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At least 577 records · Page 32Linked to original sources
PubMed2005

Lactate delivery (not oxygen) limits hepatic gluconeogenesis when blood flow is reduced.

The purpose of this study was to determine, using the isolated liver perfusion technique, whether the limiting factor for hepatic gluconeogenesis (GNG) from lactate was precursor delivery or oxygen availability during reduced flow rates of 0.85 or 0.60 ml.min(-1).g liver(-1). After a 24-h fast, three different experimental protocols were employed. Protocol 1 examined the impact on GNG when reservoir lactate concentration was maintained but oxygen delivery was elevated via increases in hematocrit (Hct). Elevating the Hct from 22.5+/- 0.8% to 30.9+/- 0.4% at a blood flow of 0.89+/- 0.01 ml.min(-1).g liver(-1) increased the oxygen consumption (Vo(2)) but did not augment GNG. Similarly, when the Hct was elevated from 22.5+/- 0.8% to 41.5+/- 0.7% at 0.59+/- 0.04 ml.min(-1).g liver(-1), Vo(2) was increased, but GNG was unaffected. Protocol 2 examined the impact on GNG when Hct was maintained but precursor delivery was elevated via increases in reservoir lactate concentration ([LA]). Specifically, elevating the [LA] from 2.31+/- 0.07 to 3.61+/- 0.33 mM at a flow rate of 0.82+/- 0.04 ml.min(-1).g liver(-1) significantly increased GNG. Similarly, elevating the [LA] from 2.31+/- 0.07 to 4.24+/- 0.37 mM at a flow rate of 0.58+/- 0.02 ml.min(-1).g liver(-1) increased GNG. Finally, we examined the impact of increasing both the oxygen and lactate delivery (Protocol 3). Again, Vo(2) was elevated with increased oxygen delivery, but GNG was not augmented beyond that observed with elevations in lactate delivery alone, i.e., Protocol 2. The results indicate that, during decrements in blood flow, GNG is limited primarily by precursor delivery, not oxygen availability.

Animals↗
PubMed1992

Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion.

T cell proliferative responses to hepatitis B virus-encoded envelope antigen (S + preS2 + preS1), recombinant core antigen (HBcAg), and natural hepatitis B e antigen (HBeAg) were examined in 22 HBeAg-positive patients with chronic type B hepatitis and 17 healthy hepatitis B surface antigen (HBsAg) carriers. The results showed that HBeAg-positive patients had (a) higher levels of T cell responses to HBcAg/HBeAg than those of healthy HBsAg carriers (P less than 0.001 and P less than 0.01, respectively); (b) a further increase in these T cell responses during acute exacerbations (P less than 0.05 and P less than 0.05, respectively); (c) subsidence in the T cell responses to HBcAg/HBeAg after recovery from acute exacerbations and HBeAg seroconversion, whereas the responses would persist at high levels if the patients did not enter a clinical remission; and (d) low levels of T cell responses to S + preS2 + preS1 either before or after HBeAg seroconversion. The appearance of increasing T cell responses to HBcAg/HBeAg usually occurred in the early phase of acute exacerbations. These findings imply that HBcAg/HBeAg-specific T cells play an important role in the exacerbations of chronic hepatitis B and in HBeAg seroconversion. HBcAg/HBeAg-specific precursor T cell frequencies were serially studied in selected cases by limiting dilution assay. Elevation (two- to fourfold) of HBcAg/HBeAg-specific precursor T cell frequencies contributed to the increase of HBcAg/HBeAg-specific T cell proliferation during acute exacerbations.

Adult↗
PubMed1994

Effects of graded amounts of duodenal infusions of lysine on the mammary uptake of major milk precursors in dairy cows.

