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Biomedical subjects

R Baron

Publications and source records attributed to R Baron.

At least 217 records · Page 12Linked to original sources

[Isokinetic measurements of the stretch strength of the femoral quadriceps muscle in surfers in comparison to healthy, untrained persons].

The strength of the quadriceps muscle of twelve male surfers who practice their sport for more than 10 years was compared with results of 15 male untrained persons. The concentric peak torque of knee extensors was measured every 10 degrees in a range from 90 to 20 degrees isometrically and dynamically with a constant angle velocity of 10 degrees/sec. The difference in torque between the left and the right leg is not significant, but there is a slight dominance in favour of the standing leg. The body weight related strength of the surfers was 3.2 Nm/kg indicating a higher strength characteristic compared to 2.7 Nm/kg of untrained subjects. Moreover the strength values of our group of athletes were above the value of 3 Nm/kg, which is referred to in the literature as representing a good training status. In view of these results it can be concluded that a long-lasting specific training like surfing will change the strength characteristics of the quadriceps muscles, although none of the surfers had undertaken an extensive strength training for the lower extremity.

Adult↗

Molecular mechanisms of bone resorption by the osteoclast.

The osteoclast is a multinucleated cell that is actively engaged in the synthesis of lysosomal enzymes, their vectorial transport toward the apical membrane, and the secretion of these enzymes at its apical pole. These secreted enzymes are targeted to the apical ruffled-border membrane by mechanisms that involve cation-independent mannose-6-phosphate receptors. These receptors bind to an enzyme-linked mannose-6-phosphate recognition marker in the Golgi complex, and the enzyme-ligand-receptor complex, carried within small coated transport vesicles, dissociates upon reaching the low pH established in the bone-resorbing compartment by the osteoclast. The apical bone-resorbing compartment is sealed off by the attachment of the osteoclast to the calcified matrix and is actively acidified by the osteoclast. The plasma membrane of the cell is divided into distinct domains. The apical membrane at the ruffled-border shares common antigenic determinants with lysosomal and endosomal membranes, including a 100 kD protein and proton pumps that may be involved in the acidification of the extracellular resorbing compartment. The basolateral membrane is highly enriched in carbonic anhydrase, and bicarbonate-chloride exchange appears to regulate the intracellular pH of this cell. These observations are consistent with a scheme in which, in the low pH environment of the bone-resorbing lacuna produced by the osteoclast, the mineral phase dissolves, exposing the organic matrix to the action of the secreted enzymes. The activity of these enzymes is in turn presumably favored by the acidic milieu. All constituents of the matrix, whether mineral or organic, then would be reduced to their elemental forms (ions and amino acids) extracellularly.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Marchiafava-Bignami disease with recovery diagnosed by CT and MRI: demyelination affects several CNS structures.

Marchiafava-Bignami disease (MBD) is a rare complication of chronic alcoholism. Most reported cases have been diagnosed at autopsy. With CT and, especially, MRI it is possible to diagnose MBD in its early stages. Lesions of CNS structures other than the typical demyelination of the corpus callosum are described ante mortem in a patient with MBD. The more frequent use of CT and MRI in sudden onset encephalopathies of alcoholics could reveal the real incidence of MBD, and the consequent detection of other involved CNS systems might improve our knowledge about the aetiology, pathogenesis, prognosis and therapy of MBD.

Alcoholism↗

Identification of a 185-kDa band 3-related polypeptide in oxyntic cells.

Polyclonal antibodies to the purified mouse erythrocyte anion exchange protein (band 3) and to a conserved COOH-terminal peptide of mouse band 3 (alpha-Ct) recognized a single major 185-kDa polypeptide in immunoblots of a membrane fraction prepared from rabbit gastric glands. Competition studies revealed that the epitopes shared between the rabbit gastric 185-kDa antigen and the approximately 100-kDa mouse erythrocyte band 3 protein are restricted to the COOH-terminal domain of band 3, which is known to contain the catalytic site for anion exchange activity. Immunofluorescence microscopy was used to demonstrate that this band 3-related polypeptide is associated with the plasma membrane in a subpopulation of gastric gland cells composed exclusively of oxyntic cells, as judged by the coincidence of immunofluorescence with alpha-Ct and with a monoclonal antibody to the gastric H+-K+-ATPase. This alpha-Ct-reactive antigen was further localized to the cytoplasmic face of the basolateral membrane of oxyntic cells, which correlates well with the physiologically determined site of anion exchange activity. These data demonstrate the presence in gastric oxyntic cells of a novel member of the family of proteins related to the erythrocyte anion exchanger. The possibility that the 185-kDa polypeptide is an anion exchanger is discussed.

