse control problems. Participants were 23 men and two women who responded to newspaper advertisements and met criteria for CSB according to diagnostic criteria established and assessed by expert clinicians. The Structured Clinical Interview for DSM-III, patient version (SCID-P) and the Structured Clinical Interview for Axis II Disorders (SCID-II) were used to interview all participants. To study compulsive or impulsive traits the authors developed a semistructured interview. Standardized rating scales were also administered. Eighty-eight percent of the sample met diagnostic criteria for an axis I disorder at the time of the interview, and 100% of the sample met criteria for an axis I disorder at some time in their lives. The most common diagnoses were mood and anxiety disorders. The sample exhibited more traits of impulsivity than compulsivity. The data are consistent with the suggestion proposed by others that argues for conceptualizing these disorders as impulsive/compulsive spectrum disorders. Attention must be given to addressing these traits, as well as to the treatment of other axis I and axis II disorders, when treating CSB.

Adult↗

PubMed2006

Cockayne syndrome B protein regulates the transcriptional program after UV irradiation.

The phenotype of the human genetic disorder Cockayne syndrome (CS) is not only due to DNA repair defect but also (and perhaps essentially) to a severe transcription initiation defect. After UV irradiation, even undamaged genes are not transcribed in CSB cells. Indeed, neither RNA pol II nor the associated basal transcription factors are recruited to the promoters of the housekeeping genes, around of which histone H4 acetylation is also deficient. Transfection of CSB restores the recruitment process of RNA pol II. On the contrary, the p53-responsive genes do not require CSB and are transcribed in both wild-type and CSB cells upon DNA damage. Altogether, our data highlight the pivotal role of CSB in initiating the transcriptional program of certain genes after UV irradiation, and also may explain some of the complex traits of CS patients.

Cockayne Syndrome↗

PubMed2003

The transcriptional response after oxidative stress is defective in Cockayne syndrome group B cells.

Cockayne syndrome (CS) is a human hereditary disease belonging to the group of segmental progerias, and the clinical phenotype is characterized by postnatal growth failure, neurological dysfunction, cachetic dwarfism, photosensitivity, sensorineural hearing loss, and retinal degradation. CS-B cells are defective in transcription-coupled DNA repair, base excision repair, transcription, and chromatin structural organization. Using array analysis, we have examined the expression profile in CS complementation group B (CS-B) fibroblasts after exposure to oxidative stress (H2O2) before and after complete complementation with the CSB gene. The following isogenic cell lines were compared: CS-B cells (CS-B null), CS-B cells complemented with wild-type CSB (CS-B wt), and a stably transformed cell line with a point mutation in the ATPase domain of CSB (CS-B ATPase mutant). In the wt rescued cells, we detected significant induction (two-fold) of 112 genes out of the 6912 analysed. The patterns suggested an induction or upregulation of genes involved in several DNA metabolic processes including DNA repair, transcription, and signal transduction. In both CS-B mutant cell lines, we found a general deficiency in transcription after oxidative stress, suggesting that the CSB protein influenced the regulation of transcription of certain genes. Of the 6912 genes, 122 were differentially regulated by more than two-fold. Evidently, the ATPase function of CSB is biologically important as the deficiencies seen in the ATPase mutant cells are very similar to those observed in the CS-B-null cells. Some major defects are in the transcription of genes involved in DNA repair, signal transduction, and ribosomal functions.

Adenosine Triphosphatases↗

PubMed2004

Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome.

UV-sensitive syndrome (UVsS) is a rare autosomal recessive disorder characterized by photosensitivity and mild freckling but without neurological abnormalities or skin tumors. UVsS cells show UV hypersensitivity and defective transcription-coupled DNA repair of UV damage. It was suggested that UVsS does not belong to any complementation groups of known photosensitive disorders such as xeroderma pigmentosum and Cockayne syndrome (CS). To identify the gene responsible for UVsS, we performed a microcell-mediated chromosome transfer based on the functional complementation of UV hypersensitivity. We found that one of the UVsS cell lines, UVs1KO, acquired UV resistance when human chromosome 10 was transferred. Because the gene responsible for CS group B (CSB), which involves neurological abnormalities and photosensitivity as well as a defect in transcription-coupled DNA repair of UV damage, is located on chromosome 10, we sequenced the CSB gene from UVs1KO and detected a homozygous null mutation. Our results indicate that previous complementation analysis of UVs1KO was erroneous. This finding was surprising because a null mutation of the CSB gene would be expected to result in CS features such as severe developmental and neurological abnormalities. On the other hand, no mutation in the CSB cDNA and a normal amount of CSB protein was detected in Kps3, a UVsS cell line obtained from an unrelated patient, indicating genetic heterogeneity in UVsS. Possible explanations for the discrepancy in the genotype-phenotype relationship in UVs1KO are presented.

Base Sequence↗

PubMed1997

Cockayne syndrome group B protein enhances elongation by RNA polymerase II.

Cockayne syndrome (CS) is characterized by impaired physical and mental development. Two complementation groups, CSA and CSB, have been identified. Here we report that the CSB gene product enhances elongation by RNA polymerase II. CSB stimulated the rate of elongation on an undamaged template by a factor of about 3. A thymine-thymine cyclobutane dimer located in the template strand is known to be a strong block to transcription. Addition of CSB to the blocked polymerase resulted in addition of one nucleotide to the nascent transcript. Finally, addition of transcription factor IIS is known to cause polymerase blocked at a thymine-thymine cyclobutane dimer to digest its nascent transcript, and CSB counteracted this transcript shortening action of transcription factor IIS. Thus a deficiency in transcription elongation may contribute to the CS phenotype.

Base Sequence↗