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Biomedical subjects

G E Johnson

Publications and source records attributed to G E Johnson.

At least 19 recordsLinked to original sources
PubMed1992

Specification of the body plan during Xenopus gastrulation: dorsoventral and anteroposterior patterning of the mesoderm.

Although the mesoderm itself is induced at the blastula stage, its subdivision mainly occurs in response to further inductive signals during gastrulation. In the late blastula, most of the mesoderm has a ventral-type commitment except for the small organizer region which extends about 30 degrees on each side of the dorsal midline. During gastrulation, dorsal convergence movements bring the cells of the lateroventral marginal zone up near the dorsal midline and into the range of the dorsalizing signal emitted by the organizer. This dorsalizing signal operates throughout gastrulation, can cross a Nuclepore membrane, and is not mimicked by lithium, FGFs or activin. Anteroposterior specification also takes place during gastrulation and is probably controlled by a dominant region at the posterior end of the forming axis. We have studied the expression patterns in Xenopus of three members of the FGF family: bFGF, int-2 and a newly discovered species, eFGF. These all have mesoderm inducing activity on isolated animal caps, but are likely also to be involved with the later interactions. RNAase protections and in situ hybridizations show that the int-2 and eFGF mRNAs are concentrated at the posterior end, while bFGF is expressed as a posterior to anterior gradient from tailbud to head. Studies of embryos in which bFGF is overexpressed from synthetic mRNA show that biological activity is far greater when a functional signal sequence is provided. This suggests that int-2 and eFGF, which possess signal sequences, are better candidates for inducing factors in vivo than is bFGF.

Activins↗
PubMed1992

Congenital pseudarthrosis.

Five cases of congenital pseudarthrosis of the clavicle were treated with open reduction and fixation with appropriate-sized contoured plates and screws. Iliac bone grafts were used to bridge the gap in four patients; local bone graft was used in the fifth patient. Consolidation was noted an average of 3 months postoperatively in all five cases. The plate and screws were removed in all patients at an average of 16 months postoperatively. Average length of follow-up for the five patients is 4 years. Roentgenograms demonstrate that the clavicle has continued to grow normally. All five patients have pain-free full range of motion and are engaged in unrestricted activities.

Bone Plates↗
PubMed1992

Lead exposure.

Explore the source record for details and available documents.

Child↗
PubMed1990

Proximal femurectomy for decubitus ulceration in the spinal cord injury patient.

The results of proximal femoral resections in nine patients were analyzed after an average four year follow-up, together with a retrospective analysis of the patients. The indication for surgery was decubitus ulceration that had failed to respond to multiple previous treatments. The decubitus ulcers were associated with septic arthritis, osteomyelitis, hip dislocation and ankylosis. All patients achieved short term healing with 50% achieving long term healing. The incidence of subsequent surgery for decubitus ulcers decreased significantly. No patient suffered a deterioration in function.

Adult↗
PubMed1989

Clinical presentation of spinal cord concussion.

Spinal cord concussion is a transient disturbance of spinal cord function, with or without vertebral damage and no demonstrable pathologic changes, that results from a rapid change in velocity following trauma, and resolves within 48 hours. In a retrospective review of patients with spinal injury referred to a tertiary care center, spinal cord concussion was observed in 3.7% of patients. Thirteen cases are presented. A variety of clinical presentations may occur, all of which can be explained on the basis of the magnitude or direction of acceleration of the spinal cord. The cervical cord is most commonly affected, but concussion can occur at any level of the spinal cord. Spinal cord concussion is often associated with pre-existing vertebral abnormalities that result in narrowing of the spinal canal or areas of hypermobility.

Adult↗
PubMed1987

Studies of the hypotensive effect of calcium injected into lateral brain ventricles.

Calcium chloride (1-2 mumole) injected into lateral brain ventricles of pentobarbital anesthetized rats markedly decreases blood pressure. The hypotensive response is not affected by vagotomy and is characteristic calcium and barium since other polyvalent cations do not have the same effect. The calcium channel blocker, verapamil given into brain ventricles prevents the depressor effect of calcium suggesting that the hypotensive action of calcium is initiated intracellularly. The well documented lowering of blood pressure by increases in dietary intake of calcium may be mediated by increases in free calcium in cerebrospinal fluid.

Animals↗
PubMed1986

Modulation of thiopurine cytotoxicity in the HL-60 cell line by physiological concentrations of hypoxanthine.

