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Biomedical subjects

J Lorenz

Publications and source records attributed to J Lorenz.

At least 19 recordsLinked to original sources
PubMed2001

Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice.

Upregulation of alphaB-crystallin (CryAB), a small heat shock protein, is associated with a variety of diseases, including the desmin-related myopathies. CryAB, which binds to both desmin and cytoplasmic actin, may participate as a chaperone in intermediate filament formation and maintenance, but the physiological consequences of CryAB upregulation are unknown. A mutation in CryAB, R120G, has been linked to a familial desminopathy. However, it is unclear whether the mutation is directly causative. We created multiple transgenic mouse lines that overexpressed either murine wild-type CryAB or the R120G mutation in cardiomyocytes. Overexpression of wild-type CryAB was relatively benign, with no increases in mortality and no induction of desmin-related cardiomyopathy even in a line in which CryAB mRNA expression was increased approximately 104-fold and the protein level increased by 11-fold. In contrast, lines expressing the R120G mutation were compromised, with a high-expressing line exhibiting 100% mortality by early adulthood. Modest expression levels resulted in a phenotype that was strikingly similar to that observed for the desmin-related cardiomyopathies. The desmin filaments in the cardiomyocytes were overtly affected, myofibril alignment was significantly impaired, and a hypertrophic response occurred at both the molecular and cellular levels. The data show that the R120G mutation causes a desminopathy, is dominant negative, and results in cardiac hypertrophy.

Animals↗
PubMed2001

[Socioeconomic relevance of acute exacerbations of chronic bronchitis in the Federal Republic of Germany. A prospective cost of illness study].

BACKGROUND AND OBJECTIVE: Prospectively determined data on costs of chronic bronchitis were not yet available for the Federal Republic of Germany. The purpose of the burden-of-illness-study conducted in the Federal Republic of Germany from October 1996 to March 1998 was to calculate direct and indirect costs of chronic bronchitis as well as its acute exacerbations per patient and year. Furthermore, the health-related quality of life of the patients was determined. PATIENTS AND METHODS: The burden-of-illness-study was conducted as an open, not randomised surveillance study. The evaluation based on 785 patients (55.4% male, 44.2% female, 0.4% unknown; mean age 60 years) who were treated by 147 general practitioners. 755 patients could be included into the cost analysis. RESULTS: Per patient and year direct costs of chronic bronchitis amounted to DM 1112.27, the calculation of indirect costs resulted in DM 959.09. 41.4% of direct costs were due to drug acquisition, hospitalisation costs shared 31.6% and costs for physicians' fee amounted to 20.6%. The severity of chronic bronchitis revealed significantly different results in cost analysis: per patient, mild disease lead to direct costs of DM 387.86, moderate disease to DM 802.62 and severe disease to DM 2224.40. This result was caused by higher costs for drug acquisition and hospitalisation costs due to chronic bronchitis in higher stages of severity. Indirect costs were calculated by applying the human-capital-approach: 45.8% of indirect costs were due to time-off-work, nursing costs amounted to 23.7%. CONCLUSION: The costs of chronic bronchitis have a considerable impact on the total costs of the health care system of Germany.

Acute Disease↗
PubMed2001

Role of bronchoalveolar lavage in immunocompromised patients with pneumonia treated with a broad spectrum antibiotic and antifungal regimen.

BACKGROUND: In a retrospective study the value of bronchoalveolar lavage (BAL) in the diagnosis of pneumonia was investigated in 95 immunocompromised patients suffering from haematological disorders and receiving a regimen of broad spectrum antibiotics and antifungal agents (BSAR). METHODS: With the exception of four afebrile patients, all had fever, raised C reactive protein (CRP) levels, and new infiltrates visible on chest radiography. All patients underwent BAL to identify the organism causing the pneumonia and surveillance cultures were performed regularly for pathogens at different sites. Following classification of the isolates, patients with positive cultures were subdivided into two groups, pathogenic or contaminated. We investigated whether relevant pathogens were cultured only from the BAL fluid and whether they were susceptible to BSAR. RESULTS: Although 77 of the 95 patients were thrombocytopenic, bleeding during BAL occurred in only 15% of all patients. Ten days after the procedure the fever improved in 88% of patients, radiographic findings improved in 71%, and CRP levels improved in 75% of patients; 22% of patients died within 28 days. Pathologically relevant isolates were found in 65% of all patients. Respiratory pathogens were detected only in the BAL fluid of 29 of the 95 patients (35% Gram positive species, 40% Gram negative species, 11% Mycobacterium, 11% fungi, and 3% cytomegalovirus). In 16 of these 29 patients (55%) the pathogens cultured only from the BAL fluid were resistant to treatment. Pathogens detected only in the BAL fluid were not susceptible to a standard broad spectrum antibiotic and antifungal regimen including teicoplanin, ceftriaxon, tobramycin, and amphotericin B in 12 of the 29 patients (41%). CONCLUSIONS: Our data suggest that 12 patients were treated with broad spectrum antimicrobial agents which were not directed at the appropriate organism on in vitro sensitivity tests without BAL. BAL is a relatively safe procedure in the diagnosis of pneumonia, supplying important information in immunocompromised patients as well as in immunocompromised patients receiving BSAR.

