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Biomedical subjects

J Weiss

Publications and source records attributed to J Weiss.

At least 91 records · Page 5Linked to original sources
PubMed1999

Decreased insulin-like growth factor-II/mannose 6-phosphate receptor expression enhances tumorigenicity in JEG-3 cells.

The insulin-like growth factor-II/mannose-6 phosphate receptor (IGF-II/M6PR) is believed to bind and degrade the potent mitogen IGF-II, a growth factor for many tumors. This receptor has been shown to be mutated and/or lost in a significant percentage of a variety of tumors, implying that it may act as a negative regulator of cell growth. In this study, we demonstrate that down-regulation of this receptor, mediated by antisense IGF-II/M6PR cDNA transfection into JEG-3 choriocarcinoma cells, results in increased growth rate in vitro and increased tumor growth rate in vivo. These findings demonstrate that a decrease in IGF-II/M6PR expression results in a growth advantage in JEG-3 cells and are consistent with the hypothesis that the IGF-II/M6PR is an inhibitor of tumor growth.

Animals↗
PubMed1999

Transmyocardial laser revascularisation compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomised trial. ATLANTIC Investigators. Angina Treatments-Lasers and Normal Therapies in Comparison.

BACKGROUND: Transmyocardial revascularisation (TMR) is an operative treatment for refractory angina pectoris when bypass surgery or percutaneous transluminal angioplasty is not indicated. We did a prospective randomised trial to compare TMR with continued medication. METHODS: We recruited 182 patients from 16 US centres with Canadian Cardiovascular Society Angina (CCSA) score III (38%) or IV (62%), reversible ischaemia, and incomplete response to other therapies. Patients were randomly assigned TMR and continued medication (n=92) or continued medication alone (n=90). Baseline assessments were angina class, exercise tolerance, Seattle angina questionnaire for quality of life, and dipyridamole thallium stress test. We reassessed patients at 3 months, 6 months, and 12 months, with independent masked angina assessment at 12 months. FINDINGS: At 12 months, total exercise tolerance increased by a median of 65 s in the TMR group compared with a 46 s decrease in the medication-only group (p<0.0001, median difference 111 s). Independent CCSA score was II or lower in 47.8% in the TMR group compared with 14.3% in the medication-only group (p<0.001). Each Seattle angina questionnaire index increased in the TMR group significantly more than in the medication-only group (p<0.001). INTERPRETATION: TMR lowered angina scores, increased exercise tolerance time, and improved patients' perceptions of quality of life. This operative treatment provided clinical benefits in patients with no other therapeutic options.

Aged↗
PubMed1999

Identification of two distinct deletion targets at 11q23 in cutaneous malignant melanoma.

Karyotypic and molecular data indicate that genetic alterations of the long arm of chromosome 11 (11q) are involved in the pathogenesis of malignant melanoma as well as of other malignancies. We have shown previously, by analysis of loss of heterozygosity (LOH), that a tumor-suppressor gene playing an important role in malignant melanoma is likely to be located within a 51-cM region at 11q23. Its loss appeared to be a late event in tumor progression and an indicator of a less favorable clinical outcome. To further test this hypothesis on a larger set of tumors and to refine the region(s) of common allelic loss, we analyzed 21 polymorphic microsatellite repeats on 11q. A PCR-based assay for LOH was used to study normal and tumor tissues from 53 individuals with primary cutaneous malignant melanoma or metastatic disease. Our findings indicate that in cutaneous malignant melanoma there are at least 2 distinct regions of common allelic loss on 11q, one of them centered around marker APOC3 at 11q23.1-q23.2 delineated by markers D11S1347 and D11S4142 and spanning approximately 5 Mb and a second 3-Mb region around marker D11S925 at 11q23.3 delineated by markers D11S528 and D11S1345. Both regions have been described as deletion targets or as being included within larger allelic deletions detected in several other common tumor types. Thus, these 2 putative melanoma-suppressor loci are likely to harbor tumor-suppressor genes relevant to tumorigenesis of melanoma and a number of other common human malignancies.

