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Biomedical subjects

J E Lang

Publications and source records attributed to J E Lang.

At least 19 recordsLinked to original sources
PubMed1999

Evidence that anticardiolipin antibodies are independent risk factors for atherosclerotic vascular disease.

Thrombophilic anticardiolipin antibodies (ACLAs) are independent risk factors for atherosclerotic vascular disease. We suggest that ACLAs IgG and IgM be routinely measured as ancillary atherothrombotic risk factors in all patients with atherosclerotic vascular disease events, in those at high risk for atherosclerotic vascular disease, and in those in whom thrombosis is a major pathoetiology.

Aged↗
PubMed1996

Induction of apoptosis by c-Fos protein.

The role of c-Fos in apoptosis was examined in two Syrian hamster embryo cell lines (sup+I and sup-II) and a human colorectal carcinoma cell line (RKO), using the chimeric Fos-estrogen receptor fusion protein c-FosER. As previously reported, contrasting responses were observed when these two cell lines were placed under growth factor deprivation conditions; sup+I cells were highly susceptible to apoptosis, whereas sup-II cells were resistant. In this report, we show that the activated c-FosER protein induces apoptosis in sup-II preneoplastic cells in serum-free medium, indicating that c-Fos protein can induce apoptotic cell death in these cells. c-Fos-induced apoptosis was not blocked by the protein synthesis inhibitor cycloheximide, suggesting that the c-Fos transcriptional activation activity is not involved. This conclusion was further supported by the observation that overexpression of v-Fos, which is highly proficient in transcriptional activation but deficient in the transcriptional repression activity associated with c-Fos, did not induce apoptosis. Constitutively expressed Bcl-2 delayed the onset of low-serum-induced apoptosis in sup+I cells and enhanced survival in sup-II cells. Further, coexpression of Bcl-2 and c-FosER in sup+I or sup-II cells protected the cells from c-FosER-induced apoptosis. The possibility that c-FosER-induced apoptosis requires a p53 function was examined. Colorectal carcinoma RKOp53+/+ cells, which do not normally undergo apoptosis in serum-free medium, showed apoptotic DNA fragmentation upon expression and activation of c-FosER. Further, when the wild-type p53 protein was diminished in the RKO cells by infection with the papillomavirus E6 gene, subsequent c-FosER-induced apoptosis was blocked. The data suggest that c-Fos protein plays a causal role in the activation of apoptosis in a p53-dependent manner. This activity does not require new protein synthesis and is blocked by overexpression of Bcl-2 protein.

Animals↗
PubMed1995

Evidence that homocysteine is an independent risk factor for atherosclerosis in hyperlipidemic patients.

In 482 patients sequentially referred for diagnosis and therapy of hyperlipidemia, our specific aim was to determine the prevalence of homocysteinemia, to assess whether it was independently associated with atherosclerotic vascular disease, and to determine how effectively high homocysteine could be treated with folic acid and pyridoxine. Of the 482 patients, 18 (3.7%) had high homocysteine (> or = 16.2 mumol/L, median = 19), 31 had high cystathionine (> or = 342 nmol/L) with normal homocysteine (median = 12), and 433 had normal cystathionine and homocysteine (median = 9). Of the 18 patients with high homocysteine, 13 (72%) had atherosclerotic vascular disease, much higher than the 44% (192 of 433 patients) with normal homocysteine (chi-square = 5.4, p = 0.02). In the 18 kindreds with a homocysteinemic proband, 14 (78%) had > or = 1 first-degree relatives with atherosclerotic vascular disease before age 65, compared with 50% (215 of 433) of the families where the proband had normal homocysteine (chi-square = 5.5, p = 0.02). In the 482 patients already at high risk for atherosclerotic vascular disease by virtue of hyperlipidemia, when assessed by logistic regression, homocysteine was an independent positive predictor of atherosclerotic vascular disease (p = 0.007); relative risk for atherosclerotic events was 2.8 times higher (p = 0.0004) in patients with top (> or = 11.4 mumol/L) than with bottom (< 6.9 mumol/L) quintile homocysteine. After 15 weeks of folic acid (5 mg/day) and pyridoxine (100 mg/day) therapy in 10 patients with high homocysteine, median homocysteine normalized, decreasing from 18 to 11 mumol/L (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Regulation of apoptosis by low serum in cells of different stages of neoplastic progression: enhanced susceptibility after loss of a senescence gene and decreased susceptibility after loss of a tumor suppressor gene.

