Biomedical subjects

J Moll

Publications and source records attributed to J Moll.

At least 55 records · Page 3Linked to original sources

PubMed1995

Alcohol and injury. A case-crossover study.

OBJECTIVE: To determine whether and to what extent alcohol consumption increases the risk of injury. DESIGN: The case-crossover study is a new research design for assessing rare acute events (such as trauma) in relation to intermittent exposures (such as alcohol use) that have transient effects. All interviewed patients serve as their own controls, and the study design compares exposure during a "case" period, such as the 6 hours prior to injury, with exposure during a "control" period, such as the same 6-hour window on the previous day. SETTING: Emergency centers of a university hospital and a private not-for-profit hospital in a small midwestern city. PATIENTS: Three hundred fifty adults who presented with an injury within 48 hours of the event. DATA COLLECTED: Retrospective self-report of alcohol use in each of the 28 days and each of the 30 hours prior to injury, demographic variables, drug use prior to injury, patients' attributions regarding causes of their injury, and weather factors. RESULTS: Primary analysis was based on pairs of observations that were discordant for alcohol use in the 6 hours prior to injury and the same 6-hour window on the previous day. The odds ratio for one or more standard drinks vs none was 2.5 (95% confidence interval, 1.2 to 5.4); for four or more drinks vs three or fewer, 5.0 (95% confidence interval, 1.4 to 27). CONCLUSION: Alcohol use in the 6 hours prior to injury is associated with an increased risk of injury. The findings are consistent with a dose-response effect, but with this sample size no threshold of risk was found.

Adult↗

PubMed1995

The role of CD44 splice variants in human metastatic cancer.

The large family of CD44 splice variants are likely to serve multiple functions in the embryo and in the adult organism. This is reflected in their complex patterns of expression. In molecular terms these functions are largely unknown. Certain splice variants (CD44v) can promote the metastatic behaviour of cancer cells. In human colon and breast cancer the presence of epitopes encoded by exon v6 on primary resected tumour material indicates poor prognosis. Metastasis-promoting splice variants differ from those that seem not to have a role in the induction of metastasis by the formation of homomultimeric complexes in the plasma membrane of cells. This may increase their affinity to ligands such as hyaluronate. The affinity can be further regulated over a range from low to very high by cell-specific modification. The fact that CD44v epitopes are found on normal epithelial cells such as skin, cervical epithelium and bladder enforces cautious evaluation of the significance of CD44v expression in human cancer. Nevertheless, certain epitopes can serve as tools in early diagnosis of certain cancers and will facilitate the development of specific targeted therapy.

Biomarkers, Tumor↗

PubMed1995

Expression of variant CD44 epitopes in human astrocytic brain tumors.

Expression of CD44 and of specific splice-variants of CD44 has been causally related to metastatic behaviour in a variety of carcinomas and lymphomas. To elucidate whether, in principle, similar splice-variants could be involved in glioma cell invasion we examined the expression of CD44 and its splice-variants in a series of 38 primary human brain tumors (28 astrocytomas, WHO grade I-III and 10 glioblastomas, WHO grade IV) and in cell lines derived from 9 glioblastomas. All brain tumors examined showed strong immunoreactivity for an N-terminal epitope present on all CD44 isoforms known. Using a polyclonal antiserum raised against the complete sequence encoded by variant exons v3 to v10, CD44 splice-variants could be detected irrespective of the grade of malignancy in many of the tumor samples at a low level and often restricted to only a few clustered tumor cells. Thus, the N-terminal epitope probably indicates the presence of the smallest and most ubiquitous isoform CD44s. Interestingly, all glioblastomas expressed CD44 variants whereas expression in astrocytomas WHO grade I, II, and III could only be detected in about half of the tumor samples. Using reverse transcriptase-PCR we were able to detect different CD44 splice-variants in the glioblastoma cell lines and in cultured primary astrocytic cells. Glioblastoma cells analyzed by flow cytometry showed the expected binding capacity for hyaluronic acid which could be increased twofold after pretreatment with hyaluronidase. The results presented show that there is low expression of CD44 variants in human tumors of astrocytic origin. Expression of CD44 and its splice-variants could contribute to the migration capacity of neoplastic astrocytes, and may be considered as a target for new diagnostic and therapeutic approaches in the clinical management of brain tumors.

