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Biomedical subjects

M C Johnson

Publications and source records attributed to M C Johnson.

At least 19 recordsLinked to original sources
PubMed2001

Resolution of right heart enlargement after closure of secundum atrial septal defect with transcatheter technique.

OBJECTIVES: The purpose of this study was to prospectively characterize the reduction in right atrial (RA) area and right ventricular (RV) volume after transcatheter closure of atrial septal defect (ASD) and to investigate factors that may predict magnitude of resolution in right heart enlargement. BACKGROUND: Secundum ASD can cause volume overload of the right side of the heart with the potential for development of late complications. Little is known about reduction in right heart size after closure of ASD. METHODS: Transthoracic echocardiography was performed in 38 patients undergoing transcatheter closure of ASD. The RA area and RV volume were measured prior (n = 38), within 24 hours (n = 37), at 3 to 6 months (n = 24), at 12 months (n = 20) and at 24 months (n = 10) after closure of ASD. Change over time within the study group was assessed and the study group was compared to a control group of 19 patients with structurally normal hearts. RESULTS: Indexed RA area decreased from baseline to 3- to 6-month follow-up (p = 0.004) as did indexed RV volume (p < 0.0001). Indexed RV volume was similar to that in the control group at 24 months (p = 0.3); however, indexed RA area remained greater than in the control group (p = 0.006). Decrease in indexed RA area over the first 12 months of follow-up was related to young age at time of closure by regression analysis (r = 0.55, p = 0.013). CONCLUSION: Closure of secundum ASD results in decreased indexed RV volume comparable to that in control subjects at 24 months following closure. Indexed RA area remains increased compared to that in control subjects but does decrease over time. Decrease in RA area is inversely proportional to age at time of ASD closure. Long-term follow-up is required to evaluate the clinical impact of persistently increased RA size.

Adolescent↗
PubMed2001

Novel 4-piperidinopyridine inhibitors of oxidosqualene cyclase-lanosterol synthase derived by consideration of inhibitor pK(a).

Potent inhibition of rat microsomal oxidosqualene cyclase-lanosterol synthase (OSC) was maintained after structural modification of the 4-piperidinopyridine OSC inhibitor series. These novel analogues with a much lower pK(a) range (5.8-6.7) gave potent oral inhibition of rat cholesterol biosynthesis (8 ED(80) 0.7 mg/kg), and diminished effects on rat feeding after a 100 mg/kg oral dose.

Enzyme Inhibitors↗
PubMed2001

Prevalence of upper respiratory symptoms in patients with symptomatic gastroesophageal reflux disease.

UNLABELLED: This study evaluated the prevalence of upper respiratory symptoms (URS) among patients with symptomatic gastroesophageal reflux disease (GERD). Seventy-four subjects with heartburn completed a URS questionnaire before dual-probe, 24-h esophageal pH monitoring. The URS questionnaire was also completed by 74 normal volunteers without previous or current symptoms of GERD. Esophageal pH monitoring results were classified as normal, distal, or proximal and distal gastroesophageal reflux using standardized criteria. Mean URS scores (+/- SD) were 8.31 +/- 3.98 in the 52 subjects with GERD and 4.57 +/- 3.57 in the 22 subjects with negative pH probe studies, p = 0.02. Subjects with negative pH probe studies and normal volunteers scored similarly on the URS questionnaire. Reflux episodes/24 h correlated with URS scores, r = 0.47, p = 0.0001. Seventy-five percent of subjects with upper reflux, 68% of subjects with lower reflux, 36% of subjects with normal esophageal pH studies, and 9% of normal volunteers reported laryngeal symptoms for at least 5 d/mo. Sixty-nine percent of subjects with upper reflux, 50% of subjects with lower reflux, 31% of subjects with normal pH studies, and 14% of normal volunteers reported nasal symptoms for at least 5 d/mo. URS are frequent among subjects with GERD. KEYWORDS: rhinitis; upper airway; gastroesophageal reflux

Adult↗
PubMed2001

Improved asthma control after changing from low-to-medium doses of other inhaled corticosteroids to low-dose fluticasone propionate.

