Biomedical subjects

R B Johnson

Publications and source records attributed to R B Johnson.

At least 37 records · Page 2Linked to original sources

PubMed2000

Synergistic enhancement of collagenous protein synthesis by human gingival fibroblasts exposed to nifedipine and interleukin-1-beta in vitro.

Gingival overgrowth commonly occurs coincident to therapy with calcium channel blockers. The biologic mechanism for this condition is unknown; however, many clinicians suggest that poor oral hygiene may contribute to development of the overgrowth. This study tests the hypothesis that collagenous protein synthesis by gingival fibroblasts is synergistically enhanced when they are exposed to both nifedipine (N) and the pro-inflammatory cytokine, interleukin-1-beta, a cytokine expressed in inflamed gingiva. Human gingival fibroblasts were isolated from biopsies of normal gingiva and cells separated into two groups. Group 1 was exposed to media containing 0, 5, 50, or 500 pg/ml IL-1-beta, or 10(-7) M N for 7 days; Group 2 was exposed to those concentrations of IL-1-beta +10(-7) M N. [3H]-proline was added to the medium for the final 24 h. Cells and matrix were harvested and radioactivity determined by liquid scintillation analysis. Means (d.p.m./10(3) cells) were compared by factorial ANOVA and Scheffé comparisons. Collagenous protein synthesis was significantly reduced by 5 pg/ml IL-1-beta +10(-7) M N and enhanced by 500 pg/ml IL-1-beta +10(-7) M N as compared to N or IL-1-beta alone. Thus, patients may be more susceptible to gingival overgrowth coincident to nifedipine therapy as a result of the synergistic enhancement of connective tissue synthesis by these agents.

Analysis of Variance↗

PubMed1999

Identification and characterization of human rhinovirus-14 3C protease deamidation isoform.

A purified recombinant human rhinovirus-14 3C protease preparation contained only approximately 50% active enzyme as titrated using specifically designed irreversible 3C protease inhibitors. Analysis of the purified 3C protein by isoelectric focusing showed differently charged 3C isoforms that had isoelectric points (pI) of 8.3 (55%) and 9.0 (45%), with the latter one being consistent with the predicted pI of the human rhinovirus-14 3C protein. Further analysis indicated that the pI 8.3 protein was the deamidated form of 3C, and it displayed approximately 10-fold reduced cleavage activity relative to the original 3C protease sample. Peptide mapping followed by sequence analysis revealed that a single asparagine, Asn-164, was deamidated to aspartic acid in the pI 8.3 isoform. Converting Asn-164 to Asp by site-directed mutagenesis resulted in a mutated 3C protease with extremely low activity, as seen with the pI 8.3 isoform, indicating a role of Asn-164 in substrate recognition and binding. In addition, the deamidated 3C protease was found to be present in vivo, and its abundance was related to the viral replication cycle. Moreover, mutant virus carrying Asp-164 showed reduced viability in infected cells. Taken together, our data suggest that 3C protein deamidation plays a role in the regulation of its enzymatic activity.

3C Viral Proteases↗

PubMed1999

The effectiveness of two sterilization methods when different precleaning techniques are employed.

The effectiveness was investigated of methods for the preparation of dental handpieces prior to sterilization procedures utilizing ethylene oxide (ETO) gas. The handpieces were cleaned using either a forced-air purging unit (group 1) or by flushing with air and water from the dental unit (group 2). They were inoculated with either Bacillus subtilis or Streptococcus mutans. After exposure to either steam or ETO gas, the handpieces were flushed with saline and the viability of recovered bacteria assessed. No viable bacteria were recovered from group 1 handpieces treated with either ETO gas or steam. However, viable S. mutans were recovered from group 2 handpieces following exposure to ETO gas. Thus, the use of a high-pressure forced-air purging unit may be required for the reliable sterilization of dental handpieces by ETO gas, as viable S. mutans could be recovered from untreated handpieces exposed to ETO gas.

Air Pressure↗

PubMed1999

Three-dimensional echocardiography improves accuracy and compensates for sonographer inexperience in assessment of left ventricular ejection fraction.

