[The medical doctor-degree under revision].
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Education, Medical, Continuing↗
Biomedical subjects
N Langeland
Publications and source records attributed to N Langeland.
Effects of intramedullary reaming and nailing on blood flow in rat femora.
The right femur in 40 rats was reamed, and in 40 others it was additionally nailed. Analysis of bone blood flow was performed by the distribution of radiolabeled microspheres at different postoperative time intervals. Blood-flow measurements were accompanied by analyses of hydroxyproline and calcium contents. Immediately after reaming, the blood flow of the diaphyseal part of the femur was reduced to approximately one third of that of the intact femur, whereas the contents of hydroxyproline and calcium were reduced by 10 percent. Within 1 week, the blood flow was normal. This study provides evidence that the presence of a nail does not interfere with the restoration of bone blood flow. Restoration of blood flow in bone apparently is a rapid process. The replacement of hydroxyproline and calcium contents seemed to be linked to flow, as no increase in these constituents were found until the blood flow had approximated the level of the intact femur.
Animals↗
[Cytomegalovirus infections. Still a challenge].
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Cytomegalovirus Infections↗
Age-dependent mechanical properties of rat femur. Measured in vivo and in vitro.
Strain gauges were implanted on the anterior surface of the femoral diaphysis of rats aged 6, 12 or 52 weeks. Strain was recorded while the rats were running on a treadmill. The peak strain was of the same magnitude at different animal ages, although there was a somewhat lower value for 52-week-old animals. Stiffness calculated from in vivo strain measurements and from a 3-point bending test on excised femora was correlated: stiffness increased with age. Maximum bending stress increased from 6-12 weeks of age, but then there was no further increase. Ultimate load, on the contrary, increased steadily over the entire 52-week period. This indicates that higher load-bearing capacity with increased age in adult rats is due to increased dimensions of the bone rather than its material properties. The present study demonstrates that conventional in vitro measurements of mechanical properties of bone correspond to measurements of strain during physical activity, and that both are valid measurements of physical properties of bone.
Age Factors↗
Effects of intramedullary reaming and nailing of rat femur. A mechanical and chemical study.
This study was undertaken to explore the association between mechanical and chemical effects of intramedullary reaming and nailing. The right femora of 80 rats were reamed and nailed with steel nails. Forty rats were evaluated from 3 days to 24 weeks postoperatively. The other 40 rats had the nail removed after 12 weeks, and they were then followed from 3 days to 24 weeks after nail extraction. Evaluation consisted of in vivo strain recording, geometric measurements, mechanical three-point bending test, and chemical analyses of hydroxyproline and calcium contents. Reaming and nailing caused immediate weakening of the bone as measured by in vitro mechanical tests, but within 3 weeks the mechanical properties were fully restored, whereas in vivo strain remained reduced throughout the experimental period in rats with nails. Removing the nail increased in vivo strain to a level close to that of the intact femur. Remodeling of the bone resulted in greater external anteroposterior diameter, cross-sectional area, area moment of inertia, and amount of hydroxyproline and calcium in the operated on femur as compared with the intact side. This indicates that the repair processes resulted in greater bone mass of the operated on femur than of the intact femur. Thus, there is evidence that nailing techniques effectively assist tissues by repair and remodeling.
Animals↗
Age-related differences in chemical composition of rat femur as determinants for strain.
We have explored previous findings of remarkably stable in vivo strain at the femoral surface in rats at different ages, and at the same time increased bone stiffness. The rate of collagen synthesis (14C-hydroxyproline/total hydroxyproline ratio) decreased with age, whereas mineralization (calcium/hydroxyproline ratio) increased. Smaller amounts of immature collagen, caused by reduced synthesis, and increased mineralization both probably produce a less flexible material. These chemical alterations support the observed increase in structural stiffness and strength with age. Both mineralization and configurations separately seemed to have effects on in vivo strain. However, none of these variables seemed to be the major determinant for strain.
Aging↗
Reduction of HSV-1 binding to BHK cells after treatment with phosphatidylinositol-specific phospholipase C.
Baby-hamster kidney cells were treated with unspecific and phosphatidylinositol-specific phospholipase C (PI-PLC) prior to infection with herpes simplex virus type 1 or 2. Subsequent to PI-PLC treatment, a 30% reduction of infectivity and receptor binding was observed for type 1 virus, while type 2 was unaffected. Treating the cells with unspecific phospholipase C did not affect subsequent infection with either virus. Treatment of the virus particles with the unspecific phospholipase reduced its infectivity, probably due to loss of the viral envelope. PI-PLC treatment of virus particles did not have any such effect on virus infectivity.
Animals↗
[Herpesvirus latency].
