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Biomedical subjects

R M Johnson

Publications and source records attributed to R M Johnson.

At least 19 recordsLinked to original sources
PubMed1995

Dose-response comparison of recombinant human nerve growth factor and recombinant human basic fibroblast growth factor in the fimbria fornix model of acute cholinergic degeneration.

Both nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) have been proposed for the treatment of Alzheimer's disease. This study describes a comparative, dose-response analysis of recombinant human (rh)NGF and rhbFGF in a rat unilateral fimbria-fornix model of acute cholinergic neuronal degeneration. Doses for rhNGF were 0.6, 6, 60, 600 and 1,800 ng/rat/day and for rhbFGF were 600, 1,800, 3,000 and 6,000 ng/rat/day, delivered for 4 weeks. The number of surviving septal cholinergic neurons was evaluated using ChAT immunohistochemistry. In control animals, the number of ChAT-positive neurons remaining on the lesioned side was between 22 and 18% compared to the non-lesioned side. Infusion with either neurotrophic factor increased the number of ChAT-positive neurons on the lesioned side in a dose-dependent manner. The maximal response to rhbFGF peaked at 3,000 ng/rat/day with a cell savings of 47%. However, there was evidence of neuropathological changes associated with rhbFGF. In contrast, rhNGF produced a maximal response with an infusion of 600 ng rhNGF/rat/day and a cell savings of 70% and no evidence of neuropathology, indicating that rhNGF was better tolerated and more efficacious than rhbFGF.

Acetylcholinesterase↗
PubMed1995

Cost-effectiveness of laparoscopic cholecystectomy.

This study retrospectively evaluated the cost-effectiveness of laparoscopic cholecystectomy compared to open cholecystectomy in a single university-affiliated community hospital. The medical records of all patients that underwent laparoscopic cholecystectomy during 1990 and open cholecystectomy during 1989 in one hospital were reviewed. Hospital stay, hospital charges, surgeons' and anesthesiologists' fees were determined. Fifty patients from each group were contacted to determine recovery time to full activity after surgery. Those having common duct exploration and those converted to open cholecystectomy after an attempted laparoscopic cholecystectomy (n = 8) were excluded. A summary of results is included below (Table 1). In our early experience with laparoscopic cholecystectomy we found that the total charges for laparoscopic cholecystectomy were more than for open cholecystectomy when one recognizes the 1-year difference in patient accrual between the two groups. Time to full recovery was markedly reduced in patients undergoing laparoscopic cholecystectomy compared to those having an open procedure. Despite the overall increased total charge with laparoscopic cholecystectomy, the shorter recovery period allowing the patients an earlier return to full preoperative activities contributes to its cost-effectiveness when compared to open cholecystectomy. Further experience with laparoscopic cholecystectomy and refinements in management of these patients should allow for further reductions in charges for this procedure.

Analysis of Variance↗
PubMed1995

Craniofacial trauma in injured motorcyclists: the impact of helmet usage.

Helmets are effective in decreasing maxillofacial trauma in motorcycle crashes. The impact, however, of motorcycle crashes on the location and patterns of craniofacial injuries among helmeted versus unhelmeted patients has not been examined. In the present study, 331 injured motorcyclists were evaluated to compare the incidence of craniofacial and spinal injury in 77 (23%) helmeted and 254 (77%) nonhelmeted patients. Nonhelmeted motorcyclists were three times more likely to suffer facial fractures (5.2% vs. 16.1%) than those wearing helmets (p < 0.01). Skull fracture occurred in only one helmeted patient (1.2%), compared with 36 (12.3%) of nonhelmeted patients (p < or = 0.01). The incidence of spinal injury was not significantly different between the two groups. Blood alcohol levels demonstrated that 12% of the helmeted group were legally intoxicated (blood alcohol level > 100 mg/dL), in contrast to 37.9% of the nonhelmeted motorcyclists (p < or = 0.01). Failure to wear a helmet resulted in a significantly higher incidence of craniofacial injury among patients involved in motorcycle crashes, but did not affect spinal injury or mortality. Alcohol usage seemed to correlate with failure to use helmets. Helmet use should be legally mandated on a national level for all motorcyclists.

Adolescent↗
PubMed1995

Effect of motion on digital nerve repair in a fresh cadaver model.