Effects of providing a limiting AA on milk secretion and mammary nutrient uptake were investigated using four lactating dairy cows given duodenal infusions of graded amounts of L-Lys-HCl (0, 9, 27, and 63 g/d). Infusions were administered over 4-d periods according to a Latin square design. Diets consisted of a 70:30 corn silage:concentrate ratio supplemented with 1.5 kg of DM/d as dehydrated alfalfa. The basal diet met requirements for energy and protein and was deficient in Lys. Cows were fitted with indwelling catheters inserted into the left carotid and left subcutaneous abdominal veins, and a transit-time flow probe was implanted around the left external pudic artery. Milk, fat, and protein yields were unaffected by infusions of Lys. Milk protein content increased to a maximum with the third treatment, and fat content showed opposite variation. Although arterial concentrations and arteriovenous differences of Lys increased to a plateau with the third treatment, the relationship between arteriovenous differences and arterial concentrations was curvilinear. Infusions of Lys tended to increase the efficiency of N utilization and the mammary extraction rates of AA to synthesize more milk proteins. Initially, Lys was extracted in a direct ratio to its milk output and then taken up in excess by the secretory cells, suggesting that Lys was no longer a limiting factor in milk protein synthesis.

Amino Acids↗
PubMed1996

Separate compartments for the production of sterols, carotenoids and gibberellins in Gibberella fujikuroi.

Substrate flows in the sterol, carotenoid and gibberellin pathways of Gibberella fujikuroi were examined by isotope-dilution experiments. The wild type and two carotenoid mutants of this fungus were grown in minimal medium with abundant glucose, limiting ammonium nitrate and a radioactively labelled precursor (either acetate, mevalonate or leucine). The precursors did not affect growth or terpenoid production, with two exceptions; leucine allowed additional growth, as expected from the nitrogen limitation in the medium, and mevalonate inhibited the accumulation of gibberellins, but only if added before the onset of gibberellin production. The relative contributions of glucose, mevalonate, leucine and acetate as terpenoid precursors, calculated from the specific radioactivities of ergosterol, neurosporaxanthin and phytoene, were different for different products and different precursors. We conclude that the biosyntheses of sterols, gibberellins and carotenoids in Gibberella are physically separated in different subcellular compartments with independent substrate pools. The same results were obtained with the three strains, except for carotenoid production, indicating that this pathway is regulated independently from other terpenoid pathways.

Acetates↗
PubMed1998

Independent origin of multiple foci of prostatic intraepithelial neoplasia: comparison with matched foci of prostate carcinoma.

BACKGROUND: Prostate carcinoma usually is heterogeneous and multifocal, with diverse clinical and morphologic manifestations. Understanding of the molecular basis for this heterogeneity is limited, particularly for the putative precursor, high grade prostatic intraepithelial neoplasia (PIN). In this study, the authors attempted to determine the genetic relation between multiple foci of PIN and matched foci of carcinoma, and whether they are independent in origin. METHODS: The distribution and prevalence of allelic imbalance at 6 microsatellite polymorphic markers on chromosomes 7q, 8p, 8q, and 18q were examined in 84 microscopically excised PIN foci (mean, 1.6 foci/case) and 95 foci of prostate carcinoma (mean, 1.8 foci/case) from 52 completely embedded, mapped whole mount prostates. RESULTS: PIN contained a lower overall proportion of allelic imbalance than matched prostate carcinoma foci for the 6 polymorphic microsatellite markers (65% vs. 82%), but this difference was not significant. The rate of allelic imbalance in PIN was similar to that in prostate carcinoma at 5 of 6 loci studied; the exception, D18S34 (18q12.2-12.3), had a significantly lower rate of allelic imbalance in PIN than in prostate carcinoma (19% vs. 52%), suggesting that genetic alterations in this chromosomal region may be important in carcinogenesis. Of 22 cases with allelic imbalance in at least 1 focus of PIN and 1 focus of prostate carcinoma, 21 informative cases (95%) showed a similar pattern of allelic imbalance at > or = 1 markers in the matched PIN and prostate carcinoma foci. Significant genetic heterogeneity was observed in both PIN and prostate carcinoma. Allelic imbalance was observed in at least 1 focus in 11 of 25 cases with multiple foci of PIN (44%) and 20 of 25 cases with multiple foci of prostate carcinoma (80%). There was no significant correlation between allelic imbalance and pathologic stage or tumor grade. CONCLUSIONS: Our findings indicate that multiple foci of PIN arise independently within the same prostate. This observation suggests that a field effect underlies prostatic neoplasia. Multiple foci of prostate carcinoma also often arise independently, lending additional support for this hypothesis. The strong genetic similarities between PIN and prostate carcinoma strongly suggest that evolution and clonal expansion of PIN may account for the multifocal etiology of carcinomas.

