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PubMed2001

The National Kidney Foundation K/DOQI clinical practice guidelines for dietary protein intake for chronic dialysis patients.

This paper discusses two of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for nutrition in chronic renal failure. These are the guidelines that recommend a dietary protein intake of 1.2 g protein/kg body weight/day for clinically stable maintenance hemodialysis (MHD) patients (Guideline 15) and 1.2 to 1.3 g protein/kg/day for clinically stable chronic peritoneal dialysis (CPD) patients (Guideline 16). These recommended protein intakes are greater than the usually ingested protein intakes of MHD and CPD patients and are also greater than the recommended protein intakes for healthy, nonpregnant, nonlactating adults. The possible mechanisms that engender these increased protein needs include (1) the substantial quantity of amino acids, peptides, and proteins removed by the dialysis procedure and (2) the protein catabolic or antianabolic state caused by the uremic milieu, the inflammatory state, the oxidative and carbonyl stress, and the bioincompatible dialysis materials to which MHD and CPD patients are exposed. There are a number of nitrogen balance studies that have been performed to identify the dietary protein needs of MHD and CPD patents. The results of this research as well as some of the methodological limitations of these studies are reviewed. The concepts of the average dietary protein intake required to maintain protein balance in MHD or CPD patients and the safe protein intake that will maintain protein balance in virtually all MHD and CPD patients are discussed.

Adult↗
PubMed1997

Nucleotide sequence context effect of a cyclobutane pyrimidine dimer upon RNA polymerase II transcription.

We have studied the role of sequence context upon RNA polymerase II arrest by a cyclobutane pyrimidine dimer using an in vitro transcription system consisting of templates containing a specifically located cyclobutane pyrimidine dimer (CPD) and purified RNA polymerase II (RNAP II) and initiation factors. We selected a model sequence containing a well characterized site for RNAP II arrest in vitro, the human histone H3.3 gene arrest site. The 13-base pair core of the arrest sequence contains two runs of T in the nontranscribed strand that impose a bend in the DNA. We hypothesized that arrest of RNAP II might be affected by the presence of a CPD, based upon the observation that a CPD located at the center of a dA6.dT6 tract eliminates bending (Wang, C.-I., and Taylor, J.-S. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 9072-9076). We examined the normal H3.3 sequence and a mutant sequence containing a T --> G transversion, which reduces bending and efficiency of arrest. We show that a CPD in the transcribed strand at either of two locations in the arrest site is a potent block to transcription. However, a CPD in the nontranscribed strand only transiently pauses RNAP II. The CPD in concert with a mutation in the arrest site can reduce the extent of bending of the DNA and improve readthrough efficiency. These results demonstrate the potential importance of sequence context for the effect of CPDs within transcribed sequences.

Animals↗
PubMed1998

Cell growth inhibition by a novel vitamin K is associated with induction of protein tyrosine phosphorylation.

We have shown that a synthetic vitamin K analog, 2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone or compound 5 (Cpd 5), potently inhibits cell growth and suggested that the analog exerts its effects mainly via sulfhydryl arylation rather than redox cycling. Since protein-tyrosine phosphatases (PTPases), which have pivotal roles in many cellular functions, have a critical cysteine in their active site, we have proposed PTPases as likely targets for Cpd 5. To test this hypothesis, we examined the effects of Cpd 5 on protein tyrosine phosphorylation of cellular proteins and on the activity of PTPases. We found that Cpd 5 rapidly induced protein tyrosine phosphorylation in a human hepatocellular carcinoma cell line (Hep3B) at growth inhibitory doses, and the effect was blocked by thiols but not by non-thiol antioxidants or tyrosine kinase inhibitors. Cpd 5 inhibited PTPase activity, which was also significantly antagonized by reduced glutathione. Furthermore, the well studied PTPase inhibitor orthovanadate also induced protein tyrosine phosphorylation and growth inhibition in Hep3B cells. These results suggest that inhibition of cellular PTPases by sulfhydryl arylation and subsequent perturbation of protein tyrosine phosphorylation may be involved in the mechanisms of Cpd 5-induced cell growth inhibition.