Adenosine Triphosphatases↗

Polarity and membrane transport in osteoclasts.

The osteoclast is a highly polarized non-epithelial cell. The apical pole of the cell is determined by the cell's attachment to the extracellular matrix. This attachment forms the sealing zone, delimiting the subosteoclastic bone resorbing compartment. The apical membrane of the cell forms the ruffled-border, which contains some specific membrane proteins and a proton pump ATPase, which acidifies the apical compartment. Newly synthesized lysosomal enzymes are vectorially transported into this apical compartment bound to mannose-6-phosphate receptors. The basolateral membrane is highly enriched in sodium pumps with beta and alpha 1 subunits. Associated with the acidification process is the carbonic anhydrase found in the cytoplasm and membrane-associated and a bicarbonate-chloride exchanger in the membrane.2 These features put the osteoclast in the same functional category as the kidney tubule intercalated cell and the gastric oxyntic cell, both of epithelial origin, which secrete acid in a polarized fashion.

Animals↗

Hypercalciuric hypophosphatemic rickets, mineral balance, bone histomorphometry, and therapeutic implications of hypercalciuria.

A 14-year-old Turkish boy had severe rickets that had been clinically evident since he was 2 years of age. When he was 5 years of age, he had normal serum calcium and phosphorus levels and increased alkaline phosphatase activity. Treatment with modest dosages of vitamin D (5000 U/d for 3 weeks) resulted in hypercalcemia. At 10 years of age, high-dose vitamin D (40,000 U/d) plus phosphorus (1.1 g/d) therapy for 20 days resulted in symptomatic nephrolithiasis. When, 14 years of age, he had normocalcemia, hypophosphatemia, increased alkaline phosphatase activity, and normal circulating parathyroid hormone concentration. Levels of 25-hydroxyvitamin D were normal but those of 1,25-dihydroxyvitamin D were markedly increased. Rickets and osteopenia were evident on radiographs, and osteomalacia was present on trabecular bone obtained at biopsy. Balance study results showed increased intestinal absorption of calcium and phosphorus, hypercalciuria, and increased urinary phosphorus excretion. This patient manifests an unusual form of hypophosphatemic rickets in which hypercalciuria is a cardinal feature. In contrast with most varieties of hypophosphatemia, this disorder is characterized by appropriately increased production of 1,25-dihydroxyvitamin D in response to hypophosphatemia. It is recommended that urinary calcium excretion be assessed in all patients with hypophosphatemic rickets so that appropriate therapy will be instituted.

Adolescent↗

A 115-kD polypeptide immunologically related to erythrocyte band 3 is present in Golgi membranes.

Band 3 multigene family consists of several distinct but structurally related polypeptides which are probably involved in the transport of anions across the plasma membrane of both erythrocytes and nonerythroid cells. A novel member of this family of polypeptides that resides in the Golgi complex was identified with antibodies to Band 3. The Golgi antigen had a larger molecular size and was antigenically distinct from Band 3 in the amino-terminal domain. It was expressed most prominently in cells that secrete large amounts of sulfated proteins and proteoglycans. This polypeptide may participate in sulfate transport across Golgi membranes.

Animals↗

Sympathetic and afferent neurons projecting in the splenic nerve of the cat.

Afferent and sympathetic postganglionic nerve cell bodies projecting in the splenic nerve of the cat have been labeled retrogradely with horseradish peroxidase (HRP) in order to study numbers and locations of these neurons. Labeled somata were found bilaterally in dorsal root and sympathetic paravertebral ganglia T3-L2 with a maximum in T10-T13 and in the coeliac superior mesenteric ganglion complex. About 13,200 neurons project into the splenic nerve of the cat, 12,550 being postganglionic and 650 afferent. About 98% of the postganglionic neurons were located in prevertebral and 2% in paravertebral sympathetic ganglia. About 73% of the afferent and 66% of the postganglionic paravertebral neurons were located on the left side. The density of the splenic innervation is about 3-4 times higher than that of the kidneys when normalized to the weight of both organs. It is discussed whether the afferent and sympathetic innervation of the spleen is not only involved in cardiovascular functions but also in regulation of the immune response of this organ.