Information in the literature regarding the postoperative management of digital nerve lacerations is vague, and postoperative immobilization for up to 3 weeks is frequently recommended. In order to define more precisely what, if any, postoperative restrictions are necessary, a fresh cadaver model was designed for digital nerve division, resection, repair, and passive motion. Ten digital nerves were divided at the proximal interphalangeal joint and then repaired, mobilized, and inspected. Intact nerve repairs were serially resected in order to determine the limits of resection that would allow motion without repair disruption. All repairs were resistant to disruption even with hyperextension up to a resection length of 2.5 mm, and all repairs were resistant to disruption if splinted in neutral up to a resection length of 5 mm. There was not 100 percent disruption of repairs until a resection length of 1 cm and range of motion including hyperextension. These results give valuable objective data that can be used to guide early motion and splinting protocols after various degrees of digital nerve injury and repair.

Cadaver↗
PubMed1995

Detection of myeloperoxidase gene expression in minimally differentiated acute myelogenous leukemia (AML-M0) using in situ hybridization.

Acute leukemias containing > 3% myeloperoxidase (MPO)-positive blast cells, as detected cytochemically, are considered to be myelogenous in origin, regardless of the immunophenotypic markers expressed. Conversely, acute leukemias that express only myeloid antigens are also considered to be acute myelogenous leukemia (AML), even in the absence of MPO. These MPO-negative AMLs, designated AML-M0 in the FAB classification, currently require either immunophenotypic or electron microscopic studies for identification. To examine the association of MPO and myeloid antigen expression in AML, particularly at the early stages of myeloid cell differentiation, we have used in situ hybridization (ISH) to evaluate MPO gene expression in myeloid leukemia cell lines and a variety of well-characterized acute leukemias, including six cases of AML-M0. Strong positivity for MPO mRNA was detected in the myeloid leukemia cell line HL-60 and in 22 of 27 AMLs (three AML-M0, four AML-M1, eight AML-M2, five AML-M4, two AML-M5a). No MPO gene expression was detected in three AML-M0, one AML-M5a, one AML-M7, 5 acute lymphoblastic leukemia, the lymphoid cell lines Molt-4 and Namalwa, or in the early myeloid cell lines KG-1 and KG-1a. Ultrastructural studies for MPO activity were performed on four AML-M0; one leukemia showed both gene expression and cytochemical activity, whereas two others contained neither MPO transcripts nor enzyme. Weak MPO gene expression was evident in one AML-M0 that was negative for enzymatic activity by electron microscopy. These studies show MPO gene expression can be detected by ISH in about half of AML-M0, supporting their presumed myelocytic derivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1995

Nutrient intake of nursing-home residents receiving pureed foods or a regular diet.

OBJECTIVE: To evaluate (1) the nutrient content of menus planned for regular consistency meals and pureed meals in a long-term care facility and (2) to assess nutrient intakes of women consuming these meals. DESIGN: A descriptive survey. SETTING: A nursing home facility in central Pennsylvania. PARTICIPANTS: Fifty-one female nursing home residents were chosen randomly. Thirty-one received a regular diet and 20 received a pureed diet. MEASUREMENTS: Demographic and health variables were collected from medical records. Nutrient variables were calculated for regular and pureed consistency meals, as served. Nutrient intake data for each woman were based on seven consecutive days of food intake and nutrient supplement use. MAIN RESULTS: Energy and nutrient values for regular diet menus (i.e., food served) were higher than for pureed menus, but both had values exceeding recommended allowances for most nutrients. Average energy and nutrient intakes were similar for both groups of women (t test, P < 0.05). Data showed that many women in both groups had lower than the recommended intakes of iron, zinc, calcium, and Vitamin D. CONCLUSIONS: Both regular and pureed consistency diets provided to residents met current recommended allowances. Diet consistency did not affect nutrient intakes. Intakes were adequate overall; however, a low intake of the same nutrients generally occurred in both groups.

Aged↗
PubMed1995

Viral determinants of the variable sensitivity of herpes simplex virus strains to gD-mediated interference.

Cells that express glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) resist infection by HSV-1 and HSV-2 because of interference with viral penetration. The results presented here show that both HSV-1 and HSV-2 gD can mediate interference and that various HSV-1 and HSV-2 strains differ in sensitivity to this interference. The relative degree of sensitivity was not necessarily dependent on whether the cell expressed the heterologous or homologous form of gD but rather on the properties of the virus. Marker transfer experiments revealed that the allele of gD expressed by the virus was a major determinant of sensitivity to interference. Amino acid substitutions in the most distal part of the gD ectodomain had a major effect, but substitutions solely in the cytoplasmic domain also influenced sensitivity to interference. In addition, evidence was obtained that another viral gene(s) in addition to the one encoding gD can influence sensitivity to interference. The results indicate that HSV-1 and HSV-2 gD share determinants required to mediate interference with infection by HSV of either serotype and that the pathway of HSV entry that is blocked by expression of cell-associated gD can be cleared or bypassed through subtle alterations in virion-associated proteins, particularly gD.