Acute Disease↗
PubMed2001

Temporal and spatial dynamics of human forebrain activity during heat pain: analysis by positron emission tomography.

To learn about the sequence of brain activation patterns during heat pain, we acquired positron emission tomographic (PET) brain scans at different times during repetitive heat stimulation (40 or 50 degrees C; 5-s contact) of each subject's left forearm. Early scans began at the onset of 60 s of stimulation; late scans began after 40 s of stimulation, which continued throughout the 60-s scan period (total stimulus duration 100 s). Each subject (14 normal, right-handed subjects; 10 male, 4 female; ages 18-42) used a visual analog scale to rate the perceived stimulus intensity (0 = no heat, 7 = pain threshold, 10 = barely tolerable pain) after each scan. The 40 degrees C stimulation received an average intensity rating of 2.19 +/- 1.22 (mean +/- SD) and the 50 degrees C an average rating of 8.93 +/- 1.33. During the scan sessions, subjects did not report a difference between early and late scans. To examine the effect of the duration of stimulation specifically, 8 of these subjects rated the perceived intensity of each of 20 sequential 5-s duration contact heat stimuli (40 or 50 degrees C; 100 s of stimulation). We used a graphical method to detect changes in perceived unpleasantness. There was no difference in perceived intensity or unpleasantness during the 40 degrees C stimulation. However, during 50 degrees C stimulation, perceived unpleasantness increased and subjects perceived the last five, but not the second five, stimuli as more intense than the first five stimuli. These psychophysical changes could be mediated by brain structures with increasing activity from early to late PET scans or that are active only during late scans. These structures include the contralateral M1/S1 cortex, bilateral S2 and mid-insular cortex, contralateral VP thalamus, medial ipsilateral thalamus, and the vermis and paravermis of the cerebellum. Structures that are equally active throughout stimulation (contralateral mid-anterior cingulate and premotor cortex) are less likely to mediate these psychophysical changes. Some cortical, but not subcortical, structures showed significant or borderline activation only during the early scans (ipsilateral premotor cortex, contralateral perigenual anterior cingulate, lateral prefrontal, and anterior insular cortex); they may mediate pain-related attentive or anticipatory functions. Overall, the results reveal that 1) the pattern of brain activation and the perception of heat pain both change during repetitive noxious heat stimulation, 2) cortical activity can be detected before subcortical responses appear, and 3) timing the stimulation with respect to the scan period can, together with psychophysical measurements, identify brain structures that are likely to participate in the perception of pain.

Adult↗
PubMed2001

Smooth muscle-targeted overexpression of insulin-like growth factor I results in enhanced vascular contractility.

Insulin-like growth factor I (IGF-I) has been postulated to function as a vasodilator. We explored the vasoactive effects of chronic elevations of arterial IGF-I levels in SMP8-IGF-I mice, in which IGF-I is overexpressed in smooth muscle (SM) by means of a SM alpha-actin promoter. Denuded aortas from SMP8-IGF-I mice generated increased force in response to KCl or phenylephrine and had greater sensitivity to KCl depolarization. This is not due to desensitization of a SM NO pathway, as pretreatment with n-omega-nitro-L-arginine affected both wild-type and SMP8-IGF-I aortas to a similar degree. The increased contractility ex vivo is not associated with changes in heart rate or blood pressure. Total smooth muscle myosin heavy chain (SMHC) messenger RNA (mRNA) was greater in SMP8-IGF-I aortas, with preferential expression of SMHC-A. Reciprocal effects on contractility and SMHC mRNA were observed in SMP8-IGFBP-4 animals, in which IGF-binding protein-4 was overexpressed through the same promoter. Also, SM alpha-actin mRNA was increased in the aortas from SMP8-IGF-I mice. In summary, chronic arterial overexpression of IGF-I is associated with increased contractility. These effects differ from those seen after acute exposure to the growth factor and may relate to IGF-mediated changes in expression and relative isoform abundance of critical contractile proteins.

