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Biomedical subjects

J Roth

Publications and source records attributed to J Roth.

At least 901 records · Page 50Linked to original sources
PubMedDate not supplied

Widening awareness of hyperglycemia unawareness.

Hyperglycemia unawareness is the term suggested to me (M. Muggeo, personal communication, 1997) to encompass very broadly all of the stages in diabetes mellitus from the onset of any degree of hyperglycemia until the diagnosis is actually made. Diabetes and its handmaiden, obesity, are growing in epidemic proportions in the US and worldwide. In contrast to obesity where the diagnosis is recognized quite early by the patient, the family and the physician, the diagnosis of diabetes may be delayed from 5 to 15 years after its onset1-5. A significant minority of adults, when newly diagnosed with Type 2 diabetes, have definable evidence of macrovascular or microvascular complications. Presumably those same individuals, were we able to examine their cells and organs, would show additional evidence of the complications of diabetes. Likewise, with the recognition that hyperglycemia per se is a very powerful determinant of the complications of diabetes, we suspect that even those people with the delayed recognition of hyperglycemia but without evidence of complications at the time of diagnosis already have sustained some of the underlying damage typical of diabetic complications. This is supported by the finding that in this group of patients, there are those who will have an 'accelerated rate' of onset of diabetic complications2 (relative to patients with Type 1 diabetes where the onset of hyperglycemia is very close to the time of the diagnosis). Our interpretation is that the progress of the disease may not really be especially rapid; rather, the dating of the onset has been incorrect.

Adult↗
PubMedDate not supplied

Tubules of the trans Golgi apparatus visualized by immunoelectron microscopy.

Tubules constitute an integral part of the Golgi apparatus and have been shown to form a complex and dynamic network at its trans side. We have studied in detail structural features of the trans Golgi network and its relationship with the cisternal stack in thin sections of Lowicryl K4M embedded human absorptive enterocytes by immunolectron microscopy. Immunoreactive sites for alpha1,3 N-acetylgalactosaminyltransferase and blood group A substance were detectable throughout the cisternal stack and the entire trans Golgi network. Furthermore, the entire trans Golgi network was reactive for CMPase activity. Evidence for two kinds of tubules at the trans side of the Golgi apparatus was found: tubules that laterally connect adjacent and distant cisternal stacks, and others extending from central and lateral portions of trans cisternae to form the complex and extensive trans Golgi network. Trans cisternae showed often the peeling-off phenomenon and were continuous with the trans Golgi network. Both, trans cisternae and tubules of the trans Golgi network exhibited regionally buds and vesicles with a lace-like, non clathrin coat, previously reported by others in NRK cells, which contained glycoproteins with terminal N-acetylgalactosamine residues. These buds and vesicle are therefore involved in constitutive exocytosis.

Acid Phosphatase↗
PubMedDate not supplied

Endocytic routes to the Golgi apparatus.

The endocytic routes of labelled lectins as well as cationic ferritin were studied in cells with a regulated secretion, i.e. pancreatic beta cells, and in constitutively secreting cells, i.e. fibroblasts and HepG2 hepatoma cells, paying particular attention to routes into the Golgi apparatus. Considerable amounts of internalised molecules were taken up into the trans Golgi network (TGN) and into Golgi subcompartments in all three cell types as well as in secretory granules of the pancreatic beta cells. The internalised materials did not pass rapidly the TGN and Golgi stacks, but were still present hours after internalisation, being then particularly concentrated in TGN-elements and in the transmost Golgi cisterna. Endocytosed materials reached forming secretory granules present in the TGN. Further, direct fusion between endocytotic vesicles and mature secretory granules was observed. Golgi subcompartments as well as endocytic TGN containing endocytosed materials were in close apposition to specialised regions of the endoplasmic reticulum. The Golgi apparatus including its parts containing endocytosed materials were transformed into a tubular reticulum upon treatment with the fungal metabolite Brefeldin A. Rarely, internalised material was observed in the lumen of the endoplasmic reticulum, thus providing evidence for an endocytic plasma membrane to endoplasmic reticulum route.

