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Biomedical subjects

R Langer

Publications and source records attributed to R Langer.

At least 361 records · Page 20Linked to original sources
PubMed1992

Obstetric outcome in women with congenital uterine malformations.

Ninety-eight cases of congenital uterine malformations were diagnosed with hysterosalpingography (HSG). Symmetric uterine malformations, composed of bicornuate uterus, uterus didelphys and septate uterus, constituted 80% of the cases. Of them, 75% were of the bicornuate type. Infertility (55%) and a suggestion of cervical incompetence (24%) were the main indication for HSG. Premature deliveries (29%), spontaneous first-trimester abortions (24%), ectopic pregnancies (3%), abnormal fetal presentations (23%) and a high cesarean section rate (27.5%) occurred in those patients. The highest rate of first-trimester abortions (47%) and the lowest rate of term deliveries (21%) occurred in the group with T-shaped uteri as compared to a 7% rate of early abortions (P less than .05) and 61% rate of term deliveries (P less than .03) in the unicornuate uterus group. In 30% of the patients with uterine malformations, cervical incompetence was diagnosed. Improved obstetric outcomes occurred in patients treated with cervical cerclage. There was a statistically significant difference between the number of premature deliveries and spontaneous late abortions in the group without cerclage (50%) and that with cerclage (21%) (P less than .001).

Abortion, Spontaneous↗
PubMed1992

[The splenic steal syndrome and the gastroduodenal steal syndrome in patients before and after liver transplantation].

The study describes new pathologic entities, the splenohepatic steal-syndrome and the gastroduodenal steal-syndrome, which could be demonstrated by angiography in 17 patients before and after liver transplantation. After the first observation of a splenohepatic steal-syndrome in a patient with unexplained elevation of hepatic enzymes after liver transplantation, a prospective angiographic study was performed, including all liver transplant recipients and patients after liver transplantation with unexplained impaired liver function tests. 9 splenohepatic steal-syndromes could be demonstrated before and 7 after hepatic transplantation, one gastroduodenal steal was seen after liver transplantation. The different therapeutic modalities are discussed.

Angiography↗
PubMed1991

The pharmacokinetics of, and humoral responses to, antigen delivered by microencapsulated liposomes.

The feasibility of creating a s.c. depot for sustained protein delivery with the goal of enhancing antigen immunogenicity was investigated. The depot was designed as antigen-laden liposomes of hydrogenated egg phosphatidylcholine and cholesterol (1:1 molar ratio) encapsulated in alginate-poly(L-lysine) microcapsules and evaluated using iodinated bovine serum albumin (BSA) as a model antigen. The in vivo release behavior of the liposomes and microencapsulated liposomes (MELs) was evaluated from the BSA serum concentration profiles after s.c. injection into rats and the pharmacokinetic parameters of 125I-labeled BSA appearance after s.c. or i.v. injections of BSA in saline. Maximal BSA concentrations were detected 11 h after s.c. injection in all rats. The BSA serum concentrations decreased rapidly in rats injected with BSA in saline or Freund's adjuvant and less rapidly in rats injected with BSA in liposomes or MELs. Four to 5 weeks after injection, BSA-associated radioactivity was detected only in sera of rats injected with BSA in liposomes or MELs. Fifty days after injection, 50% of the originally injected BSA was recovered form the s.c. sites of rats injected with BSA in MELs; no radioactivity was recovered from the other three groups of rats. The antigen-reactive antibody levels induced in rats immunized with BSA in MELs were 2- to 3-fold higher than those obtained in rats immunized with BSA in liposomes, saline, or Freund's adjuvant. More significantly, high antibody levels were maintained for more than 150 days after a single injection of BSA in MELs, suggesting that MELs can serve as a long-term single-dose immunization vehicle.

Animals↗
PubMed1991

Clear ovarian cyst aspiration guided by vaginal ultrasonography.

Thirty patients with clear ovarian cysts underwent aspiration guided by vaginal ultrasound. In 23 cases a complete aspiration was accomplished. In 4 only partial aspiration was possible, and in the remaining 3 failed aspiration led to surgery. Histological findings correspond to retroperitoneal lipoma and mucinous cystadenoma (2 cases). Malignant cells were not detected in the fluid of any of the 27 aspirates. Eight of the ten patients presenting with abdominal pain experienced a relief following aspiration. Recurrence of the cyst occurred in 12 cases (40%) with significantly smaller dimensions (P less than 0.01). Vaginal ultrasound aspiration of clear cyst is easy and safe and can be considered as an outpatient procedure.

