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Biomedical subjects

E Johnson

Publications and source records attributed to E Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1998

In Situ Observations of the Interaction of Liquid Lead Inclusions with Grain Boundaries in Aluminum.

: The evolution of liquid lead (Pb) inclusions at grain boundaries in aluminum (Al) was investigated by direct in situ TEM observation in the temperature range from 330 degrees-643 degreesC. In agreement with earlier reports on quenched alloys, the characteristic contact angle of the lens-shaped grain boundary inclusions was found to be near 120 degrees. This angle remained approximately constant over the entire temperature range, ruling out the possibility of a wetting transition. Coarsening of grain boundary inclusions was observed to proceed mainly by Ostwald ripening, although coalescence could also be observed. Inclusions at grain boundaries, at triple junctions, and at the intersection of grain boundaries with the foil surfaces adopted characteristic shapes that were shown to be equilibrium forms. At the highest temperatures, the grain boundaries were observed to detach from the inclusions and the interaction of a migrating grain boundary with inclusions could be observed.

Journal Article↗
PubMed1998

US double-blind, controlled trials of omeprazole and amoxycillin for treatment of Helicobacter pylori.

BACKGROUND: Widely variable Helicobacter pylori eradication rates have been reported with omeprazole/amoxycillin dual therapy. We present the first US double-blind, controlled trials of this dual therapy. METHODS: Three separate studies were performed: Studies 1 and 2 included patients with an active duodenal ulcer and Study 3 included patients with a documented history of duodenal ulcer. H. pylori eradication regimens in all studies were omeprazole plus amoxycillin vs. omeprazole vs. amoxycillin for 2 weeks. Doses in Study 1 were omeprazole 40 mg b.d. and amoxycillin 500 mg t.d.s., and in Studies 2 and 3 they were omeprazole 20 mg b.d. and amoxycillin 1 g t.d.s. Endoscopic biopsy tests were used for H. pylori diagnosis, and testing for H. pylori eradication was done at least 4 weeks after the completion of therapy. Amoxycillin sensitivities were performed in Study 2. RESULTS: Intention-to-treat (ITT) and per protocol (PP) analyses showed that eradication rates with omeprazole/amoxycillin [ITT: 39%, 40%, 46% (n = 72, 62, 48); PP: 50%, 46%, 54% (n = 54, 52, 37)] were significantly greater than monotherapy with either omeprazole (ITT: 0-4%); PP: 0-5%) or amoxycillin (ITT: 2-5%; PP: 0-11%). No patients taking the dual therapy discontinued therapy due to adverse events. Amoxycillin resistance was not seen at baseline (n = 76) or after amoxycillin therapy (n = 56). CONCLUSIONS: Omeprazole/amoxycillin dual therapy is well tolerated but the eradication rate which can be expected in the USA is at best about 50%.

Administration, Oral↗
PubMed1998

Helicobacter pylori eradication as a surrogate marker for the reduction of duodenal ulcer recurrence.