The article reviews present knowledge about the molecular mechanisms involved in herpes virus latency. The work on herpes virus latency has created a foundation for much of our knowledge about viral latency in general. Herpes simplex virus is perhaps best known in this respect. This virus resides latently in sensory ganglia. No herpes simplex-specific proteins have been found, but a specific RNA transcript has been identified. In varicella-zoster virus latency several latency-associated transcripts are known and, as for herpes simplex virus, sensory ganglia harbour the latent infection. There is still some dispute as to whether Epstein-Barr virus is truly latent or not. However, evidence for specific proteins associated with latency is accumulating. Little is known about cytomegalovirus latency.
Cytomegalovirus↗
Neomycin inhibits PDGF-induced IP3 formation and DNA synthesis but not PDGF-stimulated uptake of inorganic phosphate in C3H/10T1/2 fibroblasts.
Porcine PDGF was found to increase [3H]inositol trisphosphate, [3H]thymidine incorporation and 32P-labelling of polyphosphoinositides in C3H/10T1/2 Cl 8 fibroblasts. These responses to PDGF stimulation were all inhibited by 5 mM neomycin, a polycationic aminoglycoside formerly known to inhibit polyphosphoinositide turnover. PDGF also markedly increased the cellular uptake of inorganic [32P]Pi. This response of PDGF was not inhibited by neomycin (5 mM). Thus, neomycin inhibited PDGF-induced IP3 formation, 32P-labelling of polyphosphoinositides and DNA synthesis, but not cellular uptake of inorganic phosphate. These effects of neomycin suggest a bifurcation of the initial part of the PDGF-induced signal transduction, separating at the receptor level or before phospholipase C activation.
Animals↗
A monoclonal antibody against PDGF B-chain inhibits PDGF-induced DNA synthesis in C3H fibroblasts and prevents binding of PDGF to its receptor.
A monoclonal antibody (MAb 6D11) against platelet-derived growth factor (PDGF) was studied. We found that the MAb 6D11 in concentrations equimolar to PDGF blocked the [3H]thymidine incorporation in C3H/10T1/2 C18 fibroblasts stimulated by PDGF B-B and PDGF A-B. This inhibition was overcome by high doses of PDGF. The [3H]thymidine incorporation stimulated by other growth factors (aFGF, bFGF and bombesin) was not inhibited by the antibody. The MAb 6D11 blocked receptor binding of PDGF B-B, but not PDGF A-A. These findings suggest that the MAb 6D11 abolishes PDGF-induced DNA synthesis by blocking PDGF receptor binding. In this communication we demonstrate an isoform-specific monoclonal antibody against PDGF.
Animals↗
Identification and characterization of the virion protein products of herpes simplex virus type 1 gene UL47.
We have identified two encoded proteins with an antiserum raised against a synthetic oligopeptide corresponding to amino acids 671 to 684 of the predicted protein product of gene UL47 of herpes simplex virus type 1 (HSV-1). They have apparent Mrs of 82,000 and 81,000 and are both major virion components located in the tegument. The 82/81K proteins were first detected in infected cells in minor amounts 6 h after infection at 37 degrees C but were later (from 10 h until 24 h after infection) present in large amounts. UL47 regulation was investigated using phosphonoacetic acid (PAA), an inhibitor of DNA synthesis: the amounts of the 82/81K protein synthesized were compared with those of 65KDBP, an early gene product, and 21K/22K, a true late gene product. The data showed that UL47 is regulated as a true late gene.
Amino Acid Sequence↗
Localization on the herpes simplex virus type 1 genome of a region encoding proteins involved in adsorption to the cellular receptor.
We have previously shown that aminoglycosides such as neomycin and the polyamino acids polylysine and polyarginine selectively inhibit the binding of herpes simplex virus type 1 (HSV-1) to the cellular receptor, whereas HSV-2 infection is unaffected. In the present study we took advantage of this difference between HSV-1 and HSV-2 by using HSV(-1)-HSV(-2) intertypic recombinants to locate a region on the HSV-1 genome encoding proteins affecting the binding of the virion to the cellular receptor. The results were consistent with those obtained by marker rescue experiments. The identified region, which mapped between coordinates 0.580 and 0.687, contains two partial and eight complete genes, including the glycoprotein C (gC) gene and two others with potential transmembrane sequences. Various gC monoclonal antibody-resistant mutants of HSV-1 as well as a mutant completely lacking gC were found to be fully sensitive to neomycin, suggesting that gC is not the site of drug sensitivity and is not essential for adsorption of virus to the cellular receptor. However, the rate of adsorption was reduced in the absence of gC, indicating a facilitating function of the glycoprotein. The universal nature of this HSV-1 receptor binding was revealed by the similarity in drug sensitivity of infectivity in four different cell lines from various tissues and species.
