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B L Bass

Publications and source records attributed to B L Bass.

At least 73 records · Page 4Linked to original sources
PubMed1994

The cytoplasm of Xenopus oocytes contains a factor that protects double-stranded RNA from adenosine-to-inosine modification.

Here we describe studies of double-stranded RNA (dsRNA) adenosine deaminase in Xenopus laevis, in particular during meiotic maturation, the period during which a stage VI oocyte matures to an egg. We show that dsRNA adenosine deaminase is in the nuclei of stage VI oocytes. Most importantly, we demonstrate that the cytoplasm of stage VI oocytes contains a factor that protects microinjected dsRNA from deamination when dsRNA adenosine deaminase is released from the nucleus during meiotic maturation. Our data suggest that the protection factor is a cytoplasmic dsRNA-binding protein or proteins that bind to dsRNA in a sequence-independent manner to occlude dsRNA from binding to dsRNA adenosine deaminase. The cytoplasmic double-stranded RNA-binding protein(s) does not bind to other nucleic acids and can be titrated at high concentrations of dsRNA. These studies raise the question of whether all dsRNA-binding proteins share endogenous substrates and also suggest potential means of regulating dsRNA adenosine deaminase in vivo.

Adenosine Deaminase↗
PubMed1994

Esophageal mucosal blood flow: a central role for calcitonin gene-related peptide.

BACKGROUND: Esophageal mucosal blood flow is a dynamic phenomenon dependent on luminal content. Reactive hyperemia, likely a factor in mucosal protection, follows luminal exposure to noxious substances, including bile. The mediators of this response are unknown, although the likelihood is that visceral afferent nerves play a major role. The purpose of this study was to determine whether substance P, calcitonin gene-related peptide (CGRP), or adenosine could mediate this reactive blood flow response. METHODS: Esophageal mucosal blood flow was studied in a rabbit model with the radiolabeled microsphere technique. The effect of intraarterial infusion of CGRP and substance P and intravenous adenosine was studied. Subsequently, the hyperemic response to luminal deoxycholate was measured in the presence of antagonists to CGRP, substance P, and adenosine. Immunohistochemical studies were performed to determine the distribution of CGRP and substance P in the esophagus. RESULTS: CGRP proved to be a potent stimulus to mucosal blood flow. The presence of a CGRP antagonist reduced mucosal blood flow at baseline and after exposure to deoxycholate. Antagonists to substance P and adenosine had no effect on baseline and deoxycholate-stimulated blood flow. CONCLUSIONS: CGRP is likely a major mediator involved in the regulation of esophageal mucosal blood flow.

Animals↗
PubMed1994

Nitric oxide mediates the blood flow response to intravenous adenosine in the rabbit.

The objective of this study was to determine if nitric oxide mediates the effects of exogenously administered adenosine on peripheral blood flow. An intravenous infusion of adenosine (1.0 mumol/kg/min) into male New Zealand white rabbits caused an increase in blood flow, measured using radiolabeled microspheres, throughout the gastrointestinal tract, as well as in the heart and kidneys. Prior administration of nitro-L-arginine methyl ester (L-NAME) 10 mg/kg i.v. completely blocked the hyperemic effect of adenosine on all organs studied. Administration of L-arginine (300 mg/kg bolus and 50 mg/kg/min infusion) together with L-NAME restored the hyperemic effect of adenosine. This phenomenon was specified to the L-arginine/nitric oxide pathway in that a similar pressor response induced by phenylephrine (1.5 micrograms/kg/min) did not block the effects of adenosine. We conclude that the peripheral vasodilator response to intravenously administered adenosine in the rabbit is mediated by nitric oxide.

Adenosine↗
PubMed1993

Extracellular matrix composition influences insulinlike growth factor I receptor expression in rat IEC-18 cells.

BACKGROUND: The composition of the extracellular matrix (ECM) as well as insulinlike growth factor I (IGF-I) receptor density vary along the crypt-villus axis. We determined whether components of the ECM influence IGF-I receptor expression in IEC-18 rat small intestine crypt cells. METHODS: IEC-18 cells were cultured on plastic, collagen type IV, Matrigel, and laminin at the plateau and proliferative growth phases. Receptor affinity (Kd) and number (Bmax) were determined by competitive binding of 125I-IGF-I in the presence of increasing concentrations of unlabeled IGF-I. Receptor isolation was performed by affinity cross linking. Messenger RNA (mRNA) for IGF-I receptor was quantified by Northern analysis. RESULTS: Specific binding of IGF-I > IGF-II > insulin was observed. A 130,000-molecular weight protein was identified by cross-linking, consistent with the alpha subunit of the IGF-I receptor. Scatchard analysis revealed no effect of ECM on IGF-I binding affinity. In contrast, the Bmax was 18% lower for plateau-phase cells cultured on Matrigel vs. plastic and was 42% lower for cells cultured on laminin vs. collagen type IV. The Bmax for proliferative growth phase cells was decreased when cultured on Matrigel vs. plastic and was 10-fold less than for cells cultured at the plateau growth phase. Northern analysis revealed that IEC-18 cells cultured on Matrigel had less mRNA for IGF-I receptor than cells cultured on plastic. CONCLUSIONS: The rate of cell proliferation and the composition of the ECM influence IGF-I receptor expression in IEC-18 cells.

