Search PubMed⌕ Search

Biomedical subjects

J Koenig

Publications and source records attributed to J Koenig.

At least 19 recordsLinked to original sources
PubMed1999

Characteristics of skeletal muscle in mdx mutant mice.

We review the extensive research conducted on the mdx mouse since 1987, when demonstration of the absence of dystrophin in mdx muscle led to X-chromosome-linked muscular dystrophy (mdx) being considered as a homolog of Duchenne muscular dystrophy. Certain results are contradictory. We consider most aspects of mdx skeletal muscle: (i) the distribution and roles of dystrophin, utrophin, and associated proteins; (ii) morphological characteristics of the skeletal muscle and hypotheses put forward to explain the regeneration characteristic of the mdx mouse; (iii) special features of the diaphragm; (iv) changes in basic fibroblast growth factor, ion flux, innervation, cytoskeleton, adhesive proteins, mastocytes, and metabolism; and (v) different lines of therapeutic research.

Animals↗
PubMed1999

Episodes of high coarse particle concentrations are not associated with increased mortality.

Fine particle concentration (i.e., particles <2.5 microm in aerodynamic diameter; PM2.5), but not coarse particle concentration, was associated with increased mortality in six U.S. cities. Others criticized this result, arguing that it could result from differences in measurement error between the two size ranges. Fine particles are primarily from combustion of fossil fuel, whereras coarse particles (i.e., particles between 2.5 and 10 microm in aerodynamic diameter) are all crustal material, i.e., dust. One way to determine if coarse particles are a risk for mortality is to identify episodes of high concentrations of coarse, but not fine, particles. Spokane, Washington, is located in an arid area and is subject to occasional dust storms after crops have been harvested. Between 1989 and 1995, we identified 17 dust storms in Spokane. The 24-hr mean PM10 concentration during those storms was 263 microg/m3. Using control dates that were the same day of the year in other years (but with no dust storm on that day) and that had a mean PM10 concentration of 42 microg/m3, we compared the rate of nonaccidental deaths on the episode versus nonepisode days. There was little evidence of any risk [relative risk (RR) = 1.00; 95% confidence interval (CI), 0.81-1.22] on the episode days. Defining episode deaths as those occurring on the same or following day as the dust storm produced similar results (RR = 1.01; CI, 0.87-1.17). Sensitivity analyses, which tested more extensive seasonal control, produced smaller estimates. We conclude that coarse particles from windblown dust are not associated with mortality risk.

Air Pollutants↗
PubMed1999

Ballistic shock wave lithotripsy in an 18-year-old thoroughbred gelding.

Prolonged postoperative recuperation time and restricted exercise were circumvented by using ballistic shock wave lithotripsy to break up an 8-cm diameter vesical calculus and by flushing out the sand-like residue under epidural anesthesia with the horse standing. Recovery was uneventful.

Anesthesia, Epidural↗
PubMed1998

Mitochondrial oxygen consumption, lipid peroxidation and antioxidant enzyme systems in skeletal muscle of senile dystrophic mice.

To evaluate age-dependent abnormalities in mitochondrial redox metabolism specifically in dystrophic skeletal muscle, oxygen consumption, thiobarbituric acid reactivity (TBARS), free-radical scavengers and oxidative marker enzymes were measured in the skeletal muscle from adult and senile control (C57BL/10) and dystrophic (mdx/+) mice. Mitochondrial oxygen consumption in state 3 was significantly lowered with age in the senile dystrophic (-52%) and less markedly in the senile control (-30%) skeletal muscle. Compared with adult muscle, mitochondrial concentration of TBARS and cellular concentration of lipofuscin were significantly increased in senile control and dystrophic muscle. Enzymatic activity of glutathione peroxidase (GSH-Px) and concentration of alpha-tocopherol were significantly increased in the senile control (GSH-Px 43+/-5.7 vs 53+/-8.7 U/g protein, alpha-tocopherol 0.19+/-0. 09 vs 0.29+/-0.14 micromol/g total lipids), but significantly decreased in the senile dystrophic (GSH-Px 80+/-8.0 vs 53+/-12 U/g protein, alpha-tocopherol 0.45+/-0.13 vs 0.19+/-0.03 micromol/g total lipids) muscle. Selenium content was significantly decreased only in senile dystrophic muscle (1.37+/-0.42 vs 0.78+/-0.21 nmol/g wet muscle). In conclusion, the enzymatic adaptation to reactive oxygen species was limited in the dystrophic skeletal muscle, suggesting a higher need for antioxidants, especially alpha-tocopherol.

