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Biomedical subjects

J Greiner

Publications and source records attributed to J Greiner.

At least 55 records · Page 3Linked to original sources

One-step preparation of 6-perfluoroalkylalkanoates of trehalose and sucrose for biomedical uses.

The Mitsunobu reaction has been used to obtain 6-polyfluoroalkanoates of alpha,alpha-trehalose and sucrose in yields of approximately 40% and approximately 25%, respectively. 6,6'-Diesters (3-6%) were formed in some reactions and a 6-ester (1.3%) of alpha-D-glucopyranosyl 3,4-anhydro-beta-D-tagatofuranoside in one reaction. The monoesters displayed strong surfactant properties, and reduced considerably the water surface and fluorocarbon/water interfacial tensions. Preliminary results on biocompatibility were encouraging, especially for the 6-esters of alpha,alpha-trehalose.

Animals↗

Effects of the synthetic ether phospholipid KO-286011 on cells and components of rabbit blood.

The ether phospholipid KO-286011, which is related to platelet-activating factor (PAF), was examined for PAF-antagonistic action on rabbit platelets both in vitro and ex vivo. It inhibited the aggregation of washed platelets induced by PAF (5 nmol/l) concentration dependently (IC50 = 6.5 X 10(-7) mol/l). After injecting 0.5 mg/kg to rabbits, the ex vivo PAF-mediated aggregation in heparinized platelet-rich plasma was influenced selectively. The inhibition was short and maximal after 5 min. In contrast, hematocrit, counts of peripheral platelets and leukocytes, hemoglobin content, partial thromboplastin time, prothrombin time, and fibrinolytic activity in plasma were not affected. However, the therapeutic range of KO-286011 is limited because of membranolytic activity at higher dosages, leading to hemolysis and drop of circulating platelet counts.

Animals↗

Synthesis of perfluoroalkylated xylitol ethers and esters: new surfactants for biomedical uses.

New, well-defined surfactants and cosurfactants were synthesized with the objective of enhancing the stability of fluorocarbon emulsions destined to serve as oxygen carriers for biomedical applications. Monoperfluoroalkylated ethers of xylitol were achieved by addition of perfluoroalkyl iodide on the double bond of a protected xylitol allyl ether in a one-step addition-elimination reaction. Monoesters were obtained specifically on position 5 by treating 1,2:3,4-di-O-isopropylidenexylitol with perfluoroalkylated acid chlorides of various chain lengths in pyridine at room temperature. The products display strong surface activity and produce a remarkable synergistic stabilization of a fluorocarbon/Pluronic F-68 type emulsion. Biocompatibility data are reported, which include in vitro toxicity tests on Namalva cell cultures and hemolysis tests on human blood cells; the latter was found to decrease as the length of the F-alkyl chain increased. IV injection in mice (n = 10) showed that these products were innocuous at 400-1000 mg/kg of body weight. Preliminary exchange-perfusion experiments on rats with an emulsion containing the F-octyl xylitol ether were encouraging.

Animals↗

[Early amniocentesis].

Preliminary clinical experience with early amniocentesis is reported. Fifty-two amniocenteses were performed before the end of the 14th week following the last menstrual period. Cytogenetic and biochemical analyses (AFP, AChE) were performed. Increasing experience with amniotic fluid samples containing small-cell populations and the use of combined culture media improved the poor initial results to a 100% level, thus enabling the use of this technique for diagnostic purposes. The sampling technique and the post-procedural evolution of twelve amniocenteses in pregnant women, whose pregnancy is to be continued, are presented. The possibility of performing amniocentesis in early pregnancy is discussed with reference to anatomical aspects (amniotic and chorionic cavity).

Acetylcholinesterase↗

[Inflammation-inhibiting effect of magnesium ions in contact eczema reactions].

