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Biomedical subjects

S Branch

Publications and source records attributed to S Branch.

17 recordsLinked to original sources
PubMed2000

Glut-1 expression and its response to hypoglycemia in the embryonic mouse heart.

The embryonic heart depends on glucose during early organogenesis. Glut-1 functions in constitutive glucose uptake in adult tissues and is the predominant glucose transporter in embryonic and fetal tissues. This study focuses on Glut-1 expression in the heart during normal organogenesis using immunohistochemistry for Glut-1 distribution, Western analysis for Glut-1 protein levels, and reverse transcriptase polymerase chain reaction for Glut-1 mRNA levels. The role of Glut in glucose uptake response to hypoglycemia in the embryonic heart is evaluated using the Glut inhibitor cytochalasin B. Cardiac Glut-1 expression is also evaluated after in vitro hypoglycemic exposure. Glut-1 levels are highest on gestational days 9-10, intermediate on gestational day 10.5, and lowest on gestational days 11.5-13.5 in the normal embryonic heart. Cardiac Glut-1 mRNA levels similarly decline between gestational days 9.5 and gd 13.5. Cytochalasin B produces a dose-dependent decrease in glucose uptake in hearts exposed to hypoglycemia for 30 min or 6 h, implicating Glut in this response. Glut-1 protein expression is unchanged after 2 or 6 h but increased after 12 and 24 h of hypoglycemia in the gestational day 9.5 heart. Thus, Glut-1 expression is prominent in the embryonic heart and is correlated with changes in cardiac glucose requirements during normal organogenesis. Glut activity increases in response to acute hypoglycemia and the expression of Glut-1 increases in response to prolonged hypoglycemia. These results support the importance of Glut-1 during normal cardiogenesis and in response to hypoglycemia in the embryonic heart.

Age Factors↗
PubMed2000

ERCP-induced Pancreatitis.

The most important consideration in preventing ERCP-induced pancreatitis is patient selection. If you want to avoid pancreatitis, avoid performing ERCP in young patients for sphincter of Oddi dysfunction. Sphincter of Oddi manometry, difficult biliary cannulations (repeated pancreatic duct cannulations/injections), and precut and pancreatic sphincterotomy are associated with increased risk of pancreatitis. Pancreatic endotherapy, precut sphincterotomy, and Sphincter of Oddi manometry should be reserved for expert endoscopists. Short-term pancreatic stenting appears to decrease the risk of pancreatitis in patients undergoing these higher-risk procedures. Chemoprevention for ERCP-induced pancreatitis appears promising, but needs further critical study with larger patient populations and agents amenable to outpatient use. Fortunately, most ERCP-induced pancreatitis is mild. More severe pancreatitis requires a team approach to management with surgery, radiology, gastroenterology, and other specialists (eg, nephrologist) as indicated participating in the patient's care.

Journal Article↗
PubMed1999

Hexokinase I expression and activity in embryonic mouse heart during early and late organogenesis.

Hexokinase (HK) catalyzes the first step in glucose metabolism, that is, the conversion of glucose to glucose-6-phosphate (G6P). Four HK isoforms have been identified, of which HK-I is predominant in embryonic and fetal tissues. HK-I has been studied in preimplantation embryos and in fetal stages, but little is known about its activity or expression in the early postimplantation embryo. We evaluated HK-I expression, HK-I activity, and glycolytic metabolism in the embryonic mouse heart during early [gestational day (gd) 9.5] and late (gd 13.5) organogenesis. Immunohistochemistry demonstrated that HK-I is localized mainly in the heart at both stages, with stronger expression on gd 13.5. Densitometry after SDS-PAGE/western analysis confirmed higher immunodetectable HK-I protein levels in hearts on gd 13.5 vs gd 9.5. By contrast, RT-PCR demonstrated higher HK-I mRNA expression on gd 9.5 vs gd 13.5. Similarly, cardiac HK-I activity (conversion of glucose to G6P) and glycolysis (conversion of glucose to lactate) were higher on gd 9.5 than on gd 13.5. These results suggest a complex regulation of HK-I expression and activity in the embryonic heart during organogenesis, involving a change in the intrinsic activity of the enzyme with development. HK-I appears to play an important role in glucose metabolism during this critical stage of cardiogenesis.

Animals↗
PubMed1999

Expression of glucose-regulated proteins (GRP78 and GRP94) in hearts and fore-limb buds of mouse embryos exposed to hypoglycemia in vitro.