Alleles↗
PubMed1999

Recording the evoked canine detrusor electromyogram.

With increasing interest in detrusor disorders and possible detrusor myopathies, a method for recording the detrusor electromyogram (detrusor-EMG) would probably greatly assist the diagnosis of various bladder dysfunctions. Therefore, we investigated the electromyographic activity of the detrusor during sacral root stimulation and during spontaneous bladder contractions in six anesthetized dogs. In all experiments, a high correlation of detrusor-EMG recordings with bladder contraction was observed. Analysis in the time domain and power spectrum analysis revealed the most clear correlation of detrusor-EMG with intravesical pressure rise in a frequency band above 3 Hz. The spike duration was 100 to 250 ms with an amplitude of 100 to 500 microV. Low-frequency activity below 1 Hz was mainly presumed to be artifacts due to fluid movement under the electrode. Our trials indicate that smooth muscle EMG recordings from the detrusor smooth musculature are possible. The exact physiological relevance of the signal in the sub-Hertz domain (<1 Hz) is still uncertain. The presented animal model allows the pathophysiologic investigation of various pathologies of bladder dysfunction and detrusor myopathies. Neurourol. Urodynam. 18:687-695, 1999.

Animals↗
PubMed1999

Intracellular Ca(2+) dynamics and the stability of ventricular tachycardia.

Ventricular fibrillation (VF), the major cause of sudden cardiac death, is typically preceded by ventricular tachycardia (VT), but the mechanisms underlying the transition from VT to VF are poorly understood. Intracellular Ca(2+) overload occurs during rapid heart rates typical of VT and is also known to promote arrhythmias. We therefore studied the role of intracellular Ca(2+) dynamics in the transition from VT to VF, using a combined experimental and mathematical modeling approach. Our results show that 1) rapid pacing of rabbit ventricular myocytes at 35 degrees C led to increased intracellular Ca(2+) levels and complex patterns of action potential (AP) configuration and the intracellular Ca(2+) transients; 2) the complex patterns of the Ca(2+) transient arose directly from the dynamics of intracellular Ca(2+) cycling, and were not merely passive responses to beat-to-beat alterations in AP; 3) the complex Ca(2+) dynamics were simulated in a modified version of the Luo-Rudy (LR) ventricular action potential with improved intracellular Ca(2+) dynamics, and showed good agreement with the experimental findings in isolated myocytes; and 4) when incorporated into simulated two-dimensional cardiac tissue, this action potential model produced a form of spiral wave breakup from VT to a VF-like state in which intracellular Ca(2+) dynamics played a key role through its influence on Ca(2+)-sensitive membrane currents such as I(Ca), I(NaCa), and I(ns(Ca)). To the extent that spiral wave breakup is useful as a model for the transition from VT to VF, these findings suggest that intracellular Ca(2+) dynamics may play an important role in the destabilization of VT and its degeneration into VF.

Action Potentials↗
PubMed1999

Protective effects of Ginkgo biloba extract EGb 761 on the myocardium of experimentally diabetic rats. II. Ultrastructural and immunohistochemical investigation on microvessels and interstitium.

Interstitial and microvascular disorders are known as a characteristic part of the diabetic cardiomyopathy and to resist partly insulin therapy. Aim of this study was to demonstrate structure-protecting effects of Ginkgo Extract EGb 761 known as a natural radical scavenger in streptozotocin-diabetic rats on the microvascular compartment. Wistar rats (n = 5) were made diabetical by i.p. injection of 60 mg/kg body mass streptozotocin for 4 months. Rats of the protected group (n = 5) received daily 100 mg/kg body mass EGb 761 for 3 months, starting 1 month after induction of diabetes. 5 age-matched rats served as control. The volume fraction of interstitium was slightly but significantly increased only in the unprotected diabetic group. Diminishing of the capillary to the myocyte ratio was seen in the diabetic but not in the protected group. Immunostaining of collagen revealed a slight increase of type III, type IV, and type VI fibres in the interstitium, more expressed in the unprotected group. Ultrastuctural morphometry revealed significant thickening of endothelial and muscular basement membranes in diabetic animals, less expressed in the EGb- protected group. The capillary diameter was slightly increased in the diabetic and slightly decreased in the protected group. The number of plasmalemmal vesicles was tendentially more decreased, that of lysosomes more increased in the diabetic than in the protected group. It is concluded that EGb 761 can diminish partly interstitial fibrosis and reduce endothelial and muscular basement membrane thickening of the diabetic myocardium. It may contribute to prevent late diabetic complications.

