Exaggerated postprandial GLP-1 secretion following esophagectomy is not associated with gastric emptying and intestinal transit.

Esophagectomy causes postprandial symptoms associated with an exaggerated postprandial gut hormone response. This study aimed to compare the gastrointestinal transit time of patients 1 year after esophagectomy with unoperated controls, including its relation to satiety gut hormone release. In this cross-sectional study, consecutive, disease-free patients after esophagectomy with pyloroplasty were compared with unoperated control subjects to assess gastric emptying (GE) and cecal arrival time (CAT). Serial plasma samples were collected before, and for 300 minutes after, a mixed-meal challenge. Body composition was assessed, and symptom scores were calculated. Eleven patients 1 year post-esophagectomy (age: 62.6 ± 9.8, male: 82%) did not show a significantly different GE pattern compared with 10 control subjects (P = 0.245). Rather, patients could be categorized bimodally as exhibiting either rapid or slow GE relative to controls. Those with rapid GE trended toward a higher postprandial symptom burden (P = 0.084) without higher postprandial glucagon-like peptide-1 (GLP-1) secretion (P = 0.931). CAT was significantly shorter after esophagectomy (P = 0.043) but was not significantly associated with GE, GLP-1 secretion, or symptom burden. Neither early nutrient delivery to the proximal small intestine nor to the colon explains the exaggerated postprandial GLP-1 response after esophagectomy. GE varies significantly in these patients despite consistent pyloric management.

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy.

BACKGROUND: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy. METHODS: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52 weeks after surgery. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s.e.m.) 17·1(3·2) per cent, P < 0·001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0·014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0·003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0·022). Mean(s.e.m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621·5(71·7) pg/ml; 10 days: 415·1(59·80) pg/ml; 6 weeks: 309·0(42·0) pg/ml; 12 weeks: 415·8(52·1) pg/ml; 52 weeks: 547·4(83·2) pg/ml; P < 0·001) and did not predict weight loss (P = 0·198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52 weeks (mean(s.e.m.) insulin AUC0-30 min : fold change 1·7(0·4), 2·0(0·4), 3·5(0·7) and 4·0(0·8) respectively; P = 0·001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0·001), with a 3·3(1·8)-fold increase at 1 year (P < 0·001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0·041) and symptomatic neuroglycopenia (Sigstad score, P = 0·017, R2 = 0·45). GLP-1 AUC predicted loss of weight (P = 0·008, R2 = 0·52) and fat mass (P = 0·010, R2 = 0·64) at 1 year. CONCLUSION: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.

Which Organ is Responsible for the Pathogenesis of Obesity?

Obesity is associated with significant complications and healthcare costs, but our ability to treat obesity has been limited by our understanding of its pathogenesis. We surveyed diabetologists and obesity related health care professionals asking them which organ they believed to be responsible for the pathogenesis of obesity. Participants favoured a central nervous system (CNS) aetiology. The response echoes evidence from genome wide association studies identifying a link between obesity and CNS loci. Our most successful obesity therapies involve the manipulation of subcortical area of the brain involved in energy balance. Future success in the management of obesity will be determined by our ability to define the pathogenesis of the disease in individual cases, moving from a one-size-fits-all, to more focused interventions.

Calcium channel blockade reduces mechanical strain-induced extracellular matrix gene response in lamina cribrosa cells.

PURPOSE: This study examines the effect of the L-type calcium channel blocker verapamil on mechanical strain-induced extracellular matrix genes in optic nerve head lamina cribrosa (LC) cells. METHODS: Changes in LC cell intracellular calcium [Ca(2+)]i following hypotonic cell membrane stretch were measured with the fluorescent probe fura-2/AM. Fluorescence intensity was measured, after labelling, by calcium (Ca2+) imaging confocal microscopy. Confluent human LC cell cultures were serum starved for 24 h prior to exposure to cyclical mechanical strain (1 Hz, 15%) for 24 h in the presence or absence of verapamil (10 mm). Transforming growth factor-ß 1 (TGF-ß1), collagen 6A3 (COL6A3) and chondroitin sulfate proteoglycan 2 (CSPG2) mRNA expression levels were assessed by quantitative RT-PCR. RESULTS: Hypotonic cell membrane stretch of LC cells from normal donors significantly increased [Ca2+]i (p<0.05). Exposure to cyclical mechanical strain (15% strain) produced a statistically significant increase in the three matrix genes that were examined (TGF-ß1, COL6A3 and CSPG2). This response in both cyclical and mechanical stretch was significantly reduced by pretreating LC cells with the L-type calcium channel blocker verapamil (p<0.05). CONCLUSIONS: This study provides evidence of a novel mechanotransduction pathway linking mechanical strain, cation channel function and the induction of LC cell matrix gene transcription. This highlights the potential involvement of calcium influx in the activation of matrix remodelling responses in the optic nerve head and supports the rationale that calcium channel blockers may attenuate disease progression in glaucoma.

Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers.

OBJECTIVES: The relevance of spatial composition in the microbial changes associated with UC is unclear. We coupled luminal brush samples, mucosal biopsies and laser capture microdissection with deep sequencing of the gut microbiota to develop an integrated spatial assessment of the microbial community in controls and UC. DESIGN: A total of 98 samples were sequenced to a mean depth of 31,642 reads from nine individuals, four control volunteers undergoing routine colonoscopy and five patients undergoing surgical colectomy for medically-refractory UC. Samples were retrieved at four colorectal locations, incorporating the luminal microbiota, mucus gel layer and whole mucosal biopsies. RESULTS: Interpersonal variability accounted for approximately half of the total variance. Surprisingly, within individuals, asymmetric Eigenvector map analysis demonstrated differentiation between the luminal and mucus gel microbiota, in both controls and UC, with no differentiation between colorectal regions. At a taxonomic level, differentiation was evident between both cohorts, as well as between the luminal and mucosal compartments, with a small group of taxa uniquely discriminating the luminal and mucosal microbiota in colitis. There was no correlation between regional inflammation and a breakdown in this spatial differentiation or bacterial diversity. CONCLUSIONS: Our study demonstrates a conserved spatial structure to the colonic microbiota, differentiating the luminal and mucosal communities, within the context of marked interpersonal variability. While elements of this structure overlap between UC and control volunteers, there are differences between the two groups, both in terms of the overall taxonomic composition and how spatial structure is ascribable to distinct taxa.

Correlations between colonic crypt mucin chemotype, inflammatory grade and Desulfovibrio species in ulcerative colitis.

AIM: The colonic mucus gel layer is composed of mucins that may be sulphated or sialyated. Sulphated mucins predominate in health while in ulcerative colitis (UC) sulphation is reduced. These differences result directly from inflammatory events. It may also be hypothesized that they arise in part from alterations in the colonic microbiota, particularly changes in the burden of sulphated mucin-metabolizing species, such as Desulfovibrio (DSV) bacteria. The aim of this study was to correlate colonic mucin chemotypes and inflammatory scores in health and UC and relate these changes to changes in the colonization of colonic crypts by DSV. METHOD: Paired colonic biopsies from 34 healthy controls (HC) and 19 patients with active UC were collected for the purpose of parallel histological and microbiological assessment. High-iron diamine and Alcian blue staining and haematoxylin and eosin of mucosal biopsy specimens were used to assess histological changes within the clinical spectrum of UC. Quantitative real-time polymerase chain reaction analysis was employed to determine the total and DSV copy number within the colonic crypts. RESULTS: Compared with HC, the mucin chemotype in UC was less sulphated and inversely correlated with the degree of mucosal inflammation. A weak but significant negative correlation was found between the abundance of sulphated mucins and DSV burden. CONCLUSION: Mucin composition strongly correlates with the degree of mucosal inflammation, and to a lesser extent with DSV burden. These data suggest that mucin chemotype and DSV burden are linked phenomena and highlight the need to consider changes in mucin chemotype in the setting of microbial dysbiosis occurring within the colitic colon. What does this paper add to the literature? Decreased sulphation of mucins has been associated with inflammation in ulcerative colitis. Currently there are few data describing the relationship between microbial species and changes in mucin chemotype. This study validates previous findings and presents evidence of changes in mucin chemotype occurring in tandem with coherent changes in the microbiota within crypt niches.

Oxidative stress, mitochondrial dysfunction and calcium overload in human lamina cribrosa cells from glaucoma donors.