This study was performed to determine whether 3-dimensional echocardiography (3DE) with a magnetic tracking system for image plane localization, which unlike standard 2-dimensional echocardiography (2DE), does not require acquisition of specific image planes or "standard views" for quantitative measurement of left ventricular volume and ejection fraction (EF), could compensate for sonographer inexperience. Eight adults underwent magnetic resonance imaging (MRI) scanning; they also had 2DE and 3DE performed by 2 experienced and 3 novice sonographers. Data were analyzed by a single expert reader blinded to patient and sonographer identity. Linear regression of MRI EF (reference standard) against echocardiographic EF yielded the following results, where RD indicates the residual difference between measured MRI values and those predicted using echocardiographic results: expert 3DE: r = 0.97, RD = 2.4%, and r = 0.96, RD = 2.8%; novice 3DE: r = 0. 83, RD = 5.1%, to r = 0.95, RD = 4.8%; expert 2DE: r = 0.85, RD = 4. 8%, and r = 0.86, RD = 4.9%; and novice 2DE: r = 0.34, RD = 11.7%, to r = 0.69, RD = 6.6%. Comparison of error variances indicated that novices who used 3DE equaled the performance of experts who used 2DE, although experts were always more accurate than novices when both used the same echocardiographic method (3DE vs 3DE, 2DE vs 2DE). In a comparison of methods, 3DE was always superior to 2DE, regardless of sonographer experience. Three-dimensional echocardiography allows even novice sonographers to obtain diagnostic-quality data sets, which they were unable to accomplish with 2DE. These results suggest that scanning with 3DE, combined with remote expert interpretation, may be useful in providing echocardiographic services in regions where they are presently unavailable.

Adult↗

PubMed1999

Differential effects of morning and evening dosing of nisoldipine ER on circadian blood pressure and heart rate.

The time of administration of once-daily antihypertensive agents may have a significant impact on blood pressure control during awake and sleep periods. Using 24-h ambulatory monitoring, we compared the effects of morning and evening dosing of the long-acting dihydropyridine calcium channel blocker, nisoldipine extended-release (ER), on circadian blood pressure (BP) and heart rate in patients with mild-to-moderate hypertension. After completing a 3-week placebo run-in period, 85 patients were randomized to morning versus evening nisoldipine ER treatment at a fixed 20-mg dose. Patients were treated for 4 weeks, followed by crossover to the alternate dosing regimen for 4 additional weeks. Twenty-four-hour ambulatory monitoring was performed at baseline and at 4 and 8 weeks after randomization. Awake and sleep times were determined by electronic activity recorders (Actigraphy). Similar least-squares (+/-SE) mean changes from baseline in 24-h BP (systolic BP/diastolic BP: -11.9/-7.4 +/- 0.6/0.5 v -11.6/-6.5 +/- 0.6/0.5 mm Hg) and heart rate (1.0/1.7 +/- 0.4/0.4 beats/min) occurred with morning and evening administration, respectively. A significantly greater effect on awake diastolic BP (systolic BP/diastolic BP: -12.6/-8.1 +/- 0.7/0.4 v -11.3/-6.4 +/- 0.7/0.4 mm Hg; P = .16/.01) was observed with morning dosing compared with evening dosing. In addition, small increases in sleep and early morning heart rate were seen with evening compared with morning administration of nisoldipine (sleep, 3.1 +/- 0.4 v 0.4 +/- 0.4 beats/min; P < .001; early morning, 3.5 +/- 0.7 v 0.5 +/- 0.7 beats/min; P = .002). These differential effects on awake BP and sleep heart rate were also observed in patients who had normal (dippers) and elevated (nondippers) BP values during sleep. Appropriate evaluation of the efficacy and safety of long-acting antihypertensive agents is essential when evening administration is being considered. In the present study, the timing of nisoldipine ER administration had no effect on mean changes in BP and heart rate over a 24-h period. However, nisoldipine ER had some differential effects during sleep and awake periods with morning relative to evening dosing.

Antihypertensive Agents↗

PubMed1999

Treatment of typhoid fever with azithromycin versus chloramphenicol in a randomized multicentre trial in India.

