The neurobiology of interoception and affect.

Scholars have argued for centuries that affective states involve interoception, or representations of the state of the body. Yet, we lack a mechanistic understanding of how signals from the body are transduced, transmitted, compressed, and integrated by the brains of humans to produce affective states. We suggest that to understand how the body contributes to affect, we first need to understand information flow through the nervous system's interoceptive pathways. We outline such a model and discuss how unique anatomical and physiological aspects of interoceptive pathways may give rise to the qualities of affective experiences in general and valence and arousal in particular. We conclude by considering implications and future directions for research on interoception, affect, emotions, and human mental experiences.

A cohort study of the prognostic and treatment predictive value of SATB2 expression in colorectal cancer.

BACKGROUND: Special AT-rich sequence-binding protein 2 (SATB2) is a novel diagnostic marker of colorectal cancer (CRC), and loss of SATB2 has been linked to poor survival from the disease. In this study, we validated the prognostic ability of SATB2 expression in a large, prospective CRC cohort. METHODS: Immunohistochemical SATB2 expression was assessed in 527 incident CRC cases from the Malmö Diet and Cancer Study. Kaplan-Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB2 expression on cancer-specific survival (CSS) and overall survival (OS). RESULTS: High SATB2 expression was associated with a prolonged CSS in the full cohort (hazard ratio (HR)=0.61; 95% CI 0.41-0.92) and in colon cancer (HR=0.39; 95% CI 0.20-0.75), remaining significant in multivariable analysis of colon cancer (HR=0.49; 95% CI 0.25-0.96), with similar findings for OS. In curatively resected stage III-IV patients, a significant benefit from adjuvant and/or neoadjuvant therapy was observed for SATB2 high tumours (P(interaction)=0.037 for OS) and high SATB2 expression in rectal cancer correlated with an enhanced effect of neoadjuvant therapy (P(interaction)=0.033 for OS). CONCLUSION: High SATB2 expression is an independent marker of good prognosis in colon cancer and may modulate sensitivity to chemotherapy and radiation.

An observational study of the prevalence and incidence of comorbid conditions in older women with breast cancer.

BACKGROUND: Longitudinal analyses of comorbid conditions in women with breast cancer are few. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we included 51,950 women aged≥66 years with in situ and stage I to IV breast cancer diagnosed in 1998-2002. We identified the prevalence and incidence of 34 comorbid conditions in these women, as well as in a matched cohort without cancer whose rates were standardized to the age and race/ethnicity distribution of the cancer patients. We also estimated rates of office encounters and diagnostic or testing procedures during the 12 months before diagnosis. RESULTS: The prevalence of most conditions at diagnosis was comparable among breast cancer and noncancer patients. New conditions after diagnosis were more common in breast cancer patients, and the incidence rates increased with higher stage at diagnosis. Before diagnosis, women presenting with stage IV disease had 41% [95% confidence interval (CI) 38% to 43%] fewer physician encounters and 34% (95% CI 24% to 31%) fewer unique diagnostic tests than women diagnosed with carcinoma in situ. CONCLUSIONS: Many comorbid conditions are identified as a consequence of the breast cancer diagnosis. There appears to be an important contribution from a lack of interaction with the health care system before diagnosis.

Advanced glycation end product level, diabetes, and accelerated cognitive aging.

OBJECTIVE: Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. METHODS: We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident cognitive impairment (a decline of >1.0 SD on each test) was analyzed with logistic regression. RESULTS: Older adults with high pentosidine level had worse baseline DSST score (p=0.05) but not different 3MS score (p=0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall <0.001; DSST 5.9, 7.4, and 4.5 point decline, p=0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio=1.55; 95% confidence interval 1.07-2.26; DSST: 31% vs 22%, odds ratio=1.62; 95% confidence interval 1.13-2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. CONCLUSION: High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes.

Plasma F2-isoprostane level and cognitive function over eight years in non-demented older adults: Findings from the Health ABC Study.

F2-isoprostanes (F2-IsoP) are reportedly increased in dementia patients, and are considered a reliable biomarker of oxidation. However, few studies have examined the predictive value of peripheral F2-IsoP levels in non-demented older adults. This study assesses the association between plasma F2-IsoP and change in cognitive function in non-demented elderly over eight years. Plasma F2-IsoP was measured by gas chromatography-mass spectrometry in a biracial cohort of 726 elderly men and women. Digit Symbol Substitution test and the Modified Mini-Mental State Exam were administered over time. No association was found between F2-IsoP tertile and baseline or change (slope) in cognitive function over eight years. Plasma F2-IsoP is not a valuable biomarker in predicting cognitive change over years in non-demented older adults.