Water containing high concentrations of magnesium ions (e.g. Dead Sea water) is effective in the treatment of inflammatory skin diseases. Therefore, we examined the influence of Mg2+ on inflammation in allergic contact dermatitis induced by 1-chloro-2,4-dinitrobenzene (DNCB) in BALB/c mice. Animals challenged with 0.125% DNCB in the presence of magnesium chloride (28% and 14%) demonstrated significantly less pronounced contact dermatitis (ear swelling) than did animals challenged with DNCB alone (p less than 0.001 and p less than 0.01). In mice challenged with DNCB in combination with sodium chloride (14%) there was no statistically significant difference in the degree of ear swelling. These results were borne out in 5 patients known to be allergic to nickel, in whom magnesium chloride but not sodium chloride, suppressed nickel sulphate-induced contact dermatitis.

Adolescent↗

[Therapeutic use of splenopentin (DA SP-5) in patients with psoriasis arthropathica].

8 patients with confirmed psoriatic arthritis were treated with splenopentin for 12 months. A relief of joint pain could be detected under this treatment both after 6 weeks (improvement of the Ritchie-indices: 44%) and after 12 months (improvement: 28%). In contrast to this, X-ray investigations show a worsening of the disease after 12 months. Therefore we conclude that splenopentin alone is not a sufficient therapeutic drug in patients suffering from psoriatic arthritis.

Adult↗

[Abnormal hematopoiesis in psoriasis--in vitro studies].

Using mononuclear cells (MNC) of patients suffering from psoriasis for production of colony-stimulating factors (CSF) an abnormal colony formation in bone marrow of healthy volunteers was detected (colony-forming assay): Number of colonies per 10(5) bone marrow cells after cultivation with 10(6) MNC of patients suffering from psoriasis vulgaris: 65 +/- 14 (n = 8); psoriasis arthropathica: 63 +/- 11 (n = 8). Control values (10(5) bone marrow cells plus 10(6) MNC of healthy donors): 116 +/- 23 (n = 10). Statistical differences: psoriasis vulgaris: p less than 0.001; psoriasis arthropathica: p less than 0.001. The mechanisms responsible for these abnormalities in hematopoiesis are still unknown. They may be of pathogenic significance in psoriasis.

Adolescent↗

mRNA expression of transforming growth factor alpha in human breast carcinomas and its activity in effusions of breast cancer patients.

Transforming growth factor alpha (TGF alpha) mRNA expression was measured by Northern blot analysis in 18 human, primary, infiltrating, ductal breast carcinomas. Expression of a 4.8-kilobase TGF alpha mRNA transcript was detected in nine of 18 tumors. No evidence was observed of any gross amplifications or major rearrangements of the TGF alpha gene in the breast carcinoma specimens. Biologically active and immunoreactive TGF alpha was measured in the pleural effusions or in the ascitic fluids from 37 noncancer and 63 cancer patients. The TGF alpha activity detected ranged from 0.2 to 26 ng/mL in most effusions from both groups. However, 29 of 63 (46%) of the effusions from cancer patients exhibited TGF alpha levels that were 6 ng/mL or higher, whereas only seven of 37 (19%) of those from noncancer patients exceeded this level (P less than .03). In particular, effusions obtained from breast cancer patients showed a significantly higher level of TGF alpha, compared with those from noncancer patients (P less than .001). Effusions from 14 cancer patients also contained elevated levels of two tumor-associated antigens, CEA and/or TAG-72, and within this group, nine also had elevated levels of TGF alpha.

Ascitic Fluid↗

Modulation of carcinoembryonic antigen messenger RNA levels in human colon carcinoma cells by recombinant human gamma-interferon.