To compare the clinical and bacteriological efficacies of azithromycin and chloramphenicol for treatment of typhoid fever, 77 bacteriologically evaluable adults, with blood cultures positive for Salmonella typhi or Salmonella paratyphi A susceptible to their assigned drugs, were entered into a randomized open trial at four hospitals in India. Forty-two patients were randomized to receive azithromycin 500 mg p.o. od for 7 days and 35 to receive chloramphenicol 2-3 g p.o. od in four divided doses for 14 days. Thirty-seven patients (88%) in the azithromycin group responded with clinical cure or improvement within 8 days and 30 patients (86%) in the chloramphenicol group responded with cure or improvement. By day 14 after the start of treatment, all patients treated with azithromycin and all except two of the patients treated with chloramphenicol (94%) were cured or improved. Blood cultures repeated on day 8 after start of therapy showed eradication of organisms in 100% of patients in the azithromycin group and 94% of patients in the chloramphenicol group. By day 14 the eradication rate in the chloramphenicol group had increased to 97%. Stool cultures on days 21 and 35 after start of treatment showed no prolonged faecal carriage of Salmonella spp. in either group. These results indicate that azithromycin given once daily for 7 days was effective therapy for typhoid fever in a region endemic with chloramphenicol-resistant S. typhi infection and was equivalent in effectiveness to chloramphenicol given to patients with chloramphenicol-susceptible infections.

Adolescent↗

PubMed1999

A phase-II study of trovafloxacin for the treatment of Chlamydia trachomatis infections.

BACKGROUND: Chlamydia trachomatis can cause an insidious, asymptomatic infection in both men and women. Trovafloxacin, a fluoronaphthyridone antibiotic related to the fluoroquinolones, has broad antibacterial activity that encompasses C. trachomatis. GOAL OF STUDY: We designed a phase-II study to determine the efficacy and safety of trovafloxacin for chlamydial infections. STUDY DESIGN: Four once-daily dosing regimens were used: 200 mg for 7 days, 200 mg for 5 days, 100 mg for 7 days, and 50 mg for 7 days. RESULTS: Sixty-four men and 66 women were enrolled. Of the 73 bacteriologically evaluable patients, 20 received 200 mg for 7 days, 18 received 200 mg for 5 days, 14 received 100 mg for 7 days, and 21 received 50 mg for 7 days. Bacteriologic failure occurred in 1 patient (5%) in the 200-mg 7-day group, 2 patients (14%) in the 100-mg group, and 1 patient (5%) in the 50-mg group. No clinical failures were noted among the 30 C. trachomatis infected men with nongonococcal urethritis, although 1 patient had only improved at the final visit. Safety data were available from 119 patients. Of 86 patients receiving the three highest dosing regimens, 17 (20%) had at least one adverse event, judged treatment-related in only 9 (10 %). Of 33 patients receiving the lowest dose, 5 (15%) had an adverse event, three (9%) of which were considered treatment related. No adverse event was severe. CONCLUSION: In doses ranging from 200 mg to 50 mg daily for a week and 200 mg daily for 5 days, trovafloxacin appears to be effective for chlamydial infections and is well tolerated.

Adult↗

PubMed1999

Double-blind comparison of trovafloxacin and doxycycline in the treatment of uncomplicated Chlamydial urethritis and cervicitis. Trovafloxacin Chlamydial Urethritis/Cervicitis Study Group.

BACKGROUND: Chlamydia trachomatis is among the most common sexually transmitted bacteria worldwide. With excellent activity against C. trachomatis and Neisseria gonorrhoeae and prolonged elimination half-life allowing once-daily dosage, the fluoroquinolone trovafloxacin has potential advantages in the treatment of uncomplicated chlamydial infection. GOAL OF THIS STUDY: This study compared the efficacy of trovafloxacin with that of doxycycline for the treatment of uncomplicated chlamydial infection. STUDY DESIGN: In a double-blind, multicenter trial, trovafloxacin 200 mg was administered once daily for 5 days and doxycycline 100 mg was administered twice daily for 7 days to patients with uncomplicated chlamydial urethritis or cervicitis. Follow-up visits were conducted 10, 21, and 35 days after enrollment. RESULTS: Of the 970 patients (403 men, 567 women) observed, 511 were microbiologically evaluable and 360 were clinically evaluable. C. trachomatis eradication rates in the trovafloxacin and doxycycline groups were equivalent in women (95% and 97%, respectively), but not in men (89% and 99%). Similarly, rates of clinical success (cure plus improvement) demonstrated equivalence of trovafloxacin and doxycycline in women (96% and 94%), but not in men (94% and 100%). The most frequent treatment-related adverse events were dizziness, nausea, and headache in patients given trovafloxacin, and nausea, vomiting, and headache in patients given doxycycline. Treatment-related discontinuations were comparable between the drug groups. CONCLUSION: Trovafloxacin given once daily for 5 days was clinically and bacteriologically equivalent to doxycycline given twice daily for 7 days in women with uncomplicated chlamydial cervicitis. This equivalence was not demonstrated in men with uncomplicated chlamydial urethritis.

