Search PubMed⌕ Search

Biomedical subjects

M Blum

Publications and source records attributed to M Blum.

At least 379 records · Page 21Linked to original sources
PubMedDate not supplied

Theodor Leber: a founder of ophthalmic research.

Theodor Leber became famous for his dissertation on the ocular circulation in 1865 at the youthful age of twenty-five. He was Professor of Ophthalmology at Goettingen between 1870 and 1890 and at Heidelberg University between 1890 and 1910. By presenting his original descriptions of the disorders that bear his name, this article commemorates the death, seventy-five years ago, of a founder of ophthalmic research.

Blindness↗
PubMedDate not supplied

GDNF mRNA expression in normal postnatal development, aging, and in Weaver mutant mice.

Glial cell line-derived neurotrophic factor (GDNF) has been demonstrated to enhance the survival and process outgrowth of mesencephalic dopamine neurons. A nuclease protection assay was utilized to determine whether GDNF mRNA is expressed in the ventral mesencephalon and/or striatum during normal mouse postnatal development. While no GDNF mRNA was detected in the ventral mesencephalon, expression was detected in the striatum throughout postnatal development and maturity with the peak of expression being in the second postnatal week. In the process of normal aging, no change in the levels of GDNF mRNA was observed in the striatum, while a 10-fold increase in glial fibrillary acid protein (GFAP) mRNA was detected in 24-month-old relative to either 4.5- or 11-month-old mice. Further analysis addressed whether there are changes in GDNF gene expression associated with the neurodegeneration of dopamine neurons that occurs in the weaver mutant mouse. A transient 65% increase in the expression of GDNF mRNA was observed in weaver mutant striatum on postnatal day 22. The results of this study suggest that GDNF could provide target derived of dopaminergic neurotrophic support and stimulate fiber outgrowth during development and that decreased levels of GDNF expression are not responsible for either aging-associated decreases in dopaminergic neuronal plasticity or neurodegeneration in the weaver mutant mouse.

Age Distribution↗
PubMedDate not supplied

Age-related changes of the ciliary sulcus: implications for implanting sulcus-fixated lenses.

PURPOSE: To examine age-related anatomical changes of the ciliary sulcus and the implication of these changes for placement of posterior chamber intraocular lenses (IOLs). SETTING: Department of Ophthalmology, University of Heidelberg, Germany. METHODS: In this study, 64 human autopsy eyes from 38 donors were divided by age into six groups from younger than 40 years (Group 1) to 80 years and older (Group 6) in 10 year increments. External diameter, capsular bag size, and lens thickness were determined for each eye. The horizontal and vertical diameters of the ciliary sulcus were measured and histological sectioning, staining, and light microscopy performed. RESULTS: The external diameters of the eyes showed no age correlation; the lenses exhibited the expected increase in thickness with age. The mean vertical diameter of the ciliary sulcus decreased in all age groups from 12.02 mm +/- 0.12 (SD) to 10.71 +/- 0.91 mm and the mean horizontal diameter, from 11.36 +/- 0.24 mm to 10.33 +/- 0.76 mm. Statistical analysis confirmed the overall significance (P < .05) of the differences among age groups. CONCLUSION: The ciliary sulcus became smaller with age. This might affect the size of sulcus-implanted IOLs and should be noted for transsclerally sutured IOLs.

Adult↗
PubMedDate not supplied

Two variant surface glycoproteins of Trypanosoma brucei of different sequence classes have similar 6 A resolution X-ray structures.

Antigenic variation in the African trypanosome is mediated through changes in the composition of the surface coat. By controlling expression of the major surface protein, the variant surface glycoprotein (VSG), from a repertoire of perhaps 1,000 different genes the organisms exhibit a series of antigenically distinct coats and evade the host's immune system. We have determined the 6 A resolution structure of a T. brucei variant surface glycoprotein, ILTat 1.24, using X-ray crystallography. The crystallized protein consists of the N-terminal two-thirds of the intact VSG which has a relative molecular mass (Mr) of 60,000 (60K). The structure, which includes a 90 A long alpha-helical bundle, is strikingly similar to that of the N-terminal fragment of VSG MITat 1.2 (ref. 4). Although most known VSG sequences show little similarity of primary sequence in the N-terminal domain, the similarity between the structure of a Class I (ILTat 1.24) and a Class II (MITat 1.2) VSG antigen suggests that VSGs may share a common tertiary structure.

Animals↗
PubMedDate not supplied

Gonadotropin-releasing hormone and chorionic gonadotropin gene expression in human placental development.