OBJECTIVE: To evaluate the efficacy and safety of changing from low-to-medium doses of other inhaled corticosteroids to low-dose fluticasone propionate. METHODS: Data from 11 randomized, double-blind, parallel-group trials in adults (>= 12 years; n = 1453; % predicted FEV1 = 42% to 89%) and 4 trials in children (4-11 years; n = 161; % predicted FEV1 = 50% to 112%) with chronic asthma were retrospectively analyzed. Symptomatic adults (n = 1181) treated with low-to-medium doses of beclomethasone dipropionate (168-672 mcg/day), triamcinolone acetonide (400-1200 mcg/day), or flunisolide (>=1000 mcg/day) were switched to low-dose fluticasone propionate (176 or 200 mcg daily) for 6-26 weeks. Patients (n = 272) remaining on low-dose beclomethasone dipropionate (336 mcg daily) served as controls. Pediatric patients previously treated with low doses of triamcinolone acetonide (4-8 puffs/day), or low-to-medium doses of beclomethasone dipropionate (4-8 puffs/day) or flunisolide (2-6 puffs/day), were changed to low-dose fluticasone propionate (100 mcg daily) for 12-52 weeks. RESULTS: Improvements in FEV1, morning and evening peak expiratory flow (PEF), rescue albuterol use, asthma symptom scores, and symptom-free days were significantly greater in adults who changed from low-to-medium doses of beclomethasone dipropionate or triamcinolone acetonide to low-dose fluticasone propionate (P <.001). Regardless of the degree of asthma severity, these improvements were 1.5- to 4-fold greater in adult patients changed to low-dose fluticasone propionate vs those remaining on low-dose beclomethasone dipropionate. Significant improvements in lung function, albuterol use, and asthma symptoms (P <=.002) were also seen in pediatric patients who changed from beclomethasone dipropionate, flunisolide, or triamcinolone acetonide to a much lower dose of an inhaled corticosteroid (100 mcg fluticasone propionate daily). Drug-related adverse events were low in adults and children, and were comparable among adults receiving low-dose fluticasone propionate or beclomethasone dipropionate. CONCLUSIONS: Results indicate that patients with persistent asthma can change from other inhaled corticosteroids to a lower dose of fluticasone propionate and still maintain or improve asthma control.

Adult↗
PubMed2001

The esophagus.

The intent of this article is to raise the clinician's awareness of manifestations of common esophageal abnormalities and disorders of swallowing. The specifics of esophageal disorders are reviewed.

Deglutition Disorders↗
PubMed2001

A GP64-null baculovirus pseudotyped with vesicular stomatitis virus G protein.

The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) GP64 protein is an essential virion protein that is involved in both receptor binding and membrane fusion during viral entry. Genetic studies have shown that GP64-null viruses are unable to move from cell to cell and this results from a defect in the assembly and production of budded virions (BV). To further examine requirements for virion budding, we asked whether a GP64-null baculovirus, vAc(64-), could be pseudotyped by introducing a heterologous viral envelope protein (vesicular stomatitis virus G protein [VSV-G]) into its membrane and whether the resulting virus was infectious. To address this question, we generated a stably transfected insect Sf9 cell line (Sf9(VSV-G)) that inducibly expresses the VSV-G protein upon infection with AcMNPV Sf9(VSV-G) and Sf9 cells were infected with vAc(64-), and cells were monitored for infection and for movement of infection from cell to cell. vAc(64-) formed plaques on Sf9(VSV-G) cells but not on Sf9 cells, and plaques formed on Sf9(VSV-G) cells were observed only after prolonged intervals. Passage and amplification of vAc(64-) on Sf9(VSV-G) cells resulted in pseudotyped virus particles that contained the VSV-G protein. Cell-to-cell propagation of vAc(64-) in the G-expressing cells was delayed in comparison to wild-type (wt) AcMNPV, and growth curves showed that pseudotyped vAc(64-) was generated at titers of approximately 10(6) to 10(7) infectious units (IU)/ml, compared with titers of approximately 10(8) IU/ml for wt AcMNPV. Propagation and amplification of pseudotyped vAc(64-) virions in Sf9(VSV-G) cells suggests that the VSV-G protein may either possess the signals necessary for baculovirus BV assembly and budding at the cell surface or may otherwise facilitate production of infectious baculovirus virions. The functional complementation of GP64-null viruses by VSV-G protein was further demonstrated by identification of a vAc(64-)-derived virus that had acquired the G gene through recombination with Sf9(VSV-G) cellular DNA. GP64-null viruses expressing the VSV-G gene were capable of productive infection, replication, and propagation in Sf9 cells.