Carcinoma, Hepatocellular↗
PubMed1999

Inhibition of hepatoma cell growth in vitro by arylating and non-arylating K vitamin analogs. Significance of protein tyrosine phosphatase inhibition.

We recently found that a thioether analog of K vitamin (Cpd 5) inhibited the activity of protein-tyrosine phosphatases (PTPases) and induced protein-tyrosine phosphorylation in a human hepatoma cell line (Hep3B). We have now examined the structural requirements for induction of protein-tyrosine phosphorylation and PTPase inhibition by several K vitamin analogs. Thioether analogs with sulfhydryl arylation capacity, especially those with a hydroxy (Cpd 5) or a methoxy group at the end of the side chain, induced protein-tyrosine phosphorylation, but non-arylating analogs, such as those with an all-carbon or O-ether side chain, did not. Among the receptor-tyrosine kinases, epidermal growth factor receptors were tyrosine-phosphorylated by treatment with thioether analogs, whereas insulin and hepatocyte growth factor receptors were not. An increase in tyrosine-phosphorylated ERK2 mitogen-activated protein kinase was also observed. The activity of purified T cell PTPase was inhibited only by the thioether analogs, but not by non-arylating analogs. Furthermore, the epidermal growth factor receptor dephosphorylation activity of Hep3B cell lysates was inhibited by Cpd 5 treatment. A similar induction of protein-tyrosine phosphorylation by Cpd 5 was seen in other human hepatoma cell lines together with growth inhibition. However, one cell line (HepG2), which was relatively resistant to growth inhibition by Cpd 5, did not increase its phosphorylation levels upon Cpd 5 treatment. These results suggest that cell growth inhibition by thioether analogs is closely associated with inhibition of PTPases by sulfhydryl arylation and with tyrosine phosphorylation of selected proteins.

Carcinoma, Hepatocellular↗
PubMed2002

Characterization of Drosophila carboxypeptidase D.

Metallocarboxypeptidase D (CPD), is a 180-kDa protein that contains three carboxypeptidase-like domains, a transmembrane domain, and a cytosolic tail and which functions in the processing of proteins that transit the secretory pathway. An initial report on the Drosophila melanogaster silver gene indicated a CPD-like protein with only two and a half carboxypeptidase-like domains with no transmembrane region (Settle, S. H., Jr., Green, M. M., and Burtis, K. C. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 9470-9474). A variety of bioinformatics and experimental approaches were used to determine that the Drosophila silver gene corresponds to a CPD-like protein with three carboxypeptidase-like domains, a transmembrane domain, and a cytosolic tail. In addition, two alternative exons were found, which result in proteins with different carboxypeptidase-like domains, termed domains 1A and 1B. Northern blot, reverse transcriptase PCR, and sequence analysis were used to confirm the presence of the various mRNA forms. Individual domains of Drosophila CPD were expressed in insect Sf9 cells using the baculovirus expression system. Media from domain 1B- and domain 2-expressing cells showed substantial enzymatic activity, whereas medium from domain 1A-expressing cells was no different from cells infected with wild-type virus. Domains 1B and 2 were purified, and the enzymatic properties were examined. Both enzymes cleaved substrates with C-terminal Arg or Lys, but not Leu, and were inhibited by conventional metallopeptidase inhibitors and some divalent cations. Drosophila domain 1B is more active at neutral pH and greatly prefers C-terminal Arg over Lys, whereas domain 2 is more active at pH 5-6 and slightly prefers C-terminal Lys over Arg. The differences in pH optima and substrate specificity between Drosophila domains 1B and 2 are similar to the differences between duck CPD domains 1 and 2, suggesting that these properties are essential to CPD function.

3' Untranslated Regions↗
PubMed2006

Changes in nicotine intake and cigarette use over time in two nationally representative cross-sectional samples of smokers.

