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Biomedical subjects

A Weiss

Publications and source records attributed to A Weiss.

At least 271 records · Page 15Linked to original sources

[Organ manifestations of malignant lymphoma. Results of 10 years' sonographic follow-up of 550 patients].

Over a period of 10 years and by performing slightly more than 5,000 examinations, the incidence rate of organ infiltrations in case of malignant lymphomas was determined in 550 patients. 316 of these patients had non-Hodgkin lymphomas of low malignancy (NHLL), 127 non-Hodgkin lymphomas of high malignancy (NHLH) and 107 patients had lymphogranulomatosis. Liver infiltrations were detected in 30.9% of the patients with LG, in 31.5% of the patients with NHLH and in 13% of the patients with NHLL. In respect of histology, sonography had a sensitivity of 89 and a specificity of 95%. 17.8% of the patients with LG, 8.7% of those with NHLH and 6% of those with NHL had a nodular spleen infiltration; only 2 out of 21 patients of whom comparative histology was available had been falsely assessed negatively. In 2.8% of the patients with LG, 13.4% of those with NHLH and 5% of those with NHLL an infiltration of the gastrointestinal tract was seen. Compared with histological findings, sonography had a sensitivity of 85.7% and a specificity of 93.2%. Infiltrations of the pleura were more frequent in patients with lymphogranulomatosis (13.1%) than in patients with NHLH (7.8%) or NHLL (3.8%). The same phenomenon was seen in infiltrations of the pericardium (LG 10.3%, NHLH 8.7%, NHLL 2.8%). Infiltrations of thyroid, kidneys and urinary bladder are less frequent; the assessed rate of incidence is at the most 2%. Sonography is the imaging method of choice in the diagnosis and follow-up control of organ infiltrations in malignant lymphomas.

Follow-Up Studies↗

Ligand-induced association between the T-cell antigen receptor and two glycoproteins.

We have identified two cell surface glycoproteins of 34 and 38 kDa (gp34 and gp38) that associate with the T-cell antigen receptor (TCR). The coimmunoprecipitation of these proteins with the TCR is increased by treatment with monoclonal antibodies (mAbs) directed against the TCR prior to cell solubilization and immunoprecipitation. Treatment of T cells with mAbs directed against other cell surface molecules, CD2 or HLA, does not induce the association of these proteins with the TCR. The coimmunoprecipitation of gp34 and gp38 with the TCR requires solubilization in the presence of an alkylating agent, suggesting that subunit alkylation stabilizes the interaction. J.CaM1 and J.CaM2 are signal-transduction mutant cell lines derived from Jurkat. These cell lines fail to activate the inositol phospholipid second messenger pathway in response to anti-TCR mAbs. Treatment with mAb C305 (anti-TCR) induces the association of gp34 and gp38 with the TCR in J.CaM2 cells but not in J.CaM1. J.CaM1 modulates the TCR normally in response to anti-TCR antibody treatment. This observation suggests that gp34 and gp38 are involved in the signal-transduction pathway of the TCR complex rather than receptor internalization. Furthermore, since these proteins do associate with the TCR of J.CaM2, the induced association with the TCR is not a consequence of signal transduction.

Antibodies, Monoclonal↗

Severe paravalvular mechanical hemolysis with a normal blood smear.

A 74-year-old white female presented with clinical and laboratory evidence of severe hemolysis caused by paravalular leakage around a prosthetic mitral valve. The unique aspect of ther case is the absence of red blood cell fragments in the peripheral smear. Red blood cell transfusions, which averaged three to four units per week, were no longer required after operative repair of the primary suture line. All evidence for hemolysis disappeared; hematologic values returned to normal and remained so during the subsequent six months.

Acute Disease↗

Estimation of phenolic conjugation by colonic mucosa.

Conjugation of phenol by the colonic mucosa was assessed in vivo using dialysis tubing containing 1.5 ml of 1 mmol/l acetaminophen (paracetamol) and 10 mmol/l butyrate. These were allowed to equilibrate in the rectum for one hour. The glucuronidated and sulphated conjugates of acetaminophen were measured by high pressure liquid chromatography and bicarbonate concentrations by gas analysis. In 21 subjects without colonic disease sulphate conjugation was observed in all cases, with a mean (SE) of 3.86 (0.66) nmol/hour, while glucuronide conjugation was found in seven of 21 cases. Mean (SE) bicarbonate output of 42.9 (3.9) mumol/hour (n = 21) indicated healthy colonic mucosal metabolism and phenolic sulphation in dialysate and agreed with published sulphation rates obtained with cultured cells of colonic epithelium. Acetaminophen sulphation suggests that the colonic mucosa has an important role in the conjugation of phenols, and the method reported here would be useful in assessing the detoxification capacity of the colonic mucosa in diseases of the rectal mucosa.

