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Biomedical subjects

J Baron

Publications and source records attributed to J Baron.

At least 37 records · Page 2Linked to original sources
PubMed2000

Retinoic acid is a potent regulator of growth plate chondrogenesis.

Vitamin A deficiency and excess both cause abnormalities in mammalian longitudinal bone growth. Because all-trans retinoic acid (RA) is synthesized from vitamin A, we hypothesized that RA regulates growth plate chondrogenesis. Consistent with this hypothesis, a single oral dose of RA reduced the height of the rat proximal tibial growth plate. To determine whether RA acts directly on growth plate, fetal rat metatarsal bones were cultured in the presence of RA. In this system, RA inhibited longitudinal bone growth by three mechanisms: 1) decreased chondrocyte proliferation, (assessed by 3H-thymidine incorporation), particularly in the proliferative zone of the growth plate; 2) decreased matrix synthesis (assessed by 35SO4 incorporation into glycosaminoglycans); and 3) decreased cell hypertrophy (determined histologically). The growth-inhibiting effects of RA were completely reversed by a retinoic acid receptor (RAR) antagonist. In the absence of exogenous RA, this antagonist accelerated bone growth, as did an RA-specific neutralizing antibody, suggesting that endogenous RA negatively regulates growth plate chondrogenesis. We conclude that RA, acting through RARs, negatively regulates longitudinal bone growth by inhibiting growth plate chondrocyte proliferation, chondrocyte hypertrophy, and matrix synthesis.

Alkaline Phosphatase↗
PubMed2000

Suppression and recovery of GH secretion after GH injection in non-GH deficient short children.

OBJECTIVE: To identify the effect of exogenous GH on endogenous GH secretion in 48 non-GH deficient short children participating in a placebo-controlled trial of GH therapy on final adult height. DESIGN: Night GH secretion (mean of levels every 20 min from 20.00 to 08.00 h) was evaluated at baseline, 6 months before starting placebo or GH (somatotropin, 0.222 mg/kg/ week, divided into 3 doses each week). At 6 months after starting injections, blood samples for GH were obtained hourly for 24 h after an injection, and every 20 min on each of the next two nights (with no additional placebo or GH injection). RESULTS: IGF-I levels in the treatment group were elevated at 12 and 24 h but not at 36 h compared to the placebo group. Mean GH levels in the placebo group did not vary significantly among the four sampling periods. In the treatment group, the mean serum GH rose to a supraphysiological peak at an average time of 4 h after injection. Subsequently, mean GH level was significantly suppressed compared to placebo on the second night following GH injection, but returned to normal by the third night. CONCLUSION: After 6 months of a thrice weekly GH treatment regimen in non-GH deficient short children, endogenous GH secretion was reduced from 24 to 36 h after injection compared to placebo and returned to control levels by 48 to 60 h after injection.

Child↗
PubMed2000

[Extravasation injuries and subcutaneous aspiration in children].

Complications of extravasation of intravenous fluid are not rare in pediatric practice, and their local (skin necrosis) and regional (vasculo nervous) implications can be severe. Two cases are presented in order to discuss the different treatments options and to describe the subcutaneous aspiration technique, which can be immediately efficient if proposed in a short delay.

Female↗
PubMed2000

Topographical projection from the superior colliculus to the nucleus of the brachium of the inferior colliculus in the ferret: convergence of visual and auditory information.

The normal maturation of the auditory space map in the deeper layers of the ferret superior colliculus (SC) depends on signals provided by the superficial visual layers, but it is unknown where or how these signals influence the developing auditory responses. Here we report that tracer injections in the superficial layers label axons with en passant and terminal boutons, both in the deeper layers of the SC and in their primary source of auditory input, the nucleus of the brachium of the inferior colliculus (nBIC). Electron microscopy confirmed that biocytin-labelled SC axons form axodendritic synapses on nBIC neurons. Injections of biotinylated dextran amine in the nBIC resulted in anterograde labelling in the deeper layers of the SC, as well as retrogradely labelled superficial and deep SC neurons, whose distribution varied systematically with the rostrocaudal placement of the injection sites in the nBIC. Topographical order in the projection from the SC to the ipsilateral nBIC was confirmed using fluorescent microspheres. We demonstrated the existence of functional SC-nBIC connections by making whole-cell current-clamp recordings from young ferret slices. Both monosynaptic and polysynaptic EPSPs were generated by electrical stimulation of either the superficial or deep SC layers. In addition to unimodal auditory units, both visual and bimodal visual-auditory units were recorded in the nBIC in vivo and their incidence was higher in juvenile ferrets than in adults. The SC-nBIC circuit provides a potential means by which visual and other sensory or premotor signals may be delivered to the nBIC to calibrate the representation of auditory space.