A cell culture model system has been used to study the susceptibility of cells to apoptotic cell death during different stages of neoplastic progression. This system consists of normal diploid Syrian hamster embryo (SHE) cells, two preneoplastic cell lines [tumor suppressor stage I (sup +I) and non-tumor suppressor stage II (sup -II)], and hamster tumor cell lines. Stage I preneoplastic cells are nontumorigenic immortal clones that suppress tumorigenicity when hybridized to tumor cells, whereas stage II cells have lost the ability to suppress tumorigenicity in cell hybrids. We refer to these two types of preneoplastic cells as sup +I and sup -II, respectively. Neoplastic progression is generally associated with cellular alterations in growth factor responsiveness. Therefore, to study the regulation of apoptosis in the system described above, cells were cultured in low serum (0.2%) as a means of withdrawing growth factors. In low serum, normal SHE cells were quiescent (labeling index of 0.2%), with little cell death. The sup +I cells showed a relatively low labeling index (1.6%) but, in contrast to the normal cells, died at a high rate (55% cell loss after 48 h) by apoptosis, as evidenced by morphology, DNA fragmentation, and in situ end-labeling of fragmented DNA. The apoptotic cells did not go through a replicative cycle while in low serum, implying that apoptosis was initiated in the G0/G1 phase of the cell cycle. The sup -II cell line showed a high labeling index (40%) after 48 h, but cell growth was balanced by cell death that occurred at approximately the same rate. The cells died, however, predominantly by necrosis. The tumor cell lines continued to proliferate in low serum, with high labeling indices (ranging from 27% to 43%) and a low level of apoptotic or necrotic cell death. To determine the relative ability of these cells to survive in vivo, normal SHE cells, sup +I cells, and sup -II cells were injected s.c. into nude mice. At 5 or 21 days after injection, the normal SHE cells were readily retrieved from the mice and grew well in culture. In contrast, few sup +I cells were retrieved 5 days after injection and no viable cells were retrieved after 21 days. Sup -II cells were not retrieved at either the 5-day or 21-day harvest, and histological examinations of the sites of injection showed the presence of macrophages, eosinophils, and neutrophils, indicating an inflammatory response associated with necrotic cell death.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Cruciate paralysis. Case report.

A rare case of cruciate paralysis is reported in a 39-year-old man following a motor-vehicle accident. The differentiation of this syndrome from a central cervical spinal cord injury is delineated.

Adult↗
PubMed1983

Physical chemistry of freeze-drying: measurement of sublimation rates for frozen aqueous solutions by a microbalance technique.

The sublimation rate of frozen solutions was studied as a function of freezing rate, thickness of dried product (l), temperature, residual air pressure, and solute concentration. Data are presented for pure water, aqueous potassium chloride, aqueous povidone, and aqueous dobutamine hydrochloride-mannitol (System I). The resistance of the dried product to water vapor flow (Rp) was evaluated from the sublimation rate and the sample temperature. The primary experimental technique was based on freeze-drying a cylindrical microsample isothermally, with the sample suspended from one arm of a vacuum microbalance. Methodology to evaluate resistance data from vial freeze-drying experiments is also described. In separate experiments, samples in the form of a thin (15-microns) film were visually observed through a microscope during freeze-drying. Freeze-drying of most samples appeared to occur by water vapor escaping through open channels created by prior sublimation of ice. Contrary to the usual theoretical model, Rp is neither independent of temperature nor directly proportional to l. Rather, Rp decreases with increasing temperature and the l dependence is normally of the form Rp = (A0 + A1l)/(1 + A2l), where Ai (i = 0, 1, 2) are constants. In several cases, Rp is very large near l = 0, decreases sharply at l congruent to 0.1 cm, and obeys the above equation where l greater than 0.2 cm, a result suggesting an amorphous surface skin which cracks on desorption of water. The temperature dependence of Rp suggests that, as the sample temperature approaches the eutectic (or collapse) temperature, hydrodynamic surface flow of adsorbed water is an important flow mechanism.

Air Pressure↗
PubMed1981

Significance of relapse after adjuvant treatment with combination chemotherapy or 5-fluorouracil alone in high-risk breast cancer. A Western Cancer Study Group Project.