Aged↗
PubMed1990

Selective peripheral expansion and activation of B cells expressing endogenous immunoglobulin in mu-transgenic mice.

Two different lines of C57BL/6 mice (IgHb) carrying complete rearranged mu chain genes from BALB/c (IgMa) were analyzed for the expression and secretion of endogenous as well as transgenic immunoglobulins at the level of single cells. Quantitation of B cells expressing endogenous IgMb by cytofluorometry, limiting dilution analyses of clonal precursors and secretory cell assays revealed a marked selective expansion, activation and terminal differentiation of those cells producing endogenous immunoglobulins. Thus, the very infrequent IgMb-bearing B cells produced in bone marrow of transgenic mice accumulate in spleen, where they are activated and account for roughly half of all natural immunoglobulin-secreting cells. These observations indicate that mu-transgenic mice are valuable in studies of the antibody repertoire selection operating in unprimed animals but their use could be misleading in the analyzing "monoclonal" immune system.

Animals↗
PubMed2006

Precursor ion scanning for the non-targeted detection of individual arsenosugars in extracts of marine organisms.

Arsenosugars are a group of arsenic compounds reported to be present in a wide variety of marine organisms. Numerous such compounds have been identified and characterized in marine organisms; however, unknown arsenosugar species may also be present. This indicates the need for an analytical technique suitable for their non-targeted detection. One such technique is tandem mass spectrometry operated in the precursor ion scanning mode. This technique is based on scanning for precursor ions that give specific product ions, characteristic of the compounds under investigation. In the present study two subgroups of arsenosugar species were examined, the oxo- and the thioarsenosugars, the CID behavior of which is well known from previous studies. In the case of the oxoarsenosugars characteristic product ions were observed at m/z 237 and 97, and for the thioarsenosugars at m/z 253 and 97. Validation of this approach was carried out by analyzing extracts of two commercial kelp powders with known contents of arsenosugar species. All arsenosugars reported to exist in these materials were detected successfully using the precursor ion scanning approach. The limits of detection for the oxo- and the thioarsenosugar species, and the selectivity and sensitivity of the method, strongly indicate the suitability of this approach for the non-targeted detection of arsenosugars in extracts of marine origin.

Animals↗
PubMed1996

Purkinje cell lineage and the topographic organization of the cerebellar cortex: a view from X inactivation mosaics.

We utilized a strain of mice, derived from a radiation mutagenesis experiment and carrying an activity-attenuated allele of the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD), to analyze the development of the cell lineage leading to cerebellar Purkinje neurons. Due to random X inactivation during early embryonic development, X- linked genes can be used to distinguish between clonally related populations of cells in X inactivation mosaics. Following histochemical staining for G6PD activity, the numeric proportions of Purkinje cells expressing either the wild-type or the mutant enzyme and the spatial distribution of these cellular phenotypes and their relation to anatomically and genetically defined cerebellar compartments were analyzed. Our data suggest that cerebellar Purkinje neurons originate from a limited pool of some 129 precursors. The size of this pool is different from the one derived from chimeric mice, allowing us to deduce the relative timing of Purkinje cell lineage restriction. Our data also show that Purkinje neurons of distinct lineage are extensively intermingled within the cerebellar cortex. Together, these findings suggest both a role for cell-cell communication in the development of genetically defined cerebellar compartments and a temporal window during which such cellular interactions may take place.

Animals↗
PubMed1996

In vivo metabolic response of glucose to dichloroacetate in humans.