PURPOSE: Oxidative stress is implicit in the pathological changes associated with glaucoma. The purpose of this study was to compare levels of oxidative stress in glial fibrillary acid-negative protein (GFAP) lamina cribrosa (LC) cells obtained from the optic nerve head (ONH) region of 5 normal (NLC) and 4 glaucomatous (GLC) human donor eyes and to also examine mitochondrial function and calcium homeostasis in this region of the ONH. METHODS: Intracellular reactive oxygen species (ROS) production was examined by a thiobarbituric acid reactive substances (TBARS) assay which measures malondialdehyde (MDA), a naturally occurring product of lipid peroxidation and is used as an indicator of oxidative stress. Mitochondrial membrane potential (MMP) and intracellular calcium ([Ca(2+)](i)) levels were evaluated by flow cytometry using the JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetrabenzimidazolecarbocyanine iodide) and fluo-4/AM probes respectively. Anti-oxidant and Ca(2+) transport system gene and protein expression were determined by real time polymerase chain reaction (RT-PCR) using gene-specific primer/probe sets and western immunoblotting, respectively. RESULTS: Intracellular ROS production was increased in GLC compared to NLC (27.19 ± 7.05 µM MDA versus 14.59 ± 0.82 µM MDA, p < 0.05). Expression of the anti-oxidants Aldo-keto reductase family 1 member C1 (AKR1C1) and Glutamate cysteine ligase catalytic subunit (GCLC) were significantly lower in GLC (p = 0.02) compared to NLC control. MMP was lower in GLC (57.5 ± 6.8%) compared to NLC (41.8 ± 5.3%). [Ca(2+)](i) levels were found to be higher (p < 0.001) in GLC cells compared to NLC. Expression of the plasma membrane Ca(2+)/ATPase (PMCA) and the sodium-calcium (NCX) exchangers were lower, while intracellular sarco-endoplasmic reticulum Ca(2+)/ATPase 3 (SERCA) expression was significantly higher in GLC compared to NLC. Subjection of NLC cells to oxidative stress (200 µM H(2)0(2)) reduced expression of Na(+)/Ca2(+) exchanger 1 (NCX 1), plasma membrane Ca2+ ATPase 1 (PMCA 1), and PMCA 4 as determined by RT-PCR. CONCLUSIONS: Our data finds evidence of oxidative stress, mitochondrial dysfunction and impaired calcium extrusion in GLC cells compared to NLC cells and suggests their importance in the pathological changes occurring at the ONH in glaucoma. Future therapies may target reducing oxidative stress and / or [Ca(2+)](i).

Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts.

BACKGROUND: Fibroblasts play a critical role in intestinal wound healing. Lipopolysaccharide (LPS) is a cell wall component of commensal gut bacteria. The effects of LPS on intestinal fibroblast activation were characterized. METHODS: Expression of the LPS receptor, toll-like receptor (TLR) 4, was assessed in cultured primary human intestinal fibroblasts using flow cytometry and confocal microscopy. Fibroblasts were treated with LPS and/or transforming growth factor (TGF) beta1. Nuclear factor kappaB (NFkappaB) pathway activation was assessed by inhibitory kappaBalpha (IkappaBalpha) degradation and NFkappaB promoter activity. Fibroblast contractility was measured using a fibroblast-populated collagen lattice. Smad-7, a negative regulator of TGF-beta1 signalling, and connective tissue growth factor (CTGF) expression were assessed using reverse transcriptase-polymerase chain reaction and western blot. The NFkappaB pathway was inhibited by IkappaBalpha transfection. RESULTS: TLR-4 was present on the surface of intestinal fibroblasts. LPS treatment of fibroblasts induced IkappaBalpha degradation, enhanced NFkappaB promoter activity and increased collagen contraction. Pretreatment with LPS (before TGF-beta1) significantly increased CTGF production relative to treatment with TGF-beta1 alone. LPS reduced whereas TGF-beta1 increased smad-7 expression. Transfection with an IkappaBalpha plasmid enhanced basal smad-7 expression. CONCLUSION: Intestinal fibroblasts express TLR-4 and respond to LPS by activating NFkappaB and inducing collagen contraction. LPS acts in concert with TGF-beta1 to induce CTGF. LPS reduces the expression of the TGF-beta1 inhibitor, smad-7.

Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts.

BACKGROUND: Fibroblasts isolated from strictures in Crohn's disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) beta1. TGF-beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-beta1. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-beta1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen. RESULTS: Crohn's stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-beta1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-beta1 by exhibiting SBE promoter activity or producing CTGF. CONCLUSION: Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-beta1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.

Simvastatin impairs smad-3 phosphorylation and modulates transforming growth factor beta1-mediated activation of intestinal fibroblasts.