Thioguanine and mercaptopurine are clinically important agents in widespread use for the treatment of acute leukemia. In this study the effect of low, physiological concentrations of hypoxanthine on thiopurine cytotoxicity was examined in the HL-60 human acute promyelocytic leukemia cell line. Initially the effect of cell concentration on medium hypoxanthine levels was investigated. When 10(5) to 10(6) cells/ml were used, medium hypoxanthine concentrations fell to undetectable (less than 0.1 microM) levels by 24 h, due to cell utilization. However, when the cell density was reduced to 10(3) cells/ml, it was possible to maintain a medium hypoxanthine level as low as 0.5 microM for 24 h without significant hypoxanthine depletion. This allowed for the investigation of the extent to which physiological concentrations of hypoxanthine (1.0 to 10 microM) could modulate thiopurine cytotoxicity. HL-60 cells were incubated in medium containing from 1.0 to 100 microM hypoxanthine concentrations and varying levels of thioguanine or mercaptopurine for 24 h. Cells were then washed and cloned in soft agar. Physiological concentrations of hypoxanthine (1.0 to 10 microM) provided significant protection to HL-60 cells from the cytotoxic effects of both thioguanine and mercaptopurine. An increase in medium hypoxanthine level from 1.0 to 3.0 microM resulted in a 3-fold increase in the thiopurine concentration required to kill 50% of cells. There was a linear relationship between the thiopurine concentration required to reduce clonogenic survival by 50% and medium hypoxanthine level over the hypoxanthine concentrations studied. Although thioguanine was 200-fold more potent than mercaptopurine, and an analogue of guanine rather than hypoxanthine, there was a similar degree of modulation of the cytotoxicity of both agents by hypoxanthine. These results indicate that low, physiological hypoxanthine concentrations can significantly modulate thiopurine cytotoxicity and suggest that endogenous hypoxanthine pools may have an important effect on the clinical activity of thioguanine and mercaptopurine.

Cell Count↗
PubMed1985

A kinematic model of the human ankle.

The spatial gross motion of the foot with respect to the shank is modelled as rotations about two fixed ankle axes: the upper ankle rotation axis (plantar flexion/dorsiflexion) and the subtalar rotation axis (inversion/eversion). The positions of the axes are determined by externally visible bony landmarks of the lower leg, and are measured for a living subject. The model input data are the plantar flexion/dorsiflexion and inversion/eversion rotation angles; the model output is a 4 X 4 transformation matrix which quantitatively describes the relative position of a foot coordinate system with respect to a shank coordinate system.

Ankle Joint↗
PubMed1985

Cellular pharmacokinetics of mercaptopurine in human neoplastic cells and cell lines.

The accumulation, metabolism, and retention of mercaptopurine (MP) was studied in four human neoplastic cell lines (three acute leukemia lines Molt-4, CCRF-CEM, and HL-60; and one Burkitt's lymphoma line, Wilson), each of which was sensitive to MP. Two cell lines resistant to MP (WilsonR and CCRF-CEMR) were also studied. The cell lines were incubated for 3 h in 10 microM [14C]MP and then placed in drug-free media for an additional 3 h. Cell samples were obtained at regular intervals, and the intracellular MP metabolites were measured in the acid-soluble fractions by anion-exchange high-pressure liquid chromatography. MP accumulated progressively within cells during the 3-h drug exposure period and declined rapidly when the cells were placed in drug-free media. Over 80% of the intracellular MP was present in the form of three nucleotide metabolites, MP ribose monophosphate, thioxanthosine monophosphate, and thioguanosine monophosphate. MP ribose monophosphate was found in greatest amount, accounting for 59-85% of the intracellular metabolite pool. Thioxanthosine monophosphate thioguanosine monophosphate were detected in lesser amounts. Study of leukemic cells obtained from patients demonstrated a similar pattern of MP accumulation, metabolism, and retention, although the overall amounts of the various metabolites formed were less. In contrast, there was essentially no MP nucleotide metabolite formation in the two MP-resistant cell lines. A more complete understanding of the cellular pharmacokinetics of MP in human neoplastic cells is likely to lead to a more rational use of the drug in the clinical setting.

Adenosine Triphosphate↗
PubMed1979

Drug prescribing for the elderly in Saskatchewan during 1976.

Over 11% of Saskatchewan's population is 65 years of age or older. To study patterns of prescribing for the elderly a computer file of more than 3.6 million prescriptions filled in Saskatchewan in 1976 was reviewed. The elderly population (aged 65 years or more) that year was 102 070, and 77.3% received at least one prescription drug listed in the Saskatchewan Formulary. In comparison with a "middle-aged" group (persons between the ages of 35 and 54 years) the elderly showed moderately higher average numbers of prescriptions filled and drugs used per person that year. However, the prescription of antihypertensive agents and diuretics increased dramatically with age, and barbiturates, in view of their potential toxicity, appeared to be overprescribed for the elderly.

Adult↗
PubMed1977

5,7-Dihydroxytryptamine lesions of the ascending 5-hydroxytryptamine pathways: habituation, motor activity and agonistic behavior.