Hyperglycemia is common in severely ill patients and is related principally to an increase in glucose production. Dichloroacetate (DCA), which is known to increase the rate of pyruvate oxidation, has been shown to lower plasma glucose concentrations in normal fasting subjects and in diabetics and thus may be efficacious in treating stress induced hyperglycemia. However, the mechanism by which DCA lowers the plasma glucose concentration in humans has not been elucidated. To examine the human in vivo metabolic alterations induced by DCA, six fasting volunteers were infused with 6,6-D2-glucose and indirect calorimetry was performed prior to and following DCA administration. Glucose, lactate, and alanine net balance across the leg were also quantitated. Following DCA administration, plasma glucose concentrations decreased by 9% due to a proportional decrease in the rate of glucose production (P < 0.05). DCA had no affect on glucose clearance or leg net balance; however, the rate of glucose oxidation increased by 24% from baseline (P < 0.05). This increase in glucose oxidation without a compensatory change in peripheral glucose consumption suggests an improved efficiency in peripheral glucose utilization induced by DCA. Plasma concentrations of lactate and alanine were also lowered by DCA (56% for lactate, 66% for alanine, P < 0.05) without a significant alteration in leg net balance. These results suggest that DCA may decrease gluconeogenesis by limiting the availability of the precursor substrates lactate and alanine. Thus dichloroacetate may be an appropriate alternative to insulin in correcting mild elevations in plasma glucose concentrations. Furthermore, DCA may be especially effective in severely ill patients where hyperglycemia is largely due to increases in gluconeogenesis.

Adult↗
PubMed1983

A physical map of the group A streptococcal pyrogenic exotoxin bacteriophage T12 genome.

A physical map of group A streptococcal bacteriophage T12 was constructed with restriction endonucleases Sal/I, PstI, and EcoRI. The map is circularly permuted with a total length of 36.0 kb. Sub-molar quantities of certain restriction fragments, some of very precise MW and some of heterogeneous MW, were observed. This observation, together with mapping data, suggests that DNA packaging is initiated at a precise site on a concatemeric precursor and proceeds for a limited number of rounds.

Bacterial Proteins↗
PubMed2002

[Cytometric analyses in systemic autoimmune diseases].

A number of autoantibodies play a significant role in collagen vascular diseases and represent diagnostic markers of some of these entities. Despite increasing knowledge of these serological findings, data are limited about potential disturbances of precursor cells that finally lead to the autoantibody producing plasma cells. Recent evidence of disturbed B cell homeostasis indicates that the peripheral B cell compartments in systemic lupus erythematodes (SLE) and Sjögren's syndrome are characteristically different to normal. Although the identification of autoreactive B cells in peripheral blood is still subject of ongoing studies, the differences in B cell subsets add to the understanding of the immunopathogenesis of these diseases and may provide new diagnostic clues and therapeutical avenues of these entities.

Autoimmune Diseases↗
PubMed1987

Physiological and pathological effects of steroids on the function of the adrenal cortex.

The adrenal cortex is the site of the synthesis of steroid hormones such as the glucocorticoid cortisol and the mineralocorticoid aldosterone. The pathway of biosynthesis of these steroids from cholesterol involves a sequence of transformations using cytochrome P-450 enzymes which varies within the adrenal cortex as a result of the differential localization of enzymes within the zones. The hypothesis presented here is that as a result of the arrangement of the vasculature in the adrenal gland, high concentrations of steroids may be expected to accumulate and may have autoregulating effects. These may include the following: (1) the normal morphological and functional zonation of the adrenal cortex may be regulated by gradients of steroids in the adrenal cortex; (2) destruction of cytochrome P-450 enzymes on interaction with certain steroids which act as pseudosubstrates may form part of the pathogenesis of some steroidogenic enzyme deficiencies. Under normal conditions, the individual cytochrome P-450s are not rate-limiting for steroidogenesis. Under some pathological conditions, individual cytochrome P-450 enzyme activities may become rate-limiting, with consequent overproduction of precursor steroids, leading to mineralocorticoid or androgen excess.

Adrenal Cortex↗
PubMed1995

Peripheral axotomy increases the expression of galanin message-associated peptide (GMAP) in dorsal root ganglion cells and alters the effects of intrathecal GMAP on the flexor reflex in the rat.