Population surveys have observed decreases in cigarette use over time among smokers. These decreases have probably been influenced by tobacco control measures implemented over the past several decades, but few data exist on whether smokers have also reduced their nicotine intake. The authors examined data from two cross-sectional National Health and Nutrition Examination Surveys (NHANES), conducted in 1988-1994 and 1999-2002. Laboratory, examination, and interview data from current smokers not reporting nicotine intake from other sources were examined. From NHANES III (1988-1994) to NHANES 1999-2002, the average number of cigarettes smoked per day (CPD) fell by nearly 15% (three cigarettes), while the mean serum cotinine level fell by 13% (30 ng/ml). Finer breakdowns of CPD data in each time period suggested that most of the change occurred in the lower (<10 CPD) and higher (>or=20 CPD) smoking categories. These data suggest that CPD may represent a proxy for exposure to nicotine and perhaps other tobacco smoke constituents on the population level, since the decline in serum cotinine levels observed among smokers closely paralleled the decline in self-reported CPD between 1988-1994 and 1999-2002. In addition, these data are inconsistent with the hypothesis that the remaining population of smokers is becoming more dependent on nicotine over time.

Adult↗
PubMed2004

NMR structure of the DNA decamer duplex containing double T*G mismatches of cis-syn cyclobutane pyrimidine dimer: implications for DNA damage recognition by the XPC-hHR23B complex.

The cis-syn cyclobutane pyrimidine dimer (CPD) is a cytotoxic, mutagenic and carcinogenic DNA photoproduct and is repaired by the nucleotide excision repair (NER) pathway in mammalian cells. The XPC-hHR23B complex as the initiator of global genomic NER binds to sites of certain kinds of DNA damage. Although CPDs are rarely recognized by the XPC-hHR23B complex, the presence of mismatched bases opposite a CPD significantly increased the binding affinity of the XPC-hHR23B complex to the CPD. In order to decipher the properties of the DNA structures that determine the binding affinity for XPC-hHR23B to DNA, we carried out structural analyses of the various types of CPDs by NMR spectroscopy. The DNA duplex which contains a single 3' T*G wobble pair in a CPD (CPD/GA duplex) induces little conformational distortion. However, severe distortion of the helical conformation occurs when a CPD contains double T*G wobble pairs (CPD/GG duplex) even though the T residues of the CPD form stable hydrogen bonds with the opposite G residues. The helical bending angle of the CPD/GG duplex was larger than those of the CPD/GA duplex and properly matched CPD/AA duplex. The fluctuation of the backbone conformation and significant changes in the widths of the major and minor grooves at the double T*G wobble paired site were also observed in the CPD/GG duplex. These structural features were also found in a duplex that contains the (6-4) adduct, which is efficiently recognized by the XPC-hHR23B complex. Thus, we suggest that the unique structural features of the DNA double helix (that is, helical bending, flexible backbone conformation, and significant changes of the major and/or minor grooves) might be important factors in determining the binding affinity of the XPC-hHR23B complex to DNA.

Adenine↗
PubMedDate not supplied

Solute removal characteristics of continuous recirculating peritoneal dialysis in experimental and clinical studies.