Animals↗
PubMed2001

PR domain of rous sarcoma virus Gag causes an assembly/budding defect in insect cells.

While baculovirus expression of Gag proteins from numerous retroviruses has led reliably to production of virus-like particles (VLPs), we observed that expression of Rous sarcoma virus Gag failed to produce VLPs. Transmission and scanning electron microscopy analysis revealed that the Gag protein reached the plasma membrane but was unable to correctly form particles. Addition of a myristylation signal had no effect on the budding defect, but deletion of the PR domain of Gag restored normal budding. The resulting VLPs were morphologically distinct from human immunodeficiency virus type 1 VLPs expressed in parallel.

Animals↗
PubMed2000

Echocardiographic prediction of left-to-right shunt with atrial septal defects.

We investigated the ability of transthoracic echocardiography to predict a ratio of pulmonary to systemic flow (Qp/Qs) > or = 1.5 in patients with secundum atrial septal defects. The 44 study patients included 31 patients undergoing catheterization for device closure of atrial septal defects and 13 additional control patients with normal echocardiograms (median age 7.8 years, mean age 15.9 years, range 1.5 to 69 years). Right atrial end-systolic area, right ventricular end-diastolic volume, and the ratio of pulmonary annulus diameter to aortic annulus diameter were determined from standard transthoracic echocardiographic views. The 26 subjects in the shunt group had Qp/Qs between 1.5 and 3.0. The control subjects included the 5 catheterization patients with Qp/Qs between 0.9 and 1.2 and the 13 patients that did not undergo catheterization with assumed Qp/Qs = 1. The shunt patients had significantly increased median-indexed right atrial area (13.8 versus 8.5 cm(2)/M(2), P <. 0001), median-indexed right ventricular volume (85 versus 39 mL/M(2), P <.0001), and median ratio of pulmonary valve annulus to aortic valve annulus (1.26 versus 1.13, P =.008) compared with controls. Indexed right ventricular volume was the best predictor of significant shunt. A combination of right ventricular volume and right atrial area identified subjects with Qp/Qs >1.5 with 96% sensitivity, 94% specificity, and 96% positive and 94% negative predictive value. We conclude that quantitative transthoracic echocardiography can be used to screen for a significant shunt in patients with atrial septal defects.

Adolescent↗
PubMed2000

Nitric oxide induces apoptosis in the human corpus luteum in vitro.

The present study aimed to investigate the role of nitric oxide (NO) in regression of the human corpus luteum. We therefore examined the effect of both NO and human chorionic gonadotrophin (HCG) on luteal cell apoptosis, and Bcl-2 production. The effect of NO on oestrogen production during corpus luteum regression was also studied. Slices from corpus luteum collected throughout the luteal phase were incubated for 4 h with the nitric oxide synthase (NOS) substrate, L-arginine (L-Arg, 1 mmol/l), the NOS inhibitor N-monomethyl-L-arginine (L-NMMA) (1 mmol/l), or with HCG (10 IU/ml). Oestradiol concentrations were determined by radioimmunoassay; Bcl-2 concentrations were measured by enzyme-linked immunosorbent assay; apoptosis was detected in-situ by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; and inducible nitric oxide synthase (iNOS) was assessed by immunohistochemistry. Consistent with our previous findings, L-Arg elicited an inhibitory action on the production of oestradiol (P< 0.05). The number of apoptotic cells increased (P<0.05) from early to late corpus luteum, as did the number of cells positive for the expression of iNOS. The percentage of apoptotic cells in mid and late luteal phase was increased by L-Arg (56% and 310% respectively; P <0.05), and decreased by L-NMMA and HCG. Although no changes were observed in Bcl-2 concentration during the corpus luteum life span, L-Arg inhibited, and HCG augmented, Bcl-2 production (P<0.05) from mid and late corpus luteum cells in vitro. In summary, these results suggest that the opposite actions of L-Arg and HCG on human corpus luteum viability may, in part, be mediated by changes in the level of the anti-apoptotic activities caused by oestradiol and Bcl-2 protein.