Health care utilization and mortality among elderly patients with myelodysplastic syndromes.

BACKGROUND: Mortality in patients with myelodysplastic syndromes (MDS) is high, and patients are likely to require hospitalizations, emergency department (ED) visits, and transfusions. The relationships between these events and the MDS complications of anemia, neutropenia, and thrombocytopenia are not well understood. PATIENTS AND METHODS: A total of 1864 patients registered in the United States' Surveillance Epidemiology and End Results (SEER) program and aged ≥ 66 years old when diagnosed with MDS in 2001 or 2002 were included. Medicare claims were used to identify MDS complications and utilization (hospitalizations, ED visits, and transfusions) until death or the end of 2005. Mortality was based on SEER data. Kaplan-Meier incidence rates were estimated and multivariable Cox models were used to study the association between complications and outcomes. RESULTS: The 3-year incidence of anemia, neutropenia, and thrombocytopenia was 81%, 25%, and 41%, and the incidence of hospitalization, ED visit, and transfusion was 62%, 42%, and 45%, respectively. Median survival time was 22 months. Cytopenia complications were significantly associated with each of these outcomes. CONCLUSIONS: All types of cytopenia are common among patients with MDS and are risk factors for high rates of health care utilization and mortality. Management of the complications of MDS may improve patient outcomes.

COMT genotype and cognitive function: an 8-year longitudinal study in white and black elders.

OBJECTIVE: Catechol-O-methyltransferase (COMT), an enzyme that catalyzes the degradation of dopamine, is necessary for cognitive function. Few studies have examined the prospective association between COMT (val(158)met) genotype and cognition in older adults. METHODS: We assessed a biracial cohort of 2,858 elderly subjects without dementia who were followed for 8 years. The Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) were administered at baseline and years 3, 5, and 8. COMT by race, gender, and APOE status interactions were examined. RESULTS: Stratified by race and adjusted for covariates, repeated-measures mixed-effects models showed no association between COMT genotype and baseline cognitive function in black or white subjects. In white subjects, COMT was associated with change in 3MS (Met/Met: -2.3 [0.60], Met/Val: -1.7 [0.40], and Val/Val: -1.2 [0.50]) and DSST (Met/Met: -5.60 [1.00], Met/Val: -4.80 [0.70], Val/Val: -4.00 [0.90]). In black subjects, COMT was associated with change in the DSST (Met/Met: -4.10 [2.1], Met/Val: -4.80 [0.90], Val/Val -2.60 [1.00]). CONCLUSION: These findings suggest that the Val allele has a protective impact on cognitive decline in late life.

Predictors of maintaining cognitive function in older adults: the Health ABC study.

BACKGROUND: Although several risk factors for cognitive decline have been identified, much less is known about factors that predict maintenance of cognitive function in advanced age. METHODS: We studied 2,509 well-functioning black and white elders enrolled in a prospective study. Cognitive function was measured using the Modified Mini-Mental State Examination at baseline and years 3, 5, and 8. Random effects models were used to classify participants as cognitive maintainers (cognitive change slope > or = 0), minor decliners (slope < 0 and > 1 SD below mean), or major decliners (slope < or = 1 SD below mean). Logistic regression was used to identify domain-specific factors associated with being a maintainer vs a minor decliner. RESULTS: Over 8 years, 30% of the participants maintained cognitive function, 53% showed minor decline, and 16% had major cognitive decline. In the multivariate model, baseline variables significantly associated with being a maintainer vs a minor decliner were age (odds ratio [OR] = 0.65, 95% confidence interval [CI] 0.55-0.77 per 5 years), white race (OR = 1.72, 95% CI 1.30-2.28), high school education level or greater (OR = 2.75, 95% CI 1.78-4.26), ninth grade literacy level or greater (OR = 4.85, 95% CI 3.00-7.87), weekly moderate/vigorous exercise (OR = 1.31, 95% CI 1.06-1.62), and not smoking (OR = 1.84, 95% CI 1.14-2.97). Variables associated with major cognitive decline compared to minor cognitive decline are reported. CONCLUSION: Elders who maintain cognitive function have a unique profile that differentiates them from those with minor decline. Importantly, some of these factors are modifiable and thus may be implemented in prevention programs to promote successful cognitive aging. Further, factors associated with maintenance may differ from factors associated with major cognitive decline, which may impact prevention vs treatment strategies.