OBJECTIVES: An abundance of data exists documenting the association of H. pylori eradication with the reduction in duodenal ulcer recurrence. AIM: To evaluate the validity of using H. pylori eradication as a surrogate marker for the reduction in duodenal ulcer recurrence using rigorously controlled studies. METHODS: Three controlled clinical trials were conducted in patients with uncomplicated, active duodenal ulcers. Patients were treated with various combinations of omeprazole and amoxycillin. Ulcer healing and H. pylori eradication were assessed. For patients whose duodenal ulcer healed, duodenal ulcer recurrence was determined over a 6-month period in patients with H. pylori eradication and those remaining positive for H. pylori at least 4 weeks after treatment. To support the data obtained from these clinical trials, a search of the medical literature was conducted to identify additional human clinical trials in which duodenal ulcer recurrence rates were measured and categorized by H. pylori status at least 1 month post-treatment. RESULTS: In 11 controlled trials, the overall 6-18-month duodenal ulcer recurrence rate was 54% among patients remaining positive for H. pylori at least 4 weeks after treatment compared to 6% among patients with H. pylori eradication following treatment. This finding was corroborated by the uncontrolled trials, in which the duodenal ulcer recurrence rate was 64% among patients found to be H. pylori-positive and 6% for patients found to be H. pylori-negative at least 4 weeks after treatment. A time course of duodenal ulcer recurrence rates using pooled data from both controlled and uncontrolled studies demonstrated that duodenal ulcer recurrence rates for H. pylori-negative patients persisted for up to 4 years following treatment. Duodenal ulcer recurrence rates for H. pylori-positive patients increased for the first year, then levelled off. A comparison of the duodenal ulcer recurrence rates for different treatment regimens revealed that eradication regimens based on omeprazole plus antibiotics and bismuth plus antibiotics exhibited similar duodenal ulcer recurrence rates for H. pylori-positive and -negative patients. CONCLUSION: Regardless of treatment regimens, H. pylori eradication produced a consistent and significant reduction in duodenal ulcer recurrence. Therefore H. pylori eradication, 4 weeks post-therapy, can be used as a surrogate marker for reduced duodenal ulcer recurrence in investigational clinical trials.

Adult↗
PubMed1998

Effect of the introduction of total mesorectal excision for the treatment of rectal cancer.

BACKGROUND: Total mesorectal excision (TME) has been reported to reduce local recurrence and improve survival rates in patients with rectal carcinoma. This paper reports the problems that have arisen with the introduction of this new surgical technique. METHODS: This was a prospective study of two consecutive groups of patients: one who underwent TME (n = 76) and one who did not (non-TME, n = 76). RESULTS: Postoperative mortality rate in the non-TME and TME group was 5 and 7 per cent respectively, and the rate of anastomotic failure was 8 and 16 per cent respectively. Anastomotic leaks in TME patients were located in the mid and lower rectum. TME patients with anastomotic failure had lower anastomoses and a longer duration of operation than non-TME patients. Intraoperative problems were encountered in 71 per cent of the failures. All TME patients who had a leak required reoperation compared with 25 per cent of non-TME patients. TME patients without postoperative complications stayed significantly longer in hospital than non-TME patients. CONCLUSION: Anastomotic dehiscence increased after introduction of the TME technique but this improved with experience.

Adult↗
PubMed1998

Laparoscopic surgery for morbid obesity.

Morbid obesity, defined as a body mass index (BMI), i.e. weight (kg)/height (m2) over 36 for males and 38 for females, is a common condition and a threat for health, life and individual well being. Hitherto, surgery is the only effective treatment for weight reduction. Surgical methods can be malabsorptive, reducing the patients ability to absorb nutrients, or restrictive, reducing the capacity of food intake. Exclusively malabsorptive methods have been abandoned due to severe side effects. Restrictive methods, gastroplasties, reduces the compliance capacity of the stomach. Two types are performed laparoscopically, the vertical banded gastroplasty and the adjustable gastric banding. The proximal gastric by pass is also performed laparoscopically and is a combination of a restrictive proximal gastroplasty and a malabsorptive Roux-en-Y gastro-jejunal anastomosis. With laparoscopic adjustable gastric banding mean BMI was reduced from 41 kg/m2 to 33 kg/m2 (n = 43) after one year. Two years after surgery mean BMI was 30 kg/m2 (n = 16). The different operative techniques are further discussed in this paper.

Adult↗
PubMed1998

Tirapazamine with cisplatin in patients with advanced non-small-cell lung cancer: a phase II study.