Control of human chorionic gonadotropin (hCG) synthesis during pregnancy is poorly understood, although in vitro data suggest a role for placental gonadotropin releasing hormone (GnRH) in its regulation. To study GnRH regulation during placental development, placental tissue of different gestational ages was analyzed for GnRH and beta hCG mRNA content. cRNA probes to exonic/intronic sequences of GnRH and beta hCG transcripts were constructed and used to perform solution hybridization/nuclease protection and in situ hybridization assays. The levels of GnRH mRNA were approximately 0.1-1% of that of beta hCG mRNA, in agreement with its suggested paracrine, rather than endocrine, role. While beta hCG mRNA content decreased significantly from first trimester to term (643 to 21.6 pg/microgram RNA), there was no significant change in GnRH mRNA (0.179 to 0.155 pg/microgram RNA). While beta hCG mRNA was localized almost exclusively in syncytiotrophoblasts, GnRH mRNA was present in all cell types of the placenta, including the stroma. In the course of performing sense-strand controls in the in situ hybridization, we noted that the placenta appeared to express more antisense GnRH than sense GnRH mRNA, again, in all cell types. Solution hybridization/nuclease protection analysis with exon 1 and exon 3 probes confirmed this observation, showing that there is two to three times more antisense GnRH RNA than sense GnRH mRNA. These studies suggest that GnRH gene expression and its role in regulating hCG production in human placenta is complex and does not fit a simple model for paracrine regulation of hCG.

Chorionic Gonadotropin↗
PubMedDate not supplied

The autonomous nodule of the thyroid: correlation of patient age, nodule size and functional status.

In light of new techniques for measuring circulating thyroid hormones and for studying the thyroid gland, we present our experience with 35 patients with solitary autonomous nodules of the thyroid to define more precisely the clinical course of patients with this disorder. The patients ranged in age from 19 to 80 years and 31 of the 35 were female. Younger patients were generally euthyroid and sought attention because of a thyroid mass; virtually all older patients were hyperthyroid. Eighteen had obvious clinical features of hyperthyroidism and 5 over age 70 had apathetic hyperthyroidism; all 5 of the elderly and 13 of the 18 under age 70 had elevated thyroxine (T4) and triiodothyronine (T3) levels. Isolated elevation of T3 and elevated basal metabolic rate were observed in 5 previously untreated clinically hyperthyroid young patients. In each of these, thyroid uptake of 131-I was not suppressible with exogenous T3 and BMR was elevated in those tested. Two elderly patients, who had previously been treated for conventional hyperthyroidism with radioactive iodine, had T3 toxicosis when hypoethyroidism recurred. There was a strong positive correlation between the age of the patient, the size of the nodule and the thyroid functional state. The mean area of the nodules projected on 131-I rectilinear scan for euthyroid patients was 5.1 cm2. The mean area of the nodules in hyperthryoid subjects was significantly higher, 13.4 cm-2 in patients with T3 toxicosis and 19.3 cm-2 in subjects with conventional hyperthyroidism. Progression from a euthyroid state to hyperthyroidism was observed four patients. One of these became thyrotoxic within days after an injection of iodinated contrast medium. Spontaneous resolution of nodules occurred in two patients.

Adenoma↗
PubMedDate not supplied

Clinical implications of the rare thyroid carcinoma which is indistinguishable from a follicular adenoma.

The inadequacy of the standard pathologic criteria for identifying certain well-differentiated thyroid follicular carcinomas from follicular adenomas in rare instances is illustrated by four cases. The excised thyroid nodule in these patients appeared to be adenoma, but subsequent local spread in the neck or distant metastases disclosed the actual malignant nature of the lesions. This observation is not intended as a basis for more extensive operations for adenoma, but rather as an indication for close, long-term observation. Postoperative, lifelong suppressive therapy with thyroid hormone is suggested for all patients with a diagnosis of follicular adenoma.

Adenocarcinoma↗
PubMedDate not supplied

Computerized axial tomography in the diagnosis and management of thyroid and parathyroid disorders.

Computerized axial tomography (CAT) was used to study 39 patients with known thyroid disease and 14 patients with primary hyperparathyroidism. In all, CAT was performed only when information that was required for diagnosis or therapy was not available from other less expensive techniques. The greatest value was found in the evaluation of cryptic symptoms or structures in the neck after surgery for thyroid cancer, the assessment of the extent of thyroid cancer, the localization of aberrant thyroid tissue, the etiology of unexplained recurrent laryngeal nerve paralysis and the identification and delineation of mediastinal goiter. In six of 14 patients undergoing neck exploration for primary hyperparathyroidism CAT correctly localized the site of the enlarged parathyroid glands including one mediastinal parathyroid adenoma and one patient with two parathyroid adenomas.