Recombinant human interferons have recently been shown to enhance tumor antigen expression, including carcinoembryonic antigen (CEA), on the surface of human carcinoma cells, which results in an increase in the targeting of antitumor monoclonal antibodies (MAb) in vivo. We report here the effect of recombinant human gamma-interferon (HuIFN-gamma) on the expression of human CEA and its related transcripts in several human colon carcinoma and normal human fibroblast cell lines. The colon tumor cell lines HT-29, WiDr, and LS-174T were each shown to express different constitutive levels of CEA glycopeptide, as measured by the binding of the CEA-specific MAb COL-4. Treatment with HuIFN-gamma enhanced the level of binding of COL-4 in total cell extracts of HT-29 and WiDr cells 2.5- and 6.5-fold, respectively. Using a CEA complementary DNA probe, this increase in MAb binding was shown to be accompanied by a 6- to 11-fold increase in the steady state levels of three CEA transcripts with sizes of 4.2, 3.5, and 2.8 kilobases. On the other hand, HuIFN-gamma treatment had no effect on the level of COL-4 binding or expression of CEA transcripts in LS-174T colon carcinoma cells, which are high constitutive expressors of CEA glycoprotein. Normal human fibroblast cell lines MRC-5 and WI38 had no detectable cytoplasmic CEA glycopeptide levels nor did they contain detectable levels of CEA mRNA, either before or after treatment with HuIFN-gamma. In contrast, HuIFN-gamma induced the de novo expression of the normal major histocompatibility complex class II antigen, HLA-DR, on HT-29 and WiDr colon cancer cells as well as the two fibroblast cell lines. Treatment of the LS-174T cell line with HuIFN-gamma did not result in the induction of class II HLA-DR antigen. These observations suggest that some common factors may be involved in the regulation of the CEA and class II histocompatibility genes. In addition, the demonstration that HuIFN-gamma enhances CEA expression in some carcinoma cell lines but fails to induce de novo expression of CEA transcripts in fibroblasts supports the potential application of HuIFN-gamma in enhancement of tumor targeting of antitumor MAbs and adds to our understanding of the mechanism of gamma-interferon-mediated up-regulation of some tumor antigens.

Carcinoembryonic Antigen↗

The secretor locus as a marker for prenatal prediction of myotonic dystrophy (DM).

To verify the reliability of secretor status for prenatal diagnosis of myotonic dystrophy (DM), 179 amniotic fluid samples were compared with saliva or urine samples of the infants by hemagglutination inhibition. While no discrepancies were observed, problems could arise with intermediate results. Additionally, secretor typing is only informative in 8.4% of patients.

ABO Blood-Group System↗

Design, synthesis and evaluation of fluorocarbons and surfactants for in vivo applications. New perfluoroalkylated polyhydroxylated surfactants.

The progress achieved since the advent of Fluosol-DA is summarized in this paper, with special focus on the synthesis and evaluation of more adequate, reliable, industrially feasible fluorocarbons, structure/property relationships--molecular weight being recognized as the pre-eminent determining factor of both the fluorocarbon's excretion rate and the emulsion's stability-, the preparation of significantly more concentrated, more efficacious emulsions, etc. The key to further progress and better mastery of the emulsions' characteristics, especially in relation to increased shelf-life, prolonged i.v. persistence, and versatility, now lies in the development of new surfactants, better adapted to this objective. New families of well defined, monodisperse perfluoroalkylated polyhydroxylated surfactants derived from sugars and related compounds have been synthesized and fully characterized. Preliminary evaluation of their surface-active properties, emulsion stabilizing capacity and biocompatibility are reported.

Biocompatible Materials↗

Monoclonal antibodies to breast cancer-associated antigens as potential reagents in the management of breast cancer.

Monoclonal antibodies reactive with the surface of human breast carcinoma cells have been generated and characterized. The immunogens used were membrane-enriched fractions of metastatic carcinoma lesions. The various monoclonals were shown to react with previously known as well as with novel tumor-associated antigens (TAAs). The most specific of the latter group is monoclonal B72.3, which is reactive with a 220,000 to 400,000 high-molecular-weight glycoprotein complex found in 50% of human mammary carcinomas and 80% of human colon carcinomas. Monoclonal antibody B6.2, which recognizes a 90,000-d glycoprotein, was radiolabeled and shown to efficiently localize human carcinoma transplants in athymic mice via gamma imaging without the use of second antibody or background subtraction manipulations. F(ab')2 and Fab' fragments were shown to be more efficient for tumor localization than intact immunoglobulin. Whereas the phenomenon of antigenic heterogeneity of tumor cell populations has long been known to exist, this phenomenon was also shown to manifest itself as antigenic modulation, in which specific TAAs can modulate their expression on the cell surface concurrent with different phases of the cell cycle. A phenomenon known as antigen evolution, in which a specific cloned tumor cell population can gradually drift in antigenic phenotype, has also been demonstrated. Recombinant interferon has been employed to (1) enhance the expression of specific TAAs on the surface of tumor cells already expressing the antigen; and (2) induce the expression of specific TAAs on the surface of carcinoma cells not previously expressing the antigen. The clinical implications of such phenomena in gamma scanning for the detection of tumor masses and for tumor immunotherapy are discussed. Methods for circumvention of problems inherent in the clinical use of monoclonal antibodies are also addressed.