Aging↗
PubMed1999

Protected Values and Omission Bias.

Protected values (PVs) are those that people think should not be traded off. Baron and Spranca (1997) proposed that such values result from rules concerning actions (as opposed to values for outcomes). This proposal implies that PVs should show a particularly large bias against harmful acts that undermine the value in question, as opposed to harmful omissions (omission bias). We found this correlation between PVs and omission bias in 3 experiments, using stimuli of the sort that we used before to demonstrate omission bias. In 2 experiments, we also found a weak tendency for PVs to be associated with lack of concern for the number of acts involved, which is analogous to earlier results showing an association with lack of concern for the quantity of outcomes. Finally, 1 experiment showed that some people are willing to sacrifice values to prevent losses more than they are willing to sacrifice these values for gains. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Control of Bone Growth by Fibroblast Growth Factors.

Fibroblast growth factors (FGFs) and their receptors (FGFRs) negatively regulate longitudinal bone growth. Activating FGFR3 mutations impair growth, causing human skeletal dysplasias, whereas inactivating mutations stimulate growth. Systemic administration of FGF-2 to mice stimulates bone growth at low doses but inhibits growth at high doses. In organ culture, FGF-2 inhibits growth by decreasing growth plate chondrocyte proliferation, hypertrophy and cartilage matrix synthesis. Local FGF-2 infusion accelerates ossification of growth plate cartilage. Thus, FGFs may regulate both growth plate chondrogenesis and ossification.

Journal Article↗
PubMed1999

Continuing medical education for life: eight principles.

Continuing medical education (CME) is being pressured to change in response to increasing and changing educational needs of practicing physicians, fostered by technical innovations, evolution of practice styles, and the reorganization of health care delivery. Leadership in the reform of CME falls primarily to the medical specialty societies in light of their traditional responsibilities for accrediting CME and maintaining professional standards. To address the need for reform, the American College of Obstetricians and Gynecologists in 1997 organized a conference to assemble CME program administrators from several medical specialties and academicians with expertise in postgraduate learning. At the conference, issues facing CME were examined. The authors, who were conference participants, state and explain eight principles that emerged from conference discussions. (For example: "Educational activities should be supportive of and coordinated with the transition to evidence-based medicine.") The principles reflect the interspecialty and interdisciplinary consensus achieved by the conference participants and can serve as useful guideposts for educators as they work to improve CME in their institutions. The authors conclude by noting the need for a more systematic and rigorously analytic approach, where CME content is determined according to assessed needs and CME is evaluated by measuring outcomes; for this to happen, CME educators and faculty must be brought up to date through training, including the use of problem-based learning. CME must also instill collegiality, interaction, and collaboration into the learning environment instead of being a solitary learning activity. Finally, CME must not only emphasize the acquisition of knowledge but also instruct physicians in the process of decision making to help them better use their knowledge as they make clinical judgments.

Clinical Competence↗
PubMed1999

Safety of perioperative subcutaneous heparin for prophylaxis of venous thromboembolism in patients undergoing craniotomy.