Aging↗
PubMed1998

Accumulation of acetylcholine receptors is a necessary condition for normal accumulation of acetylcholinesterase during in vitro neuromuscular synaptogenesis.

To study a step of the very complex processes of the formation of the neuromuscular junction (NMJ), we have analysed the clustering of acetylcholine receptors (AChR) and acetylcholinesterase (AChE) in myotubes cultured in various conditions. On the surface of rat myotubes cultured in the presence of spinal cord cells from embryonic rat, numerous AChE clusters appeared. Such clusters are always co-localized with AChR clusters, but the reverse is not true: the number of AChR clusters largely exceeds that of AChE clusters. Very few AChE clusters formed when such co-cultures were treated with monoclonal antibodies (mAbs) against the main immunogenic region (MIR) of the AChR, which provoke internalization and degradation of the AChRs of the muscular membrane. The total levels of AChE and proportions of molecular forms were unaffected. We also used non-innervated myotubes in which addition of agrin, a protein normally synthesized by motoneurons, transported to nerve terminals and inserted into the synaptic basal lamina, induces the formation of small clusters of AChE. When added to rat myotubes devoid of membrane AChR, agrin-induced AChE clusters did not form. Finally, we analysed the capacity of the variant of the C2 mouse muscle cell line deficient in AChR (1R-) to form clusters of AChE in co-cultures with spinal cord cells from rat: no formation of AChE clusters could be observed. In all these different systems of cultures, the conditions which prevented clustering of AChR (anti-AChR antibodies, deficiency of the variant C2 cell line) also suppressed AChE clustering. We concluded that clustering of AChR is a prerequisite for clustering of AChE, so that NMJ formation implies the sequential accumulation of these two components.

Acetylcholinesterase↗
PubMed1998

Call 1-888-NOT-2-LATE: promoting emergency contraception in the United States.

In 1997, the nonprofit Reproductive Health Technologies Project and the Office of Population Research at Princeton University, together with the communications firm Elgin DDB, planned and executed a mass media campaign to advertise the Emergency Contraception Hotline and more generally to further awareness of emergency contraception as a last chance means of pregnancy prevention in the United State. We produced a variety of public service announcements (PSAs) including television and radio spots in English and Spanish and several print versions adaptable for newspapers and magazines as well as outdoor settings such as billboards, transit shelters, and the sides of buses. Working with local coalitions, we succeeded in placing the PSAs free of charge in six pilot cities. We also generated coverage about the campaign in local and national news outlets. We chronicle the development of the media campaign, discuss the challenges and obstacles faced, and conclude with a review of the principal lessons learned.

Advertising↗
PubMed1997

Schwann cells modify expression of acetylcholinesterase and butyrylcholinesterase at rat neuromuscular junctions.

Using a monoclonal antibody (6.17) directed against a Schwann antigen, we have shown that Schwann cells synthesize a molecule implicated in a change of expression of synaptic cholinesterases, AChE and BChE, during muscle differentiation. In vitro, during synaptogenesis, the two enzymes are first present at developing synapses, and addition of Schwann cells to muscle-neuron co-cultures induces a disappearance of BChE, leaving only AChE activity as in the adult neuromuscular junction. This effect is inhibited by the 6.17 antibody. Thus, a molecule produced by Schwann cells is involved in the maturation of the neuromuscular synapse, in addition to the neuronal factors (CGRP, ARIA/heregulin, agrin), which are known to control the synthesis, maturation and accumulation of acetylcholine receptors and other synaptic components. In addition, in vivo, in the newborn rat, butyrylcholinesterase and acetylcholinesterase activities are initially present in equal amounts in the neural zone, but butyrylcholinesterase levels diminish sharply between 7 and 15 days after birth, the stage at which the synaptic Schwann cell membrane becomes juxtaposed with the muscle membrane.