Animals↗
PubMed2001

Comparison of balloon- and mushroom-retained large-bore gastrostomy catheters.

OBJECTIVE: We conducted a retrospective study to evaluate two different types of percutaneous fluoroscopic gastrostomy procedures and catheters. MATERIALS AND METHODS: Between July 8, 1999, and August 4, 2000, 80 percutaneous gastrostomy catheters were placed in 80 patients in 80 attempts. Twenty-five 16-, 18-, or 20-French balloon-retained catheters and 55 20-French mushroom-retained catheters were inserted. Typically, the type of catheters placed was based on operator preference. However, balloon-retained tubes were preferred for use in patients with obstructive head and neck or esophageal malignancies, and mushroom-retained catheters were preferred for use in demented or combative patients. Follow-up was conducted through chart reviews and telephone interviews. The technical success, procedural complications, and catheter complications were recorded. Chi-square statistical analysis was performed. RESULTS: Technical success was 100% (80/80 patients), and no procedural complications occurred. In patients who received balloon-retained catheters, the major complication rate was 0%, the minor complication rate was 8% (2/25 patients), and the tube complication rate was 68% (17/25 patients). The following complications occurred: catheter dislodgment (n = 17), superficial cellulitis (n = 1), and bleeding gastric ulcer (n = 1). In patients who received mushroom-retained catheters, the major complication rate was 0%, the minor complication rate was 3.6% (2/55 patients), and the tube complication rate was 3.6% (2/55 patients). The following complications occurred: superficial cellulitis (n = 2), tube occlusion (n = 1), and peristomal tube leakage (n = 1). No significant differences in major or minor complications were found between the gastrostomy procedures. Balloon-retained catheters had a significantly higher rate of tube complications (p < 0.001). CONCLUSION: Compared with balloon-retained catheters, mushroom-retained gastrostomy catheters are significantly more durable, more secure, and less prone to tube dysfunction. Mushroom-retained catheters should be the preferred type of gastrostomy catheter to place in patients whenever possible.

Catheterization↗
PubMed2001

Superselective microcoil embolization of colonic hemorrhage.

OBJECTIVE: We evaluated therapeutic microcoil embolization in a group of patients with severe colonic hemorrhage. MATERIALS AND METHODS: Twenty-seven patients with severe colonic bleeding due to diverticular disease (n = 19), angiodysplasia (n = 6), cecal ulcer (n = 1), or unknown cause (n = 1) underwent attempted microcoil embolization (n = 25). Microcatheters were used in all procedures, and embolization was performed at the level of the vasa recta or the marginal artery of Drummond. Branches of the superior mesenteric artery were embolized in 12 patients, branches of the inferior mesenteric artery were embolized in 12 patients, and branches of both the superior and inferior mesenteric arteries were embolized in one patient. RESULTS: Technical success was achieved in 93% (25/27) of the procedures. However, immediate hemostasis occurred in 96% (26/27) of patients because in one failed procedure, an occlusive dissection of the inferior mesenteric artery arrested bleeding. Three patients rebled within 24 hr. One patient was treated with endoscopic cauterization, and two patients underwent right hemicolectomy. One patient who underwent right hemicolectomy for rebleeding had ischemic changes found on pathologic analysis of the resected specimen, and a second patient who underwent embolization of branches of the superior and inferior mesenteric arteries developed bowel infarction requiring left hemicolectomy. Prolonged clinical success occurred in 81% (22/27) of patients. CONCLUSION: Therapeutic microcoil embolization for severe colonic hemorrhage is an effective and well-tolerated procedure.

Aged↗
PubMed2000

Implications of the distribution of Albumin Naskapi and Albumin Mexico for new world prehistory.