Animals↗
PubMedDate not supplied

Fever response in lean (Fa/-) and obese (fa/fa) Zucker rats and its lack to repeated injections of LPS.

The thermal responses of Fa/- and fa/fa Zucker rats to injections of sterile saline and to four injections of 20 micrograms/kg LPS at 3-day intervals were measured by means of radiotelemetry. In response to injections of saline, only the Fa/- rats developed a short stress-induced increase in abdominal temperature. Such a stress-induced rise of core temperature was also monitored in Fa/- rats after a change of the animals' cages. In response to the first injection of LPS, the Fa/- rats developed the same stress-induced rise in abdominal temperature as observed after injection of solvent followed by a biphasic fever, the first phase within 100 and 225 min, and the second phase within 240 and 480 min after LPS injection. In the fa/fa rats the stress-induced rise in body temperature and the first phase of LPS-induced fever were significantly suppressed, whereas the second phase of LPS-fever was identical in FA/- and fa/fa rats. In response to further injections of LPS no febrile response was measurable at all; just the short stress-induced rise in abdominal temperature remained manifest in the Fa/- rats. When the first injection of 20 micrograms/kg LPS was followed by injections of 100 and 1000 micrograms/kg LPS, a febrile response remained manifest, but the second phase of fever was attenuated in response to the repeated challenge with higher doses of LPS. The complete endotoxin tolerance observed in response to the second and further injections of 20 micrograms/kg seems thus to be due to a strongly reduced sensitivity to LPS after its first administration. Because data from the literature indicate a reduced sympathetic outflow to brown adipose tissue of fa/fa rats in general and during fever in particular, we tried to determine the activity of the sympathetic nervous system by measurement of excreted amounts of noradrenaline. Attempts failed to determine noradrenaline excretion during fever in lean and in obese animals. The daily excretion of noradrenaline at an ambient temperature of 22 degrees C (basal values) was 53.8 +/- 4.7 nmol/kg in Fa/- and 25.9 +/- 3.4 nmol/kg in fa/fa rats. These values were increased by a cold exposure (5 degrees C) for 24 h to 123.1 +/- 12.4 nmol/kg in Fa/- rats (229% of the basal value) vs. just 48.7 +/- 2.5 nmol/kg in fa/fa rats (188% of the basal value). This small, but significantly larger rise of cold-stimulated noradrenaline excretion in Fa/- rats is indicative of a reduced sympathetic function in the fa/fa rats, but does not explain the lack of stress-induced rise in body temperature and of the first phase of LPS-induced fever in the obese animals.

Animals↗
PubMedDate not supplied

The use of fluorescein isothiocyanate labelled lectins for immuno-histological demonstration of saccharides. III. Studies by use of Ricinus communis lectin and wheat germ agglutinin.

Cryostat sections of heart, skeletal muscle, spleen, liver, cartilage, brain, nerve, tongue, esophagus and salivary gland from man, rabbit, rat and guinea pig were stained with fluorescein isothiocyanate labelled Ricinus communis lectin and wheat germ agglutinin. The stained sections were examined by fluorescence microscopy. The general pattern of fluorescence is very similar to that obtained with labelled Lens culinaris lectin and Concanavalin A. Particularly the lectins stain connective tissue structures of the organs. The staining intensity in these structures was weaker by wheat germ agglutinin as compared to the other lectins.

Animals↗
PubMedDate not supplied

Afferent nerves are involved in the febrile response to injection of LPS into artificial subcutaneous chambers in guinea pigs.

In guinea pigs, fever was induced by injections of 100 or 10 microgram/kg lipopolysaccharide (LPS) into artificial subcutaneous chambers and analysed under the influence of the local anesthetic, ropivacaine (ROPI), which was administered into the chamber at a dose of 10 mg/kg 30 min prior to LPS. In response to injections of 100 microgram/kg LPS into the subcutaneous chambers, fever was not modified by pretreatment with ROPI. High amounts of bioactive tumor necrosis factor (TNF) alpha and interleukin-6 (IL-6) were measured in the lavage of the chambers after administration of LPS. Comparatively low concentrations of both cytokines (0.5-4% of the concentrations in the lavage fluid) were detected in blood plasma simultaneously. In response to injections of 10 microgram/kg LPS into the subcutaneous chambers, fever was significantly reduced by pretreatment with ROPI to about 60% of the febrile response of control animals. Levels of TNF and IL-6 were lower in response to the reduced dose of LPS. TNF in plasma was even below the limit of detection. The suppression of fever by the local anesthetic was not observed when ROPI was subcutaneously injected into the contralateral site of the chamber position so that a systemic effect of ROPI in the reduction of fever can be excluded. The results indicate a participation of afferent neural signals in the manifestation of fever. This effect becomes obvious only if the dose of the applied inflammatory stimulus (LPS) is not high enough to activate a systemic generalised inflammatory response.