Adolescent↗

PubMed1999

Hospital executives and ethics committees: an effective collaboration.

Should hospital and healthcare executives participate on their organization's ethics committee? This question becomes more relevant in the current healthcare environment as nurses and physicians assume more managerial responsibilities. This article reviews functions of the ethics committee and discusses moral, conceptual, and practical issues surrounding managerial participation on these committees. The authors conclude that executive management's participation on ethics committees is both appropriate and necessary in the current healthcare environment.

Conflict of Interest↗

PubMed1999

Protein recovery from several paper types used to collect gingival crevicular fluid.

The purpose of this study was to compare the efficiency of protein elution from several types of gingival crevicular fluid (GCF) collection papers when the volume of the inoculated protein and the elution methods were constant. Various concentrations of bovine serum albumin (BSA) and 14C-BSA were placed onto strips of Whatman #1 [W1], Whatman 3 MM chromatographic [W3], Periopaper (ProFlow) [P] and Periopaper (Harco) [H], and recovered proteins measured following a non-optimized centrifugal elution technique. There were significant differences in % recovery of BSA and 14C-BSA from the papers, which was dependent on both the type of paper and the concentration of the inoculated protein; that is, proteins at the lowest concentrations were less efficiently eluted from GCF collection papers than those at higher concentrations. Equations for regression lines of elution efficiency were quadratic. Thus, our data suggest significant differences in the efficiency for elution of BSA from absorbent papers when the volume of the inoculated fluid and the elution technique were constant. Previous variable or conflicting experimental data between research groups may have resulted from incomplete elution of proteins from GCF collection papers, possibly due to entrapment within, or binding of GCF proteins to the paper.

Absorption↗

PubMed1999

Relationship between oral alveolar bone loss and aging among African-American and Caucasian individuals.

BACKGROUND: The periodontal attachment apparatus consists of the periodontal ligament, alveolar bone, cementum and supra-crestal connective tissue. They are interdependent and provide protection and support to the dentition. It is theorized that the integrity of the periodontal apparatus can be maintained throughout life by exercising comprehensive oral hygiene practices and routine dental care. Additionally, it appears to be unaffected by aging. As a consequence, the investigators performed a study to determine the effects of chronological aging on alveolar bone loss. OBJECTIVE: The present study was conducted to determine the relationship between oral alveolar bone loss, oral hygiene, and aging among African-American and Caucasian populations. METHODS: The population consisted of 229 individuals. There were 131 men and 98 women. With respect to race there were 89 African-Americans and 140 Caucasians. Oral examinations, oral hygiene and missing teeth determinations and bitewing radiographs were performed on all the individuals. Radiographs were digitized and measurements were made from the cementum/enamel junction to the alveolar bone crest. Measurements were made for both the maxillary and mandibular jaws. RESULTS: The results of the study showed a significant multiple linear regression model relationship between oral bone loss and aging. Oral hygiene was a factor, but contributed only slightly to the overall model. Race, gender and the number of missing teeth were not significant variables in the overall model. CONCLUSION: The results of this study suggest age-related alveolar bone loss.

Adult↗

PubMed1999

Vascular endothelial growth factors and progression of periodontal diseases.