Adult↗
PubMed1991

Kinetics of insulin aggregation in aqueous solutions upon agitation in the presence of hydrophobic surfaces.

The stability of protein-based pharmaceuticals (e.g., insulin) is important for their production, storage, and delivery. To gain an understanding of insulin's aggregation mechanism in aqueous solutions, the effects of agitation rate, interfacial interactions, and insulin concentration on the overall aggregation rate were examined. Ultraviolet absorption spectroscopy, high-performance liquid chromatography, and quasielastic light scattering analyses were used to monitor the aggregation reaction and identify intermediate species. The reaction proceeded in two stages; insulin stability was enhanced at higher concentration. Mathematical modeling of proposed kinetic schemes was employed to identify possible reaction pathways and to explain greater stability at higher insulin concentration.

Adsorption↗
PubMed1991

Lipid-alginate interactions render changes in phospholipid bilayer permeability.

Lipid vesicles, e.g. liposomes, generally release their contents in a continuous manner. However, when these vesicles are entrapped in Ca-alginate and coated with poly(L-lysine), they release their contents in an unusual fashion, in 'bursts'. Molecular-level studies indicated that lipid-alginate interactions are responsible for changes in the barrier properties of lipid vesicles. Differential scanning calorimetry revealed that exposure of liposomes to alginate resulted in a 4-fold reduction in the phase transition enthalpy, with no change in the melting temperature. Size-exclusion chromatography of liposomes-in-alginate gave an additional liposomal peak with a smaller elution volume. These studies suggested that alginate is inserted into the lipid bilayer of vesicles. Lipid-alginate interactions were highly dependent on phospholipid head group charge and the phase transition temperature of the phospholipid. Based on these interactions, a mechanism to explain the 'burst' from these entrapped liposomes is suggested.

Alginates↗
PubMed1991

Biocompatible controlled release polymers for delivery of polypeptides and growth factors.

The development of biocompatible, controlled release systems for macromolecules has provided the opportunity for researchers and clinicians to target and deliver, on site, biologically active factors. This advance has also facilitated the purification and characterization of a number of important biomolecules. These systems include controlled release delivery systems which release proteins through porous polymer matrices, degradable polymeric delivery systems, and modulated polymer release systems. These areas of research will be reviewed with regards to their design, release kinetics, and biocompatibilities. The utilization of these systems to release such biologically important polypeptides as growth factors (e.g., fibroblast growth factor, epidermal growth factor, transforming growth factor-B) as well as a number of important inhibitory factors (e.g., nitrosoureas, angiogenesis inhibitors) in both in vivo and in vitro studies will be discussed.

Animals↗
PubMed1991

A metalloproteinase inhibitor as an inhibitor of neovascularization.

Metalloproteinases and their endogenous inhibitors are key components of an enzyme system which is important in a number of fundamental biochemical and cellular processes. Our recent work has focused on the role of a particular metalloproteinase, collagenase, and the role of an endogenous inhibitor of this enzyme in the control of neovascularization. The proteolytic degradation of extracellular matrix components by capillary endothelial cells (EC) has been shown to be one of the key prerequisites of the angiogenic process. As part of a study of the effect(s) of the inhibition of collagenase on neovascularization, we have recently reported the purification, characterization and partial NH2-terminal sequence of a cartilage-derived inhibitor (CDI) of angiogenesis in vivo and in vitro. Evidence is presented which suggests that one means of controlling deregulated vascular growth characteristic of a number of "angiogenic diseases" may be at the level of the control of metalloproteinase activity.

Amino Acid Sequence↗
PubMed1991

The release of heparinase from the periplasmic space of Flavobacterium heparinum by three-step osmotic shock.

Heparinase was released from the periplasmic space of Flavobacterium heparinum by three-step osmotic shock procedure. The procedure involves resuspending exponentially growing cells consecutively into (1) 40% sucrose, (2) 10 mM sodium phosphate, 2 mM magnesium chloride, pH 7, and (3) 10 mM sodium phosphate, 300 mM sodium chloride, 2 mM magnesium chloride, pH 7. Typically, 50-75% of the total heparinase activity is recovered by this procedure with an observed 7-15-fold increase in purity. The majority of heparinase activity is released in the final step of the procedure allowing for resolution from cytoplasmic and nonspecific periplasmic material. F. heparinum cells can be stored in 40% sucrose at 4 degrees C for up to one week without significant losses in recovery yields.

Biotechnology↗
PubMed1991

Controlled and modulated release of basic fibroblast growth factor.