OBJECTIVE: To determine whether perioperative subcutaneous heparin is safe to use for patients undergoing craniotomy and to determine the incidence of venous thromboembolism in patients undergoing craniotomy. METHODS: Perioperative prophylaxis with subcutaneous heparin, 5000 U every 12 hours, was begun at induction of anesthesia for craniotomy and continued for 7 days postoperatively or until the patient was ambulating. Entry criteria to the study included patient age over 18 years and no evidence of deep vein thrombosis (DVT) preoperatively as judged by lower limb duplex ultrasound. Patients were excluded if they had duplex evidence of DVT or clinical evidence of pulmonary embolus (PE) preoperatively, had hypersensitivity to heparin or related products, had sustained a penetrating head injury, or refused informed consent. Any patient undergoing craniotomy was eligible, including patients with a ruptured aneurysm or arteriovenous malformation and those with spontaneous intracranial hemorrhage. Patients underwent duplex study 1 week after surgery and 1 month of clinical follow-up. Records were also kept on 68 nonstudy patients who refused consent. All patients were treated with lower limb pneumatic compression devices. RESULTS: One hundred six patients were treated. No differences were noted between study and nonstudy patients in some individual risk factors for DVT or PE, such as obesity, smoking, paralysis, infection, pregnancy or postpartum state, varicose veins, heart failure, or previous DVT or PE. Significantly more (43 of 106) patients in the study group had a history of risk factors for DVT or PE, particularly malignancy, however, compared with nonstudy patients (20 of 68 patients; chi2, P < 0.01). There were no differences between groups in intraoperative blood loss, transfusion requirements, or postoperative platelet counts. Four clinically significant hemorrhages occurred during surgery in patients receiving heparin. Three resulted from intraoperative aneurysm rupture and one from intraventricular bleeding during resection of an arteriovenous malformation. These events were believed to be related to known complications of these operations, not to heparin. Of the study patients, two developed symptomatic DVT and one developed a nonfatal PE during the 1-month postoperative period. One additional study patient developed DVT below the popliteal veins, which was not treated. Four study patients developed DVT 1 to 2 months after surgery. In nonstudy patients, three developed DVT and two developed PE (one fatal, one nonfatal). CONCLUSION: Perioperative heparin may be safe to administer to patients undergoing craniotomy, but a larger study is needed to demonstrate efficacy.

Adult↗
PubMed1999

The colonoscopic miss rate and true one-year recurrence of colorectal neoplastic polyps. Polyp Prevention Study Group.

OBJECTIVE: Studies of tandem colonoscopies have reported that 15-25% of neoplastic polyps <1 cm in size and 0-6% of larger polyps are overlooked at the time of colonoscopy. We determined the miss rate and "true" 1-yr recurrence of neoplastic polyps in a population of patients reflecting a broad spectrum of different gastroenterology practice settings. METHODS: Patient data from several sources were examined for repeat colonoscopies performed on the same patient within 120 days of each other. Examination pairs were included for analysis if both colonoscopies had good preps and reached the cecum. The miss rate was calculated by two methods: 1) a pooled rate, the total number of polyps on all second examinations divided by the total number on both examinations, and 2) a within-person rate, the average of the individual miss-rates. We estimated a "true" 1-yr recurrence rate by subtracting the proportion of patients with a missed neoplastic polyp from the proportion of patients with a neoplastic polyp found at 1 yr. RESULTS: A total of 76 colonoscopy pairs a mean 47 days apart (range, 1-119 days) were identified from a total of approximately 15,000 examinations and used to calculate the overall miss rates. For the category "all polyps" (neoplastic and nonneoplastic polyps), 17% by the pooled method and 11% by the within-person method were missed. The corresponding rates for neoplastic polyps were 12% by the pooled method and 8% by the within-person method. A total of 17% of patients had one or more neoplastic polyps missed on the initial examination. The observed 1-yr recurrence rate was determined from 1,314 colonoscopy pairs performed a mean of 379 days apart and found to be 28% for neoplastic polyps. By comparing this to the proportion of patients with one or more missed neoplastic polyps, we found the true 1-yr recurrence of neoplastic polyps to be 11%. CONCLUSION: There is a significant colonoscopic miss rate for neoplastic polyps and "all polyps" in clinical practice that is comparable to that previously stated in special research settings. The within-person rate more accurately reflects the true colorectal polyp miss rate for any given colonoscopic exam than does the pooled rate. The difference between the observed 1-yr recurrence rate and the proportion of patients with a missed polyp represents the true 1-yr recurrence of neoplastic polyps.

Adenomatous Polyps↗
PubMed1999

Determinants of spatial polarity in the growth plate.