Animals↗
PubMed1999

[Histologic-histochemical and immunocytochemical investigations of cartilage canals in human rib cartilage].

In contrast to articular cartilage the hyaline rib cartilage takes up a special position due to its size, shape and the kind of mechanical stress as well. These facts may influence the metabolism of rib cartilage. In our histological, histochemical and immunohistochemical investigations on pieces of rib cartilages of 34 persons at the age of fourth fetal month up to 60 years we could regularly demonstrate cartilage canals containing blood vessels without any spatial or temporal relationship to degenerative changes in cartilage tissue. Many of these cartilage canals are located in the center of the rib cartilage. Blood vessels as well as neuronal structures in the connective tissue of cartilage canals were detected by means of antibodies against components of the vessel wall (Von Willebrand factor) and nerve fibers (PGP 9.5). Nerves may have sensoric or vasomotoric functions as well, and they may influence cell differentiation and regeneration processes, respectively. Cartilage can not be regarded as vascularized like other tissues, but cartilage canals may have great functional importance for the metabolism of rib cartilage.

Adolescent↗
PubMed1999

Heart rate and oxygen saturation correlates of infant apnea.

OBJECTIVE: To analyze the effects of apnea duration on changes in heart rate and oxygen saturation and to examine the temporal relationships among these variables. STUDY DESIGN: An event analysis sheet was designed to analyze numerous variables reflecting changes in heart rate and oxygen saturation associated with infant apnea. From July 1, 1991 through June 30, 1992 we identified 32 infants enrolled in The Infant Apnea Program at St. Peter's Medical Center, New Brunswick, NJ who had apnea > or = 15 seconds in duration on consecutive 12-hour multichannel recordings of heart rate, thoracic impedance, nasal thermistry, and oxygen saturation. The apnea epochs of these patients were subdivided into apnea of short (10 to 14 seconds), medium (15 to 19 seconds), and long (> or = 20 seconds) duration, and a total of 236 apnea epochs were analyzed. The significance of differences was assessed by analysis of variance and Newman-Keuls multiple comparisons. RESULTS: We found that the duration of apnea has significant effects on perturbations in both heart rate and oxygen saturation, however, the degree of oxygen desaturation can not be predicted by the perturbation in heart rate. Analysis of the temporal relationship of apnea, bradycardia, and oxygen desaturation reveals that, although apnea precedes both heart rate and oxygen saturation drops in most infants as the length of apneic interval increases, the interval between apnea onset and associated drops in heart rate and/or oxygen saturation also increases. CONCLUSION: Oxygen saturation monitoring may provide important physiologic data that can not be assessed by cardiorespiratory monitoring alone.

Apnea↗
PubMed1999

Adult ontogeny of rat working memory of social interactions.

BACKGROUND: Social memory has features that may make it uniquely appropriate for studying normal aging. We used a cross-section experimental design with an animal model to survey the lifetime adult ontogeny of memory of a brief social interaction. METHODS: Groups of healthy adult male rats representing young adulthood (5 months), middle age (10 months), or old age (19-27 months) were tested weekly over a month in two paradigms. Basic social memory and social interference memory were quantified by differences between investigation times of a juvenile rat during a 5-min interaction (acquisition trial) and a second exposure (recall testing), with interexposure intervals (IEI) ranging from 15 min to 24 h. RESULTS: Although basic social memory of all age groups was similar at the brief or longer IEI, there were memory declines at intermediate IEI delays in older males, especially the oldest groups. Decrements to working memory appeared as early as middle-age when an unfamiliar juvenile was inserted between acquisition and recall testing. Nonetheless, our healthy old animals retained a robust ability to recall identity of a conspecific that a minute by minute comparison suggested involves similar behavioral means of gathering social information. CONCLUSIONS: Normative aging of working social memory in male rats can be characterized as being more fragile, beginning at middle age but without significant further decline until near the end of the life span. Functional impact of these age-dependent changes in social memory, on the other hand, may be minimal for all but the very oldest animals in the social group.