BACKGROUND: Transforming growth factor (TGF) beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. Simvastatin exhibits antifibrotic properties. This study assessed the effects of simvastatin on TGF-beta1-mediated intestinal fibroblast activation. METHODS: Human intestinal fibroblasts were activated with TGF-beta1 with or without simvastatin or the cholesterol pathway intermediates farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Collagen-Ialpha2 expression was assessed by reverse transcriptase-polymerase chain reaction. Connective tissue growth factor (CTGF) and smad phosphorylation were evaluated by western blot, and plasminogen activator inhibitor (PAI) 1 activity by enzyme-linked immunosorbent assay. Fibroblast filamentous (F)-actin accumulation was assessed by confocal microscopy and contraction by a fibroblast-populated collagen lattice (FPCL) model. RESULTS: TGF-beta1 treatment of fibroblasts induced smad-2/3 phosphorylation, CTGF and collagen-Ialpha2 production, F-actin bundling, FPCL contraction and PAI-1 activation. Pretreatment with simvastatin inhibited the induction of CTGF and collagen-Ialpha2, PAI-1 activation, F-actin bundling and FPCL contraction. The inhibitory effect of simvastatin on PAI-1 activation was reversed by GGPP and FPP. Simvastatin pretreatment inhibited TGF-beta1-mediated phosphorylation of smad-3. CONCLUSION: Simvastatin abrogates TGF-beta1-mediated intestinal fibroblast activation by inhibition of smad-3 phosphorylation. These findings offer a mechanism for the antifibrotic effects of simvastatin and a therapeutic entry point in the treatment of intestinal fibrosis.

Sulphate-reducing bacteria and hydrogen sulphide in the aetiology of ulcerative colitis.

BACKGROUND: The aetiology of ulcerative colitis is uncertain but may relate to environmental factors in genetically predisposed individuals. Sulphate-reducing bacteria (SRB) have been implicated through the harmful effects of hydrogen sulphide, a by-product of their respiration. Hydrogen sulphide is freely permeable to cell membranes and inhibits butyrate. This review examines the available evidence relating to SRB as a possible cause of ulcerative colitis. METHODS: A literature search was conducted using the PubMed database and search terms 'sulphate reducing bacteria', 'hydrogen sulphide', 'ulcerative colitis', 'mucous gel layer' and 'trans-sulphuration'. RESULTS: Search results were scrutinized and 113 pertinent full-text articles were selected for review. Collected data related to hydrogen sulphide metabolism, SRB respiration, mucous gel layer composition and their association with ulcerative colitis. CONCLUSION: There is evidence to implicate SRB as an environmental factor in ulcerative colitis. More sophisticated mucosal dissection and molecular techniques using bacteria-directed probes are required to determine an association definitively.

Arousability in schizophrenia: relationship to emotional and physiological reactivity and symptom severity.

OBJECTIVE: Socioenvironmental stressors have been linked with increased symptom severity and relapse in those with schizophrenia. However, little is known about how individual differences in stress reactivity may contribute to these outcomes. METHOD: This study examined the association between the temperament characteristic of arousability and changes in negative affect and cardiovascular activity during a challenge task in 58 in-patients with diagnosis of schizophrenia and 21 controls. RESULTS: In the patient group, levels of arousability were significantly associated with increases in negative affect in response to the task and greater severity of affective symptoms. Levels of arousability were associated with decreased heart rate during the challenge task in our patient group. CONCLUSION: These findings suggest that greater attention be given to individual differences, such as temperament and personality characteristics, and their role in the experience of stressors, including emotional and physiological response, as well as symptom development.

Temporal changes in renal endoglin and TGF-alfa1 expression following ureteral obstruction in rats

Chronic renal disease is characterized by the accumulation of extracellular matrixproteins in the kidney and a loss of renal function. Tubulointerstitial fibrosis hasbeen reported to play an important role in the progression of chronic renal diseases.Transforming growth factor-beta1 (TGF-alpha1) is a profibrotic cytokine playing amajor contribution to fibrotic kidney disease. Endoglin is a membrane glycoproteinof the TGF-alpha1 receptor system. The aim of this work was to determine the timecourseexpression of renal type I and IV collagens, endoglin and TGF-alpha1 in a ratmodel of induced tubulointerstitial fibrosis at 1, 3, 10 and 17 days after unilateralureteral obstruction (UUO). In 17 days-ligated (L)-renal samples, a marked interstitialfibrosis was detected by Masson’s trichromic and Sirius red staining, accompaniedby an increase in type I collagen expression as shown by immunohistochemicalanalysis. Northern blot studies revealed a progressive increase in collagen alpha2(I),TGF-alpha1 and endoglin mRNA expression in L kidneys when compared with the correspondingnon-ligated (NL) kidneys from the animals subjected to left UUO. Seventeendays after UUO, significant increases in collagen alpha2(I), collagen alpha1(IV),TGF-alpha1 and endoglin mRNA levels were detected in L kidneys vs NL kidneys. Significantlyhigher levels of the protein endoglin were found in L kidneys than in NLkidneys 10 and 17 days following obstruction. A marked increase expression forendoglin and TGF-alpha1 was localized in renal interstitium by immunohistochemical studies 17 days after obstruction. In conclusion, this work reports the upregulationof endoglin coincident to that of its ligand TGF-alpha1 in the kidneys of rats with progressivetubulointerstitial fibrosis induced by UUO (AU)

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Temporal changes in renal endoglin and TGF-beta1 expression following ureteral obstruction in rats.