Acetaminophen↗

Ultrasound assessment of the bladder volume after anterior colporrhaphy.

In 40 gynecological patients 44 different determinations of the bladder volume were made using ultrasonic methods. The product of bladder depth, height, and width, as determined from transverse and sagittal scans, showed the best correlation with the bladder volume measured by urethral catheter (r = 0.981). For 73% of the measurements the error was under 20% when the true bladder volume was greater than 100 cm3. This method gives a reasonable assessment of the bladder residual volume. It is quick, safe, and repeatable and, therefore, useful in postoperative clinical practice.

Adult↗

The lysine residue in the membrane-spanning domain of the beta chain is necessary for cell surface expression of the T cell antigen receptor.

The TCR is a complex receptor composed of seven polypeptide chains consisting of a ligand-binding subunit, Ti, and a putative signal-transducing subunit, CD3. Phylogenetically conserved charged amino acid residues within the membrane-spanning domains present in all seven chains of the TCR have been proposed to be important in the association between Ti and CD3. Using a Ti beta chain-deficient mutant of the cell line Jurkat, site-directed mutagenesis and transfection of Ti beta chain cDNA was performed to assess the importance of the lysine residue at position 290 within the membrane-spanning domain of the Ti beta chain to expression of the TCR complex. These studies demonstrated that the lysine residue, and not simply conservation of either basic charge or secondary structure, is important at this position.

Blotting, Northern↗

The CD2 ligand LFA-3 activates T cells but depends on the expression and function of the antigen receptor.

The T cell Ag receptor (CD3/Ti) and the sheep E receptor (CD2) expressed on the surface of human T cells are both capable of initiating intracellular signals necessary for T cell activation. CD3/Ti interacts with Ag to initiate cellular immune responses. Although the exact function of CD2 is unknown, lymphocyte function-associated Ag 3 (LFA-3), a 55- to 70-kDa receptor expressed on a broad spectrum of hemopoietic and nonhemopoietic cells, has recently been shown to be its natural ligand. We show here that although purified multimeric LFA-3 is not capable of initiating transmembrane signaling events on its own, the combination of LFA-3 and the anti-CD2 mAb CD2.1 induces intracellular calcium increases, phosphatidylinositol second messenger generation and lymphokine secretion in the T cell leukemic line Jurkat. In order to study the signaling requirements of CD2, we compared the ability of CD2 mAb and LFA-3 to initiate activation signals in Jurkat and in three Jurkat-derived mutants. A CD3-CD2+ mutant failed to increase calcium or exhibit phosphatidylinositol hydrolysis to either the combination of agonist CD2 mAb 9-1 and 9.6 or LFA-3 and CD2.1. Reconstitution of the Ag receptor by transfection of the Ti-beta-chain restored the expression of the CD3/Ti complex and the ability to respond to either combination of CD2 ligands. However, no response to CD2 ligands was detected in a CD3+CD2+ mutant selected for signaling defects to CD3/Ti ligands. Complementation of the CD3/Ti signaling defect by cell fusion also restored competency to respond to CD2 agonists. These results demonstrate that LFA-3 under appropriate conditions can activate T cells via the CD2 complex and that this activation requires not only the cell surface expression of the CD3/Ti complex but also a functional Ag receptor pathway.

Adjuvants, Immunologic↗

Early signal transduction by the antigen receptor without commitment to T cell activation.

The T lymphocyte antigen-receptor complex mediates antigen-specific cell activation, at least in part, through the production of inositolphospholipid-derived second messengers. Little is known about how second messenger events, typically measured within minutes of ligand binding, eventually lead to distal biologic responses such as expression of lymphokine genes. Several monoclonal antibodies directed against the receptor complex were tested for their ability to elicit transmembrane signaling in the parental Jurkat line and in a somatic mutant (J.CaM1) with a deficient receptor function. One antibody elicited substantial early Ca2+ mobilization responses in both cells but was unable to promote expression of the interleukin-2 gene in J.CaM1. In J.CaM1 there was a diminished production of phosphatidylinositol second messengers, and the elevation in intracellular free Ca2+ was transient. Thus, short-term Ca2+ mobilization does not always indicate complete signal transmission and lead to a full cellular response.

Calcium↗

Evidence for IL-2 independent proliferation in human T cells.