Alternative Splicing↗

PubMed1995

Schwann cell tumors express characteristic patterns of CD44 splice variants.

Members of the CD44 family of cell surface hyaluronate-binding proteins have been implicated in cell migration, cell-matrix interactions and tumor progression. To determine whether these proteins might play a role in the normal functions of Schwann cells and in their tumorigenesis, we examined the patterns of CD44 expression in Schwann cells from rat peripheral nerve, rat Schwann cell tumor lines, and human schwannomas. Normal rat spinal nerves and primary Schwann cell cultures expressed standard CD44 (CD44s) but not alternatively spliced variant isoforms. In contrast, rat Schwann cell tumor lines expressed both CD44s and a number of variants, including proteins containing sequences encoded by exon v6. Furthermore, we found that these cell lines bind hyaluronate, and that their cell surface hyaluronate binding correlates with CD44 expression. All of the human schwannomas also expressed CD44 variants, especially epitopes encoded by exon v5, the border between v7 and v8, and v9-10. These data indicate that Schwann cells normally express CD44s, that Schwann cell tumors express both CD44s and particular variants of CD44, and that CD44s and possibly variants of CD44 are involved in hyaluronate recognition by Schwann cell tumors.

Alternative Splicing↗

PubMed1995

Molecular identification of steroid analogs with dissociated antiprogestin activities.

Antiprogestins of the 11 beta-aryl-substituted 19-norsteroid family are effectively used in inhibiting nidation and in terminating pregnancies. They are potentially useful in the treatment of progesterone-related diseases such as meningiomas and endometriosis and in inhibiting the growth of mammary tumors. However their long-term use is limited because of their inherent antiglucocorticoid activity. Here we have used molecular biological techniques to examine the antiglucocorticoid activity of a series of antiprogestins. The compounds we have analyzed contain different substituents at the C-17 position and a change from the trans to cis configuration of the C-D steroid rings. Our results show that minor changes at the C-17 position but not in the configuration of the C and D rings produced antiprogestins with reduced antiglucocorticoid activity. Thus only subtle changes in the structure of classical antiprogestins are needed for the reduction of their antiglucocorticoid activities.

Androgen Receptor Antagonists↗

PubMed1994

The glomerulosclerosis gene Mpv17 encodes a peroxisomal protein producing reactive oxygen species.

The mutant mouse strain Mpv17 carries a retroviral insert in its genome which inactivates the Mpv17 gene. At a young age these mice develop glomerulosclerosis and nephrotic syndrome which resembles human disease. We show here that the Mpv17 gene product is highly conserved and encodes a peroxisomal protein. Loss of the Mpv17 protein does not impair peroxisome biogenesis but instead leads to a reduced ability to produce reactive oxygen species (ROS). In turn, overproduction of the Mpv17 gene in transfected cells results in dramatically enhanced levels of intracellular ROS indicating a direct involvement of Mpv17 in ROS production. These data reveal a role for the Mpv17 protein in peroxisomal reactive oxygen metabolism and establish a novel link between peroxisomal ROS production and glomerulosclerosis.

Amino Acid Sequence↗

PubMed1994

Outcome of insulin-treated diabetics receiving epinephrine during cardiac arrest.