Continuous recirculating peritoneal dialysis (CRPD) was introduced to enhance solute removal efficiency in conventional peritoneal dialysis (PD) therapies such as continuous ambulatory peritoneal dialysis (CAPD). In CRPD, a portion of the dwell dialysate in the patient's peritoneal cavity is drained through a double-lumen catheter and purified by an extracorporeal dialyzer. In this study, solute removal characteristics and safety of CRPD are examined in ex vivo and clinical studies. Recirculation dialysis experiments using nine dogs (13.6 +/- 2.5 kg of body weight) were carried out for 240 min in the ex vivo study, whereas another seven dogs (12.1 +/- 2.8 kg) received conventional peritoneal dialysis (CPD) (120 min dwelling x 2) and six additional dogs (11.9 +/- 2.7 kg) received a Tidal PD (20 min dwelling x 12; 50% of tidal volume ratio) as controls. The ex vivo study revealed that CRPD has a higher efficiency for solute removal than CPD and is equivalent to Tidal PD. In the BUN reduction rate, the 19.4 +/- 5.5% in 240 min CRPD (n = 9) was significantly higher (p < 0.05) than the 3.5 +/- 3.6% in 240 min CPD (n = 7) and equivalent to the 17.3 +/- 4.7% in 240 min Tidal PD (n = 6). Continuous recirculating peritoneal dialysis maintained a low UN level in the peritoneal cavity due to dialysis with an extracorporeal dialyzer. This tendency was also seen in creatinine removal. In the clinical study, CRPD (n = 10) and CPD (n = 5) treatments were used in three renal failure patients. Higher solute removal efficiency was shown in CRPD than in CPD treatments, and the urea peritoneal clearance was 14.1 +/- 4.4 ml/min in CRPD (n = 10), significantly higher (p < 0.05) than the 7.3 +/- 2.1 ml/min in CPD (n = 5). No fibrin formation occurred during CRPD treatments.

Adult↗
PubMed2002

Increased oxidative damage to peripheral blood leukocyte DNA in chronic peritoneal dialysis patients.

This study focuses on the extent of oxidative DNA damage in peripheral blood leukocytes of chronic peritoneal dialysis (CPD) patients. 8-Hydroxy 2'-deoxyguanosine (8-OHdG) contents in peripheral leukocyte DNA were measured by an HPLC-electrochemical detection method in 24 age- and sex-matched healthy subjects, 22 nondialyzed patients with advanced renal failure, and 42 CPD patients. Mean 8-OHdG content was the highest in CPD patients, followed by the nondialyzed patients, and then by the healthy subjects (19.4 versus 11.9 versus 8.3/10(6) dG; ANOVA P < 0.001). In nondialyzed subjects, peripheral leukocyte 8-OHdG contents inversely correlated with renal creatinine clearance (r = -0.772; P < 0.001). Deficiency of blood antioxidants in CPD and nondialyzed patients was expressed by the lower plasma levels of ascorbate, cholesterol-standardized alpha-tocopherol and whole-blood reduced glutathione, and the higher levels of whole-blood oxidized glutathione as compared with healthy subjects (ANOVA P < 0.05). Mean serum ferritin and iron levels and transferrin saturation were higher in the CPD patients than those in the nondialyzed patients and controls (ANOVA P < 0.05). Flow cytometric analyses of intracellular reactive oxygen species production of peripheral leukocytes showed that spontaneous production by granulocytes, as well as phorbol-12-myristate-13-acetate (PMA)-induced production by granulocytes, lymphocytes and monocytes, were the highest from CPD patients, followed by nondialyzed patients, and then by the healthy subjects (ANOVA P < 0.05). Forward stepwise multiple regression disclosed that uremia, PD treatment, spontaneous and PMA-induced reactive oxygen species production in leukocytes, and serum iron were the independent determinants of peripheral leukocyte 8-OHdG content (R(2) = 0.769; P < 0.001). In conclusion, profound increased 8-OHdG levels in peripheral leukocyte DNA occur in the course of chronic renal failure, gradually increase with its progression, and are further exacerbated by PD treatment.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Differences between depressed patients with heart failure and those with pulmonary disease.

OBJECTIVE: The objective of this study was to examine differences between depressed medical inpatients with congestive heart failure (CHF) and chronic pulmonary disease (CPD) that could impact the etiology and management of depression in this setting. METHODS: Patients aged 50 years or over consecutively admitted to Duke University Medical Center and three community hospitals were screened for depressive disorder using the Structured Clinical Interview for Depression (SCID-IV). Characteristics of depressed patients with CHF (N = 174) and CPD (N = 527) were compared. Analyses were stratified by type of depressive disorder (major versus minor). RESULTS: Depressed hospitalized medical patients with CHF and CPD are similar to one another in many respects, particularly with regard to severity of depressive symptoms and shortness of breath. However, patients with CHF in this study had greater medical comorbidity and overall more severe medical illnesses but less severe CHF-specific disease severity compared with patients with CPD. Patients with CPD, however, were more likely to have psychologic risk factors such as a psychiatric history, comorbid psychiatric illness, and stressful life events. CONCLUSION: These findings suggest important differences between depressed patients with CHF and those with CPD, perhaps reflecting differences in depression etiology and need for specific strategies for managing depression in each of these conditions.