Acetylcholinesterase↗
PubMed1997

Preventing unintended pregnancy: the cost-effectiveness of three methods of emergency contraception.

OBJECTIVES: This study examined the cost-effectiveness of emergency contraceptive pills, minipills, and the copper-T intrauterine device (IUD) as emergency contraception. METHODS: Cost savings were modeled for both (1) a single contraceptive treatment following unprotected intercourse and (2) emergency contraceptive pills provided in advance. RESULTS: In a managed care (public payer) setting, a single treatment of emergency contraception after unprotected intercourse saves $142 ($54) with emergency contraceptive pills and $119 ($29) with minipills. The copper-T IUD is not cost-effective as an emergency contraceptive alone, but savings quickly accrue as use continues. Advance provision of emergency contraceptive pills to women using barrier contraceptives, spermicides, withdrawal, or periodic abstinence saves from $263 to $498 ($99 to $205) annually. CONCLUSIONS: Emergency contraception is cost-effective whether provided when the emergency arises or in advance to be used as needed. Greater use of emergency contraception could reduce the considerable medical and social costs of unintended pregnancies.

Contraceptives, Oral, Hormonal↗
PubMed1996

Immunocytochemical characterization of a new marker of fibrous and reactive astrocytes.

A specific monoclonal antiserum (Mab 6.17) inducing a strong immunostaining of the neuromuscular junction has been used to detect the possible occurrence of the corresponding antigen throughout the intact or lesioned central nervous system of adult rats. In intact animals, 6.17-immunolabeling was essentially detected in astrocyte-like structures located in white matter fasciculi of the brain, such as the optic tract, corpus callosum, fornix, and in the white matter of the spinal cord. The astroglial nature of such 6.17-immunolabeled profiles was verified by performing double or triple immunofluorescent labeling with Mab 6.17 and with specific antisera against astrocytic markers, such as S100 protein, glial fibrillary acidic protein and vimentin. In the white matter, all the structures reactive to Mab 6.17 were also reactive to antibodies against S100 protein, glial fibrillary acidic protein and vimentin. On the other hand, astrocytes of the grey matter that were immunoreactive to S100 and glial fibrillary acidic protein but negative to vimentin, were devoid of 6.17-immunoreactivity. After lesions including stab wound through the diencephalon or transection of the spinal cord, a marked increase of 6.17-immunostaining was noted in the regions surrounding the lesions. In these regions, 6.17-immunolabeling was associated with S100-, GFAP- and vimentin-positive astrocytes constituting the glial scar. The ultrastructural localization of 6.17-immunoreactivity indicated that, similar to glial fibrillary acidic protein and vimentin, the recognized antigen was mainly associated with gliofilaments. These observations indicate that, in the central nervous system of adult rats, Mab 6.17 recognizes a molecule associated with gliofilaments, which is essentially associated to reactive astrocytes expressing high levels of vimentin.

Animals↗
PubMed1995

Functional and structural recovery of myotubes from mice with muscular dysgenesis after co-culture with normal, non-myoblastic cells.

