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Biomedical subjects

L D Prockop

Publications and source records attributed to L D Prockop.

At least 19 recordsLinked to original sources
PubMed1994

Modulation of endothelin-1 production by a pulmonary epithelial cell line. I. Regulation by glucocorticoids.

Endothelin-1 (ET-1) is one of the most potent bronchoconstrictor agents yet described. Bronchial epithelial cells of asthmatic patients in vivo express preproET-1 and in vitro release high amounts of ET-1. Healthy and chronic bronchitic controls do not express preproET-1 or release ET-1. Interleukin-2 (IL-2) and other cytokines up-regulate the in vitro ET-1 release in guinea pig airway epithelial cells. We explored whether two glucocorticoids, dexamethasone (Dex) and triamcinolone acetonide (TA), inhibit the synthesis and release of ET-1 by A549 cells, a transformed human pulmonary epithelial cell line, since ET-1 may have a basic role in the pathogenesis of asthma. Cells were grown to confluence in RPMI 1640 plus 10% fetal bovine serum (FBS). Cells were then cultured for 3 days without serum to obtain ET-1 basal levels. The effects of 10% FBS, IL-2 (10 U/mL), Dex, TA or mifepristone, a steroid antagonist (1, 10 or 100 nM), were evaluated on ET-1 as measured by radioimmunoassay (RIA). ET-1 production increased from 57.6 +/- 5 pg/mg cell protein at 6 hr to 170 +/- 9 pg/mg cell protein at 72 hr in control cultures. Ten percent FBS increased ET-1 production from 58.7 +/- 9.6 to 399 +/- 14.5 pg/mg cell protein. IL-2 significantly increased ET-1 from 100.7 +/- 6.1 to 144 +/- 6.7 at 24 hr and from 170 +/- 9 to 207.7 +/- 24 at 72 hr. Dex and TA (10 and 100 nM) at 24-72 hr decreased ET-1 under basal conditions. Both drugs (only at 100 nM) decreased ET-1 production in 10% FBS- and IL-2-stimulated cells. Mifepristone (10 and 100 nM) reversed the decreased production of ET-1 induced by Dex (100 nM) at 24-72 hr. Northern blot analysis showed that Dex (100 nM) decreased the expression of ET-1 mRNA at 6 and 24 hr, but that mifepristone (100 nM) reversed this effect in cells cultured with Dex. In conclusion, Dex and TA down-regulate the synthesis and production of ET-1 by this human pulmonary epithelial cell line under basal or stimulated conditions, and these effects are reversed by mifepristone. These findings suggest a novel mechanism of glucocorticoid effect during the treatment of asthma.

Cell Line↗
PubMed1992

Evaluation of blood-brain barrier permeability and the effect of interferon in mouse glioma model.

The aim of this study was to evaluate whether interferon [IFN] can affect intracerebrally grown glioma and how alteration of the blood-brain barrier [BBB] may influence this effect. An intracerebrally implanted glioma G-26 (G-26) mouse brain-tumor model was developed and used in these studies. Histological characterization of this intracerebrally grown tumor revealed its anaplastic character. The astrocytic origin of G-26 was evidenced by glial fibrillary acidic protein staining and electron microscopic visualization of glial filaments. A study of tumor progression and animal survival showed development of a well defined tumor nodule within approximately seven days after the implantation. The median animal survival time was 27 +/- 3.8 days. The integrity of the blood-brain barrier [BBB] within the tumor was evaluated by the intravenous injection of horseradish peroxidase at days 3, 7, 10 and 20 after brain tumor implant and compared to 'sham' controls. The tumor-induced BBB alteration was progressive from day 3 to day 20. Glioma-26 subcutaneously passed in C57BL/6 mice was also continuously cultured in vitro. Its proliferation was inhibited by homologous mouse interferon alpha/beta [MuIFN alpha/beta] but not by human interferon alpha lymphoblastoid or human interferon beta. The in vivo studies of G-26 glioma treatment with MuIFN alpha/beta were performed using single bolus of IFN in osmotically altered animals or slow IFN infusion through osmotic micro-pumps. The slow infusion of IFN had no effect on animal survival. However, a statistically significant increase in animal survival was observed after single bolus IFN treatment following osmotic BBB alteration.

Animals↗
PubMed1991

Pseudohypoparathyroidism and cerebrovascular disease with dural calcification.

A 53-year-old woman is reported with recurrent cerebrovascular disease, pseudohypoparathyroidism and dural calcification without basal ganglia calcification. She had typical clinical and laboratory features of pseudohypoparathyroidism and a family history of the condition. One case has been reported previously with pseudohypoparathyroidism and Parkinson's disease without basal ganglia calcification. Patients with widespread intracranial calcification should be evaluated for underlying abnormalities in calcium metabolism. Calcium supplementation and administration of vitamin D frequently correct the metabolic abnormality and halt clinical progression.