Aged↗
PubMedDate not supplied

Predicted hemodynamic benefits of counterpulsation therapy using a superficial surgical approach.

A volume-displacement counterpulsation device (CPD) intended for chronic implantation via a superficial surgical approach is proposed. The CPD is a pneumatically driven sac that fills during native heart systole and empties during diastole through a single, valveless cannula anastomosed to the subclavian artery. Computer simulation was performed to predict and compare the physiological responses of the CPD to the intraaortic balloon pump (IABP) in a clinically relevant model of early stage heart failure. The effect of device stroke volume (0-50 ml) and control modes (timing, duration, morphology) on landmark hemodynamic parameters and the LV pressure-volume relationship were investigated. Simulation results predicted that the CPD would provide hemodynamic benefits comparable to an IABP as evidenced by up to 25% augmentation of peak diastolic aortic pressure, which increases diastolic coronary perfusion by up to 34%. The CPD may also provide up to 34% reduction in LV end-diastolic pressure and 12% reduction in peak systolic aortic pressure, lowering LV workload by up to 26% and increasing cardiac output by up to 10%. This study demonstrated that the superficial CPD technique may be used acutely to achieve similar improvements in hemodynamic function as the IABP in early stage heart failure patients.

Computer Simulation↗
PubMed1988

Comparison of the effects of critical point-drying and freeze-drying on cytoskeletons and microtubules.

We have compared the effects of critical point-drying (CPD) and freeze-drying (FD) on the morphology of Triton-resistant cytoskeletons and microtubules by scanning (SEM) and transmission electron microscopy (TEM). In general, cytoskeletons attached to Formvar films suffer less structural damage than cells or cytoskeletons attached to glass, because the Formvar film absorbs some of the stress associated with shrinkage during drying. However, as seen in stereo-pair electron micrographs, the three-dimensional structure of cytoskeletons prepared by FD is better preserved and shows fewer artefacts than those prepared by CPD. CPD specimens are flatter, often have a concave and apparently collapsed nuclear matrix and show large cracks both in the perinuclear zone and through the cytoskeleton. At least some of the damage appears to be due to residual water in the CO2 used as the substitution fluid, because cytoskeletons dried with a water filter attached to the CPD apparatus show substantially less damage than those dried without the filter. Freeze-dried cytoskeletons consist mostly of unbroken, smooth filaments and have no perinuclear open space. Comparison of the effects of drying on the diameters of in vitro polymerized microtubules showed that the diameter of microtubules is reduced after drying, but that FD causes significantly less shrinkage than CPD. Addition of 0.2% tannic acid to the glutaraldehyde fixative significantly reduces the shrinkage of CPD microtubules, but has no effect on FD microtubules. The observations on microtubules support the hypothesis that drying-induced shrinkage is the result of both pressure and solvent evaporation and they indicate that tannic acid stabilizes samples against the former but not the latter.

Cytoskeleton↗
PubMed2005

Encapsulating peritoneal sclerosis in paediatric peritoneal dialysis patients.