PPAR-gamma Pro12Ala genotype and risk of cognitive decline in elders.

BACKGROUND: The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been associated with decreased risk of diabetes and obesity, both disorders linked to cognitive impairment. We tested whether this polymorphism is associated with cognition. METHODS: Two thousand nine hundred sixty-one participants (mean age, 74.1; 41% Black; 52% women) were administered the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and 4 year follow-up. Test scores were adjusted for age, sex, education, cerebrovascular disease, depression and APOE genotype and additionally for race. We determined the association between Ala allele and development of cognitive decline (3MS decline of > or = 5 points). RESULTS: At baseline, unadjusted scores on both cognitive tests were higher for Ala carriers compared to non-carriers (3MS, 94.2 versus 92.5, p<0.001; DSST, 40.2 versus 34.5, p<0.001). Similarly, follow-up scores were higher for Ala carriers. Multivariable adjustment led to similar results; additional adjustment for race attenuated the baseline 3MS results. After 4 years, 17.5% of Ala carriers developed cognitive decline compared to 25% among non-carriers (unadjusted OR=0.61; 95%CI, 0.46-0.82; adjusted OR=0.75; 95%CI, 0.55-1.02). Further adjustment for metabolic variables including fasting blood glucose and lipid level did not change the results. CONCLUSIONS: The PPAR-gamma Ala12 allele carriers may have less risk of developing cognitive decline.

Endogenous sex hormone levels and risk of cognitive decline in an older biracial cohort.

BACKGROUND: Older women treated with conjugated estrogens may have an increased risk of dementia, but the effect of naturally occurring sex hormones on cognition is not certain. METHODS: Bioavailable estradiol and free testosterone level were obtained from 792 (55% men, 51% black) participants. We assessed cognition with the Modified Mini-Mental State Examination (3MS), Selective Reminding Test (SRT) and CLOX 1 at baseline and 2 years later. RESULTS: Women in the lowest estradiol tertile were more likely than those in the highest tertile to decline (> or = 1.0 S.D. of change) on 3MS (25% versus 9%, adjusted odds ratio [OR] = 3.9; 95% confidence interval [CI] = 1.6-9.6) and on SRT (28% versus 12%, adjusted OR [95% CI] = 3.3 [1.4-7.9]) but not CLOX 1. There was a borderline association between low estradiol tertile and decline on SRT in men (22% versus 14%, adjusted OR [95% CI] = 1.9 [0.9-3.9]). Testosterone level was not associated with decline in cognition in either men or women. Findings did not differ by race. CONCLUSIONS: Older women with low estradiol levels were more likely to experience decline in global cognitive function and verbal memory, and a similar trend was observed for verbal memory in men. This supports the hypothesis that endogenous sex hormones may play an important role in the maintenance of cognitive function in older adults.

20-Hydroxyecdysone indirectly regulates Hemolin gene expression in Hyalophora cecropia.

Development and innate immune defence are two vital processes that have been demonstrated to use the same or similar molecules and signalling pathways in insects. Hemolin is a moth haemolymph protein belonging to the immunoglobulin superfamily. It is strongly induced upon bacterial infection. However, recent studies indicate a developmental regulation of hemolin. We show that the steroid hormone 20-hydroxyecdysone (20E) can activate the expression of Hyalophora cecropia Hemolin (HcHemolin) in the fat body of diapausing pupae. Using the protein synthesis inhibitor cycloheximide we demonstrate that Hemolin up-regulation by 20E requires ongoing protein synthesis. Moreover, 20E enhances transcription of the Hemolin gene in response to bacteria. Comparing the upstream regions of Manduca sexta Hemolin (MsHemolin) and HcHemolin, we identified four putative regulatory sites. Two are putative hormone response elements (HREs), one with an imperfect inverted repeat (HRE-IR) and one with a monomeric site (HRE-M). An additional monomeric hormone receptor site (MRE) is present only in HcHemolin. The third conserved motif is similar to the interferon (IFN) regulatory factor binding element (IRF-E) and IFN-stimulated response element (ISRE). The fourth conserved element is a kappaB motif situated between the Cap-site and the TATA-box. Finally, by electrophoresis mobility shift assay we demonstrate that the HRE-IR forms specific complexes with nuclear extract proteins of normal pupae that increase after 20E stimulation.

Inflammatory markers and cognition in well-functioning African-American and white elders.