Adult↗
PubMed2000

DNA vaccines encoding viral glycoproteins induce nonspecific immunity and Mx protein synthesis in fish.

Protective immunity by vaccination with plasmid DNA encoding a viral glycoprotein (G) has long been assumed to result from the induction of a specific immune response. We report here that the initial protection may be due to the induction of alpha/beta interferon, with long-term protection due to a specific response to the encoded viral G. DNA vaccines encoding the Gs of three serologically unrelated fish rhabdoviruses were used to vaccinate rainbow trout against a lethal challenge with infectious hematopoietic necrosis virus (IHNV). All three vaccines, each encoding the G gene of either IHNV (IHNV-G), snakehead rhabdovirus (SHRV) (SHRV-G), or spring viremia of carp virus (SVCV) (SVCV-G), elicited protective immunity against IHNV. Vaccinated fish were challenged at 30 or 70 days postvaccination with lethal doses of IHNV. At 30 days postvaccination, only 5% of fish that had received any of the G vaccines died, whereas more than 50% of the control fish succumbed to virus challenge. When fish were vaccinated and challenged at 70 days postvaccination, only 12% of the IHNV-G-vaccinated fish died compared to 68% for the SHRV-G- and 76% for the SVCV-G-vaccinated fish. Assays for trout Mx protein, an indicator of alpha/beta interferon induction, showed that only fish vaccinated with a G-containing plasmid produced high levels of Mx protein in the kidneys and liver. Interestingly, at day 7 after virus challenge, all of the fish vaccinated with the IHNV-G plasmid were negative for Mx, but the SHRV-G- and SVCV-G-vaccinated fish still showed detectable levels of Mx. These results suggest that DNA vaccines in fish induce an early, nonspecific antiviral protection mediated by an alpha/beta interferon and, later, a specific immune response.

Amino Acid Sequence↗
PubMed2000

Production of recombinant snakehead rhabdovirus: the NV protein is not required for viral replication.

Snakehead rhabdovirus (SHRV) affects warm water fish in Southeast Asia and belongs to the genus Novirhabdovirus by virtue of its nonvirion gene (NV). Because SHRV grows best at temperatures between 28 and 31 degrees C, we were able to use the T7 expression system to produce viable recombinant SHRV from a cloned cDNA copy of the viral genome. Expression of a positive-strand RNA copy of the 11, 550-nucleotide SHRV genome along with the viral nucleocapsid (N), phosphoprotein (P), and polymerase (L) proteins resulted in the generation of infectious SHRV in cells preinfected with a vaccinia virus vector for T7 polymerase expression. Recombinant virus production was verified by detection of a unique restriction site engineered into the SHRV genome between the NV and L genes. Since we were now able to begin examining the function of the NV gene, we constructed a recombinant virus containing a nonsense mutation located 22 codons into the coding sequence of the NV protein. The NV knockout virus was produced at a concentration as high as that of wild-type virus in cultured fish cells, and the resulting virions appeared to be identical to the wild-type virions in electron micrographs. These initial studies suggest that NV has no critical function in SHRV replication in cultured fish cells.

Amino Acid Sequence↗
PubMed2000

[Microdeletion of Y chromosome in severe olygozoospemic infertile patient].