The purpose of this study was to determine the effects of epinephrine in insulin-treated diabetics (DM) compared with nondiabetic (ND) controls during cardiopulmonary resuscitation (CPR). A retrospective analysis from a multicenter study of out-of-hospital cardiac arrest included 62 DM and 1,151 ND. Outcome parameters included return of spontaneous circulation (ROSC), blood pressure (BP), emergency department admissions (EDA), hospital admissions (HA), and hospital discharge (DC). In DM treated with standard-dose epinephrine (SDE), there were trends toward improved ROSC, BP, EDA, and HA compared with ND. DC was not different. With high-dose epinephrine (HDE) these outcomes were not different. Comparison of the outcomes of DM given SDE versus those given HDE were not different. However, none of the DM given HDE (n = 24) were discharged from the hospital. These results suggest that DM may have improved resuscitation rates with SDE and may be adversely affected with HDE. Larger prospective studies are needed to confirm these findings.

Aged↗

PubMed1994

Analysis of molecular functions of the tumor metastasis promoting surface molecule CD44v4-v7 using transgenic mice.

In certain circumstances, metastatic tumor cells may mimic the molecular properties and behaviour of lymphocytes. Support for this hypothesis has come from the observation that activated lymphocytes and some tumor cells need a CD44 variant isoform (CD44v) to survive and/or expand in the lymphatic system. CD44 variant (CD44v) isoforms are created by differential splicing from a pool of at least ten variant exons (v1-v10), the encoded sequences of which are absent in the CD44 standard isoform (CD44s). To dissect the molecular interactions of CD44v, transgenic animals have been generated that constitutively express a variant of CD44 containing sequences encoded by exons v4 to v7 on the surface of T cells. Lymphocytes derived from these transgenic animals show accelerated entry into S phase upon antigenic stimulation, and a subpopulation of the cells constitutively express early lymphocyte activation markers. Our data support the hypothesis that the presence of CD44v4-v7 on the surface of T cells mediates intercellular or intracellular processes which result in the promotion of T cells towards a preactivated state.

Animals↗

PubMed1992

Thymic hyperplasia in transgenic mice caused by immortal epithelial cells expressing c-kit ligand.

To dissect mechanisms that co-ordinate specific events in thymopoiesis we have characterized alterations in thymic structure and function caused by expression of a transgene. This gene encodes SV40Tag and is specifically expressed in a subset of thymic epithelial (TE) cells around birth. As a result the number of immortal TE cells increases, thymic mass increases (up to 3 g), and thymopoiesis is expanded. The latter is reflected by a approximately 100-fold increase of the major thymocyte subsets and increased peripheral T cell counts. Grossly hyperplastic thymi retain many but not all morphological features of a normal thymus. Also in grafts, SV40Tag+ TE cells steer expansion (up to 8 g) and organize a tissue with mainly cortex-like features that includes mainly SV40Tag+ TE cells, thymocytes, and macrophages. To investigate expression of specialized gene functions in the immortal TE cells, a cell line was derived. The Epi-A1 cell line expresses the genes for major histocompatibility complex class I and II, Thy-1, interleukin (IL)-6, IL-7, macrophage-colony-stimulating factor, and transforming growth factor-beta 3. Most importantly, Epi-A1 cells also express the IL-4 receptor and the c-kit ligand (KL), a factor that, in concert with commitment factors, channels progenitors into hemopoietic lineages. The expression of low constitutive levels of KL mRNA does not require IL-4, but KL mRNA levels are increased dramatically in response to IL-4. Since constitutive expression of KL mRNA in vivo is restricted to a small subset of TE cells in the thymus, our findings reveal a novel specific interaction between thymocytes and a specialized subset of TE cells.

Age Factors↗

PubMed1992

Transgenes encoding mutant simian virus 40 large T antigens unmask phenotypic and functional constraints in thymic epithelial cells.