Previous models of human T cell proliferation have assumed IL-2 to be largely responsible for the clonal expansion observed after TCR complex (CD3/Ti)-mediated stimulation. By using mAb to the CD3 component of CD3/Ti as well as mAb to other nonpolymorphic T cell surface molecules, we demonstrate T cell proliferation in the absence of detectable IL-2 and define some of the conditions necessary for IL-2 production in vitro. PBL cultured with soluble OKT3 alone or OKT3 plus PMA proliferated nearly equally, but IL-2 was detectable only in the supernatants in the latter condition. RNA blot analyses at 8, 16, and 36 h consistently showed high levels of IL-2 transcripts in the OKT3 + PMA stimulated cells. In contrast, when stimulated with OKT3 alone IL-2 transcripts were barely detectable at the 8-h time point only. Anti-Tac only partially inhibited proliferation induced by either OKT3 or OKT3 + PMA, but consistently prevented it when PBL were stimulated by PMA plus exogenous human rIL-2. Cyclosporin A (CsA) was added in varying doses to PBL cultured in the presence of OKT3 + PMA. At 0.05 microgram/ml, proliferation was only partially inhibited, whereas IL-2 was undetectable. To examine the possibility that IL-4 could account for the observed proliferative response, CsA was added to PBL cultured with either OKT3 alone or OKT3 and PMA. Although IL-4 transcript levels were detectable in the presence of OKT3 alone or OKT3 + PMA, CsA at 0.05 microgram/ml allowed proliferation to occur in the absence of detectable IL-2 as well as IL-2 and IL-4 transcripts. Finally, T cell-enriched PBL were shown to proliferate and also to produce substantial quantities of IL-2 in response to immobilized OKT3 + either OKT11 or 9.3. These results strongly suggest the existence of an IL-2 and IL-4 independent pathway of human T cell proliferation and demonstrate that IL-2 production may result only when a closely defined set of stimuli are present.

Antibodies, Monoclonal↗

[Fatal complication of fine-needle biopsy of the liver].

A 62-year-old woman with cirrhosis of the liver was suspected of also having a primary liver-cell carcinoma. After puncture of a circumscribed liver process with a biopsy fine-needle there occurred massive bleeding which could not be surgically stopped, and the patient died. This was the first fatal outcome among 2760 fine-needle punctures in the author's personal series (0.036%).

Biopsy, Needle↗

Growth and repair of cartilage: organ culture system utilizing chondroprogenitor cells of condylar cartilage in newborn mice.

The zone of progenitor cells of mandibular condyles of neonatal mice was kept in an organ culture system for up to 8 days. Qualitative and quantitative determinations indicated a pronounced proliferative activity during the initial phases of the culture followed by a differentiation phase and the acquisition of typical hyaline cartilage. The mature hypertrophic chondrocytes were found to be surrounded by cartilage-specific macromolecules such as type II collagen, cartilage proteoglycans, and cartilage anchorin. The extracellular mineralization proceeded along matrix vesicles as is usually noted in vivo. A unique finding in this study was the observation that explants comprising cartilage progenitor cells and their adjacent extracellular matrix succeeded in repairing the damaged condylar in vitro.

Animals↗

Function of the antigen receptor in T cell activation.

The studies described here, including ours and those of others, were aimed at understanding the mechanism(s) by which the T cell antigen receptor transmits signals that result in expression of lymphokine genes. They have focused both on the proximal molecules and biochemical events that account for transmembrane signalling, as well as on the more distal nuclear regulatory events. It is now clear that the receptor is coupled to the PI pathway, apparently via conformational changes in Ti, possibly amplification by CD3, and likely a G protein. PI second messengers appear to contribute to subsequent gene expression events, but may not be required for receptor down-regulation. How these biochemical events are coupled to gene expression still remains a mystery. However, studies of the regulation of the IL-2 gene indicate that the proximal receptor-mediated events must occur continuously for 2-4 hours to support transcriptional activation of the IL-2 gene, and that protein synthesis during this time is required. Other genes, such as the proto-oncogene c-fos, become transcriptionally active within 15 minutes of receptor triggering even in the presence of protein synthesis inhibitors. Thus, coupling of the proximal biochemical events to expression of the IL-2 gene may be dependent on the induction of a regulatory protein(s). This protein(s) may act to activate the IL-2 gene via a 275 bp segment that lies upstream of the IL-2 coding region. Studies are now in progress to understand better the molecular requirements for competence in signal transduction and conversion of these signals into gene expression events.

Animals↗

Triamcinolone impairs the synthesis of collagen and noncollagen proteins in condylar cartilage of newborn mice.