Animals↗
PubMed1993

Use of the radiolabeled murine monoclonal antibody, 111In-CYT-103, in the management of colon cancer.

Monoclonal antibodies directed at tumor-associated antigens may be useful adjuncts for the management of patients with colorectal cancer. The murine monoclonal antibody, B72.3, binds Tag-72, a cell-surface antigen, which is expressed by colorectal carcinoma cells. We investigated the benefit of indium-111-labeled B72.3, 111In-CYT-103, in localizing the presence and extent of disease in patients with suspected or biopsy-proven primary colorectal cancer and in patients with apparently localized recurrent colorectal adenocarcinoma. Twenty patients were enrolled in this study. Each patient received 1 mg of B72.3 labeled with 4 to 5 mCi of 111In. Patients then underwent planar and single-photon emission computed tomographic imaging 2 to 5 days after infusion. Fifteen patients underwent surgery 1 to 14 days after scanning. There were 11 true positives, 1 false positive, 2 true negatives, and 1 false negative. The 111In-CYT-103 scan correctly identified the presence or absence of tumor in the 15 patients in whom biopsies were obtained, for an accuracy rate of 87%. Overall, 111In-CYT-103 supplied clinically useful information regarding the extent of disease that was not previously reported by standard techniques in 33% (5 of 15) of patients who underwent surgical exploration. We conclude that 111In-CYT-103 is a promising imaging agent for patients with potentially resectable recurrences and for those patients with a presumed isolated primary tumor requiring preoperative staging.

Adenocarcinoma↗
PubMed1993

Early and late VEPs for reading stimuli are altered by common binocular misalignments.

Effects of mild binocular anomalies on early and late evoked response complexes to word stimuli were examined in visual evoked potentials (VEPs) recorded over occipital cortex, Wernicke's area, and its right side homolog in university students with (fixation disparity group) and without (normal group) fixation disparity. Stimuli were monocularly or binocularly viewed words of a paragraph presented individually for 100 ms, one per second, and a binocular control condition without linguistic content. An early complex (P125-N170) recorded at Oz and a late complex (N170-late P) recorded from the temporoparietal placements were analyzed. The early complex was not influenced by linguistic content. Binocular stimuli generally resulted in larger early and late VEP amplitudes than did monocular stimuli except that the fixation disparity group had no binocular amplitude enhancement at Oz. Left hemisphere amplitude was greater than right for all conditions, more so for words than for nonlinguistic stimuli. For words, the left hemisphere advantage was significant only for the normal group. Relationships between basic visual processing and language processing in relation to early and late complexes are considered from several perspectives.

Cognition↗
PubMed1991

The mechanism of adenosine to inosine conversion by the double-stranded RNA unwinding/modifying activity: a high-performance liquid chromatography-mass spectrometry analysis.

We have used directly combined high-performance liquid chromatography-mass spectrometry (LC/MS) to examine the mechanism of the reaction catalyzed by the double-stranded RNA unwinding/modifying activity [Bass & Weintraub (1988) Cell 55, 1089-1098]. A double-stranded RNA substrate in which all adenosines were uniformly labeled with 13C was synthesized. An LC/MS analysis of the nucleoside products from the modified, labeled substrate confirmed that adenosine is modified to inosine during the unwinding/modifying reaction. Most importantly, we found that no carbons are exchanged during the reaction. By including H2(18)O in the reaction, we showed that water serves efficiently as the oxygen donor in vitro. These results are consistent with a hydrolytic deamination mechanism and rule out a base replacement mechanism. Although the double-stranded RNA unwinding/modifying activity appears to utilize a catalytic mechanism similar to that of adenosine deaminase, coformycin, a transition-state analogue, will not inhibit the unwinding/modifying activity.

Adenosine↗
PubMed1991

Somatostatin analogue treatment inhibits post-resectional adaptation of the small bowel in rats.