PURPOSE: A phase II study was conducted to evaluate the safety and efficacy of tirapazamine combined with cisplatin for the treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-four patients with stage IIIB/IV NSCLC were treated with a combination of tirapazamine and cisplatin. Patients received tirapazamine 260 mg/m2 administered intravenously over 2 hours, followed 1 hour later by cisplatin 75 mg/m2 administered over an additional hour, repeated every 21 days. The duration of therapy was meant to be limited to four cycles for nonresponders and eight cycles for responders. RESULTS: Ten of 44 patients (23%) showed a partial response. The estimated median survival for all patients was 37 weeks. Toxicities were treatable and included grade 3 nausea or vomiting (25%), fatigue (27.3%), and muscle cramps (4.5%). No dose reductions were necessary. CONCLUSION: The results show that tirapazamine can safely be added to cisplatin. Both the median survival and response rate observed strongly suggest that tirapazamine with cisplatin is more active than cisplatin alone.

Adult↗
PubMed1998

Genetic and pharmacological identification of ion channels central to the Drosophila cardiac pacemaker.

Drosophila provides an excellent model for delineating the role of ion channels in the origin and transmission of heartbeat. We report here tests in Drosophila on a wide range of mutations and pharmacological agents known to interfere with K+, Ca2+, Na+, and Cl- ion channels in well-characterized ways. We find K+ channels are central to heart function. Tetraethylammonium, which blocks all four K+ currents, slowed the heart. We were able to distinguish among these currents. The mutation slowpoke and the agent charybdotoxin, both of which affect a fast Ca(2+)-gated K+ channel, virtually eliminate heartbeat. Shaker and ether-a-go-go, which encode subunits of K+ channels, have moderate, possibly regulatory effects. "OPQ-type" Ca2+ channels are critical. omega-Conotoxin MVIIC, which blocks these channels, virtually stops the heart. Amiloride, which may affect T-type Ca2+ channels, has no effect, nor do the L-type Ca2+ blockers verapamil and diltiazem. temperature induced paralysis E, involved in the function of Na+ channels, the Na+ channel blockers tetrodotoxin and amiloride, and the Cl- blockers mefanamic and niflumic acids have no effect. Na+ and Cl- channels thus appear unnecessary for cardiac function.

Animals↗
PubMed1998

Analysis of donor versus nondonor demographics.

A retrospective analysis of the demographic features of all potential organ donors over a 3-year period (1994-1996) at one organ procurement organization was conducted. The potential donor pool of 495 people was 42% female and 58% male, with a slight difference in consent by gender. The mean income difference between donors and nondonors was less than $3000 per year (obtained from zip code census data). Educational achievement affected donation at the lowest educational levels. Cause of death influenced donation, with motor vehicle crash victims donating more often. The strongest factor in consent for donation was ethnicity; whites were more likely to donate than were other ethnic groups. The combination of gender, ethnicity, and cause of death improved the probability of determining a positive outcome to 63%. Demographic information on donors and nondonors can increase public and professional understanding as well as influence decision making to improve donation.

Adult↗
PubMed1998

Glaucoma drops control intraocular pressure and protect optic nerves in a rat model of glaucoma.

PURPOSE: To determine whether chronic topical glaucoma therapy can control intraocular pressure (IOP) and protect nerve fibers in a rat model of pressure-induced optic nerve damage. METHODS: Sixteen adult Brown Norway rats were-administered unilateral episcleral vein injections of hypertonic saline to produce scarring of the aqueous humor outflow pathways. Twice daily applications of either artificial tears (n = 6), 0.5% betaxolol (n = 5), or 0.5% apraclonidine (n = 5) were delivered to both eyes, and awake pressures were monitored with a TonoPen XL tonometer for 17 days before the rats were killed. RESULTS: For animals administered artificial tears, the mean IOP of the experimental eyes was 39 +/- 2 mm Hg compared with 29 +/- 1 mm Hg for the control eyes. This difference was statistically significant (P < 0.001). Mean IOPs in the experimental eyes of animals administered betaxolol and apraclonidine were 29 +/- 7 and 29 +/- 4 mm Hg, respectively, whereas the mean IOP in the control eyes was 28 +/- 1 mm Hg for both groups. There was no statistically significant difference among these values. The mean IOP for the experimental eyes in the betaxolol and apraclonidine groups was lower than that in animals administered artificial tears (P = 0.003). Quantitative histologic analysis of optic nerve damage in experimental eyes showed that four of the six animals administered artificial tears had damage involving 100% of the neural area. This degree of damage appeared in only 3 of 10 animals administered glaucoma therapy. Optic nerve protection was closely correlated with IOP history because damage was limited to less than 10% of the cross-sectional area in all animals in which the maximal IOP was less than or equal to 39 mm Hg, more than 2 SD below the mean value for eyes administered artificial tears. CONCLUSIONS: Topical glaucoma therapy in this model can prevent IOP elevation and protect optic nerve fibers.