The effects of triamcinolone hexacetonide (TH) on the synthesis of collagen and noncollagen proteins were tested in mandibular condylar cartilage of newborn mice. Four-day-old ICR mice received a single i.p. injection of TH at doses ranging from 0.4 to 4.0 mg/kg body weight. Hydrocortisone, deoxycorticosterone, dexamethasone, and progesterone were administered at a dose of 4.0 mg/kg. Test animals and nontreated and vehicle-treated controls were sacrificed after 24, 48, and 72 hours and were processed for electron microscopy. Additional animals were injected with 5 microCi of 3H-proline 2 hours before sacrifice. The specimens were extracted with 5% TCA containing 1 mM proline followed by 5% TCA, acetone, and ether, homogenized and digested with purified bacterial collagenase, and the amounts of radioactivity in collagenase digestible (CDP) and noncollagen proteins (NCP) were determined. The present results revealed that triamcinolone led to a significant dose-dependent decrease in the protein content of the tissue that lasted for 3 days (12-14% at the dose of 4 mg/kg). The incorporation of 3H-proline into CDP was reduced by 39, 57, and 42% at 24, 48, and 72 hours, respectively whereas the incorporation into NCP was reduced by 20, 35, and 23%, respectively. When compared with other steroids, dexamethasone revealed a similar inhibitory effect, whereas hydrocortisone and deoxycorticosterone had no significant effect. Progesterone, on the other hand, showed a transient (24 hours) stimulatory effect on the synthesis of collagen synthesis (21%, P less than 0.05). Electron microscopy showed an atypical arrangement of collagen fibers and accumulation of large aggregates of collagen that filled the entire matrical space between cartilage cells.

Adrenal Cortex Hormones↗

Differentiation of cartilage cells studied by quantitative [3H]thymidine autoradiography in vitro.

The apical segments of the mandibular condylar cartilage of newborn ICR mice, containing the intact zones of progenitor cells along with a few rows of chondroblasts were initially prelabelled in vitro with [3H]thymidine and were subsequently chased and cultured for as long as eight days. Such explants underwent a process of tissue regeneration, as after three days in culture they reconstituted the original structure of the organ, thus resembling the in vivo appearance of neonatal mandibular condylar cartilage. Cellular proliferation with subsequent differentiation in the regenerating tissue was followed by means of quantitative autoradiography. Immediately after labelling, the autoradiography-positive grains were confined exclusively to progenitor cells. The latter revealed a substantial ability to proliferate in vitro, a fact that was manifested by a progressive increase in the labelling index along the course of the culture. The latter process was followed by cellular differentiation thereby obtaining hypertrophic chondrocytes. The increase in the rate of labelling index and in the total number of [3H]thymidine-labelled cells was significantly correlated with the overall growth of the regenerating explants.

Animals↗

Historical communication: Philadelphia-positive chronic myelogenous leukemia followed for 27 years.

The patient we studied was diagnosed as having chronic myelogenous leukemia (CML), possibly radiation-induced, in 1960 at age 9, and a Philadelphia chromosome was first demonstrated in the neoplastic cells in 1961. Her subsequent clinical course has been cyclic, requiring periodic therapy, but there has been no karyotypic progression. A study in 1987 continued to show the typical t(9;22) translocation as the only cytogenetic alteration, and concurrent molecular investigation of the neoplastic cells revealed a breakpoint cluster region rearrangement, also typical of CML. The chromosomal and molecular data provide no obvious explanation for her remarkably prolonged survival.

Bone Marrow↗

A comparative study of frequency domain and time domain analysis of signal-averaged electrocardiograms in patients with ventricular tachycardia.

Although both time domain and frequency domain analysis of signal-averaged electrocardiograms (ECGs) may distinguish patients with and without sustained ventricular tachycardia, it remains unclear which method is superior. Both methods were assessed in 55 subjects comprising 26 patients with sustained ventricular tachycardia (Group I), 18 control patients with organic heart disease but without sustained ventricular tachycardia (Group II) and 11 normal volunteers (Group III). Time domain analysis was performed with high pass filtering of 25, 40 and 80 Hz and low pass filtering of 250 Hz. Frequency domain analysis was performed on the terminal 40 ms of the QRS complex, either alone or with 216 or 150 ms of the ST segment. Absolute summed energies of discrete frequency bands and band energy ratios were calculated. The effectiveness of discrimination between Groups I and II was evaluated in terms of group means, sensitivity, specificity and an information content index based on receiver operating characteristic curve analysis. Group I showed a uniform decrease in amplitude across all frequencies derived from the terminal 40 ms of the QRS complex (p less than 0.005). This was abolished by the inclusion of ST segment data in frequency domain analysis. No frequency band was unique for Group I. At a specificity of 78%, the best time domain sensitivity was 85%, and the best frequency domain sensitivity was 77%. The best time domain information content index was 0.156, the best index for frequency domain analysis was 0.077 using absolute band areas. It is concluded that patients with sustained ventricular tachycardia have decreased energy content across all frequencies in the terminal 40 ms of the QRS complex. Frequency domain analysis was not an improvement over time domain analysis in differentiating patients with ventricular tachycardia from those without.

Adult↗