BACKGROUND: Tissues become hemorrhagic and edematous coincident to periodontal diseases; however, there is little information concerning the biologic mechanisms which may produce these changes. Vascular endothelial growth factor (VEGF) is a macromolecule which enhances blood vessel growth and permeability. However, there is no information concerning gingival VEGF concentrations within normal or diseased gingiva. The purpose of this study was to assess changes in gingival concentrations of VEGF during initiation and progression of periodontal diseases and compare them to changes in the number of blood vessel profiles and concentration of recognized markers of periodontal disease severity (interleukin-6[IL-6]). METHODS: Normal (non-hemorrhagic gingiva adjacent to a < or =3 mm gingival sulcus) and inflamed gingiva (hemorrhagic gingiva adjacent to a < or =3 mm, 4 to 6 mm, or >6 mm periodontal pocket) were studied. VEGF and IL-6 concentrations were assessed by ELISA and the number of blood vessels determined by histomorphometric techniques. Data were placed into one of the following groups: < or =3 mm, normal; < or =3 mm, diseased; 4 to 6 mm, diseased; and >6 mm, diseased. These groups were compared by factorial ANOVA and Scheffe comparisons. In addition, groups were compared by simple and multiple regression and regression ANOVA to determine possible correlations between them. RESULTS: VEGF and IL-6 concentrations were significantly lower within normal than within diseased gingiva. The number of blood vessel profiles and mean IL-6 concentrations were highest in diseased tissues adjacent to >6 mm sulci and were significantly correlated with sulcular depth (P <0.001). In contrast, VEGF concentrations were highest within diseased gingiva adjacent to 4 to 6 mm periodontal pockets (P <0.001) and were not correlated with sulcular depth. CONCLUSIONS: VEGF may be a factor in initiation and progression of gingivitis to periodontitis, possibly by promoting expansion of the vascular network coincident to progression of the inflammation.

Analysis of Variance↗

PubMed1999

The effect of nicotine on growth of Streptococcus mutans.

There is little information available concerning the effects of nicotine on oral bacteria; and in particular, Streptococcus mutans, an important microbe in the etiology of dental caries. To test the effects of nicotine, Streptococcus mutans were incubated in either 0 or 10(-1)-10(-7) M concentrations of nicotine and then plated onto mitis-salivarius-bacitracin agar. Colonies were counted and treatment groups compared. Both 10(-1) and 10(-2) M nicotine caused total inhibition of bacterial growth, while 10(-3) and 10(-4) M produced significantly more colonies than control. Also, 10(-6) and 10(-7) M nicotine produced a significant reduction in the mean number of colonies. These results suggest a biphasic, dosage-dependent effect of nicotine on the growth of Streptococcus mutans. Since 10(-3) M nicotine has been reported within the saliva of smokeless tobacco users, use of these products could stimulate growth of Streptococcus mutans and possibly place the user at increased risk for dental caries.

Dental Caries↗

PubMed1998

Development of in vitro peptide substrates for human rhinovirus-14 2A protease.

Purified 2A protease from human rhinovirus serotype-14 (HRV14) was unable to efficiently cleave a 16-mer peptide representing its authentic cis-cleavage site on the viral polyprotein, implying that in vivo cis cleavage by this enzyme might be very different from its in vitro trans activity. Presence of a serine at position P2 and a leucine at P2' in the 16-mer peptide was found to be responsible for the low peptide cleavage efficiency. To search for an efficient peptide substrate for HRV14 2A, small peptides derived from other rhinovirus 2A protease cleavage sites were synthesized and tested. These results suggested that the N-terminal 8 amino acids were sufficient for HRV14 2A cleavage to occur, although the P1' and P2' residue identities were important to the cleavage of peptides with amino acids occupying both sides of the scissile bond. On the basis of the 2A substrate requirements, a sensitive fluorometric assay for the viral 2A proteases was developed using peptides with anthranilide and 3-nitrotyrosine as the resonance energy transfer donor/quencher pair. Our data indicated that these fluorescent peptide substrates were suitable for 2A protease characterization and inhibitor evaluation.

Amino Acid Sequence↗

PubMed1998

The bearable lightness of being: bones, muscles, and spaceflight.