Amino Acid Sequence↗
PubMed1994

Recombinant human ciliary neurotrophic factor stimulates the metabolic activity of SH-SY5Y cells as measured by a cytosensor microphysiometer.

Information on the transmembrane signaling events and subsequent biochemical processes initiated by ciliary neurotrophic factor (CNTF) receptor activation in neurons is lacking. SH-SY5Y cells, a human neuroblastoma cell line expressing CNTF receptors, were used to study metabolic changes associated with functional ligand-receptor interactions. Real-time measurements quantifying the rate of extracellular acidification by SH-SY5Y cells (a measure of metabolic activity) were made using a silicon-based cytosensor. Application of recombinant human CNTF (rhCNTF) to resting SH-SY5Y cells increased their acidification rate in a concentration and time-dependent manner with an apparent EC50 of 60 ng/ml. Pretreatment of cells with phosphatidylinositol-specific phospholipase C (PI-PLC) prevented the CNTF, but not an NGF-stimulated increase in acidification rate. Collectively, these results demonstrate that: (1) SH-SY5Y cells express functional CNTF receptors; and (2) the initial signal transduction mechanism activated by the CNTF receptor in SH-SY5Y cells is distinct from that activated by the NGF receptor; however, both may ultimately stimulate the same downstream biochemical messengers to increase cellular metabolism.

Animals↗
PubMed1994

Bepridil as an antisickling agent: membrane internalization and cell rigidity.

The calcium channel antagonist, bepridil, beta-(2-methylpropoxy)methyl-N-phenyl-N-(phenylmethyl)-1-pyrrol idineethanamine monochloride monohydrate, inhibits the sickling of deoxygenated sickle (SS) erythrocytes, as determined by light microscopy. The anti-sickling effect was seen only in dilute suspensions of red cells. In concentrated erythrocyte suspensions, sickling was not inhibited and measurements of hematocrit and cell density were unchanged by bepridil. The determination of cell volume in dilute suspensions was complicated by bepridil's tendency to aggregate, but rapid measurements by electronic sizing also indicated no increase in cell volume, up to a bepridil concentration of 200 microM. Ektacytometry of dilute sickle cell suspensions suggested an explanation for the anti-sickling action of bepridil. Osmotic scan ektacytometry disclosed that bepridil initially increased the surface area of the red cell, as shown by a shift in the low osmolality minimum. This change was complete in 10 sec, the shortest time that could be measured. Subsequently, at concentrations that were observed to inhibit the sickling of deoxygenated sickle cells (100 microM or greater), red cells underwent a loss in surface area that was complete in 1 min. There was a concomitant loss of cell deformability. Light and scanning electron microscopy has previously shown that bepridil is a stomatocytic agent. Using transmission electron microscopy, we verified that the loss of surface area was a consequence of endocytosis, presumably as the end stage of the stomatocytic transformation induced by bepridil. Bepridil did not inhibit intracellular hemoglobin S polymerization even at 200 microM, as shown by oxygen scan ektacytometry. Bepridil thus appears to inhibit the sickling of deoxygenated SS cells by inducing endocytosis and lowering cell deformability. This mechanism may explain the anti-sickling effect of other basic amphiphiles, such as chlorpromazine.

Anemia, Sickle Cell↗
PubMed1994

Linopirdine (DuP 996) improves performance in several tests of learning and memory by modulation of cholinergic neurotransmission.