Adrenergic alpha-Agonists↗
PubMed1997

Evidence for inhibition of MyEF-2 binding to MBP promoter by MEF-1/Pur alpha.

Myelin basic protein (MBP) is a major component of the myelin sheath whose production is developmentally controlled during myelinogenesis. Earlier studies have indicated that programmed expression of the MBP gene is regulated at the level of transcription. Evidently, the MB1 regulatory motif located between nucleotides -14 to -50 plays an important role in transcription of the MBP promoter in both in vivo systems. The MB1 element contains binding sites for the activator protein MEF-1/Pur alpha and the repressor protein MyEF-2. In this study we use bandshift assays with purified MEF-1/Pur alpha and MyEF-2 and demonstrate that binding of MyEF-2 to its target sequence is inhibited by MEF-1/Pur alpha. Under similar conditions, MyEF-2 enhances the association of MEF-1/Pur alpha with MB1 DNA. MEF-1/Pur alpha binds to MB1 in mono- and dimeric forms. Inclusion of MyEF-2 in the binding reaction increases the dimeric association of MEF-1/Pur alpha with the MB1 sequence. The use of MEF-1/Pur alpha variants in the bandshift assay suggests that two distinct regions of this protein may be involved in its binding to the MB1 sequences, and its ability to block MyEF-2 interaction with the MB1 sequence. Based on previous studies on the programmed expression of MEF-1/Pur alpha and MyEF-2 during myelination and the current findings on their interplay for binding to the MB1 motif, a model is proposed for their involvement in transcriptional regulation of the MBP gene during the course of brain development.

Adenosine Triphosphate↗
PubMed1997

HIV-1 Env glycoproteins from two series of primary isolates: replication phenotype and immunogenicity.

Seven envelope regions from two series of patient isolates have been molecularly cloned and analyzed for replication phenotypes and immunogenicity. Growth potential was analyzed for env sequences substituted into an HIV-1-NL4-3 backbone (NL4-3/env recombinants). Immunogenicity studies were conducted on secreted monomeric (gp120) and oligomeric (gp140) forms of the Envs using Env-expressing plasmid DNAs for immunizations. The env regions of the patient isolates conferred a spectrum of replication kinetics and cytotropisms on the NL4-3/env recombinants. Both patient series included non-syncytium-inducing viruses with no ability to grow on T-cell lines, and highly syncytium inducing viruses which grew well on T-cell lines. These differences in growth potential did not correlate with the ability of the DNA-expressed Envs to raise antibody in rabbits. Rather, the relative immunogenicity of the Envs was patient and form specific. The Envs from patient 5 raised higher titers of antibody than the Envs from patient 6. For each primary Env, the gp120 form of the Env raised higher titers of antibody than the gp140 form. Thus, structural features of Env that affect replication do not necessarily affect the ability to raise antibody.

AIDS Vaccines↗
PubMed1997

Modification of reproductive function in the rat by 3-methylcholanthrene.