Encapsulating peritoneal sclerosis (EPS) is a serious complication of chronic peritoneal dialysis (CPD). In contrast to the adult population, there are few studies regarding EPS in paediatric CPD patients, and the majority of reported patients are from Japan. The aim of the present report is to define the incidence of EPS in our paediatric CPD patients and to describe the clinical and laboratory characteristics. A total of 104 paediatric patients were followed from November 1989 to November 2003 and two were diagnosed as EPS (1.9%). The dialysis periods of these patients were 45 and 53 months with 6 and 8 peritonitis episodes, respectively. Clinical signs of EPS developed 7 and 14 days after the removal of the dialysis catheter, and CPD was replaced by haemodialysis because of persistent peritonitis. One patient was well after surgical management but died 6 months later. The second patient who was treated with prednisolone remained well at 16 months. In conclusion, EPS is a rare but important complication of CPD. We recommend that all patients on CPD who develop ultrafiltration failure be evaluated radiologically for the occurrence of EPS. Management should be tailored to the individual patient.

Adolescent↗
PubMed1997

UVB-induced cyclobutane pyrimidine dimer frequency correlates with skin cancer mutational hotspots in p53.

Ultraviolet light has been identified as the major carcinogen in skin cancer and the p53 tumor suppressor gene is a major target for UV-induced mutations. The mutations are probably caused by unrepaired UV-induced cyclobutane pyrimidine dimers (CPD) and possibly by the less frequent pyrimidine (6-4) pyrimidone photoproducts. While hot spots for p53 mutations in human nonmelanoma skin tumors correspond quite well to slow spots for CPD repair in cultured cells irradiated with the model mutagen 254 nm UVC (which is not present in terrestrial sunlight), they do not all coincide with sequences that are initially frequently damaged by 254 nm UVC. Using LMPCR (ligation-mediated polymerase chain reaction), we show that environmentally relevant UVB light induces CPD at CC and Pyr(m)C positions much more frequently than does UVC light, and that all eight skin cancer hot spots in p53 are also hot spots for UVB-induced CPD. Our results show that methylation of dipyrimidine sites (Pyr(m)CpG) is associated with an increase rate of CPD formation upon UVB irradiation. Consequently, DNA methylation may increase the mutagenic potential of UVB and explains that several p53 mutation hot spots are found at Pyr(m)CpG. The distribution patterns of CPD formation and the photofootprint patterns found along exons 5 and 6 of p53 gene are suggestive of DNA folding into nucleosomes.

Base Sequence↗
PubMed1998

13C labelled cholesteryl octanoate breath test for assessing pancreatic exocrine insufficiency.

BACKGROUND: A non-invasive test for assessment of fat digestion has been developed based on the intraluminal hydrolysis of cholesteryl-[1-13C]octanoate by pancreatic esterase. AIMS: To determine the diagnostic performance of this breath test in the assessment of exocrine pancreatic function. METHODS: The test was performed in 20 healthy controls, 22 patients with chronic pancreatic disease (CPD), four with biliopancreatic diversion (BPD), and 32 with non-pancreatic digestive diseases (NPD); results were compared with those of other tubeless tests (faecal chymotrypsin and fluorescein dilaurate test). RESULTS: Hourly recoveries of 13CO2 were significantly lower in CPD when compared with healthy controls or NPD. In patients with CPD with mild to moderate insufficiency, the curve of 13CO2 recovery was similar to that of healthy controls, while in those with severe insufficiency it was flat. In three patients with CPD with severe steatorrhoea, a repeat test after pancreatic enzyme supplementation showed a significant rise in 13CO2 recovery. The four BPD patients had low and delayed 13CO2 recovery. Only eight of the 32 patients with NPD had abnormal breath test results. There was a significant correlation between the results of the breath test and those of faecal chymotrypsin, the fluorescein dilaurate test, and faecal fat measurements. For the diagnosis of pancreatic disease using the three hour cumulative 13CO2 recovery test, the sensitivity was 68.2% and specificity 75.0%; values were similar to those of the other two tubeless pancreatic function tests. In seven healthy controls, nine patients with CPD, and nine with NPD a second breath test was performed using Na-[1-13C]octanoate and a pancreatic function index was calculated as the ratio of 13C recovery obtained in the two tests: at three hours this index was abnormal in eight patients with CPD and in three with NPD. CONCLUSION: The cholesteryl-1[1-13C]octanoate breath test can be useful for the diagnosis of fat malabsorption and exocrine pancreatic insufficiency.