Post-resectional hyperplasia is the phenomenon in which residual small bowel increases in size and absorptive capacity after segmental enterectomy. This experiment studied the effect of somatostatin analogue therapy on the development of two structural parameters of post-resectional hyperplasia in rats subjected to 40% proximal small bowel resection. Octreotide acetate-treated rats failed to develop increased villus height (902 +/- 50 microns) relative to saline-treated rats (1,103 +/- 98 microns). Augmentation of residual intestinal weight was also significantly impaired in analogue-treated rats (92 +/- 3 versus 118 +/- 5 mg/cm). We conclude that somatostatin analogue treatment during the early postoperative period does impair the growth of residual bowel in rats. These findings raise concern regarding the use of this drug for postoperative patients who have undergone massive small bowel resection in whom the process of post-resectional adaptation may be critical to allow sustenance with enteral nutrition.

Adaptation, Physiological↗
PubMed1991

Capsaicin-sensitive nerves mediate esophageal mucosal protection.

The esophageal mucosa is exposed to damaging agents both by ingestion and reflux. Using our in vivo rabbit model of esophagitis, we have observed that acute luminal exposure (within 1 to 5 minutes) to potentially harmful agents, such as acid, bile, or ethanol, induces a rapid increase in mucosal blood flow; whereas prolonged exposure (10 to 60 minutes) results in mucosal injury and ablation of blood flow. We have also shown that capsaicin-sensitive mucosal afferent nerves can modulate esophageal blood flow. These findings led us to hypothesize that the reactive increase in blood flow induced by luminal agents represents a mechanism of protection mediated by capsaicin-sensitive nerves. The objective of these experiments was to determine if luminal capsaicin, a specific probe for visceral afferent nerves, could both preserve mucosal blood flow and protect against ethanol injury. Rabbits were subjected to luminal instillation of 50% ethanol with or without 1% capsaicin. Blood flow was measured with microspheres at baseline and after 2 and 10 minutes. Rabbits exposed only to ethanol developed severe mucosal injury coincident with near ablation of mucosal blood flow. In contrast, rabbits exposed to ethanol with capsaicin showed protection of the epithelium with a sixfold increase in mucosal blood flow. We conclude that capsaicin-sensitive nerves in the esophagus are local effectors of mucosal protection by virtue of preserving blood flow.

Animals↗
PubMed1989

VIP receptors and content after bowel transplantation.

Advances in immunosuppressive therapy have renewed interest in small bowel transplantation. Little is known, however, about the functional capacity of transplanted intestine. To clarify the potential for normal function, we investigated whether elements of the enteric nervous system are preserved after denervation in our rat model of intestinal transplantation. We investigated whether VIP, a major peptide neurotransmitter of the enteric nervous system, and its receptors are preserved in the bowel after transplantation. In our model of transplantation, avascular fetal jejunum from term Fisher rats is transplanted to the subcutaneous tissues of host syngeneic rats. This "neogut" becomes vascularized and develops characteristics of native small bowel. VIP content was measured by RIA and the in situ distribution of VIP receptors was determined by the technique of receptor autoradiography. Neogut was studied 1 and 3 weeks after transplantation and compared with age-matched rat pup jejunum. Autoradiographs showed high silver grain density, representing VIP binding sites, in the mucosal layers of all tissues studied. VIP content in the transplanted bowel was comparable to that of native gut and showed a rise with developmental age similar to that of native gut. VIP levels (pmole/mg protein, x +/- SEM) were neogut 1 week, 0.26 +/- 0.14; jejunum 1 week, 0.25 +/- 0.07; neogut 3 weeks, 0.60 +/- 0.21; and jejunum 3 weeks, 0.69 +/- 0.16. These results show that VIP receptors and content are preserved in this model of transplantation. This suggests that the enteric nervous system and receptors for peptide neurotransmitters remain intact after transplantation and may retain the potential for regulatory function.

Animals↗
PubMed1989

Esophageal blood flow in the rabbit: response to calcium channel blockers.

Calcium channel blockers have recently been added to the therapeutic regimen for patients who have chest pain of esophageal origin. Although relief of symptoms has been reported, this has not always been associated with changes in esophageal contraction pressures or luminal pH. Myoischemia has been proposed as one possible mechanism for esophageal chest pain. We have investigated the effect of the calcium channel blockers verapamil, nifedipine, and diltiazem on esophageal blood flow in the rabbit model. Esophageal blood flow was measured three times in each rabbit with use of the radiolabeled microsphere technique after a 30-minute continuous infusion of (1) saline solution (baseline), (2) a low dose, and (3) a high dose of each agent. Esophageal mucosal blood flow significantly decreased with nifedipine but was unchanged with verapamil and diltiazem. Esophageal muscle blood flow significantly increased--approximately 100% after administration of each of the calcium channel blockers. Thus esophageal muscle blood flow is enhanced after administration of calcium channel blockers, and this may be one therapeutic mechanism of the calcium channel blockers in the relief of esophageal chest pain in some esophageal diseases.