Adult↗
PubMedDate not supplied

Gender differences in referral to cardiac rehabilitation programs after revascularization.

BACKGROUND: This study examines the influence of gender on the healthcare provider's secondary prevention instruction and cardiac rehabilitation (CR) referral after coronary revascularization procedures such as balloon angioplasty/coronary stenting and coronary bypass surgery (CABG). Cardiac rehabilitation decreases mortality and morbidity, yet only a small percentage of women and men are referred to these programs. The patient population of our university-affiliated CR program consisted of 88% men and 12% women. METHODS: In a matched case observational study, 80 patients (40 men, 40 women) who had undergone coronary revascularization procedures between 1997 and 1998 completed a questionnaire on secondary prevention instruction and written referral to CR programs. Patients were matched for age and coronary revascularization procedure. RESULTS: Women were less likely to be instructed on secondary prevention strategies and CR or referred to CR as compared to men despite being matched for age and undergoing the same procedure. The data demonstrate a gender difference in hospital teaching and referral information for CR after revascularization (P < 0.001). Being a woman was associated with a decreased likelihood of receiving a physician referral to CR after revascularization (P < 0.001). CONCLUSION: The instruction of patients concerning secondary prevention and CR postrevascularization procedures is poor. Within that group, women were far less likely to have CR discussed or referrals made by healthcare professionals. This study demonstrates the need for education initiatives of all healthcare providers on the comprehensive nature and benefits of CR in the secondary prevention of cardiovascular disease, with a particular emphasis on women.

Adult↗
PubMedDate not supplied

Characterization of parvalbumin cDNA clones and gene expression in normal and dystrophic mice of strain 129 ReJ.

Parvalbumin is a calcium-binding protein found in fast-twitch skeletal muscles and selected cells in the brain. In several dystrophic mutants in the mouse, the parvalbumin content of skeletal muscles and brain is reduced and this deficiency appears to correlate with the inability of these mice to handle enhanced calcium uptake associated with the dystrophic process. In this study, two overlapping cDNA clones of 392 and 1268 base pairs were isolated from a mouse cDNA library in lambda gt11, characterized, and used as probes to study the involvement of the parvalbumin gene and its expression in various tissues of dystrophic mice of strain 129 ReJ. Southern blot analyses of restriction fragments of genomic DNA from normal and dystrophic mice indicate the same number and size of parvalbumin-specific gene fragments observed by other researchers, suggesting that the size of the Pva gene is the same in both normal and dystrophic mice of strain 129 ReJ. Northern blot analyses of total RNA from hind-limb muscles using cloned parvalbumin cDNA as probes revealed an abundant 800-nucleotide mRNA with lesser amounts of a 1000-nucleotide mRNA transcript in both normal and dystrophic mice of strain 129 ReJ. The amount of these mRNAs was reduced by 65-77% in dystrophic muscles preparations and was similar to the levels of beta-actin mRNA in these animals. These results suggest that parvalbumin gene expression is not down regulated in dystrophic mice of strain 129 ReJ.

Amino Acid Sequence↗
PubMedDate not supplied

Myogenic response reduction by high blood glucose levels in human retinal arterioles.

PURPOSE: The effect of elevated blood glucose level on the myogenic response of human retinal arterioles to acute increases in blood pressure is investigated. METHODS: The vascular response to raised blood pressure (Bayliss effect) was measured in 12 healthy volunteers by use of the retinal vessel analyzer (RVA). For a 9-minute period an on-line measurement of the diameter of a retinal branch arteriole was performed. After the first 3 minutes (baseline measurement) a second phase with 3 minutes of isometric exercise caused an acute rise in blood pressure, followed by 3 minutes of recovery (phase III). After the first session 100 g glucose were administered per os. After 30 minutes blood glucose was measured again and an identical second session was performed with higher blood glucose levels. The Wilcoxon test was used for statistical analysis. RESULTS: During the first session a rise in mean arterial pressure of 22.8 (+/-8.4) mmHg was followed by an arterial vasoconstriction of -6.6 (+/-1.7) %. The administration of 100 g glucose resulted in a significant rise in blood glucose levels within 30 minutes between the two sessions (4.35 mmol/L vs 7.46 mmol/L) (p=0.002). The blood pressure rise of 25.7 (+/-7.3) mm Hg in the second session was associated with a significant loss in arterial vasoconstriction of -2.3 (+/-1.4) % (session I vs session II p=0.002). CONCLUSIONS: The myogenic response of the arterial wall in human retinal arterioles was significantly reduced during acute rise of blood glucose levels.