We are reporting a 37 year old male with severe oligozoospermia and a history of infertility for thirteen years and surgery for severe unilateral varicocele. The hormonal levels for FSH, LH and T, and karyotype were within the normal range. Multiplex PCR revealed the presence of a de novo microdeletion in the azoospermia factor (AZF) c region involving the deleted in azoospermia (DAZ) and basic protein Y-2 (BPY2) genes. These results suggest that severe oligozoospermia should be considered for the screening of microdeletions of Yq involving the AZFc region even in the presence of a varicocele.

Adult↗
PubMed1999

Quinuclidine inhibitors of 2,3-oxidosqualene cyclase-lanosterol synthase: optimization from lipid profiles.

Novel 3-substituted quinuclidine inhibitors of cholesterol biosynthesis are reported. Compounds were optimized against oxidosqualene cyclase-lanosterol synthase (OSC) inhibition in vivo, rather than by the conventional optimization of structure-activity relationship information based on in vitro OSC inhibition. Thus, examination of HPLC lipid profiles from orally dosed rats showed cholesterol biosynthetic intermediates and whether cholesterol levels were reduced. A new substituted quinuclidine pharmacophore 18a-c was rapidly found for the inhibition of OSC, and the most promising inhibitors were validated by the confirmation of potent OSC inhibition. Compound 16 gave an IC50 value of 83 +/- 11 nM for human and an IC50 value of 124 +/- 14 nM, for rat, coupled with oral and selective inhibition of cholesterol biosynthesis derived from OSC inhibition (rat, ED50 = 1.3 +/- 0.7 mg/kg, n = 5; marmoset, 15 mg/kg dose, n = 3, caused complete inhibition). These 3-substituted quinuclidines, which were derived from a quinuclidine series previously known to inhibit cholesterol biosynthesis at the squalene synthase step, may afford a novel series of hypocholesterolemic agents acting by the inhibition of OSC.

Administration, Oral↗
PubMed1999

Molecular characterization of the glycoproteins from two warm water rhabdoviruses: snakehead rhabdovirus (SHRV) and rhabdovirus of penaeid shrimp (RPS)/spring viremia of carp virus (SVCV).

We have determined the complete coding sequences for the glycoprotein (G) genes from two rhabdoviruses that infect warm water aquatic animals, the snakehead rhabdovirus (SHRV) and rhabdovirus of penaeid shrimp (RPS). Surprisingly, the G nucleotide sequence from RPS, a virus which has been isolated from diseased shrimp in Hawaii on numerous occasions, was over 99% identical to the G nucleotide sequence from spring viremia of carp virus (SVCV), a fish virus from Europe and Asia. This is the first report of SVCV isolation outside of Europe and Asia, and it is also the first report of SVCV infecting a non-vertebrate species. The G gene from SHRV was most closely related to the G genes from the three Novirhabdoviruses, viral hemorrhagic septicemia virus (VHSV), infectious hematopoietic necrosis virus (IHNV), and hirame rhabdovirus (HIRRV), with 47, 37, and 36% amino acid identity, respectively. In addition, a phylogenetic analysis using the amino acid sequence from rhabdovirus G genes indicated that SHRV should be classified within the Novirhabdovirus genus. Finally, the SHRV-G gene was successfully expressed in mammalian cells under the control of the cytomegalovirus (CMV) promoter, establishing that it can potentially be used in the production of pseudotyped retroviruses designed to infect fish.

Amino Acid Sequence↗
PubMed1999

Diastolic function and tachycardia in hypertensive children.