The actions of linopirdine (DuP 996; 3,3-bis[4-pyrindinylmethyl]-1-phenylindolin-2-one) were evaluated in rats and mice in several cognitive behavioral tests, and for its effects on hippocampal acetylcholine (ACh) overflow in rats. Using mice treated with the muscarinic receptor antagonist, scopolamine, we studied the effects of linopirdine on retention of a passive avoidance task. Linopirdine (0.1 and 1 mg/kg) ameliorated the scopolamine-induced deficit, but at doses ranging from 0.01-1 mg/kg, it did not affect passive avoidance retention in normal (untreated) mice. In a scopolamine-induced hyperactivity test, linopirdine (1 mg/kg) decreased the motoric stimulation associated with the cholinergic hypofunction, without affecting locomotor activity on its own. Using rats, we studied the effects of linopirdine on performance in the Morris water maze spatial memory task. Young rats treated with atropine (30 mg/kg), a muscarinic receptor antagonist, took significantly longer to locate the submerged platform across 12 trials. Linopirdine (0.01 and 0.1, but not 1 mg/kg) ameliorated the atropine deficit. In addition, linopirdine (0.1 mg/kg) ameliorated the deficit in cognition-impaired aged rats (23-24 mo), but did not affect unimpaired aged rats. In terms of neurochemical action, linopirdine (1, 10, and 100 microM) produced a concentration-dependent increase in K(+)-evoked ACh overflow from superfused rat hippocampal slices. Also, linopirdine (10 microM) similarly increased ACh release in young control rats and cognition-impaired and nonimpaired aged rats. Our results confirm and extend findings from other studies that demonstrate the cognition-enhancing action of linopirdine in rodent models.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Membrane stress increases cation permeability in red cells.

The human red cell is known to increase its cation permeability when deformed by mechanical forces. Light-scattering measurements were used to quantitate the cell deformation, as ellipticity under shear. Permeability to sodium and potassium was not proportional to the cell deformation. An ellipticity of 0.75 was required to increase the permeability of the membrane to cations, and flux thereafter increased rapidly as the limits of cell extension were reached. Induction of membrane curvature by chemical agents also did not increase cation permeability. These results indicate that membrane deformation per se does not increase permeability, and that membrane tension is the effector for increased cation permeability. This may be relevant to some cation permeabilities observed by patch clamping.

Biophysical Phenomena↗
PubMed1994

Characterization of an antibiotic produced by Alteromonas luteoviolacea Gauthier 1982, 85 isolated from Kinko Bay, Japan.

An antibiotic produced by Alteromonas luteoviolacea strain 9K-V10 was recovered after cold acetone precipitation of culture supernatant fluids or lysates that had been frozen and thawed. The precipitate obtained from cell-free lysates was fractioned by DEAE ion-exchange chromatography. Further purification by gel-filtration chromatography yielded a single peak of antibiotic activity that corresponded to a protein peak with a molecular mass of approximately 100 kDa. After non-denaturing polyacrylamide gel electrophoresis, antibiotic activity co-migrated with a protein band. The isoelectric point of the antibiotic was estimated to be 7.7. Treatment of the concentrated active fraction with proteinase K or heating at 70 degrees C for 10 min resulted in total loss of antibiotic activity. These results show that the antibiotic produced by Alt. luteoviolacea 9K-V10 is of a proteinaceous nature.

Anti-Bacterial Agents↗
PubMed1994

Neuroleptic exposure following inpatient treatment of acute mania with lithium and neuroleptic.

The authors examined continued neuroleptic exposure following inpatient treatment of mania with neuroleptics and lithium through structured chart review of 40 consecutive patients. At discharge, patients were receiving a mean of 793 mg/day (SD = 695) chlorpromazine equivalents; 6 months later they were receiving a mean of 634 mg/day (SD = 684). This decrease was statistically significant, but the patients' ongoing neuroleptic exposure remained substantial.

Adult↗
PubMed1992

Induction of a Ca(2+)-activated K+ channel in human erythrocytes by mechanical stress.

Mechanical deformation of normal ATP-replete human erythrocytes increased their permeability to Ca2+ sufficiently to turn on the Ca(2+)-activated K+ channel (the Gardos channel). When Ca2+ is absent, mechanical deformation of normal erythrocytes induces an equivalent increase the permeability of both Na+ and K+, In the presence of 0.1 to 1 mM Ca2+, a further increase in the K+ efflux rate was seen. There was no increase in Na+ flux above that induced by deformation itself. The involvement of the Ca(2+)-activated H channel was verified by showing the specific inhibitors of the channel, quinine and charybdotoxin, prevent the Ca(2+)-induced increase in K+ efflux. These results are consistent with a model of sickle cell dehydration proposed by Bookchin et al. ((1987) Prog. Clin. Biol. Res. 240, 193-200). The estimated rate of Ca2+ entry under these conditions (37 degrees C, 1000 dyne/cm2, and laminar shear) was about 1 mmol/loc per h.

Adenosine Triphosphate↗