Animals↗
PubMed1988

An unwinding activity that covalently modifies its double-stranded RNA substrate.

An activity that unwinds double-stranded RNA has been reported to exist in several organisms. We have analyzed the RNA intermediates and final products of the unwinding reaction. Although the RNA becomes sensitive to single strand-specific ribonucleases during the reaction, the duplex is never completely unwound. Furthermore, the base pairing properties of the RNA are permanently altered; the reacted RNA cannot rehybridize to form the original duplex. We demonstrate that during the reaction many, but not all, of the adenosine residues are converted to inosine residues, and we propose that the covalent modification is responsible for the irreversible change in base pairing properties. Possible biological roles for the unwinding/modifying activity, as well as its relevance to antisense RNA experiments, are discussed.

Adenosine↗
PubMed1987

A developmentally regulated activity that unwinds RNA duplexes.

We have attempted to use antisense RNA techniques in the developing Xenopus embryo and found that although hybrids form between sense and antisense RNAs, they are transient. Our studies indicate that this is due to the presence of an activity that unwinds RNA:RNA hybrids. The activity is present at low, but detectable, levels in Xenopus oocytes, increases during oocyte maturation, and exists at high levels throughout early embryogenesis. The activity has been characterized in S100 extracts. The denaturation of a specific RNA:RNA hybrid is inhibited by the addition of a second duplexed RNA but not by the addition of single-stranded RNA, single-stranded DNA, or double-stranded DNA.

Animals↗
PubMed1987

Lipid solubilization during bile salt-induced esophageal mucosal barrier disruption in the rabbit.

Bile salts in the gastric contents are one of the harmful agents that may contribute to the mucosal injury found in clinical reflux esophagitis. To clarify the mechanism by which bile salts can injure the esophageal mucosa, we studied the effects of exposure to the bile salts taurocholate and deoxycholate in an in vivo perfused rabbit model of esophagitis. Specifically we examined the roles of accumulation of bile salt by the mucosa and solubilization of mucosal lipid into the lumen during bile salt-induced mucosal injury. Results showed a consistent association between bile salt accumulation by the esophageal mucosa and bile salt-induced disruption of the physiologic barrier to diffusion. Under certain conditions, bile salts caused barrier disruption with no release of lipid from the mucosa. Whenever exposure to bile salt did cause release of mucosal lipid into the lumen, a significant amount of morphologic injury was also observed by light microscopy. The findings suggest that the presence of bile salt in the mucosa is an important aspect of the mechanism of bile salt-induced barrier disruption. Solubilization of mucosal lipids into the lumen occurs when bile salts cause an injury that is severe enough to result in light microscopic evidence of morphologic damage.

Animals↗
PubMed1986

Ribozyme inhibitors: deoxyguanosine and dideoxyguanosine are competitive inhibitors of self-splicing of the Tetrahymena ribosomal ribonucleic acid precursor.

The intervening sequence (IVS) of the Tetrahymena rRNA precursor catalyzes its own splicing. During splicing the 3'-hydroxyl of guanosine is ligated to the 5' terminus of the IVS. One catalytic strategy of the IVS RNA is to specifically bind its guanosine substrate. Deoxyguanosine (dG) and dideoxyguanosine (ddG) are found to be competitive inhibitors of self-splicing. Comparison of the kinetic parameters (Ki = 1.1 mM for dG; Ki = 5.4 mM for ddG; Km = 0.032 mM for guanosine) indicates that the ribose hydroxyls are necessary for optimal binding of guanosine to the RNA. dG is not a substrate for the reaction even at very high concentrations. Thus, in addition to aiding in binding, the 2'-hydroxyl is necessary for reaction of the 3'-hydroxyl. A second catalytic strategy of the IVS RNA is to enhance the reactivity of specific bonds. For example, the phosphodiester bond at the 3' splice site is extremely labile to hydrolysis. We find that dG and ddG, as well as 2'-O-methylguanosine and 3'-O-methylguanosine, reduce hydrolysis at the 3' splice site. These data are consistent with an RNA structure that brings the 5' and 3' splice sites proximal to the guanosine binding site.

Animals↗