Bones and muscles support and move the body. Tendons link the two tissues and serve as a mechanism for transfer of forces from muscle to bone. These three tissues interact and respond to periods of activity or inactivity with appropriate alterations in structure and strength. There is substantial evidence that an environment devoid of mechanical stress on the skeleton (such as reduced gravitational forces during spaceflight, a "microgravity environment") produces direct effects on bone structure and function. There is little agreement concerning the biologic mechanisms for these atrophic changes. Changes in fluid balance and distribution coincident to spaceflight also affect muscles and bones by an unknown mechanism. Tendon-bone junctions are presumed to be spared from the effects of spaceflight. However, recent evidence from rodents suggests that spaceflight profoundly effects both the skeleton and the tendon-bone junctions. These effects include cortical bone resorption, which undermines the Sharpey's fibers that anchor the tendon to the bone matrix. The challenge to biomedical scientists is to devise methods for protecting spaceflight crews from these atrophic changes; such protection would allow for longer and more extensive spaceflights.

Animals↗

PubMed1998

Randomized trial of trovafloxacin and ofloxacin for single-dose therapy of gonorrhea. Trovafloxacin Gonorrhea Study Group.

PURPOSE: To compare trovafloxacin, a new quinolone antibiotic with enhanced activity against Neisseria gonorrhoeae, with ofloxacin as single-dose oral therapy for uncomplicated gonococcal urethritis or cervicitis. PATIENTS AND METHODS: In this multicenter, double-blind trial, 625 patients (270 men, 355 women) with uncomplicated gonococcal urethritis or cervicitis received one 100-mg tablet of trovafloxacin or two 200-mg capsules of ofloxacin as a single dose under direct supervision. RESULTS: Single-dose oral therapy with trovafloxacin was equivalent both bacteriologically and clinically to ofloxacin. Among evaluable patients, N gonorrhoeae was eradicated in 99% of trovafloxacin recipients and in 98% of ofloxacin recipients. Each treatment was well tolerated; vaginitis was the most frequently observed side effect (4% trovafloxacin, 7% ofloxacin). CONCLUSION: Based on the results presented here, trovafloxacin is a promising agent for single-dose therapy of uncomplicated gonorrhea.

Adolescent↗

PubMed1998

Effects of sodium acetate on rat bone-nodule formation and mineralization in vitro.

Sodium acetate reportedly promotes bone atrophy by inducing resorption and inhibiting osteoprogenitor-cell proliferation, but little is known about its effects on bone-matrix deposition and mineralization by a population containing osteoprogenitor cells. The objective here was to assess the effects of 1-20 mM sodium acetate on the proliferation and differentiation of these cells and their resultant bone-nodule formation and mineralization in an in vitro assay. Exposure to 10 mM sodium acetate had no effect on cellular proliferation but significantly increased the production and mineralization of bone nodules (p < 0.01), suggesting that it affected osteoprogenitor differentiation and subsequent metabolism. However, 10 mM acetate did not increase net bone mass. Dilutions of 1-5 and 20 mM inhibited cellular proliferation and resultant bone-nodule formation and mineralization, significantly reducing the percentage bone area as compared to controls (p < 0.001). These data suggest that 1-5 and 20 mM sodium acetate significantly inhibit bone deposition, whereas 10 mM has no effects, which could contribute to iatrogenic metabolic bone disease in patients receiving either renal dialysis or total parenteral nutrition.

Analysis of Variance↗

PubMed1998

Factors for progression of periodontal diseases.

Progression factors for periodontal diseases have been suggested by in vitro study of peripheral blood and gingival cells; however, those factors are not established in vivo. This investigation assessed biopsies of three groups of gingival tissues: those adjacent to a 1) < or =3 mm (normal), 2) 4-6 mm, and 3) >6 mm gingival sulcus, to determine changes in the gingival microenvironment coincident to the progression of periodontal disease. Superoxide dismutase (SOD) and catalase activity, and IL-12 and bcl-2 levels, were decreased at >6 mm; total protein and IL-6 concentrations were increased adjacent to >6 mm, as compared to < or =3 and 4-6 mm, sites. Apoptotic cells were evident only within gingiva adjacent to >6 mm sites. These data suggest that IL-12 is an important factor in the shift from a TH1 to TH2 cell profile and that a favorable gingival microenvironment for hyperinflammation may develop coincident to progression of periodontal diseases due to decreased bcl-2 and increased IL-6 concentrations within gingiva. These changes in the gingival microenvironment could impair apoptosis and promote enhanced release of reactive oxygen species (ROS) by phagocytes; decreased catalase and SOD activity could promote accumulation of ROS and result in additional tissue destruction.

Analysis of Variance↗