Transgenes encoding simian virus 40 (SV40) T antigen (Tag) can cause hyperplastic or tumorigenic lesions of desired but also of unforeseen cellular origin. Unexpectedly the human growth hormone-releasing factor (GRF) gene promoter directs expression of SV40 Tag specifically in thymic epithelial (TE) cells. Expression starts in the neonate, in which GRF-Tag+ cells display strict numerical and spatial constraints. Tag supersedes mechanisms that constrain these features and GRF-Tag mice develop thymic hyperplasia. To characterize GRF-Tag+ TE cells and their putative normal counterparts we compared phenotypic and functional effects caused by transgenes encoding mutant large T antigens. This strategy is applicable to any situation in which T antigen is used to alter development. One large Tag mutant (K1 + 5080) does not cause thymic hyperplasia. GRF-Tag (K1 + 5080)+ TE cells display strict temporal and spatial constraints throughout life. TE cells expressing other mutant large T antigens that cause thymic hyperplasia do not obey these rules and reveal that phenotypically distinct GRF-Tag+ TE-cell stages exist in vivo. Analysis of conditional immortal GRF-Tag(tsA58)+ TE cells expressing a temperature-sensitive large Tag shows that large Tag blocks differentiation in these cells. Phenotype and functions in these cells are regulated by cellular differentiation and interleukin 4 (IL-4).

Animals↗

PubMed1992

[A case of direct right pulmonary artery-left atrium fistula].

An unusual case of cyanotic heart disease in a 20-year-old male has been presented. Cyanosis was due to right to left shunt through direct right pulmonary artery--left atrium fistula. After successful operative ligation of the fistula, the patient got rid of cyanosis and is doing well.

Abnormalities, Multiple↗

PubMed1992

[Anatomical correction of transposition of the great arteries in 7 newborn infants].

In the presented article, the course and results of anatomical correction of transposition of great arteries (TGA) in 7 neonates (2 females and 5 males) with mean body mass of 3250 g and 2 to 5 days old (mean 3 days) are reviewed. Surgery was performed in moderate hypothermia. St. Thomas cold cardioplegia was used. Mean aortic clamping time was 70 min (55-115), and the time of extracorporeal circulation was 165 min (117-210). Low cardiac output in all patients in the postoperative period required prolonged mechanical ventilation and positive inotropic drugs. Out of 7 patients operated, two died (29%). The cause of death in both cases was myocardial ischemia of right ventricle. The other 5 patients were discharged after healing of operational wound. In the control echocardiographic examination performed 3 to 12 months postoperatively, apart from one case of moderate pulmonary artery stenosis, no other haemodynamically significant complications were noted.

Coronary Vessel Anomalies↗

PubMed1991

[Cardiogenic shock. Surgical reperfusion and myocardial revascularization].

Emergency coronary bypass for cardiogenic shock has been associated with a high operative mortality. From February 1986 through October 1989, 40 patients with acute myocardial infarction were operated. Ten pts (25%) were in shock despite intensive treatment (intra-aortic balloon pump in 4, catecholamines in 10). Seven pts. required cardiopulmonary resuscitation before operations. After operations 66% of the patients required catecholamine support and 60% were treated with intra-aortic balloon pump. There were three (30%) hospital deaths (one in the operating room due to acute cardiac failure). Follow-up (100%),(mean 26 months) revealed one late death--39 months after operations. In functional class I were 2 patients, II--one, and III--two pts. One pt is in group IV (transplant candidate). Myocardial infarction complicated by cardiogenic shock can produce a mortality rate in excess of 85%. Contemporary medical management has had little effect on mortality, hence effective surgical therapy has evolved for this lesion.

Aged↗

PubMed1991

[Supravalvular aortic stenosis in two black patients].

Two male black patients, 18 and 12-year-old, with mental retardation and typical elfin face, presented with severe supravalvular aortic stenosis, thus characterizing Williams's or aortic supravalvular stenosis syndrome. Both were submitted to surgical treatment of the stenosis, and are asymptomatic after a one and four years follow-up. For the first time this syndrome, in its classical form, is described in black patients.

Adolescent↗

PubMed1991

The murine rac1 gene: cDNA cloning, tissue distribution and regulated expression of rac1 mRNA by disassembly of actin microfilaments.