Adult↗
PubMedDate not supplied

Polymorphisms of N-acetyltransferase genes.

1. A genetic polymorphism of human liver arylamine N-acetyltransferase (NAT) enzyme activity leads to wide variation in the disposition of many drugs and potential carcinogens, resulting in differential susceptibility to chemical-induced toxicity. 2. During studies to determine the biochemical and molecular mechanisms underlying this pharmacogenetic defect, we cloned two human genes, NAT1 and NAT2, which encode the functional acetylating enzymes NAT1 and NAT2. 3. NAT1 and NAT2 are both expressed in human liver cytosol, the latter as two closely related isoforms NAT2A and NAT2B. 4. NAT2 gene locus is the site of the human acetylation polymorphism, because its products NAT2A and NAT2B selectively acetylate 'polymorphic' arylamine substrates (e.g. sulphamethazine), and since the liver content of these isozymes is markedly reduced in genetically slow acetylator subjects. 5. NAT1 shows marked kinetic selectivity for 'monomorphic' substrates (e.g. p-aminobenzoic acid) whose in vivo acetylation rates do not correlate with the acetylation polymorphism. 6. Despite the drastic reduction in NAT2A/B proteins in livers from phenotypically slow acetylators, levels of the NAT2 gene transcript are not altered. 7. Three common mutant alleles at the NAT2 gene locus have so far been identified, which may be detected by restriction fragment length polymorphism (RFLP) analysis on Southern blots or by allele-specific polymerase chain reaction amplification.

Acetylation↗
PubMedDate not supplied

The outcome of non-selective vs selective nitric oxide synthase inhibition in lipopolysaccharide treated rats.

UNLABELLED: Nitric oxide (NO), generated by inducible nitric oxide synthase (NOS) following lipopolysaccharide (LPS) administration, produces renal failure through autoinhibition of glomerular endothelial NOS activity. Preadministration of selective iNOS inhibitors abolishes this effect. Although nonselective NOS inhibitors further decrease GFR, current clinical trials investigate the effect of nonselective NOS inhibition in septic patients. The goals of our study were to determine whether treatment with selective NOS inhibitors can reverse the decrease in GFR in LPS treated rats with already established renal failure and to define the outcome of LPS treated rats following nonselective NOS inhibition. Four hours following the administration of LPS (4 mg/kg), we measured creatinine clearance (CrCl) before and after the administration of either L-NIL (selective iNOS inhibitor, 3 mg every 20 minutes) or saline. Selective iNOS inhibition attenuated the decrease in blood pressure [ CONTROLS: 105 +/- 6 to 98 +/- 5, LPS: 92 +/- 5* to 83 +/- 4*, LPS + L-NIL: 88 +/- 6* to 94 +/- 6 mm Hg; *p < 0.05, vs controls (n = 6)], and reversed the decrease in GFR after LPS [ CONTROLS: 2.21 +/- 0.13 to 2.07 +/- 0.11, LPS: 0.82 +/- 0.18* to 0.66 +/- 0.22*, LPS + L-NIL: 0.76 +/- 0.15* to 1.86 +/- 0.15 ml/min; *p < 0.05 vs controls (n = 6)]. We next studied the effect of complete non-selective NOS inhibition (L-NAME 200 mg, 2 hours after LPS) on LPS treated rats. All (6/6) animals treated with both LPS and L-NAME died within 2 hours following LPS, while rats treated with either LPS, L-NAME, or LPS + L-NIL survived. Histologic studies performed in all experimental groups were unremarkable. Overnight mortality was studied using smaller doses of L-NAME. All LPS + L-NAME (10/10) and 1/10 LPS treated rats died. L-NAME, control, and LPS + L-NIL animals survived. The characteristic histologic findings in LPS + L-NAME rats were diffuse ischemic changes, most importantly acute myocardial infarction. IN CONCLUSION: Selective iN-OS inhibition might prove to have clinical application as it prevents the decrease in GFR following LPS, even after renal failure is established. Treatment with a non selective NOS inhibitor in septic patients should be reconsidered.

Analysis of Variance↗