We have previously reported that galanin message-associated peptide (GMAP), a fragment of galanin precursor protein, occurs in a limited number of dorsal root ganglion (DRG) cells in rats with intact sciatic nerves. In the present study, the localization of GMAP in dorsal root ganglia, dorsal roots and dorsal horn was analyzed immunohistochemically and compared between rats with intact and sectioned sciatic nerves. Furthermore, the effects of intrathecal (i.t.) GMAP on the flexor reflex in rats with intact and sectioned nerves were examined. In rats with intact sciatic nerves, i.t. GMAP elicited a moderate facilitation of the flexor reflex. The facilitation of the flexor reflex induced by conditioning stimulation (CS) of cutaneous C-fibers was strongly blocked by GMAP. GMAP also selectively antagonized the reflex facilitatory effect of i.t. substance P (SP), but not i.t. vasoactive intestinal peptide (VIP). Unilateral sciatic nerve section induced an upregulation of GMAP in the ipsilateral dorsal root ganglia 2 weeks after axotomy. The effect of GMAP on the baseline reflex was similar in normal and axotomized rats, but the blocking effect of GMAP on C-fiber CS-induced facilitation was significantly reduced after axotomy. GMAP did not antagonize the reflex facilitatory effect of SP after axotomy, whereas an antagonism on VIP-induced facilitation was observed. The possible role of GMAP in spinal transmission and comparison with the effects of galanin are discussed.

Animals↗
PubMed1990

CD7+ acute non-lymphocytic leukemia: evidence for an early multipotential progenitor.

Nineteen of 71 (26%) cases of acute myelogenous leukemia (AML) were found to express CD7, a cell surface marker found early during T lineage differentiation. These myeloid leukemias often expressed other lymphoid markers and frequently had rearranged T-cell receptor beta and immunoglobulin heavy chain genes. We propose that in CD7+ AML, the malignant transformation occurred in a CD7+ progenitor cell. CD7+ myeloid leukemic precursors may be capable of limited differentiation with loss of CD7 during the initial phase of the disease, but this capacity may diminish during the course of treatment such that CD7 expression persists.

Antigens, CD7↗
PubMedDate not supplied

Production of VIP- and PHM (human PHI)-related peptides in human neuroblastoma cells.

We demonstrated the production and release of a peptide structurally identical with porcine and bovine VIP-28 in human neuroblastoma NB-OK-1 cell line. In the cells, VIP-like immunoreactive (IR-VIP) components of 8 K dalton (Kd), 11 Kd, 18 Kd and 30 Kd were also detected and the 8 Kd and 18 Kd components were apparently released into the culture medium, indicating the possibility of less extended or limited processing of the VIP precursor in the cultured cells of tumor origin. The cells were also shown to produce, simultaneously with the VIP-28, a PHI/PHM-like immunoreactive (IR-PHI/PHM) component which coeluted with synthetic PHM-27, not PHI-27, in reverse-phase high performance liquid chromatography (HPLC). In addition to the PHM-27-like component, another IR-PHI/PHM component was detected in the cell extract which eluted in HPLC immediately before synthetic PHM-27 and crossreacted with PHI-27 amino-terminal specific antiserum but not with PHI-27 central-portion specific or PHM-27 carboxyl-terminal specific antiserum. The presence in NB-OK-1 cells of this IR-PHI/PHM component related to the amino-terminal portion of PHI/PHM suggested possible alternative(s) of post-translational processing of the VIP precursor in the cells in terms of the production of PHM-27-related peptides.

Amino Acid Sequence↗
PubMed1995

Bursal antisteroidogenic peptide alters the activity of steroidogenic enzymes in chicken granulosa cells.