Adult↗
PubMed2006

The role of chronic peritoneal dialysis in the management of the patient with chronic kidney disease.

The role of chronic peritoneal dialysis (CPD) in the management of patient with chronic kidney disease is being reexamined. There has been a decline in CPD utilization in the United States, which has been attributed to a variety of factors. It is important that these factors be understood and addressed, since nephrologists feel that about 30% of end-stage renal disease patients should be maintained on CPD and patients are more satisfied with CPD and feel that CPD has a less negative impact on their lives than hemodialysis. The present chapter discusses some of the reasons for decline in CPD utilization in the United States.

Chronic Disease↗
PubMed1987

Differential plasma corticosterone responses to electrical stimulation of the medial and lateral septal nuclei.

To pursue the possibility that subdivisions within the medial and lateral septal nuclei are differentially involved in adrenocortical function, plasma samples obtained prior to and following electrical stimulation of the septal nuclei of urethane (1.30 g/kg)-anesthetized female rats were assessed for corticosterone concentration. Hippocampal EEG, ECG, heart rate (HR), mean arterial pressure (MAP) and respiration were routinely monitored, and timed blood samples (0.15 ml) were obtained from a catheterized tail artery. Blood samples were taken 0.5 min prior to and at 5, 10, 15 and 30 min after initiation of stimulation. Whereas no change in Cpd B levels were observed following sham stimulation or stimulation of the corpus callosum, fornix or anterior commissure, stimulation of the medial septal nuclei produced differential responses. Decreased plasma Cpd B responses followed stimulation of the medial septal nucleus (MS); increases in plasma Cpd B followed stimulation of the dorsal (LSD) and ventral (LSV) division of the lateral septal nucleus. The overall increase in plasma Cpd B levels following LSD and LSV stimulation was 16 and 32%, respectively. The overall decrease in corticosterone concentration subsequent to MS stimulation was 18%. The largest increases in Cpd B levels occurred at 5 min (36%) and 10 min (24%) for LSV and LSD groups, respectively; the largest decrease was noted at 15 min (25%). Plasma Cpd B responses to stimulation of the intermediate area of the lateral septal nucleus produced varying and inconsistent responses. Collectively, these data support the hypothesis that subdivisions within the septal nuclei are differentially involved in adrenocortical function.

Animals↗
PubMed2001

Immunohistochemical localization and comparison of carboxypeptidases D, E, and Z, alpha-MSH, ACTH, and MIB-1 between human anterior and corticotroph cell "basophil invasion" of the posterior pituitary.

Basophil invasion, i.e., invasion of basophilic corticotrophs from the residual intermediate lobe into the posterior lobe of the human pituitary gland, is believed to be a physiological phenomenon. This study evaluated the distribution of CPE, CPD, CPZ, alpha-MSH, ACTH, and Ki-67 immunoreactivity between human anterior pituitary and basophil invasion of the neurohypophysis. Mild to moderate immunoreactivities for CPE and CPZ were distributed relatively uniformly in the majority of the anterior pituitary cells and basophil invasion. In contrast, only corticotrophs exhibited intense CPD immunoreactivity. Basophil invasion showed similar immunoreactivities for alpha-MSH, ACTH, CPE, and CPZ as corticotrophs in the anterior pituitary, except for CPD, which was detected much less frequently. In the posterior lobe, CPE, CPD, and CPZ were present within the Herring bodies. Although no MIB-1 immunoreactivity was identified in anterior pituitary cells, limited MIB-1 labeling was detected in basophil invasion in five of ten cases. Highly selective expression of CPD in corticotrophs suggests that CPD plays a particularly important role in prohormone (POMC) processing in corticotrophs, with minimal or no significant roles in non-corticotrophs. Evidence that corticotrophs in basophil invasion are undergoing proliferation and are also phenotypically different from their counterpart in the anterior pituitary has further raised the possibility of some neoplastic potential.

Adrenocorticotropic Hormone↗