Amides↗
PubMedDate not supplied

Genetic susceptibility testing in smoking-cessation treatment: one-year outcomes of a randomized trial.

This study evaluated the long-term impact of genetic susceptibility biomarker feedback on smoking behavior change and symptoms of depression in 426 male and female smokers. Smokers were randomized to one of three smoking-cessation interventions: minimal contact quit-smoking counseling (QSC), QSC + exposure biomarker feedback (EBF), and QSC + EBF + biomarker feedback about genetic susceptibility to lung cancer (SBF). The logistic regression model for quit attempt revealed a significant main effect for treatment such that participants in the SBF group were more than two times more likely to make a quit attempt than participants in the QSC group. There was not a significant difference between EBF and QSC participants. The results also revealed a significant effect for baseline stage of change. Those smokers in the preparation stage at baseline were more than three times more likely to make a quit attempt over the 12 months following treatment. The models for 30-day cessation and follow-up smoking rate revealed no significant main or interacting effects for treatment. A repeated measures analysis of variance revealed a significant main effect for time, indicating that an initial increase in depression in the genetic susceptibility group was not maintained over time. Genetic susceptibility feedback has the intended effects on motivation to quit, but it may need to be delivered within a more intensive smoking-cessation treatment for the heightened motivation to translate into smoking cessation.

Adolescent↗
PubMedDate not supplied

The clinical course of a child with CINCA/NOMID syndrome improved during and after treatment with thalidomide.

Chronic, infantile, neurological, cutaneous, and articular (CINCA) syndrome, also known as neonatal-onset multisystem inflammatory disease (NOMID), is a rare autosomal dominant inherited disease. It is characterized by a persistent rash with onset during the neonatal period, neurological and ocular manifestations, and articular involvement with abnormal ossification. Mutations within the CIAS1 gene are found in up to 60% of CINCA cases, but the exact underlying pathogenetic mechanisms causing this disorder are still unclear. Although the interleukin-1 (IL-1) receptor antagonist anakinra (rHuIL-1Ra) has recently been reported to be effective, no formal recommended treatment protocols exist thus far. Herein, we describe a 17-year-old girl with CINCA for whom numerous medication trials had been unsuccessful. After the introduction of thalidomide, the symptoms of arthropathy improved dramatically even months after the medication was discontinued by the patient. We propose that thalidomide can be beneficial in select patients with CINCA syndrome.

Adolescent↗
PubMedDate not supplied

Morphological and physiological responses to altitude in deer mice Peromyscus maniculatus.

Individuals within a species, living across a wide range of habitats, often display a great deal of phenotypic plasticity for organ mass and function. We investigated the extent to which changes in organ mass are variable, corresponding to environmental demand, across an altitudinal gradient. Are there changes in the mass of oxygen delivery organs (heart and lungs) and other central processing organs (gut, liver, kidney) associated with an increased sustainable metabolic rate that results from decreased ambient temperatures and decreased oxygen availability along an altitudinal gradient? We measured food intake, resting metabolic rate (RMR), and organ mass in captive deer mice (Peromyscus maniculatus bairdii) at three sites from 1,200 to 3,800 m above sea level to determine whether energy demand was correlated with organ mass. We found that food intake, gut mass, and cardiopulmonary organ mass increased in mice living at high altitudes. RMR was not correlated with organ mass differences along the altitudinal gradient. While the conditions in this study were by no means extreme, these results show that mice living at high altitudes have higher levels of energy demand and possess larger cardiopulmonary and digestive organs than mice living at lower altitudes.