Hypoglycemia, the classic inducer of glucose-related protein (GRP) synthesis, is dysmorphogenic in rodent embryos and detrimentally affects the heart. This study compares GRP induction in a target vs non-target tissue by evaluating GRP expression in hearts and fore-limb buds of mouse embryos following exposure to hypoglycemia in vitro. Gestational day 9.5 embryos were exposed to 2, 6, and 24 h of either mild (80 mg/dl glucose) or severe (40 mg/dl glucose) hypoglycemia using the method of whole-embryo culture. GRP78 increased in a dose- and time-dependent fashion in embryonic hearts exposed to either 40 mg/dl or 80 mg/dl glucose, whereas GRP94 levels increased in hearts only after 24 h of hypoglycemia. In contrast to the heart, GRP induction in fore-limb buds occurred only with GRP78 following the most severe level and duration of hypoglycemia. RT-PCR analysis demonstrated an elevation in GRP78 and GRP94 message levels in embryonic hearts following severe hypoglycemia. However, mRNA levels did not increase in response to mild hypoglycemia. Overall, these data demonstrate the preferential induction of GRPs in the heart as compared to fore-limb buds in mouse embryos exposed to hypoglycemia. Increases in GRP protein levels may be a more reliable biomarker of stress than message levels. However, both tissues and methods should be examined for enhanced biomarker sensitivity.

Animals↗
PubMed1999

5-AZA-2'-deoxycytidine-induced dysmorphogenesis in the rat.

5-aza-2'-deoxycytidine (d-AZA) causes temporally related defects in the developing mouse. Treatment of 1.0 mg/kg on gestation day (GD) 8 results in axial skeletal defects; on GD9, cleft palate and vertebral defects; on GD10, hindlimb phocomelia; and on GD11, digital defects. An unusual aspect of d-AZA teratogenicity in mice is that the phocomelia appears to be specific to the hindlimb, and the forelimb is not similarly affected regardless of treatment day. The current study was initiated to evaluate the embryonic response of another species, the rat, to this unique teratogen. Pregnant Sprague Dawley (CD) rats were treated with d-AZA or vehicle control. The compound was administered i.p. on GD9, 10, 11, or 12 to parallel developmental staging of the mouse. The highest dose (1.0 mg/kg) elicited effects indicating increased sensitivity to the compound in the rat as compared to the mouse. GD9 treatment was characterized by massive resorptions; GD10, by a predominance of axial skeletal defects and cleft palate; GD11, by a predominance of forelimb phocomelia and missing ribs; and GD12 by hindlimb phocomelia and forelimb digit defects. These data indicate significant differences in the developmental responses to d-AZA of the mouse and the rat. This may reflect interspecies differences in the temporal expression of genes involved in morphogenesis and/or the methylation patterns of such genes. Molecular data generated in the mouse will be compared to that of the rat to further characterize the developmental dynamics responsible for the interspecies differences. Teratogenesis Carcinog. Mutagen. 19:329-338, 1999.

Abnormalities, Drug-Induced↗
PubMed1998

Differentially expressed genes associated with 5-Aza-2'-deoxycytidine-induced hindlimb defects in the Swiss Webster mouse.

5-Aza-2'-deoxycytidine (d-AZA) inhibits methylation of DNA, a process that serves as an epigenetic regulator of gene expression. We have shown that d-AZA causes temporally related defects in mice. Gestational day (GD) 10 treatment induced severe long-bone defects of the hindlimb but not the forelimb. Exposure of younger embryos (GD 8 or 9) does not induce similar defects in forelimbs. This limb-dependent response suggests that methylation alterations in genes specific for fore- or hindlimbs may contribute to the observed pattern of defects. Subtraction hybridization (SH) studies were conducted to identify differential expression of DNA subsequent to the administration of d-AZA to mice on GD 10. Hindlimb buds collected from both treated and untreated embryos at 4, 12, and 24 hours post-treatment were used. A clone isolated from the untreated sample (down-regulation in treated tissue) was identified as a member of the murine B1 family of repetitive sequences. The two other clones isolated from the treated tissue (up-regulation) were homologous to avian myogenic regulatory protein mRNA and activin receptor type II gene. Both species are active during embryogenesis. These findings suggest that the isolated clones may have roles in abnormal embryonic development when inappropriately expressed.

Animals↗
PubMed1998

Infectious dermatitis in a ball python (Python regius) colony.

Seven wild-caught ball pythons (Python regius), including six gravid females and one male, were obtained from Africa and were housed in a government animal facility in Research Triangle Park, North Carolina. Upon arrival, the snakes were found to be infested with ticks (Aponomma latus), which were manually removed. Four weeks following arrival, vesicular skin lesions began to appear on the snakes. Despite treatment of all affected female snakes with amikacin (5 mg/kg i.m., every 3 days) and cefotaxime (25 mg/kg i.m., every 3 days), the condition progressed and five of the female snakes died 7 wk after arrival. The remaining male and one female improved after an increase in environmental temperature, with ecdysis followed by healing. Physiologic stress, ectoparasites, and shipping may have predisposed the snakes to sepsis.