We have previously reported that a peptide from chicken bursa of Fabricius, bursal antisteroidogenic peptide (BASP), inhibits luteinizing hormone-stimulated progesterone biosynthesis by chicken ovarian granulosa cells. The objective of this study was to determine the site(s) of BASP inhibition within the steroidogenic pathway of chicken granulosa cells. The effects of BASP on key steroidogenic enzymes, including adenylyl cyclase (AC), phosphodiesterase, the cholesterol side-chain cleavage enzyme complex and 3 beta-hydroxysteroid dehydrogenase were determined. Luteinizing hormone (10 ng/tube) stimulated a fivefold increase in granulosa cell progesterone production that was inhibited by BASP (0.06, 0.12 or 0.25 bursal equivalents) in a dose-dependent manner. Luteinizing hormone stimulated a sixfold increase in cyclic 3',5'-adenosine monophosphate (cAMP) formation, and this increase was potentiated by BASP in a dose-dependent manner. In addition, BASP stimulated cAMP formation in the absence of luteinizing hormone without affecting progesterone production. The AC activator forskolin (0.1 mM) stimulated a 4.5-fold increase in progesterone synthesis, which was inhibited by BASP. In the presence of forskolin. BASP increased cAMP formation in a dose-dependent manner. A fivefold increase in progesterone synthesis induced by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (1.0 mM) was inhibited by BASP. In the presence of 3-isobutyl-1-methylxanthine, BASP increased cAMP formation in a dose-dependent manner. Finally, 22(R)-hydroxycholesterol (250, 500, 1,000, or 2,500 ng/tube) or pregnenolone (50, 100, 200, or 500 ng/tube) resulted in up to 15- or 10-fold increases in progesterone production, respectively. Increasing concentrations of BASP caused a dose-dependent suppression of the conversion of 22(R)-hydroxycholesterol, but not pregnenolone, to progesterone. The inhibition of steroidogenesis by BASP is not associated with reduced cAMP levels, and BASP appears to strongly stimulate AC activity. In addition, these findings suggest that BASP may limit the availability of progesterone precursors by inhibiting the activity of the cholesterol side-chain cleavage enzyme complex.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Limiting dilution analysis of proliferating and cytotoxic lymphocytes in the peripheral blood and tumours of oral cancer patients.

Frequencies of proliferating and cytotoxic lymphocytes from the peripheral blood and tumour tissue of oral cancer patients and healthy individuals were monitored using limiting dilution analysis. Significantly lower precursor frequencies of proliferating lymphocytes were observed in the peripheral blood and tumour tissue of oral cancer patients. A high frequency of natural killer (NK) cells but low cytotoxic T lymphocytes (CTL) was observed in the peripheral blood compartment of oral cancer patients as compared to healthy individuals. A marked reduction in both NK and CTL frequencies in the tumour tissue compared to the peripheral blood was observed. In the tumour tissues, increased percentages of activated CD4+ lymphocytes as compared to CD8+ lymphocytes were observed. Our results suggest that impaired proliferative and cytotoxic potential of tumour infiltrating lymphocytes may play an important role in the escape of tumour cells from the immune system.

Adult↗
PubMed2006

Antibodies, immunoglobulin genes and the bursa of Fabricius in chicken B cell development.

The bursa of Fabricius is critical for the normal development of B lymphocytes in birds. It is productively colonized during embryonic life by a limited number of B cell precursors that have undergone the immunoglobulin gene rearrangements required for expression of cell surface immunoglobulin. Immunoglobulin gene rearrangement occurs in the absence of terminal deoxynucleotidyl transferase and generates minimal antibody diversity. In addition, observations that immunoglobulin heavy and light chain variable gene rearrangement occur at the same time and that allelic exclusion of immunoglobulin expression is regulated at the level of variable region gene rearrangement provide a striking contrast to rodent and primate models of immunoglobulin gene assembly. Following productive colonization of the bursa, developing B cells undergo rapid proliferation and the immunoglobulin V region genes that generate the specificity of the B cell surface immunoglobulin receptor undergo diversification. Immunoglobulin diversity in birds is generated by somatic gene conversion events in which sequences derived from upstream families of pseudogenes replace homologous sequences in unique and functionally rearranged immunoglobulin heavy and light chain variable region genes. This mechanism is distinct from and much more efficient than mechanisms of antibody diversification seen in rodents and primates. While the bursal microenvironment is not required for immunoglobulin gene rearrangement and expression, it is essential for the generation of antibody diversity by gene conversion. Following hatch, gut derived antigens are taken up by the bursa. While bursal development prior to hatch occurs in the absence of exogenous antigen, chicken B cell development after hatch may therefore be influenced by the presence of environmental antigen. This review focuses on the differences between B cell development in the chicken as compared to rodent and primate models.

Animals↗