Afferent Pathways↗

Sympathetic and afferent somata projecting in hindlimb nerves and the anatomical organization of the lumbar sympathetic nervous system of the rat.

The anatomy of the sympathetic pathways from the spinal cord to the lumbar sympathetic trunk and the inferior mesenteric ganglion was studied systematically in the rat. Details of the arrangements of white and gray rami communicantes, sympathetic trunk ganglia, the intermesenteric nerve, and the lumbar splanchnic nerves are summarized. A modified nomenclature for the segmental ganglia of the paravertebral sympathetic chain is proposed. Cell bodies of sensory and sympathetic axons projecting to the skin and skeletal muscle of the rat hindlimb were labeled retrogradely with horseradish peroxidase (HRP) in order to study numbers, segmental distribution, and location of the somata of these neurons quantitatively. HRP was applied to the nerves supplying skeletal muscle (gastrocnemius-soleus, GS), hairy skin (sural, SU; saphenous, SA) and to a mixed nerve (tibial, TI). All sensory somata and 96.4% of the sympathetic cell bodies were located ipsilaterally. Sensory somata were commonly restricted to two adjacent dorsal root ganglia (usually L3-4 for SA; L4-5 for GS, TI; L5-6 for SU). Although the sympathetic somata were more widely distributed rostrocaudally (four to six segments), their maximum was always located one or two segments more cranially than the sensory outflow, i.e., corresponding to the rami communicantes grisei. From the data, it is estimated that 420 sympathetic and 530 afferent neurons project into GS, 590 and 3,610 into SU, 920 and 3,750 into SA, and 1,070 and 5,760 into TI. These absolute neuron numbers are compared with electron microscopic fiber counts from the literature.

Adrenergic Fibers↗

[Principles and general practice of a goal-oriented training plan for diabetic patients participating in sports].

Due to a well known experience physical work in patients with diabetes mellitus II is a very important part of the therapy beside diet and medicament treatment. To guarantee a high training efficiency an individual training regimen has to be worked out for the patient. To influence the impaired glucose metabolism the endurance exercise should be carried out at an intensity near the anaerobic threshold. Therefore it is necessary to have a stepwise incremental exercise test including lactate determination after each work load of the patient. Basing on exercise test this paper is designed to give an example of a training regimen in various sport activities (bicycle, running, ski cross country running, swimming) which enables the physician to handle his diabetic patient with an stepwise increasing training program to an optimal training intensity.

Blood Glucose↗

Bone resorption by isolated chick osteoclasts in culture is stimulated by murine spleen cell supernatant fluids (osteoclast-activating factor) and inhibited by calcitonin and prostaglandin E2.

The question of whether any of the agents known to activate bone resorption in vivo or in organ cultures acts directly on the osteoclast or via intermediate target cells that secondarily secrete locally paracrine factors is important for our understanding of bone remodeling. In an attempt to clarify this issue for some of the agents, we have taken advantage of the recent progress in obtaining and culturing relatively pure populations of osteoclasts. We performed an in vitro bone-resorbing assay in which isolated and partially purified chick osteoclasts were cultured on devitalized, paired and standardized bone disks prepared from rat calvaria prelabeled with both 45Ca and 3H-proline. Some of the isolated osteoclasts attached to the devitalized bone matrix, formed a ruffled border, and acidified the bone-resorbing compartment that they established with the matrix, thereby indicating that they resorbed bone in a physiologic manner. Salmon calcitonin added to these cultures (0.3 U/ml = 60 ng/ml) and prostaglandin E2 (PGE2) (10(-6) M) inhibited both basal and stimulated 45Ca and 3H-proline release. Neither parathyroid hormone (PTH) 1-34 (1 U/ml), 1,25-(OH)2-D3 (10(-8) and 10(-9) M), nor interleukin 1 (IL-1) (purified from P388D1 macrophage culture supernatant fluids or recombinant murine IL-1-alpha) (100 ng/ml) stimulated bone resorption in these cultures. In contrast, supernatant fluids from concanavalin A (Con-A)-activated murine spleen cell cultures (murine osteoclast-activating factor; OAF) consistently and significantly induced a 3- to 5-fold stimulation of bone resorption in this system.