Repeated exposure of adult female Wistar rats to 3-methylcholanthrene (MC) (25 mg kg(-1) b.w., i.p., 2xwk, 1 mo) was associated with a significant increase in estrus cycle length. In addition, an increased frequency of females with constant diestrus and abnormal cycles was observed. Young females which had been exposed to MC prepubertally or whose parents had been treated with MC before and during mating also demonstrated cycle prolongation and an increased incidence of constant diestrus and abnormal cycles. These changes in female reproductive function were not associated with measurable changes in plasma sex hormone levels. In contrast, MC exposure in adult males was associated with significant reductions in circulating plasma testosterone levels. The present data also suggest that the offspring of parents who had been exposed repeatedly to MC before and during mating are also affected. Although the central nervous system in offspring of MC-treated parents appeared to be intact, their oral body temperature was significantly lower.

Animals↗
PubMed1997

Modulation of Drosophila heartbeat by neurotransmitters.

The heart of Drosophila melanogaster is a simple muscular tube with a posterior pulsatile portion and a thoracic-cranial vessel. The pacemaker, located caudally, is myogenic. Its rate of firing is modulated by neurotransmitters. Serotonin, octopamine, norepinephrine, dopamine, and acetylcholine accelerate the heart, in that order of potency. Dihydroxyphenylalanine, gamma-aminobutyric acid, glutamate, and glycine have no effect. Generally, the regularity of the heartbeat is not adversely affected by treatment with any of these neurotransmitters. We show here that amnesiac, a neurological mutation, and Dihydroxyphenylalanine decarboxylasetemperature sensitive, a mutation that interferes with synthesis of dopamine, norepinephrine, and serotonin, result in slower heart rate and reduced regularity across a normal range of temperatures for these flies. Dopamine-N-acetyltransferase, which is on the catabolic route to dopamine, serotonin, and octopamine, has no effect. hypoactiveC reduces the rate of the heart, but its mechanism of action is unknown.

Acetylcholine↗
PubMed1997

Suppression of the acquisition of conditioned avoidance behavior in the rat by 3-methylcholanthrene.

Repeated treatment with 3-methylcholanthrene (MC; 25 mg/kg body weight, i.p., two times per week, 1 month) in both male and female Wistar rats resulted in decreased performance in two sessions of a two-way active avoidance procedure. In addition, young male rats that were injected repeatedly with MC prepubertally showed diminished acquisition in conditioned avoidance behavior during both sessions. It appears that MC can alter both avoidance acquisition and retention test performance in adult male and female rats, as well as in young males. This effect was not associated with alterations in sex hormone levels. The findings of this study suggest a significant influence of MC on specific mental functions.

Animals↗
PubMed1997

Monosomy 7 and 7q--associated with myeloid malignancy.

An association between the complete or partial loss of chromosome 7 and preleukaemic myelodysplasia or acute myeloid leukaemia has been recognized from the early days of tumour cytogenetic analysis. Detection of such abnormalities usually heralds a poor prognosis. The loss of DNA on chromosome 7 has led to speculation that tumour-suppressor genes may play a significant role in this form of leukaemogenesis, although it may be part of a multistep process. A further association with leukaemia secondary to carcinogen exposure including previous chemotherapy or a number of congenital anaemias has increased the interest in discovering the gene or genes on chromosome 7. Banded chromosome analysis has suggested that there are two broad critical regions on the long arm of chromosome 7 at bands 7q22 and 7q34-q36 that may contain the relevant genes. Initial molecular analysis has confirmed these two regions to be of significance. The advent of fluorescence in-situ hybridization techniques has facilitated some definition of the 7q22 region, with identification of candidate genes for further functional analysis. It is becoming clear that there will be more than one gene on chromosome 7 involved in the leukaemic process and with the definition of these genes it may be possible to look for associations with different phenotypes and prognosis. As for the reason for chromosome 7 showing a particular predisposition to total or partial loss we may speculate that the DNA sequence and structure may confer a 'fragility' on the chromosome. A greater understanding of the DNA structure of the long arm may provide real insight into the mechanisms of leukaemia. We would like to speculate in the long term that this could lead to the ability to screen for leukaemia susceptibility and avoidance of 'inducers' in those at risk.

Acute Disease↗