Chronic renal disease is characterized by the accumulation of extracellular matrix proteins in the kidney and a loss of renal function. Tubulointerstitial fibrosis has been reported to play an important role in the progression of chronic renal diseases. Transforming growth factor-beta1 (TGF-beta1) is a profibrotic cytokine playing a major contribution to fibrotic kidney disease. Endoglin is a membrane glycoprotein of the TGF-beta1 receptor system. The aim of this work was to determine the time-course expression of renal type I and IV collagens, endoglin and TGF-beta1 in a rat model of induced tubulointerstitial fibrosis at 1, 3, 10 and 17 days after unilateral ureteral obstruction (UUO). In 17 days-ligated (L)-renal samples, a marked interstitial fibrosis was detected by Masson's trichromic and Sirius red staining, accompanied by an increase in type I collagen expression as shown by immunohistochemical analysis. Northern blot studies revealed a progressive increase in collagen alpha2(I), TGF-beta1 and endoglin mRNA expression in L kidneys when compared with the corresponding non-ligated (NL) kidneys from the animals subjected to left UUO. Seventeen days after UUO, significant increases in collagen alpha2(I), collagen alpha1(IV), TGF-beta1 and endoglin mRNA levels were detected in L kidneys vs NL kidneys. Significantly higher levels of the protein endoglin were found in L kidneys than in NL kidneys 10 and 17 days following obstruction. A marked increase expression for endoglin and TGF-beta1 was localized in renal interstitium by immunohistochemical studies 17 days after obstruction. In conclusion, this work reports the upregulation of endoglin coincident to that of its ligand TGF-beta1 in the kidneys of rats with progressive tubulointerstitial fibrosis induced by UUO.

Affective reactivity of language symptoms, startle responding, and inhibition in schizophrenia.

The speech of some schizophrenia patients becomes markedly more disordered when negative affect is aroused. The authors tested associations between affective reactivity of speech and responsiveness and inhibition on an acoustic startle task in a sample of 27 outpatients. Patients whose language was reactive to negative affect showed significantly higher initial startle amplitudes than those whose language was not reactive. However, they also showed greater habituation to repeated startle stimuli over trials, even after differences in initial amplitudes were controlled statistically. These findings suggest that affective reactivity of speech is associated with higher initial startle responsiveness but also with greater habituation and, conversely, that patients who are relatively nonreactive to excitatory affective and sensory stimuli are also less reactive to inhibitory input.

Factor analysis of the Communication Disturbances Index.

The present study utilized factor analysis to investigate possible underlying processes in schizophrenic thought disorder. Using the Communication Disturbances Index [CDI; Arch. Gen. Psychiatry, 53, (1996) 358], a measure of disruption in the communication of meaning from speaker to listener, we examined the speech of 58 stable schizophrenia outpatients for six different types of referential communication disturbances. We calculated instances of disturbance per 100 words and then factor-analyzed our data using the SAS statistical package. Principal components analysis with an oblique rotation produced both a two- and a three-factor solution, depending on factor inclusion criteria. In the three-factor solution, the first two factors reflected weaknesses in language structural organization and in concept-boundary definition, respectively. The third factor appeared to reflect weaknesses in specific facets of memory functioning. In the two-factor solution, the aforementioned structural organization and concept-boundary definition factors were combined into a single executive functioning factor. Results from the study may be heuristic in the development of models of language disturbance in schizophrenia patients.

Conceptual sequencing and disordered speech in schizophrenia.

This study examined associations between impairments of attention, memory, and conceptual sequencing ability, and specific schizophrenia thought and language symptoms. Speech samples of stable schizophrenia outpatients were assessed for frequencies of six different types of communication failures. The classification of types of failures was based on hypothesized differences in underlying cognitive process. Frequencies of the four types of communication failures believed to involve language structural weaknesses all were significantly and fairly strongly related to conceptual sequencing ability. In addition, regression analyses indicated that each of these four types of communication failures was associated with a unique configuration of attentional, memorial, and conceptual sequencing processes. In contrast, the two types of communication disturbances not suggestive of language structural problems were not positively associated with any of the cognitive weaknesses assessed.