The known distributions of two mutational variants of the albumin gene that are restricted to Mexico and/or North America, Albumin Mexico (AL*Mexico) and Albumin Naskapi (AL*Naskapi), were expanded by the electrophoretic analysis of sera collected from more than 3, 500 Native Americans representing several dozen tribal groups. With a few exceptions that could be due to recent, isolated cases of admixture, AL*Naskapi is limited to groups that speak Athapaskan and Algonquian, two widely distributed language families not thought to be related, and to several linguistically unrelated groups geographically proximate to its probable ancestral homeland. Similarly, AL*Mexico is limited to groups that speak Yuman or Uto-Aztecan, two language groups in the American Southwest and Baja California not thought to be closely related to each other, and to several linguistically unrelated groups throughout Mexico. The simultaneous consideration of genetic, historical, linguistic, and archaeological evidence suggests that AL*Naskapi probably originated on the northwestern coast of North America, perhaps in some group ancestral to both Athapaskans and Algonquians, and then spread by migration and admixture to contiguous unrelated, or distantly related, tribal groups. AL*Mexico probably originated in Mexico before 3,000 years BP then spread northward along the Tepiman corridor together with cultural influences to several unrelated groups that participated in the Hohokam culture.

Albumins↗
PubMed2000

cDNA cloning, chromosomal mapping, and expression analysis of human VE-Cadherin-2.

Murine vascular endothelial cadherin-2 (VE-cad-2) is a cellular adhesion molecule that is distinct from vascular endothelial cadherin 1 (VE-cad-1) in that it does not interact with catenins and does not appear to affect cell migration or growth. In this study, we have cloned a full-length cDNA of the human homolog of VE-cad-2 and used it to map the chromosomal locus of the VE-cad-2 gene. Human VE-cad-2 maps to Chromosome (Chr) 5q31. The cDNA of human VE-cad-2 is highly homologous to mouse VE-cad-2, except for a C-terminal tail. The genomic structure of VE-cad-2 is strikingly similar to that reported for a large family of neuronal protocadherin genes mapped to Chr 5q, yet the amino acid sequences between VE-cad-2 and the protocadherins are substantially divergent. The promoter of human VE-cad-2 contains two TATA boxes and transcription initiates from a single site 3' to these elements. Similar to mouse VE-cad-2, the human gene is expressed primarily in highly vascularized tissues.

5' Untranslated Regions↗
PubMed2000

Percutaneous treatment of portal venous stenosis in children and adolescents with segmental hepatic transplants: long-term results.

PURPOSE: To evaluate the long-term effectiveness of the percutaneous treatment of portal venous stenoses in children and adolescents with reduced-size hepatic transplants. MATERIALS AND METHODS: During the past 5 years, percutaneous transhepatic balloon venoplasty was attempted in 25 children and adolescents with anastomotic portal venous stenoses that occurred after reduced-size hepatic transplantation. All procedures were performed with direct puncture of the intrahepatic portal vein and with subsequent balloon dilation. Intravascular stents were deployed in patients with suboptimal results after dilation or with recurrent stenoses. RESULTS: Percutaneous venoplasty was technically successful in 19 of 25 patients. In the remaining six patients, portal venous occlusion precluded access to the extrahepatic portal vein. Intravascular stents were deployed in 12 patients for "elastic" (n = 5) or recurrent (n = 7) stenoses. Seven patients who underwent successful venoplasty without stent placement have required no further intervention. All stents have remained patent without further intervention. Portal venous patency has been maintained for 5-61 months (mean time, 46 months) in all 19 patients. CONCLUSION: Percutaneous treatment of portal venous stenoses is effective and long lasting in children with reduced-size hepatic transplants. In patients with elastic or recurrent lesions, portal venous stents have excellent long-term primary patency despite continued patient growth. Successful, percutaneous transhepatic venoplasty eliminates the need for surgical revision, portacaval shunting, or repeat transplantation.

Adolescent↗
PubMed2000

Radiologic gastrostomy placement: pigtail- versus mushroom-retained catheters.