Growth of long bones occurs at the growth plate, a layer of cartilage that separates the epiphysis from the metaphysis. Growth plate exhibits spatial polarity. Proliferative chondrocytes undergo terminal differentiation when they approach the metaphyseal, but not the epiphyseal, border of the growth plate. The adjacent bone also exhibits spatial polarity. Metaphyseal, but not epiphyseal, blood vessels and bone cells invade the adjacent growth plate, remodeling it into bone. As a result, the metaphysis, but not the epiphysis, elongates over time. To determine whether cartilage polarity determines bone polarity and/or whether bone polarity determines cartilage polarity, rabbit distal ulnar growth plates were excised, inverted, and reimplanted in their original beds. Thus, cartilage polarity was inverted relative to bone polarity. Histological examination showed that the inverted cartilage polarity was maintained over time. In contrast, the polarity of the adjacent bone reversed after surgery, to match that of the cartilage. Blood vessel and bone cell invasion ceased in the metaphysis and arose in the epiphysis. Longitudinal bone growth (measured with weekly radiographs) occurred at the epiphyseal, not at the metaphyseal, surface of the growth plate. We conclude that the polarity of growth plate cartilage is determined by intrinsic factors. The cartilage polarity then determines the polarity of the adjacent bone and, consequently, the functional polarity of longitudinal bone growth.

Animals↗
PubMed1999

Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis.

Familial hypoparathyroidism is an unusual and genetically heterogeneous group of disorders that may be isolated or may be associated with congenital or acquired abnormalities in other organs or glands. We have evaluated a family with a novel syndrome of autosomal dominant hypoparathyroidism, short stature, and premature osteoarthritis. A 74-yr-old female (generation I) presented with hypoparathyroidism, a movement disorder secondary to ectopic calcification of the cerebellum and basal ganglia, and a history of knee and hip replacements for osteoarthritis. Two members of generation II and one member of generation III were also documented with hypoparathyroidism, short stature, and premature osteoarthritis evident as early as 11 yr. Because of the known association between autosomal dominant hypoparathyroidism and activating mutations of the calcium-sensing receptor (CaR) gene, further studies were performed. Sequencing of PCR-amplified genomic DNA revealed a leucine to valine substitution at position 616 in the first transmembrane domain of the CaR, which cosegregated with the disorder. However, this amino acid sequence change did not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected HEK-293 cells. In conclusion, a sequence alteration in the coding region of the CaR gene was identified, but is not conclusively involved in the etiology of this novel syndrome. The cosegregation of hypoparathyroidism, short stature, and osteoarthritis in this kindred does suggest a genetic abnormality involving a common molecular mechanism in parathyroid, bone, and cartilage.

Adolescent↗
PubMed1999

[Chosen function of peripheral blood neutrophils in workers operating X-ray equipment].

Examinations were carried out in 44 persons (29 women and 15 men) who operated X-ray equipment in radiology departments. Neutrophil adherence and spontaneous migration of leukocytes were estimated in this group. Investigations' results were compared with the results in the control group. In the group of employees who operated X-ray units, the examinations were additionally performed taking sex into consideration. In the persons employed in radiology departments statistically significant reduction of neutrophil adherence was shown, which especially in the subgroup of men was observed. Statistically significant reduction of spontaneous migration area of leukocytes was revealed and it concerned both the subgroup of men and subgroup of women. On the basis of the obtained results the following conclusions were drawn: leukocyte spontaneous migration estimated in three-hour test decreases in employees who operated X-ray units; it may be used as the estimation test of influence of the X-ray on employees operating X-ray equipment when the routine tests are in the normal range.

Adult↗
PubMed1998

Body size in different periods of life and breast cancer risk in post-menopausal women.

Adult obesity has been associated with an increased risk of post-menopausal breast cancer, but it is unclear whether this relationship reflects a causal role of obesity during childhood and adolescence, of weight gain during adult life or of adult obesity per se. In a population-based case-control study in all of Sweden, we included 3,345 (84% of all eligible) women aged 50-74 years with invasive breast cancer, and 3,454 (82% of all selected) controls of similar age. Mailed questionnaires and telephone interviews were used to collect detailed information on anthropometric measures. Odds ratios were estimated through multiple logistic regression. Women with the leanest somatotype at age 7 had about a 3-fold higher risk of breast cancer than the most obese (P for trend 0.0009). A suggested protective effect of a high body mass at age 18 and a detrimental influence of body mass 1 year prior to data collection largely reflected the effect of weight gain after age 18, a strong predictor of breast cancer risk. Among women at least 20 years post menopause, those who had gained 30 kg or more since age 18 had an odds ratio of 2.04 (95% confidence interval 1.20-3.48) of breast cancer compared with those who had maintained their weight unchanged. The effect of weight gain was unequivocal among non-users but not among users of hormone replacement therapy. Our findings have important implications, suggesting weight preservation as a means for prevention of post-menopausal breast cancer as well as a causal role of childhood body build in breast cancer etiology.