Amikacin↗
PubMed1996

Teratogenic effects of the demethylating agent 5-aza-2'-deoxycytidine in the Swiss Webster mouse.

5-Aza-2'-deoxycytidine (d-AZA) replaces cytidine in DNA thereby altering gene expression by passively removing methyl groups. This study determined the temporal patterns of morphological defects induced by d-AZA in mice. The dosages (0, 0.3, or 1.0 mg/kg) were administered by a single i.p. injection on gestational days (GD) 8, 9, 10, or 11. Mice were killed on GD 17 and fetal skeletons examined. The 1.0 mg/kg dose elicited characteristic defects for each treatment day: GD 8, supernumerary ribs, (significantly above background), fused vertebrae and ribs; GD 9, cleft palate and vertebral variations; GD 10, hind limb defects (especially phocomelia); GD 11, digital defects of fore and hindlimbs. The known demethylating ability of d-AZA coupled with the induction of longbone defects only in the hindlimbs suggests that d-AZA may act by disrupting specific hindlimb gene function through DNA hypomethylation.

Analysis of Variance↗
PubMed1996

Prospective multicenter trial of esophageal Z-stent placement for malignant dysphagia and tracheoesophageal fistula.

BACKGROUND: Conventional esophageal prosthesis placement has been associated with a 6% to 8% perforation rate and numerous postplacement complications. Expandable esophageal stents have been developed to preclude the above but there are few studies that have prospectively defined clinical results and subsequent stent-related complications. METHODS: All patients who underwent esophageal Z-stent placement at nine university or referral hospitals were prospectively assessed. Data collected included patient demographics, acute and subacute placement problems, the ability to occlude airway fistulas, prestent and poststent dysphagia scores, and patient survival. RESULTS: Fifty-four of 56 patients (96%) with refractory dysphagia or malignant esophagoairway fistulae had 73 Z-stents successfully inserted. Initial distal deployment occurred in 13% of the patients and an additional 17% required balloon dilation to achieve maximal diameter. Acute placement complications occurred in 11% of patients and included severe pain (3), bleeding from necrotic tumor (2), and hiatal hernia intussusception (1). No perforations occurred. Eight of 11 patients (73%) had complete tracheoesophageal fistula occlusion and mean dysphagia score (+/- SD) improved from 2.6 (0.7) to 1.1 (1.2) (p < 0.01). Fifteen stents (27%) had delayed migration at a mean of 1 month and 3 required surgery for retrieval. Three patients had ultimate stent erosion resulting in bleeding in 2 (exsanguination 1) or fistula (treated with a conventional stent). CONCLUSIONS: The authors conclude that esophageal Z-stents can be placed safely and successfully in the majority of patients. The tendency of distal deployment during placement and subsequent migration problems at a time distant from placement in a patient subset deserve attention and are currently being addressed.

Adult↗
PubMed1994

Plasma arginine kinetics in adult man: response to an arginine-free diet.

To explore the response of whole-body arginine metabolism to a change in arginine intake, plasma arginine kinetics were investigated in eight healthy adult men who received an L-amino acid diet supplying an Arg-rich or Arg-free intake for 6 days before undergoing a tracer study on day 7. The tracer protocol lasted for 8 hours. For the first 3 hours subjects remained in the postabsorptive (fasted) state, and during the following 5 hours they consumed small meals at 30-minute intervals. Primed continuous intravenous infusions of L-[guanidino-13C]arginine, L-[5,5,5-2H3]leucine, and [15N2]urea were administered to estimate plasma amino acid fluxes and the rate of urea production. For the fasted and fed states, plasma arginine fluxes (mumol.kg-1.h-1, mean +/- SD) were 69 +/- 8 and 87 +/- 12 (P < .01), respectively, for the Arg-rich diet and 63 +/- 14 and 51 +/- 7 (P < .01, from Arg-rich) for the Arg-free diet. Compared with the Arg-rich results, fed-state plasma arginine and ornithine concentrations were decreased (P < .01) and citrulline concentration was increased (P < .01) during the Arg-free diet period. Leucine fluxes and rates of urea production did not differ between the diet groups. The lower fed-state arginine flux in subjects receiving the Arg-free compared with the Arg-rich diet appears to be entirely due to the decreased rate of entry of arginine from the intestine in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Management of major biliary complications after laparoscopic cholecystectomy.