OBJECTIVE: Two different types of percutaneous fluoroscopic gastrostomy procedures were prospectively evaluated. SUBJECTS AND METHODS: Between January 1, 1998, and August 10, 1999, 127 percutaneous gastrostomy catheters were placed in 128 patients in 128 attempts. Seventy-five 12- or 14-French pigtail-retained catheters and fifty-two 20-French mushroom-retained catheters were inserted. Catheters were generally placed on the basis of operator preference except pigtail-retained tubes were preferentially placed in patients with head and neck or esophageal malignancies and mushroom-retained catheters were preferentially placed in neurologically compromised or combative patients. The technical success, procedural complications, and catheter complications were recorded. Statistical analysis was performed. RESULTS: Ninety-nine percent (127/128) of the procedures were successful, and there were no procedural complications. One catheter was not placed because the colon intervened between the abdominal wall and stomach. In patients who received pigtail-retained catheters, the major complication rate was 3% (2/75), the minor complication rate was 8% (6/75), and the tube complication rate was 36% (27/75). The following complications were seen: tube occlusion (n = 12), inadvertent catheter removal (n = 8), peristomal tube leakage (n = 7), superficial cellulitis (n = 4), aspiration pneumonia (n = 2), and T-fastener cellulitis (n = 2). In patients who received mushroom-retained catheters, the major complication rate was 0%, the minor complication rate was 2% (1/52), and the tube complication rate was 2% (1/52). Complications were superficial cellulitis (n = 1) and partial catheter fracture (n = 1). There were no significant differences in major and minor complications between procedures. Pigtail-retained catheters had a significantly higher rate of tube complications (p < 0.001) CONCLUSION: Compared with pigtail-retained catheters, mushroom-retained gastrostomy catheters are more durable and secure and are less prone to tube dysfunction. These catheters should be preferentially placed when possible.

Adolescent↗
PubMed1999

Abnormal cardiac structure and function in mice expressing nonphosphorylatable cardiac regulatory myosin light chain 2.

A role for myosin phosphorylation in modulating normal cardiac function has long been suspected, and we hypothesized that changing the phosphorylation status of a cardiac myosin light chain might alter cardiac function in the whole animal. To test this directly, transgenic mice were created in which three potentially phosphorylatable serines in the ventricular isoform of the regulatory myosin light chain were mutated to alanines. Lines were obtained in which replacement of the endogenous species in the ventricle with the nonphosphorylatable, transgenically encoded protein was essentially complete. The mice show a spectrum of cardiovascular changes. As previously observed in skeletal muscle, Ca(2+) sensitivity of force development was dependent upon the phosphorylation status of the regulatory light chain. Structural abnormalities were detected by both gross histology and transmission electron microscopic analyses. Mature animals showed both atrial hypertrophy and dilatation. Echocardiographic analysis revealed that as a result of chamber enlargement, severe tricuspid valve insufficiency resulted in a detectable regurgitation jet. We conclude that regulated phosphorylation of the regulatory myosin light chains appears to play an important role in maintaining normal cardiac function over the lifetime of the animal.

Amino Acid Sequence↗
PubMed1999

Cardiac specific overexpression of transglutaminase II (G(h)) results in a unique hypertrophy phenotype independent of phospholipase C activation.

Tissue type transglutaminase (TGII, also known as G(h)) has been considered a multifunctional protein, with both transglutaminase and GTPase activity. The role of the latter function, which is proposed as a coupling mechanism between alpha(1)-adrenergic receptors and phospholipase C (PLC), is not well defined. TGII was overexpressed in transgenic mice in a cardiac specific manner to delineated relevant signaling pathways and their consequences in the heart. Cardiac transglutaminase activity in the highest expressing line was approximately 37-fold greater than in nontransgenic lines. However, in vivo signaling to PLC, as assessed by inositol phosphate turnover in [(3)H]myoinositol organ bath atrial preparations, was not increased in the TGII mice at base line or in response to alpha(1)-adrenergic receptor stimulation; nor was protein kinase Calpha (PKCalpha) or PKCepsilon activity enhanced in the TGII transgenic mice. This is in contrast to mice moderately (approximately 5-fold) overexpressing G(alphaq), where inositol phosphate turnover and PKC activity were found to be clearly enhanced. TGII overexpression resulted in a remodeling of the heart with mild hypertrophy, elevated expression of beta-myosin heavy chain and alpha-skeletal actin genes, and diffuse interstitial fibrosis. Resting ventricular function was depressed, but responsiveness to beta-agonist was not impaired. This set of pathophysiologic findings is distinct from that evoked by overexpression of G(alphaq). We conclude that TGII acts in the heart primarily as a transglutaminase, and modulation of this function results in unique pathologic sequelae. Evidence for TGII acting as a G-protein-like transducer of receptor signaling to PLC in the heart is not supported by these studies.

Animals↗