Basic fibroblast growth factor has multivariate effects in stimulating cell growth and the processes that surround tissue repair. Pathophysiologic studies have been hampered by the stability of the compound. Though very potent, basic fibroblast growth factor is rapidly degraded when injected or ingested. Controlled release of basic fibroblast growth factor would allow for examination of the chronic effects of this compound. Conventional matrix polymer-based release devices were fabricated and basic fibroblast growth factor released in a sustained fashion, but 99% of basic fibroblast growth factor mitogenic activity was lost. The source of these losses was identified and preventative measures examined. Preservation and stabilization of basic fibroblast growth factor was accomplished by binding the factor to heparin-Sepharose beads. This permitted prolonged storage, repeated handling, and the encapsulation of basic fibroblast growth factor within a microspherical controlled-release device using a naturally occurring polymer material, alginate. Encapsulation was accomplished with 77% efficiency and 87.5 +/- 12% of the basic fibroblast growth factor was released in a biologically active form. Release activation and regulation was achieved when cleavage of the basic fibroblast growth factor-heparin bonds was enhanced (e.g. by enzymatic bond cleavage with heparinase). Kinetic profiles were identified for a variety of experimental conditions and the effects of the controlled release of basic fibroblast growth factor on BALBc/3T3 fibroblasts examined.

Alginates↗
PubMed1991

The absence and effect of induced menopause by gonadotropin-releasing hormone analogs on lower urinary tract symptoms and urodynamic parameters.

The clinical and urodynamic relationship between the onset of menopause and the appearance of lower urinary tract symptoms has been studied in 12 premenopausal urinary symptom-free patients in whom hypoestrogenism was induced by treatment with gonadotropin-releasing hormone analogs. No urodynamic changes in the cystometric, uroflowmetry, and urethral pressure profile measurements were found after 6 months of treatment. Clinically, only one patient had diurnal frequency after treatment. We conclude that estrogen deficiency in the absence of aging and other factors leading to urinary symptoms is probably of minimal significance as a cause of lower urinary tract disability in the immediate menopausal period.

Adult↗
PubMed1991

Controlled delivery systems for proteins based on poly(lactic/glycolic acid) microspheres.

This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled horseradish peroxidase, were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 55-95 microns and encapsulated more than 90% of the protein. The preparation method was gentle and maintained enzyme activity and protein solubility. Stability studies showed that the encapsulation of an enzyme inside PLGA microspheres can protect them from activity loss. When not placed inside PLGA microspheres, (fluorescein isothiocyanate)-labeled horseradish peroxidase lost 80% of its activity in solution at 37 degrees C in a few days, whereas inside the PLGA microspheres it retained more than 55% of its activity after 21 days of incubation at 37 degrees C. In vitro release studies revealed that different release profiles (i.e., near-constant or biphasic) and release rates can be achieved by simply modifying factors in the preparation procedure such as mixing rate and volume of inner water and organic phases. Degradation studies by scanning electron microscopy and gel-permeation chromatography suggested that the mechanism responsible for protein release is mainly through matrix erosion.

Biological Availability↗
PubMed1991

A novel synthetic method for hybridoma cell encapsulation.

We report here what we believe is the first example of the encapsulation of hybridoma cells within a synthetic polymer by a simple gelation with dissolved cations in water, and at room temperature. Two lines of hybridoma cells were encapsulated within calcium cross-linked polyphosphazene gel microbeads without affecting their viability or their capability to produce antibodies. Interaction of these gel beads with the positively-charged polyelectrolyte, poly(L-lysine), of 102-kD molecular weight, produced a semipermeable membrane that was capable of retaining the cell-secreted antibodies inside the beads. Cell density increased 3.5-fold within 13 days concomitant with a 6.4-fold increase in antibody production. These synthetic membranes have the potential to aid in protein recovery schemes.

Antibodies, Monoclonal↗
PubMed1991

Inhibitors of angiogenesis.

Angiogenesis, the formation of new capillaries, is essential to a number of important physiological events, both normal and pathological. Recently, increased attention has focused on the purification and characterization of inhibitors of this process, because of the potential therapeutic value of angiogenesis inhibitors in controlling such "angiogenic diseases" as proliferative retinopathy, solid tumors, rheumatoid arthritis, and neovascular glaucoma. We review the process of neovascularization and the assays that have been developed to study its inhibition in vivo and in vitro. We also discuss the properties of different angiogenesis inhibitors and examine the mechanisms by which such inhibitors could potentially intervene in the process of neovascularization.

Animals↗