Adsorption↗
Herpes simplex virus-1-specific proteins are involved in alteration of polyphosphoinositide metabolism in baby-hamster kidney cells.
Herpes simplex virus type 1 (HSV-1) induces altered phosphoinositide metabolism in baby hamster kidney (BHK) cells, measured as incorporation of [3H]inositol or [32P]Pi [Langeland, Haarr & Holmsen (1986) Biochem. J. 237, 707-712]. We now report that this response in the inositol phospholipids is dependent on virus-specific proteins synthesized in the beta (early) stage of virus protein synthesis. This was demonstrated both by resistance to the inhibitory effect of cycloheximide after this stage of infection, and by the use of temperature-sensitive (ts) mutants of HSV-1; ts mutants in which protein synthesis was blocked so that only the alpha proteins were expressed showed a PIP2/PIP (phosphatidylinositol 4,5-bisphosphate/phosphatidylinositol 4-monophosphate) ratio similar to uninfected cells, while ts mutants which were defective in protein synthesis at a late beta stage or later showed increased PIP2/PIP ratios similar to cells infected by wild type HSV-1.
Animals↗
Platelet-derived-growth-factor-stimulated heterogeneous polyphosphoinositide metabolism and phosphate uptake in C3H fibroblasts.
Pig platelet-derived growth factor (PDGF) increased the rate of [32P]Pi uptake by murine fibroblasts, resulting in a 3-9-fold elevation of the specific radioactivity of ATP, PtdInsP, PtdInsP2, PtdIns and phosphatidic acid. The specific radioactivity was 10-60-fold higher in ATP than in the four phospholipids. These substances are therefore not in metabolic equilibrium, which complicates determination of inositol phospholipid turnover.
Adenosine Triphosphate↗
Immediate strain shielding after femoral reaming and nailing. An in vivo study in rat femora.
Following intramedullary reaming and nailing of rat femora, in vivo changes in dynamic strain were correlated with in vitro measurements of the bones. Reaming and nailing procedures were performed 2 days after implantation of unidirectional strain gauges at the anterior, mid-diaphyseal level of the femur. Structural stiffness of polyacetal nails were three times as stiff as intact bone. Reaming only decreased the median strain value by 26 percent, and this value was not reduced by insertion of polyacetal nails. Steel nailing reduced the strain by 74 percent. Tested by three-point bending, reaming increased stiffness by 5 percent at the anterior aspect. The presence of nails gave stiffness values that were 9 percent (polyacetal) and 56 percent (steel) higher than the reamed only condition. Our results indicate that steel nailing following reaming causes marked reduction in strain at the anterior, mid-diaphyseal surface, whereas reduction in strain caused by polyacetal nails is negligible.
Animals↗
Interaction of polylysine with the cellular receptor for herpes simplex virus type 1.
We earlier reported that neomycin blocked reversibly the binding of herpes simplex virus type 1 (HSV-1) to the receptor of BHK cells, while the binding of HSV-2 to the receptor was unaffected. We could not determine whether the effect was on the virus particle, the receptor, or both. We have now tested several other cationic substances, and report that polylysine (and polyarginine) block the binding of HSV-1 to the receptor by interfering with the cellular receptor function; higher molecular weight polylysines were more potent than those of lower molecular weight. Polylysine and neomycin showed additive effects. In vitro, polylysine showed the same strong binding to the plasma membrane phosphoinositides as did neomycin. Together these data suggest that the drugs may have a common target in the cell membrane. The HSV-1 and HSV-2 virus particles were unaffected by the drugs, as was the cellular HSV-2 receptor.
Animals↗
[Neomycin. An aminoglycoside in the study of signal processing].
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Cations↗
Controlled bending instability in the healing of diaphyseal osteotomies in the rat femur.
Ninety-six rats underwent a midshaft transverse osteotomy followed by osteosynthesis with an intramedullary nail, so that the effect of bending instability on time to union and on the mechanical properties of experimental diaphyseal fracture could be evaluated. Rotation was reduced by cementing both nail ends to the bone. Rigid nails made of stainless steel were used on one group and flexible nails made of polyacetal resin were used on another group. Serial radiographs were evaluated at 4-6-week intervals. Twelve animals with either nail type were killed at 4, 8, 16, and 24 weeks. Both femora were mechanically tested and the callus diameters were measured. There was no significant difference in time to union between the two groups. The cross-sectional area of callus was significantly higher at 8 and 16 weeks in femora with flexible nails. The strength, toughness, and resilience of the bone increased in this group until 24 weeks. Between 16 and 24 weeks, these parameters did not improve in femora with rigid nails. Poorer mechanical properties in femora with steel nails are interpreted as an effect of stress protection of the bone. This study, therefore, indicates that flexible nails prevent stress protection effects without delaying union.
Acetals↗