OBJECTIVE: A total of 50 major bile duct injuries after laparoscopic cholecystectomy were managed by the Duke University Hepatobiliary Service from 1990-1992. The management of these complex cases is reviewed. SUMMARY BACKGROUND DATA: Laparoscopic cholecystectomy is the preferred method for removing the gallbladder. Bile duct injury is the most feared complication of the new procedure. METHODS: Review of videotapes, pathology, and management of the original operations were reviewed retrospectively, and the injuries categorized. Major biliary injury was defined as a recognized disruption of any part of the major extrahepatic biliary system. Biliary leakage was defined as a clinically significant biliary fistula in the absence of major biliary injury, i.e., with an intact extrahepatic biliary system. RESULTS: Thirty-eight injuries were major biliary ductal injuries and 12 patients had simple biliary leakage. Twenty-four patients had the classic type injury or some variant of the classic injury. A standard treatment approach was developed which consisted of ERCP for diagnosis, preoperative PTC with the placement of stents, CT drainage immediately after the PTC for drainage of biliary ascites, and usually Roux-en-Y hepaticojejunostomy with placement of O-rings for future biliary access if necessary. Major ductal injuries were high in the biliary system involving multiple ducts in 31 of the 38 patients. Re-operation was required in 5 of the 38 patients with particularly complex problems. CONCLUSIONS: Successful management of bile duct injury after laparoscopic cholecystectomy requires careful understanding of the mechanisms, considerable preoperative assessment by experts, and a multidisciplinary approach.

Anastomosis, Roux-en-Y↗
PubMed1992

Phenylalanine and tyrosine kinetics in relation to altered protein and phenylalanine and tyrosine intakes in healthy young men.

Plasma phenylalanine (Phe) and tyrosine (Tyr) turnover and the rate of conversion of phenylalanine to tyrosine (Phehyd) and of phenylalanine oxidation (Pheox) after reduced intakes of Phe and Tyr were determined in a metabolic study involving five healthy young adult men. In a pilot study, six postabsorptive young men received either 12- or 4-h infusions of [2H2]Phe and [1-13C]Tyr or [1-13C]Phe and [2H2]Tyro. From these results a primed 8-h constant infusion of [1-13C]Phe and [2H2]Tyr and [2H3]leucine was used in the metabolic study (first 3 h fasted, the 5 h fed) at the end of 1-wk periods during which subjects received an adequate nitrogen L-amino acid based-diet followed by a restricted intake of Phe and Tyr. This procedure was again repeated after 1 and 3 wk when subjects were given a diet low in both nitrogen and Phe and Tyr. Phe and Tyr fluxes were not significantly affected by diet during the fasted metabolic state but Tyr fluxes were lower when the restricted intakes were given. Compared with the rate during the fasting state, Pheox was significantly higher (P less than 0.01) when the adequate diet was consumed; Pheox and Phehyd for fed and fasted states were similar when Phe and Tyr were restricted.

Adult↗
PubMedDate not supplied

Supernumerary lumbar rib: manifestation of basic alteration in embryonic development of ribs.

Supernumerary ribs (SNR) are a common variant in some strains of mice used in standard teratology bioassays. We have previously demonstrated that increased incidence of SNR may be induced by a wide variety of xenobiotics and/or general maternal stress. The significance of this defect in cross-species extrapolations has been problematic and recent studies, including this one, have shown that this anomaly is more complex than previously thought. The SNR in mice have a bimodal distribution composed of 'rudimentary ribs' (RR) with a mode of 0.3-0.4 mm and 'extra ribs' (ER) with a mode of 0.9-1.1 mm. The studies reported here examine the relationship between the presence of SNR and the 13th rib length and the gross morphological development of the anomaly. Supernumerary ribs were induced in CD-1 mice by surgical stress (subcutaneous micropump implanted on gestational day (GD), restraint stress (GD8), food and water deprivation (GD8) or maternal administration of the pesticide dinoseb (50 mg kg-1 on GD7 and GD8). Fetuses from untreated litters were also examined. Dinoseb-treated mice were killed on GD14, 15, 16 or 17. All other groups were killed on GD17. The lengths of the 13th and 14th ribs were measured and other anomalies were recorded. Femur length was used as an indicator of fetal size. The SNR frequency was higher in all treatment groups compared to controls. We found that ER and RR were morphologically distinct. The ER were flat ended and distally joined by a cartilaginous portion, while RR were usually rounded distally and were without cartilaginous extensions. The 13th ribs were significantly longer in fetuses having SNR than in those not having SNR, whether treated or untreated. This relationship was present in all fetal ages examined and with both ER and RR groups. These results suggest that SNR are indicative of basic alterations in the development of the axial skeleton.

2,4-Dinitrophenol↗