Animals↗

A phase II study of recombinant alpha interferon in patients with recurrent or metastatic breast cancer.

Thirty-three patients with advanced breast cancer were treated with a recombinant alpha interferon (rIFN-alpha 2). All patients were ambulatory (performance status greater than or equal to 50 Karnofsky scale) and almost all had received previous chemotherapy. Large intravenous dosages of 30 to 50 X 10(6) IU/m2 were given for five consecutive days every two to three weeks to 22 patients and smaller subcutaneous dosage of 2 X 10(6) IU/m2 three times a week to 11 patients. No complete or partial responses were seen. Two patients had stable disease and the remainder progressed. Flu-like syndromes were seen in all patients. Nausea, vomiting, and anorexia were frequent. Hypotension and confusion were noted in six and five patients, respectively. Life-threatening leukopenia was noted in two patients receiving intravenous dosage and thrombocytopenia was noted in one; no sepsis or bleeding complications were noted. In this study, a highly purified and biologically active rIFN-alpha 2 was not associated with activity in previously treated women with metastatic breast cancer.

Adult↗

A linkage study of acrokeratoelastoidosis. Possible mapping to chromosome 2.

As evidenced by a large pedigree with 21 affected members, acrokeratoelastoidosis (AKE) is an autosomal dominant skin disease (10185; McKusick 1978). Linkage with genetic markers already assigned to human chromosomes could help to map the gene for this disease. Therefore 22 markers were investigated in 61 members of the AKE family. Loose linkage is possible between AKE and ACP1, IGKC, and Jk, but the estimated recombination fractions do not reach significant deviations from 0.5. However, since the three marker loci have been previously assigned to chromosome 2, the AKE locus might be assigned tentatively to the same chromosome. Of the provisionally and inconsistently assigned markers, only blood group P is seen to be in linkage with HLA.

Acid Phosphatase↗

Comparative effects and mechanisms of castration, estrogen anti-androgen, and anti-estrogen-induced regression of accessory sex organ epithelium and muscle.

We examined the effects and mechanisms of action of various endocrine manipulations on the epithelium and muscle preparations of the guinea pig seminal vesicle. Castration, which reduced the plasma testosterone level to 10 percent of normal, caused approximately 80 per cent reductions in epithelium wet weight and RNA and DNA contents. Estradiol benzoate effected similar reductions in plasma androgen and epithelial cell function in intact males. Reduction in plasma androgen level accounted for the estrogen-induced epithelial regression; no antiandrogenic effect of estrogen on the epithelium was detectable. All anti-androgens tested, flutamide, spironolactone, and cyproterone acetate, reduced epithelium weight in intact animals. Studies of the mechanism of cyproterone acetate action indicated its effects were attributable solely to an anti-androgenic action on the epithelium. The anti-estrogens, tamoxifen and nafoxidine, had no effect on the epithelium of intact animals when tested alone or in combination with cyproterone acetate. Regression of seminal vesicle muscle occurred only after castration or treatment of intact animals with cyproterone acetate. The action of cyproterone acetate on the muscle was attributable to blockade of the androgenic stimulus. The drug had no effect on plasma testosterone or estradiol levels and had no anti-estrogenic activity. In intact males estradiol reduced plasma testosterone to castrate levels, but did not alter muscle weight and nucleic acid levels. The potential deleterious effects of reduced plasma testosterone on the muscle were surmounted by direct estrogenic stimulation of the tissue. The anti-androgens, flutamide and spironolactone, and the anti-estrogens, tamoxifen and nafoxidine, had no effect on the muscle of intact males. Inasmuch as the regressive effects of castration on the epithelium and muscle can be duplicated in intact animals only by treatment with cyproterone acetate, this particular drug may provide the most effective nonsurgical treatment of prostatic neoplasia.

Androgen Antagonists↗