Beginning in 1974, patients undergoing mastectomy at high risk for recurrence (greater than or equal to 4 nodes positive; median, 9.4 positive; range, 4 to 28) were randomized after stratification for menopausal status and radiotherapy to receive either 5-fluorouracil (5-FU, 500 mg/sq m i.v. every week) or cyclophosphamide, 400 mg/sq m; methotrexate, 30 mg/sq m; and 5-FU, 500 mg/sq m (CMF; all given i.v. every 2 weeks) in a 12-month program. All 62 patients remain evaluable with median follow-up now exceeding 70 months (range, 60 to 80 months). CMF significantly prevented early disease recurrence (97% relapse free on CMF versus 75% on 5-FU at 12 months; p less than 0.05) and demonstrated survival advantage during the initial 40-month follow-up. This significance was subsequently lost, and the percentages of relapse free and overall survival after 70 months are: (formula, see text) The apparently paradoxical relationship between relapse and survival on the 5-FU arm was related to survival after recurrence. Survival after recurrence was significantly longer on the 5-FU compared to the CMF arm (median of greater than 38 versus 10 months, respectively; p less than 0.01). These results suggest (a) long-term survival in adjuvant trials cannot be accurately predicted by short-term differences in relapse frequency, (b) survival after relapse may be influenced by the antecedent adjuvant therapy received, and (c) disease relapse does not necessarily preclude long-term survival.

Breast Neoplasms↗
PubMed1978

Quantitative crystallinity determinations for beta-lactam antibiotics by solution calorimetry: correlations with stability.

The solution calorimetry method is based on the observation that amorphous forms are normally significantly higher in energy than are crystalline forms. The utility and validity of the calorimetric method were investigated for cephalothin sodium, cefazolin sodium, cefamandole nafate, and cefamandole sodium. Amorphous, partially crystalline, and crystalline forms were prepared and characterized by X-ray diffraction (powder), by solution calorimetry, and, for cephalothin sodium, by the thermal decomposition rate at 50 degrees. Qualitatively, there was a good correlation between calorimetric crystallinity and the (less precise) crystallinity derived from X-ray data. The energy and structure of the amorphous state depend on the history of the sample; even samples of the same crystalline polymorph, containing no amorphous phase, may differ in energy. Thus, the absolute value of the crystallinity (X-ray or calorimetric) depends on the choice of amorphous and crystalline standards. The heat of solution is a precise (+/- 1%) and unambiguous measure of the relative crystallinity; and provided amorphous and crystalline standards are appropriately chosen, the calorimetric crystallinity correlates well with chemical stability.

Absorption↗
PubMed1977

Thermal decomposition of amorphous beta-lactam antibacterials.

Thermal decomposition rates for amorphous samples of penicillin G potassium, cephalothin sodium, cefamandole sodium, and cefamandole nafate were determined as a function of water content and temperature. Even when rigorously dry, amorphous cephalosporins were at least one order of magnitude less stable than the corresponding unsolvated crystalline form. Absorbed water generally increased both the number of decomposition products and the net decomposition rate. Reaction kinetics were usually apparent first order, but an anomalously high effective reaction order was observed in several systems. Nonlinear Arrhenius plots were observed, and a qualitative model based on molecular relaxation in glayses is proposed. Although decomposition rates at 25 degrees were small for dry samples, even slight decomposition produced visually detectable changes. Thus, the unsolvated crystalline form was noticeably more stable, even at 25 degrees.

Anti-Bacterial Agents↗
PubMed1976

In vitro production of platelet-binding IgG in childhood idiopathic thrombocytopenic purpura.

We studied two boys, 9 and 10 years old, respectively, who underwent splenectomy eight months and six weeks after initially presenting as "typical" cases of childhood ITP. Splenic leukocytes from each child were cultured and net synthesis rates of IgG determined. Splenic synthesis rates of IgG were five-and sevenfold greater, respectively, than in spleens of control subjects. A significant portion of the splenic culture-produced IgG from each patient demonstrated specificity for homologous and autologous platelets. Synthesis rates of IgG were determined on serial cultures of bone marrow cells from the 10-year-old boy who failed to respond to splenectomy. His initial marrow synthesis rate of IgG was five times greater than mean control values. His synthesis rate of IgG in marrow decreased to the control range in association with immunosuppressive therapy and intesive platelet transfusions. These data suggest that (1) the spleen was a production site of platelet-binding IgG in the two children, and (2) the bone marrow may have been an additional site of production in our second patient.

Antibodies↗
PubMed1975

Human myeloma IgG half-molecules. Structural and antigenic analyses,.