Animals↗

Malignant osteoporosis and defective immunoregulation.

The linkage between immune cells and the osteoclast has become partially understood in the laboratory, but the full spectrum of clinical disorders of this relationship remain to be elucidated. We report a 29-month-old girl with recurrent infections and multiple fractures. Immune evaluation showed normal quantitative serum immunoglobulins but absent antibodies to the respiratory viruses and tetanus toxoid and decreased in vitro polyclonal-induced immunoglobulin production. Further analysis in vitro with separated lymphocyte populations showed normal B cell function but markedly increased suppressor T cell activity. The bone evaluation showed diffuse osteopenia on x-ray. Serum calcium, phosphorus, PTH, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal for age. Urinary calcium excretion (24 h) was, however, two times normal. An iliac crest biopsy confirmed the presence of extreme osteopenia with normal mineralization and numerous small atypical osteoclasts resorbing the bone. No circulating plasma resorptive activity was demonstrated. Calcitonin therapy markedly diminished the patient's hypercalciuria. We speculate that this patient's increased bone resorption, decreased bone formation, and suppressor activity may be linked by a common pathway involving the abnormal function of immune cells. Since no similar constellation of findings has been previously reported, this case may represent a new congenital disorder: severe osteopenia associated with increased osteoclast activity in association with a defect in T cell immunoregulation.

Biopsy↗

Neurons projecting rostrally in the hypogastric nerve of the cat.

Afferent, pre- and postganglionic nerve cell bodies projecting rostrally in the hypogastric nerve have been labelled retrogradely with horseradish peroxidase, in order to study number and location of these neurons. Labelled somata were found in the ganglia of the pelvic plexus, in sacral spinal ganglia and in the sacral spinal cord. They were located mainly ipsilateral with a maximum of afferent and preganglionic neurons at the segmental level S2. The numbers of labelled cells were small (less than 3.5% of all axons in the hypogastric nerve) and varied considerably between animals. Therefore this population of neurons is probably small and of limited functional significance. Enteric neurons (probably afferent) that have their cell bodies within the pelvic viscera and project rostrally in the hypogastric nerve to the inferior mesenteric ganglion were not included in this study and might be of more functional importance.

Afferent Pathways↗

Polarized secretion of lysosomal enzymes: co-distribution of cation-independent mannose-6-phosphate receptors and lysosomal enzymes along the osteoclast exocytic pathway.

The osteoclast is a polarized cell which secretes large amounts of newly synthesized lysosomal enzymes into an apical extracellular lacuna where bone resorption takes place. Using immunocytochemical techniques, we have localized the cation-independent mannose-6-phosphate (Man6P) receptor and lysosomal enzymes in this cell type in order to determine the expression and distribution of this receptor and its ligands. The results demonstrate that the osteoclast expresses large amounts of immunoreactive cation-independent Man6P receptors, despite the fact that most of the lysosomal enzymes it synthesizes are secreted. The lysosomal enzymes and the receptors are co-distributed along the exocytic pathway, i.e., the endoplasmic reticulum, including the perinuclear envelope, the Golgi stacks as well as numerous small transport vesicles that appear to fuse with the ruffled border membrane. Within the Golgi complex, the receptors and lysosomal enzymes were found distributed in two predominant patterns; (a) in all the cisternae, from cis to trans, or (b) predominantly in cis- and trans-Golgi cisternae, with the middle Golgi cisternae being unstained or depleted in antigen. This pattern suggests that enzymes and receptors traverse the Golgi from cis to trans and preferentially accumulate in cis- and in trans-cisternae. This study therefore suggests that, in the osteoclast, Man6P receptors are involved in the vectorial transport and targeting of newly synthesized lysosomal enzymes, presumably via a constitutive pathway, to the apical membrane where they are secreted into the bone-resorbing compartment. This mechanism could insure polarized secretion of lysosomal enzymes into the bone-resorbing lacuna.

Animals↗