Adaptation, Physiological↗
PubMedDate not supplied

Massive ovarian edema: ultrasound and MR characteristics.

Massive ovarian edema (MOE) is a benign enlargement of the ovary caused by edema, which is believed to result from intermittent or partial torsion of the ovarian pedicle. We report a case of MOE in a pregnant patient.

Adult↗
PubMedDate not supplied

Esophageal replacement in the dog by microvascular colon transfer.

An orthotopic colon graft based on the middle colic artery and vein was implanted with microvascular technique and a stapling instrument in five dogs. The grafts were successful in four dogs. A similar colon autograft was used to replace the entire thoracic esophagus in five dogs. The recipient vessels were the left carotid artery and left external jugular vein. Four of the grafts failed because of kinking and thrombosis of the arterial supply (2 dogs) or the venous outflow (2 dogs). One graft, which had a viable vascular supply, developed a severe leak at the colon-to-stomach anastomosis, and the dog was euthanatized on day 3. The recipient vascular pedicle was modified and used successfully to replace a portion of the cervical esophagus in three dogs. The grafts survived, the dogs could swallow liquids and semisolid food well, and, at necropsy after 4 weeks, the anastomotic sites were well healed. The graft sites contained essentially normal colon mucosa.

Anastomosis, Surgical↗
PubMedDate not supplied

Insulin binding to its receptor: is the receptor more important than the hormone?

The development of methods to measure insulin showed that many (if not most) patients with disorders of glucose metabolism have a target cell disorder rather than a secretory defect. Methods to measure the insulin receptor have shown that in patients with target cell disorders the receptor is often involved in a meaningful way. Furthermore, even in diseases where hormone secretion (deficiency or excess) is dominant, the receptor may play an important role in the clinical state of the patients. In the future, development of techniques to assess postreceptor events should uncover defects at these sites as well.

Diabetes Mellitus↗
PubMedDate not supplied

Immunolabeling with the protein A-gold technique: an overview.

The protein A-gold technique is a postembedding immunolabeling method that permits light- and electron-microscopic localization of intracellular antigens on tissue sections with high sensitivity and resolution. The article reviews practical aspects of tissue fixation and embedding protocols as well as methodologic aspects of the protein A-gold technique; careful control of these interrelated factors is the prerequisite for successful application. The technique is demonstrated by a few selected examples of application in basic research and in applied medical research. The protein A-gold technique provides a good alternative to existing techniques for immunolabeling in diagnostic pathology.

Animals↗
PubMedDate not supplied

Myeloid related proteins MRP8/MRP14 may predict disease flares in juvenile idiopathic arthritis.

OBJECTIVE: An unsolved problem in juvenile idiopathic arthritis (JIA) is to identify patients at special risk for relapse. It is important to adjust anti-inflammatory and immunosuppressive therapy to the children's actual disease activity especially in times of remission. Our aim was to analyze if the serum levels of MRP8/MRP14 are reliable predictive markers for the risk of relapse in clinically inactive juvenile idiopathic arthritis. METHODS: Serum concentrations of MRP8/MRP14 were determined by ELISA and correlated with laboratory and clinical parameters for disease activity in patients with JIA. 29 patients with changing disease activity were followed up for a mean time of 2.9 years. Two groups of patients--one before relapse (mean 3.7 months) but without clinical signs of disease reactivation, and one in remission for 12 further months--were compared. RESULTS: MRP8/MRP14 serum levels in patients before relapses were significantly higher than the levels in patients in stable remission for one year (662 ng/ml versus 395 ng/ml; p < 0.05). Using a cut-off for MRP8/MRP14 of 450 ng/ml the likelihood ratio for relapse was 3.7 (positive predictive value 80%), while no differences were found for C-reactive protein and erythrocyte sedimentation rate between the two groups. CONCLUSION: MRP8/MRP14 correlate with individual disease activity in patients with JIA. Our data suggest that local disease activity may be present even months before flares become clinically apparent. Serum levels of MRP8/MRP14 can give a hint as to clinically occult disease activity, in this way helping to adjust therapy in times of low disease activity.

Adolescent↗