BACKGROUND: Several lines of evidence suggest that inflammatory mechanisms contribute to AD. OBJECTIVE: To examine whether several markers of inflammation are associated with cognitive decline in African-American and white well-functioning elders. METHODS: The authors studied 3,031 African-American and white men and women (mean age 74 years) enrolled in the Health, Aging, and Body Composition Study. Serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) and plasma levels of tumor necrosis factor-alpha (TNFalpha) were measured at baseline; cognition was assessed with the Modified Mini-Mental State Examination (3MS) at baseline and at follow-up. Cognitive decline was defined as a decline of >5 points. RESULTS: In age-adjusted analyses, participants in the highest tertile of IL-6 or CRP performed nearly 2 points lower (worse) on baseline and follow-up 3MS (p < 0.001 for all) and declined by almost 1 point over the >2 years (p = 0.01 for IL-6 and p = 0.04 for CRP) compared with those in the lowest tertile. After multivariate adjustment, 3MS scores among participants in the highest tertile of IL-6 and CRP were similar at baseline but remained significantly lower at follow-up (p < or = 0.05 for both). Those in the highest inflammatory marker tertile were also more likely to have cognitive decline compared with the lowest tertile for IL-6 (26 vs 20%; age-adjusted odds ratio [OR] = 1.34; 95% CI 1.06 to 1.69) and for CRP (24 vs 19%; OR = 1.41; 95% CI 1.10 to 1.79) but not for TNFalpha (23 vs 21%; OR = 1.12; 95% CI 0.88 to 1.43). There was no significant interaction between race and inflammatory marker or between nonsteroidal anti-inflammatory drug use and inflammatory marker on cognition. CONCLUSIONS: Serum markers of inflammation, especially IL-6 and CRP, are prospectively associated with cognitive decline in well-functioning elders. These findings support the hypothesis that inflammation contributes to cognitive decline in the elderly.

An intron enhancer activates the immunoglobulin-related Hemolin gene in Hyalophora cecropia.

Hemolin is the only insect member of the immunoglobulin (Ig) superfamily reported to be up-regulated during an immune response. In diapausing pupae of Hyalophora cecropia the gene is expressed in fat body cells and in haemocytes. Like the mammalian Ig kappa light chain gene, the Hemolin gene harbours an enhancer including a kappaB motif in one of its introns. This motif binds the H. cecropia Rel factor Cif (Cecropia immunoresponsive factor). The Hemolin third intron also mediates transient reporter gene expression in immunoresponsive Drosophila mbn-2 cells. Co-transfections of Drosophila SL2 cells showed that the Drosophila Rel factor Dif (Dorsal-related immunity factor), transactivates reporter gene constructs through the intron. Moreover, a 4.8-fold synergistic activation was obtained when Dif is combined with the rat C/EBP (CCAAT/enhancer element-binding protein) and human HMGI (high mobility group protein I). This is the first report of an insect immune-related gene that is up-regulated by an enhancer activity conferred through an intron.

Cell cycle-dependent effects of wortmannin on radiation survival and mutation.

Wortmannin, a known radiation sensitizer, has been used in experiments with synchronized cells to compare its effect on radiation survival and mutation induction within the cell cycle. PL61 cells (CHO cells with an inactivated HPRT gene containing a single active copy of a bacterial gpt gene) were synchronized by mitotic selection. Wortmannin administered before gamma irradiation caused a greater sensitization in G(1)-phase cells relative to late S/G(2)-phase cells. Preferential radiosensitization of G(1)-phase cells by wortmannin sets a limit to the proposed use of wortmannin in radiation therapy, since, in contrast to normal tissues, tumors usually have high proportions of S-phase cells. Wortmannin increased mutation frequencies in both G(1)- and S/G(2)-phase cells. Interestingly, relative increases in radiation-induced mutations in G(1) and S/G(2) phases were comparable. The results are discussed in terms of the contributions of different repair modes in the production of mutations.

The Drosophila gene Yippee reveals a novel family of putative zinc binding proteins highly conserved among eukaryotes.

An intracellular Drosophila protein, Yippee, was identified in a yeast interaction trap screen as physically interacting with Hyalophora cecropia Hemolin. The Yippee gene was isolated, structurally characterized, and mapped to the region 12A on the X-chromosome. Yippee contains a putative zinc-finger-like metal binding domain. It is the first characterized member of a conserved gene family of proteins present in diverse eukaryotic organisms, ranging from cellular slime mould to humans. A human cDNA clone was isolated and shown to be 76% identical to Drosophila Yippee. Yippee is ubiquitously expressed in different developmental stages of Drosophila and in different fetal tissues from human. Although the Hemolin-Yippee interaction remains to be further elucidated, the high degree of Yippee sequence conservation between a wide range of species suggests that this protein is of general importance in eukaryotes.