Age Factors↗
PubMed1998

Immunohistochemical demonstration of beta-naphthoflavone-inducible cytochrome P450 1A1/1A2 in rat intrahepatic biliary epithelial cells.

Although intrahepatic biliary epithelial cells are targets for certain hepatotoxic chemicals, including some procarcinogens, their ability to monooxygenate, and thereby bioactivate and inactivate xenobiotics, remains to be established. Thus, the present study was undertaken to immunohistochemically determine if cytochrome P450 (CYP) 1A1/1A2 is present and can be induced within these nonparenchymal liver cells. Immunoperoxidase and immunofluorescent staining for CYP1A1/1A2 was detected within intrahepatic biliary epithelial cells as well as hepatocytes of control rats and was markedly enhanced in both cell types by beta-naphthoflavone (BNF). Color confocal laser microscopic analyses of dual immunofluorescent staining for CYP1A1/1A2 and cytokeratins 6 and 9 (56 and 64 kd, respectively) provided unequivocal evidence for the presence and induction of CYP1A1/1A2 within intrahepatic bile duct epithelia. Moreover, microdensitometric analyses of immunoperoxidase staining intensities for CYP1A1/1A2 revealed that intrahepatic biliary epithelial cells of control rats contain 44%, 56%, and 58% as much CYP1A1/1A2 as do centrilobular, midzonal, and periportal hepatocytes, respectively. These analyses further revealed that BNF increased the content of CYP1A1/1A2 in biliary epithelial cells by approximately 120%, while CYP1A1/1A2 levels in centrilobular, midzonal, and periportal hepatocytes were increased by 82%, 159%, and 160%, respectively. The results of this study represent the first in situ demonstration that mammalian intrahepatic biliary epithelial cells contain a CYP isoform, and further that CYP1A1/1A2 can be induced in these cells by BNF. These findings therefore indicate that intrahepatic biliary epithelial cells can oxidatively metabolize xenobiotics in situ and that their ability to bioactivate and inactivate xenobiotics can be significantly enhanced by CYP1A1/1A2 induction.

Animals↗
PubMed1998

Activating mutations of the Ca2+-sensing receptor.

The Ca2+-sensing receptor (CaR) is a member of the seven-transmembrane domain, G-protein-coupled receptor superfamily. It is expressed in parathyroid, kidney, and other tissues. In parathyroid, activation of the CaR by extracellular Ca2+ negatively regulates the secretion of parathyroid hormone. In the the thick ascending limb of Henle's loop, receptor activation decreases renal reabsorption of Ca2+. Heterozygous inactivating mutations of the CaR cause familial benign hypocalciuric hypercalcemia while homozygous inactivating mutations cause neonatal severe hyperparathyroidism. Conversely, activating mutations of the CaR cause autosomal dominant and sporadic hypoparathyroidism. Affected individuals have hypocalcemia which ranges from mild and asymptomatic to life-threatening. They also show a greater tendency to hypercalciuria than do other patients with hypoparathyroidism. Most, but not all, of the reported activating mutations occur in the amino-terminal, extracellular domain of the receptor. When expressed in cultured cells, mutant receptors can show both increased receptor sensitivity to Ca2+ and increased maximal signal transduction capacity.

Calcium↗
PubMed1998

Generation and subcellular distribution of histamine in human blood monocytes and monocyte subsets.

OBJECTIVE AND DESIGN: This study was designed to establish the sites of formation and storage of histamine and histidine decarboxylase (HDC) in human monocytes and two of their subsets. MATERIALS AND METHODS: The experiments were carried out using monocytes from buffy coats of healthy blood donors. Histamine was quantitated by RIA, HDC activity by the formation of histamine. RESULTS: The monocyte subtype RM3/1 contained significantly more histamine than the subset 27E10 (0.041+/-0.025 vs. 0.005+/-0.004 pg/cell, p < 0.05) and also more HDC activity and HDC mRNA. After fractionation of monocyte homogenates in a discontinuous Percoll gradient or by differential centrifugation more than 80% of both, HDC activity and histamine, were recovered from the cytosolic fractions. About 50% of this histamine was found to be bound to proteins. CONCLUSIONS: In monocytes histamine and HDC are colocalized in the cytoplasm indicating a subcellular distribution different from mast cells or basophils. The data also show that histamine is synthesized by the monocytes themselves.

Cell Fractionation↗