Muscular dysgenesis is a mutation which is characterized by paralysis of skeletal muscle cells. Excitation-contraction coupling is deficient and muscle cells display atypical ultrastructure. In vitro, mutant myotubes recover a normal phenotype when co-cultured with spinal cord cells from normal animals or with normal fibroblasts. We have shown that other types of cells, eg certain glial cells present in the spinal cord or in other tissues, have this capacity. In contrast, intervention of neurons in the recovery does not appear likely. Very different types of non-myoblastic cells, then, are capable of restoring contractile activity of dysgenic myotubes in vitro, suggesting that a non-specific mechanism is involved in the phenotypic reversion of affected muscle cells. The restoration process seems to imply a close relationship between myotubes and normal glial cells.

Animals↗
PubMed1995

Inhibition of proliferation in 8-week-old mdx mouse muscle fibroblasts in vitro.

Our purpose is to understand why mdx muscle does not show the progressive degeneration observed in human Duchenne muscular dystrophy (DMD) muscle. In the mouse, the regenerative process compensates for the necrosis of the muscle fibers, particularly during the acute phase of the disease (5-9 weeks). In DMD muscle, there is a gradual failure of the regenerative process and the muscle fibers are replaced by connective and fatty tissue. We propose that distinct properties of mdx and DMD muscle fibroblasts could be one of the reasons for the differences between the mdx and DMD phenotypes. We found that fibroblasts taken from human DMD and control muscle had similar in vitro proliferative capacities. The proliferation rate of mouse muscle fibroblasts decreased during the acute phase of the disease, and inhibition was complete in fibroblasts from 8-week-old mdx mice. Moreover, the medium conditioned by these cells inhibited fibroblast proliferation. The effect was specific for fibroblasts, since this conditioned medium stimulated myoblast proliferation, as did control fibroblast-conditioned medium. These results suggest that 8-week-old mdx mouse muscle fibroblasts produce an inhibitor of their own proliferation and a growth factor specific for myoblasts in vitro. If these factors are secreted in vivo, the growth inhibitory factory may stop fibroblast proliferation whereas the mitogenic activity could stimulate satellite cell proliferation, thus favouring muscle regeneration.

Adolescent↗
PubMed1995

Facilitation of thin-layer chromatographic identification of opiates by derivatization with acetic anhydride or methoxyamine.

Qualitative identification of opiates in urine is commonly achieved in two stages, the first involving immunoassay screening and the second involving chromatographic confirmation. Identification of specific opiates is often requested to determine whether the source of opiates is from diet, prescription pharmaceuticals, or illicit drugs. During evaluation of the Toxi-Lab thin-layer chromatographic system as a confirmatory technique for urinary opiates, we encountered difficulty distinguishing opiates with similar retention factor values and colorimetric behavior. By exploiting chemical differences of the comigrating opiates through preparation of acetate or methoxime derivatives, followed by chromatography of the underivatized and derivatized samples in adjacent lanes, we were able to more easily distinguish codeine from hydrocodone, 6-acetylmorphine from oxymorphone, and dihydrocodeine from hydromorphone.

Acetic Anhydrides↗
PubMed1995

Spatial and temporal distribution of [Ca2+]i in normal human myotubes. A fura-2 imaging study.

The spatio-temporal distribution of intracellular, free calcium ions, [Ca2+]i, induced in human myotubes by electrical stimulation typically showed a relatively large increase of [Ca2+]i in the vicinity of the plasmalemma. The similarity of this distribution, with that observed after the application of caffeine, and the lack of any effect of lanthanum, strongly suggest that the main source of Ca2+ participating in the electrically induced transient is the sarcoplasmic reticulum. Aneurally cultured human myotubes therefore display a 'skeletal muscle type' coupling between membrane depolarization and calcium release. However, the relatively slow time course of the electrically induced transients compared to rat and mouse myotubes, together with the inability of Ca2+ released from the sarcoplasmic reticulum to activate the contractile machinery, implies that aneurally cultured human myotubes achieve only a limited degree of differentiation. The relevance this may have to an apparent delay between the electrically induced rise in intranuclear Ca2+ relative to cytosolic Ca2+ remains to be determined but, at this stage of differentiation, there appears to be some form of barrier to free diffusion between the two cellular compartments.

Caffeine↗