A study of plasma immunoglobulins profile in connection with restorative proctocolectomy.

BACKGROUND: Restorative proctocolectomy is an operative procedure that in principle means proctocolectomy, preserving the anal sphincters and construction of an ileal pouch which is sutured to the dentate line. The method is used mostly in case of surgical treatment of ulcerative colitis or familial polyposis coli. The procedure means different manipulations with the distal ileum that may influence the function of gut-associated lymphoid tissues, a major subdivision of the immune system. AIM: The aim of the present investigation was to study the plasma concentration of immunoglobulins in connection with the restorative proctocolectomy operation. METHODS: Forty five patients received an ileoanal pouch (IAP) because of ulcerative colitis. Twenty seven patients were males and 18 females. The mean age was 34 (range 18-55) years. Twenty six patients were first operated on emergency by subtotal colectomy with terminal ileostomy. In a second operation, the rectum was excised and an ileoanal pouch and a loop ileostomy that diverted the bowel content from the distal ileum was performed. Eighteen elective patients had their colectomy performed at the same time as the pouch operation. As a last procedure the diverting loop ileostomy was closed and thereby the distal ileum and the ileoanal pouch was put into function. Blood samples for plasma immunoglobulin analyses was collected from the patients before the colectomy, after colectomy with terminal ileostomy before construction of the pouch, during the period with pouches prior to loop ileostomy closure and 12 months after its closure. Immunoglobulins in plasma were determined by nephelometry method. The data was analyzed statistically by ANOVA and linear regression analysis. RESULTS: There was a significant difference preoperatively, in plasma immunoglobulin G (P-IgG) between the patients who were operated on electively compared to the emergency patients (p < 0.03). This was the only significant difference between values for the emergency and elective groups throughout the study. In the emergency patients after colectomy and with terminal ileostomy plasma immunoglobulin A (P-IgA) and immunoglobulin A (P-IgM) concentrations in plasma had increased significantly compared to preoperative (p < 0.03) and (p < 0.002) respectively. During the time with loop ileostomy plasma IgM was still found to be significantly elevated (p < 0.02) compared to the level before colectomy. In the electively operated patients plasma IgA and IgM were significantly increased after colectomy and pouch construction during the time with loop ileostomy compared to preoperatively (p < 0.04) and (p < 0.0004). After 12 months with functional pouches the plasma immunoglobulins in both groups were similar to the elective patients preoperatively. CONCLUSION: The immunoglobulins IgG, IgA and IgM were studied in connection with restorative proctocolectomy. Preoperatively, IgG was found to be significantly lower in emergency compared to elective patients. The difference is probably due to increased losses and impaired production of IgG in the acute phase of ulcerative colitis. IgA and IgM were found to increase significantly after colectomy and construction of an ileostomy but how these measures were responsible for the changes could not be determined in the present study. Twelve months after loop ileostomy closure there were no longer any significant changes of the immunoglobulins compared to elective patients with ulcerative colitis preoperatively.

Observations in the blood lipid profile in patients undergoing restorative proctocolectomy.