We investigated the prevalence and potential predictors of Doppler echocardiographic evidence of diastolic function in untreated hypertensive children. Doppler and M-mode echocardiographic values from 42 children (mean age 13, range 5-17 years) from a pediatric hypertension clinic were retrospectively reviewed and compared to data from 39 age and gender matched normotensive children in a control group. Compared to the participants in the control group, hypertensive patients had increased mean body mass index (29 v 19 kg/M2, P < .0001), peak mitral A velocity (57 v 42 cm/sec, P < .0001), isovolumic relaxation time (65 v 42 msec, P < .0001, resting heart rate (90 v 74 bpm, P < .0001), mitral E deceleration time (150 v 137 msec, P = .006), indexed left ventricular mass index (32 v 26 g/M2.7, P < .0001), relative left ventricular wall thickness (0.32 v 0.29, P = .02), and decreased ratio of peak mitral E velocity/peak mitral A velocity (1.7 v 2.1, P = .0001). Mean age, height, mitral E velocity, mitral A deceleration time, fractional shortening, and indexed left ventricular diastolic dimension were similar in patients and control group children. In the hypertensive patients, multivariate analysis demonstrated that heart rate (P = .0008) and systolic blood pressure (P = .03) were significant predictors of peak A velocity. In addition, heart rate (P = .0003), body mass index (P = .04), and indexed left ventricular diastolic dimension (P = .04) predicted the ratio of peak E/peak A velocity. None of the measures of diastolic function correlated with left ventricular mass index or relative wall thickness. Furthermore, none of the analyzed variables predicted isovolumic relaxation time or mitral E deceleration time. We conclude that untreated hypertensive children have Doppler indices suggestive of impaired left ventricular relaxation. Resting heart rate was the strongest predictor of abnormal diastolic indices.

Adolescent↗
PubMed1999

Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways.

Heterozygous mutations in NKX2.5, a homeobox transcription factor, were reported to cause secundum atrial septal defects and result in atrioventricular (AV) conduction block during postnatal life. To further characterize the role of NKX2.5 in cardiac morphogenesis, we sought additional mutations in groups of probands with cardiac anomalies and first-degree AV block, idiopathic AV block, or tetralogy of Fallot. We identified 7 novel mutations by sequence analysis of the NKX2.5-coding region in 26 individuals. Associated phenotypes included AV block, which was the primary manifestation of cardiac disease in nearly a quarter of affected individuals, as well as atrial septal defect and ventricular septal defect. Ventricular septal defect was associated with tetralogy of Fallot or double-outlet right ventricle in 3 individuals. Ebstein's anomaly and other tricuspid valve abnormalities were also present. Mutations in human NKX2.5 cause a variety of cardiac anomalies and may account for a clinically significant portion of tetralogy of Fallot and idiopathic AV block. The coinheritance of NKX2.5 mutations with various congenital heart defects suggests that this transcription factor contributes to diverse cardiac developmental pathways.

DNA Mutational Analysis↗
PubMed1999

Antisteroidogenic action of nitric oxide on human corpus luteum in vitro: mechanism of action.

To analyze the mechanism by which nitric oxide (NO) exerts its antisteroidogenic action, human luteal cells were cultured during 24 and 48 h with L-arginine (L-Arg, 1 mmol/L); 1,2(2-trifluoromethylphenyl)imidazole (TRIM) (50 micromol/L and 1 mmol/L) and cyclic guanosine monophosphate (cGMP) analog (8-Br-cGMP, 1 mmol/L). Estradiol, nitrite, and P450 AROM activity were determined in culture media. Total cGMP concentration was evaluated in the cells and culture media by radioimmunoassay, and NADPH diaphorase was used as a histochemical marker for NO synthase (NOS) activity. During the corpus luteum (CL) life-span, NO affected estradiol secretion in an age-dependent manner, with an inhibition in mid-CL (37%; p < 0.05) in agreement with our previous results, and no significant modification in early and late CL. Basal nitrite concentration in 24 and 48 h of midluteal cell cultures (42 and 93 pmol/10(6) cells, respectively) was increased by L-Arg (53% and 88%) and inhibited by the two TRIM concentrations; also, an intense diaphorase reactivity was observed in endothelial cells and luteal parenchyma. Total cGMP was not detected in cell cultures and 8-Br-cGMP did not modify estradiol secretion, whereas aromatase activity was strongly inhibited by L-Arg (70%, p < .05). These results suggest that both NOS isoforms are active in midluteal cells, and the mechanism of action for NO on in vitro estradiol secretion may be an inhibition of P450 AROM activity.

Adult↗