Rats were injected stereotactically in mesencephalon with 5,7-dihydroxytryptamine (5,7-DHT) in the medial 5-hydroxytryptamine (5-HT) pathway (n = 8) and in the medial plus the lateral 5-HT pathways (n = 7) or injected with vehicle (n = 8), or sham-operated (n = 8). The 5,7-DHT lesions reduced the in vitro 3H-5-HT uptake in the hypothalamus and the cortex cerebri to 27-51% of control values, 3H-noradrenaline uptake was not significantly changed. 5,7-DHT lesions of the medial, and of the medial plus the lateral, 5-HT induced mouse killing behavior and increased number of boxing positions in the shock elicited fighting test. Both lesions also reduced the rate of habituation to touch, but only the lesion of the medial plus the lateral 5-HT pathway significantly reduced the rate of habituation to acoustic stimulation. Activity in the home cage was not significantly changed by the lesions. It was concluded that selective chemical lesions of the ascending 5-HT pathways result in prolonged habituation of the orienting response and increase in particular components of agonistic behavior. The increase in locomotor activity observed after electrolytic lesions of nucleus raphe medianus seems not to be due only to lesion of the 5-HT neurons ascending from this nucleus.

5,7-Dihydroxytryptamine↗
PubMed1977

Popliteal entrapment syndrome.

A probable cause of popliteal artery entrapment is proposed. The medial head of the gastrocnemius muscle during its embryological development crosses the popliteal fossa from lateral to medial. It is proposed that the migrating medial head carries the popliteal artery and vein across the fossa and entraps them against the medial condyle of the femur. Dissection of 86 anatomical specimens revealed two cases of unilateral and one case of bilateral entrapment of both popliteal vessels. Two surgical cases of popliteal entrapment are presented. This entrapment syndrome is a remedial cause of claudication and when considered, it is readily diagnosed and surgical correction is effective. Because of distal embolisation and occlusions, early recognition and treatment is desirable. Forty-seven cases from the literature are reviewed as to the entrapment type and the age and sex of the patients.

Adult↗
PubMed1976

Improved theophylline serum analysis by an appropriate internal standard for gas chromatography.

A gas chromatographic method is presented for the measurement of theophylline in serum. To serum samples containing the drug the internal standard, 3-isobutyl-l-methylxanthine, was added and the serum was saturated with ammonium carbonate. A mixture of isopropanol-chloroform (5:95) was used for extraction. The organic phase was filtered and evaporated. The residue, dissolved in chloroform, was extracted with sodium hydroxide. The basic solution was acidified, washed with hexane and reextracted with isopropanol-chloroform. The organic phase was dried with anhydrous sodium sulphate before evaporation. The sample was derivatized with n-Butyl-8 reagent. 85% of theophylline was recovered by extraction. 3-Isobutyl-l-methylxanthine was recovered with the same efficiency as theophylline and gas chromatographed well. The standard curve was linear between 1.0 and 50.0 mug/ml theophylline. No interference was encountered from normal serum constituents or methylxanthines such as caffeine, theobromine, or 3-methylxanthine. Serum samples were stared in the refrigerator for two weeks without significant loss of drug. The precision and accuracy of the method were good.

Chromatography, Gas↗
PubMed1976

Diagnosis and treatment of minimal brain dysfunction in adults: a preliminary report.

Minimal brain dysfunction (MBD) has long been considered a disorder limited to childhood. A number of longitudinal and adoption studies suggest that MBD may persist into adult life where its existence is concealed by the application of a variety of diagnostic labels. In order to test the hypothesis that MBD does persist into adulthood, 15 putative MBD adults were identified on the basis of current MBD-like complaints, self-description of MBD characteristics in childhood, and a parental rating (on a standardized form) of "hyperactivity" in childhood. Eleven of the 15 subjects were given a double-blind trial of methylphenidate hydrochloride, and all 15 were given an open trial of pemoline, imipramine hydrochloride, or amitryptiline hydrochloride. Eight of the 11 showed a significant response to the double-blind trial of methylphenidate. Of the 15, eight showed a good response to stimulants or tricyclic antidepressants, two showed a moderately favorable response, and five were unresponsive to drug therapy.

Adult↗
PubMed1976

The necessity of drug level monitoring in anticonvulsant drug therapy.

A survey of 'steady-state' serum levels of anticonvulsant drugs from 221 epileptic patients at a university hospital was conducted. Serum concentrations of phenobarbital, primidone, and diphenylhydantoin were determined by a gas chromatographic method. Sixty-five percent (130) of the patients receiving diphenylhydantoin had levels below the therapeutic range of 10-20mug/ml. Subtherapeutic levels appear to be due to inadequate dosage adjustment. Only 25% (33) of the patients receiving phenobarbital had levels below the therapeutic range. Serum levels of diphenylhydantoin or phenobarbital could not be predicted from dosage. Most patients received two or more drugs. Over 10% of the patients had potentially toxic levels of anticonvulsant drugs. High levels of diphenylhydantoin were easily recognized clinically but high levels of phenobarbital were not.

Body Weight↗