A 886 bp cDNA encoding the murine rac1 protein has been isolated. The abundance of rac1 mRNA was determined in fourteen tissues from both mouse and pig. The mRNA 5' non-coding sequence is very rich in G + C, and has the potential to form several stable secondary structures. In addition, this region contains a putative open reading frame of 57 amino acids. Disruption of the actin microfilament network by cytochalasin B in LLC-PK1 cells results in down regulation of rac1 mRNA. In agreement with the proposed role of rac1 in exocytosis, these results could explain the inhibitory effect of cytochalasin B on secretory processes.

Actin Cytoskeleton↗

PubMed1990

[Surgical treatment of paroxysmal ventricular tachycardia (personal observations)].

Five patients with recurrent VT/VF resistant to medical treatment were successfully treated surgically. In 3 patients excision of the altered endocardium by Harken's method (endocardial peeling) was done; in 2 of the patients it was preceded by intraoperative electrophysiological study. Two other patients were treated alternatively: a 45-year old patients with post-MI cardiomyopathy had a cardiac transplantation and a 57-year old patient with good left ventricular function an implantation of a automatic cardioverter-defibrillator (AICD). No patient had VT and/or VF during the 14-35 month follow-up. Exercise tolerance improved in all patients. Good short- and longterm results of surgical treatment show that these methods can be effective in treating patients with life-threatening arrhythmias resistant to pharmacological therapy.

Aged↗

PubMed1989

Beneficial effects of coronary venous retroinfusion of superoxide dismutase and catalase on reperfusion arrhythmias, myocardial function, and infarct size in dogs.

The efficacy of coronary venous retroinfusion of superoxide dismutase and catalase was studied in anesthetized closed chest dogs with 90-min left anterior descending coronary artery (LAD) occlusion followed by 3-h reperfusion. In group A, superoxide dismutase (2.5 mg/kg) and catalase (2.5 mg/kg) were administered by a 30-min continuous right atrial infusion beginning 15 min before reperfusion and supplemented by a bolus injection of superoxide dismutase (2.5 mg/kg) and catalase (2.5 mg/kg) through the great cardiac vein immediately before reperfusion. The treatment in group B was similar to that in group A, except that the bolus injection was into the right atrium. In the control group (group C), saline was administered in the same manner as in group A. Infarct size, expressed as a percentage of the risk area, was significantly smaller in group A (11.3 +/- 8.9%) than in groups B (31.3 +/- 21.1%) and C (43.0 +/- 16.9%; p less than 0.05). Regional function of the ischemic zone measured by two-dimensional echocardiography exhibited significantly (p less than 0.05) greater recovery after 3-h reperfusion in group A (30.3 +/- 8.4%) versus groups B (12.5 +/- 13.7%) and C (12.1 +/- 11.7%). Moreover, there were significantly fewer postreperfusion ventricular arrhythmias in group A as compared with groups B and C. The results of this study indicate that coronary venous retroinfusion is an effective method for delivery of superoxide dismutase and catalase.

Animals↗

PubMed1987

The corrinoid from Methanobacterium thermoautotrophicum (Marburg strain). Spectroscopic structure analysis and identification as Co beta-cyano-5'-hydroxybenzimidazolyl-cobamide (factor III).

The corrinoids from Methanobacterium thermoautotrophicum were extracted as the Co-cyano derivative, which was isolated in crystalline form. A consistent set of spectroscopic data was acquired (ultraviolet/visible, circular dichroic, infrared, fast-atom-bombardment mass, 1H-NMR and 13C-NMR spectra), which allowed the structural analysis of this complete corrinoid. It was assigned the structure of the Co beta-cyano-5'-hydroxybenzimidazolyl-cobamide and was identified with Friedrich and Bernhauer's 'factor III' by comparison with an authentic sample.

Circular Dichroism↗