BACKGROUND: Ileal dysfunction, and resection or exclusion may affect intestinal bile acid resorption resulting in alterations in serum lipid concentration. In restorative proctocolectomy, the different procedures may involve the ileum in all three ways. AIM: The aim of the present study was to analyse possible changes of the blood lipid profile during the different steps of restorative proctocolectomy operative procedure. METHOD: There were nineteen elective patients on their ordinary diet and 19 emergency patients on total parenteral nutrition. The former group were primarily operated on with colectomy; ileoanal pouch and loop ileostomy while the later group had had an emergency colectomy and terminal ileostomy before the pouch operation. Thirty five of the patients had ulcerative colitis, 2 had familial colon polyposis and 1 familial cancer syndrome. Blood specimens were collected in the mornings with the patients in a fasting state. The emergency patients were on unchanged ordinary diet during the preoperative period. Serum cholesterol and triglyceride were determined by enzymatic methods. Lipoproteins, studied only in the elective patients, were analysed by a combination of ultracentrifugation and precipitation. Student's t-test with Bonferroni's correction for multiple comparisons was used for statistic calculations. RESULTS: Preoperatively, the emergency group had significantly lower serum cholesterol but not serum triglycerides values compared to the elective group. This finding is probably due to difference in the preoperative nutrition. The cholesterol levels among patients who received steroids in the two groups were compared and found to be significantly lower in the emergency group. Later, no significant differences concerning cholesterol and triglycerides were found between the groups. The cholesterol level was not significantly different in the elective group between patients who receive hydrocortisone and those who did not. During the period with loop ileostomy cholesterol was significantly lowered while the triglycerides were significantly increased compared to the preoperative values of the elective group. The decrease of serum cholesterol levels was correlated to the length of the excluded ileum. During the same period alpha-lipoprotein decreased significantly and reached values below the normal of the reference material. Beta-lipoproteins, which were subnormal already preoperatively, increased but not significantly. Pre-beta-lipoproteins were at the same level at all stations. At 12 months with functioning pouches all analysed values, with the exception of beta-lipoproteins. were within the normal limits set by the reference material. In the emergency group the patterns for triglycerides and cholesterol were similar but for the preoperatively depressed cholesterol values. After 12 months with functioning pouch the serum cholesterol and triglycerides were at the same level as for the elective patients. CONCLUSION: A serum lipid profile was studied in patients undergoing restorative proctocolectomy. Serum cholesterol and alpha-lipoprotein decreased and triglycerides increased when the patients had a diverting loop ileostomy. At 12 months after it's closure and with a functioning pouch, the patients had the same profile as the elective patients preoperatively, and with exception of beta-lipoproteins within normal limits in spite of the loss of the colon and the construction of a pouch of the distal ileum.

Effect of restorative proctocolectomy on gastric acid secretion and serum gastrin levels: a prospective study.

PURPOSE: The aim of the present study was to analyze gastric acid secretion after restorative proctocolectomy, because it has been shown that ileal resection or exclusion may increase gastric acid secretion. An increased output of gastric acids may decrease the intestinal passage time and contribute to looser stools. METHODS: Eleven patients who had elective colectomy and ileoanal pouch because of ulcerative colitis were investigated. Eight patient were males. Eight S-pouches and three J-pouches were constructed. Gastric acid secretion (retention, basic, and stimulated) was studied, together with serum gastrin, pentagastrin, and pepsinogen, in patients before colectomy and after having had the pelvic pouch functioning for 12 months. RESULTS: A significant increase, compared with preoperative levels, in retention, basic, and stimulated gastric acid secretion was found after 12 months with the pouch functioning. Levels of serum gastrin, pentagastrin, and pepsinogen were unchanged. CONCLUSION: Restorative proctocolectomy leads to a significant increase in gastric acid secretion. These findings may be of importance with regard to intestinal passage time and consistency of the stools.

Cell adhesion properties of hemolin, an insect immune protein in the Ig superfamily.

The isolation of antibacterial peptides from the giant silkmoth Hyalophora cecropia has opened the area of animal antibiotics [Boman, H. G. (1991) Cell 65, 205-207] and the study of insect immune genes has revealed striking similarities to many immune response genes in mammals [Hultmark, D. (1994) Nature 267, 116-117]. However, the molecules and mechanisms behind primordial immune recognition are not understood. One candidate for one such recognition molecule is hemolin, a 48-kDa immunoglobulin-related protein first isolated from H. cecropia, where it is up-regulated upon infection and secreted into the hemolymph. Hemolin was shown to bind to bacteria and to hemocytes, giving rise to changes in hemocyte adhesiveness and intracellular phosphorylation patterns [Faye, I. & Kanost, M. (1997) in Molecular mechanisms of immune responses in insects (Brey, P. T. & Hultmark, D., eds) Chapman and Hall, London]. In the present publication, we give evidence for the presence of a 52-kDa membrane form of hemolin on hemocytes, based on flow-activated cell sorting and membrane protein extractions. In addition we reveal calcium-dependent homophilic binding properties of hemolin, using hemolin-coated microspheres. When biotinylated recombinant hemolin was allowed to bind to hemocyte membranes, higher molecular-mass complexes were formed. Furthermore, we used immunological methods and Northern-blot analysis to demonstrate the presence of hemolin in embryos and retinal discs, suggesting that hemolin is expressed in several tissues at different developmental stages. These results show novel cell adhesion features of hemolin, corroborating its multifunctional character with putative roles in cellular and humoral immunity and in development.