Aging↗
PubMed1999

A simple, inexpensive and effective artificial cycle with exogenous transdermal oestradiol and vaginal progesterone for the transfer of cryopreserved pronucleated human oocytes in women with normal cycles.

Supernumerary pronucleated stage oocytes (PN) are usually cryopreserved. PN are transferred in spontaneous, stimulated or artificial cycles. In this study, an artificial cycle with a transdermal therapeutic system was used for oestradiol release (Estraderm TTS 100) in combination with a targeted drug delivery system for vaginal progesterone release (Crinone 8%). Patients started transdermal 17beta-oestradiol treatment on cycle day 1. Only one clinical monitoring was necessary on day 14 for confirmation of satisfactory endometrial development and exclusion of ovulation by transvaginal ultrasound and endocrine determinations (oestradiol, progesterone and luteinizing hormone). Embryo transfer was performed on the third day of progesterone treatment (day 17). The first 25 cycles were recently completed in a prospective study; no cycles were cancelled due to ovulation or unsatisfactory endometrial development. In comparison with the previous protocol of embryo transfer in stimulated cycles in our clinic which required extensive ultrasound and endocrine monitoring, the pregnancy rate in these oestrogen- and progesterone-supplemented cycles was nearly twice as high (34.8%). Two pregnancies were even achieved with zygotes after micro-injection of frozen-thawed late spermatids extracted from testicular tissue (cryo-TESE). In these cycles, the Estraderm TTS 100/Crinone 8% protocol seems to be superior to stimulation protocols and even to other protocols reported so far for artificial cycles with exogenous oestradiol and progesterone treatment.

Administration, Cutaneous↗
PubMed1999

Identification of naturally occurring follistatin complexes in human biological fluids.

Follistatin (FS) binds activin and inhibin proteins. Many organs are sensitive to activin and inhibin; thus the formation of FS-activin/inhibin complexes is important to our understanding of ligand activity. Other investigators studying FS have detected large molecular weight immunoreactive FS bands (greater than the expected molecular weight of FS alone) that have not been well characterized. The goal of this study was to identify naturally occurring FS monomers and FS-activin/inhibin complexes in several organ systems. The pituitary, ovary, kidney, and urine were chosen for this investigation. Molecular masses were assigned to in vitro assemblies of complexes containing recombinant inhibin or activin with FS for comparison with naturally occurring FS forms. The recombinant complex of FS-activin was primarily 97-kDa size, while FS-inhibin complexes were detected in a range of molecular sizes from 66 kDa to 97 kDa, 133 kDa, and > 220 kDa. FS-containing complexes of 66-kDa, 97-kDa, and 133-kDa were identified in the tissues examined and in pregnant urine. Our study points to the assembly of a series of FS-activin/inhibin complexes in a variety of organ systems that may impact upon the available amount of free versus bound (or "complexed") ligand, which must be considered when investigating the biology of activin- or inhibin-responsive cells. In addition, urine may be an important biological fluid that can be used to measure significant changes in circulating FS complexes.

Activins↗
PubMed1999

Antibacterial action of extracellular mammalian group IIA phospholipase A2 against grossly clumped Staphylococcus aureus.