The structure and antigenic characteristics of a human k, IgG myeloma protein that formed half-molecules were analyzed. Most of the myeloma protein found in the patient's serum and urine consisted to two chain 4.3S half-molecules. A small amount of four chain 7S myeloma protein was, however, found in the serum and was apparently formed by the same clone of tumor cells. Polyacrylamide gel electrophoresis in 8 M urea and 1% sodium dodecyl sulfate and analytical ultracentrifugation in 6 M guanidine of the fully reduced and alkylated half-molecule indicated that this myeloma protein had a heavy chain of a smaller molecular weight (approximately 45,000) than that of normal gamma chains, Except for this apparent deletion, the heavy chain resembled gamma1 chains. The amino acid composition of the peptides containing the half-cysteine residues forming the interchain disulfide bonds, the glycopeptide of the Fc fragment and the COOH-terminal structure were similar if not identical with the analogous structures of gamma1 chains. No Fc fragment could be prepared because the Fc portion of the heavy chain of the myeloma protein was extremely susceptible to degradation with papain. After mild reduction and alkylation, the 7S myeloma protein dissociated into half-molecules, indicating a lack of noncovalent interactions in the Fc fragment that are present in all classes of human immunoglogulins and are responsible for the formation ofFc dimers. The half-molecule was antigenically deficient in the Fc fragment. It failed to precipitate with anti-Fc fragment antisera in double gel diffusion tests and inhibited a Fc-anti-Fc fragment binding reaction weakly and incompletely. The half-molecule and the 7S protein had the same genetic markers on the first and second homology region of the gamma chain. The half-molecule lacked, however, the corresponding markers on the third homology region, These findings suggest that this myeloma protein had a deletion in the gamma chain which was probably located in third homology region and was likely the structural abnormality responsible for the lack of noncovalent interaction in the Fc fragment and absence of most of the antigenic determinants characteristic of gamma chains.

Amino Acid Sequence↗
PubMed1975

IgG half-molecules: clinical and immunologic features in a patient with plasma cell leukemia.

The clinical manifestations and immunologic features of a patient with plasma cell leukemia who produced k, IgG half-molecules are described. His serum contained both 7S myeloma protein and 4.3S half-molecules, whereas his urine contained predominantly half-molecules. The half-molecules were discovered because the serum and urine formed double precipitin lines when analyzed by commercially available IgG radial immunodiffusion plates that contained antibodies to determinants on both the Fab and Fc fragments. Immunoelectrophoresis also revealed double precipition lines with such antisera. In contrast, when antisera specific for the IgG Fc fragment were used, the serum showed only a single line formed by intact IgG, and the urine failed to react, indicating that the half-molecule was antigenically deficient in the Fc fragment. The half-molecule consisted of one covalently linked heavy and light chain, both having about normal molecular weights, suggesting that they did not have a large deletion which could have caused the half-molecule production. Comparison of the clinical manifestations of the patient with those of four other known patients who produced half-molecules suggested that half-molecule formation is not associated with a distinct clinical syndrome.

Aged↗
PubMed1975

Coagulation changes in baboons during acute experimental hemoglobinemia and dextran infusion.

Evidence of disseminated intravascular coagulation (DIC) was dought in normal baboons infused with autologous hemolyzed whole blood, preceded or followed by infusion of dextran (molecular weight, 70,000). Mean peak plasma hemoglobin following a rapid single injection was 370 mg/100 ml in 2 animals and 1,236 mg/100 ml in 1 animal, while levels during continuous 5 hour infusion in 2 animals averaged 326 and 474 mg/100 ml, respectively. Dextran infusion immediately preceded hemoglobin injection in 2 baboons and followed hemoglobin injection by 1 1/2 and 2 1/2 hours, respectively, in 2 baboons. Coagulation studies showed a moderate although significant fall in platelet count with prolongation of the partial thromboplastin time following hemoglobin infusion, and shortening of the thrombin time after dextran. Fibrin degradation products developed in four of five experiments after hemolysate injection. The induction of acute experimental hemoglobinemia results, therefore, in the development of coagulation changes consistent with milk DIC. Preliminary infusion of dextran (molecular weight, 70,000) may facilitate this response by either initiating the development or impeding the clearance of fibrin degradation products.

Acute Disease↗
PubMed1974

Klippel-Feil syndrome; a constellation of associated anomalies.

Of fifty patients with the diagnosis of Klippel-Feil syndrome, less than half had the classic clinical triad of findings, while more than half had scoliosis, and a third had renal anomalies. All patients were at risk of having other serious, but less apparent, anomalies, including: Sprengel's deformity (twenty-one patients), impairment of hearing (fifteen patients), synkinesia (nine patients), and congenital heart disease (seven patients). The discovery of one of these lesions should, therefore, stimulate a careful search for associated anomalies.

Abnormalities, Multiple↗