Fibrinogen-dependent interactions of Staphylococcus aureus are believed to contribute to bacterial virulence by promoting bacterial attachment to fibrinogen-coated surfaces and inducing the formation of bacterial clumps that are likely resistant to phagocytosis. Although S. aureus produces several fibrinogen-binding proteins, the cell wall-associated protein clumping factor (encoded by clfA) appears to be most important in bacterial interactions with immobilized or soluble purified fibrinogen. We have compared bacterial clumping in several strains of S. aureus, including isogenic ClfA+ and ClfA- Newman strains, in the presence of purified rabbit fibrinogen, human plasma, and inflammatory fluid and examined the effect of clumping on bacterial sensitivity to mammalian group IIA phospholipase A2 (PLA2). This enzyme is the major extracellular bactericidal agent in inflammatory fluid active against S. aureus. Both ClfA-dependent and ClfA-independent bacterial clumping was observed, depending on the source and fibrinogen content of the biological fluid. In each case, clumping only partially reduced the antibacterial activity of PLA2, suggesting that this extracellular enzyme can substantially penetrate dense bacterial clumps. Bacterial clumps could be dispersed by added proteases, restoring full antibacterial activity to PLA2. Thus, the extracellular mobilization of group IIA PLA2 during inflammation may provide a mechanism by which the host can control the proliferation and survival of S. aureus even after bacterial clumping.

Animals↗
PubMed1999

Deacylation of purified lipopolysaccharides by cellular and extracellular components of a sterile rabbit peritoneal inflammatory exudate.

The extent to which the mammalian host is capable of enzymatic degradation and detoxification of bacterial lipopolysaccharides (LPS) is still unknown. Partial deacylation of LPS by the enzyme acyloxyacyl hydrolase (AOAH) provides such a mechanism, but its participation in the disposal of LPS under physiological conditions has not been established. In this study, deacylation of isolated radiolabeled LPS by both cellular and extracellular components of a sterile inflammatory peritoneal exudate elicited in rabbits was examined ex vivo. AOAH-like activity, tested under artificial conditions (pH 5.4, 0.1% Triton X-100), was evident in all components of the exudate (mononuclear cells [MNC] > polymorphonuclear leukocytes [PMN] > inflammatory [ascitic] fluid [AF]). Under more physiological conditions, in a defined medium containing purified LPS-binding protein, the LPS-deacylating activity of MNC greatly exceeded that of PMN. In AF, MNC (but not PMN) also produced rapid and extensive CD14-dependent LPS deacylation. Under these conditions, almost all MNC-associated LPS underwent deacylation within 1 h, a rate greatly exceeding that previously found in any cell type. The remaining extracellular LPS was more slowly subject to CD14-independent deacylation in AF. Quantitative analysis showed a comparable release of laurate and myristate but no release of 3-hydroxymyristate, consistent with an AOAH-like activity. These findings suggest a major role for CD14(+) MNC and a secondary role for AF in the deacylation of cell-free LPS at extravascular inflammatory sites.

Acylation↗
PubMed1999

Effect of training on the phagocytic capacity of peritoneal macrophages from rats exposed to swim stress.

Since strenuous effort may affect the immune system, a study was designed to examine the impact of the progressive training of rats exposed to swim stress. Rats (trained swimmers) were forced to swim daily in a water bath for progressively longer periods. At the end of the study, which continued for a total of 6 weeks, the superoxide anion generation and phagocytic capacity of peritoneal macrophages, the mitogen response of splenic cells (splenocytes) and the serum corticosterone level were examined. The results, compared to those of animals taken in and out of their cages (nonswimmers), showed an increase in superoxide anion generation, as well as a decrease in both the percentage of phagocytosing cells and the number of particles internalized by each individual cell. In trained swimmers, the mitogen response to phytohemagglutinin and concanavalin A (Con A), as well as the corticosterone level, did not change significantly from those of nonswimmers. A third group of animals were forced to swim once only for 30 min, until the appearance of signs of marked fatigue (acute swimmers). Their peritoneal macrophages showed an increased superoxide anion generation and a significantly decreased response to Con A compared to those of the nonswimmers. The serum corticosterone level in acute swimmers was found to be increased compared to that of an additional group of animals kept at complete rest. The findings indicate that the progressive training of rats exposed to swim stress does not prevent alterations in certain immune responses, a fact that should be considered by intensive exercisers.

Animals↗