Brain↗
PubMed1990

Magnetic resonance imaging of the brain and spinal cord in cerebrotendinous xanthomatosis.

This reports a 40 year old man with cerebrotendinous xanthomatosis who had bilateral cataracts, enlarged Achilles tendons, progressive dementia, gait disturbance and peripheral neuropathy. Electroencephalography, electromyography, and magnetic resonance imaging (MRI) of the brain and spine were performed. Magnetic resonance imaging revealed cerebral, cerebellar and cervical cord atrophy and white matter involvement in the cerebrum and cerebellum correlating well with the clinical findings. To date there has been one previous report of MRI of the brain in cerebrotendinous xanthomatosis and none of the spinal cord.

Achilles Tendon↗
PubMed1989

Cerebral interferon entry in mice after osmotic alteration of blood-brain barrier.

Systemically administered interferon (IFN) is not readily detected in the central nervous system (CNS) due to the presence of the blood-brain barrier (BBB). A method of osmotic BBB alteration in a mouse model was established in this laboratory. IFN's entry into the normal and osmotically altered brain after its intracarotid injection was investigated. Significant IFN levels (100-1,000 units) in the brain can be achieved by this method. The highest IFN activity was found in the brain hemisphere ipsilateral to the injection site within 20 min to 1 h after injection. IFN activity in the brain was detectable up to 4 h. Animals injected in this manner with murine IFN-alpha/beta (MuIFN-alpha/beta) and observed for a 6-month time interval showed no signs of neurological dysfunctions and resumed their normal activities. The therapeutic value of this method will be tested in a murine model of malignant glioma.

Animals↗
PubMed1989

Fatal pontine metastasis: clinical, CT, MRI and pathological correlates.

Progressive brainstem and cerebellar signs developed in a previously healthy 70-year-old man over a course of seven days. A pontine mass characterized by CT and MRI suggested an infiltrating primary pontine glioma. Gross postmortem examination showed a medullary-pontine hemorrhage. Microscopic analysis disclosed an undifferentiated large cell carcinoma which was found to originate from the lung. Differential diagnoses in cases of suspected brainstem lesions are given, including metastatic tumors which are rare when presenting as a solitary brainstem mass. Optimal patient management should be formulated on the basis of histopathological diagnosis rather than imprecise imaging data. Exact tissue diagnosis will also avoid an extensive and expensive search for an occult systemic cancer. The roles of radiation, chemotherapy and surgery are also discussed.

Aged↗
PubMed1988

A mouse model for the study of blood-brain barrier permeability.

This article describes a C57BL/6 mouse model for the investigation of blood-brain barrier (BBB) alteration. Osmotic modification of BBB was achieved by infusion of 1.6 M arabinose solution into the internal carotid artery with or without occlusion of the external carotid artery. BBB alteration was measured by infusing 2% Evans blue dye. Only 1.6 M arabinose-treated animals but not 0.9% NaCl controls displayed prominent ipsilateral staining of frontal and temporal lobes. Light blue staining occurred in animals sacrificed within 10 min after injection. Prominent staining occurred in animals sacrificed 1-6 hours later. Identically treated animals were maintained for up to 6 months without signs of systemic or neurological dysfunction. This model may permit study of the effects of biological response modifiers (BRMs) upon the central nervous system (CNS) in healthy and diseased mice.

Animals↗
PubMed1988

AIDS dementia complex.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Distribution of muscle changes in experimental ischemic myopathy.

The distribution of ischemic changes was examined in the medial gastrocnemius muscle of the cat, following transient simultaneous clamping of the aorta and femoral artery. Initial changes occurred in the middle portion of the muscle, in the areas corresponding to watershed zones of the primary arteries of the muscle. The superficial layers of the muscle, the regions close to the main stem of the primary arteries, and the entire distal portion of the muscle were the most resistant to ischemic damage. These studies demonstrate that in the feline medial gastrocnemius muscle, the vascular pattern is the primary factor in determining the distribution of ischemic changes. The role of differential muscle fiber vulnerability is only secondary.

Adenosine Triphosphatases↗
PubMed1983

Nearly fatal muscle carnitine deficiency with full recovery after replacement therapy.

A 23-year-old woman became quadriplegic and respirator-dependent after 18 years of weakness and rhabdomyolysis. Her muscle tissue and that of a deceased sister contained lipid-laden fibers. Treatment with D,L-carnitine 4 grams per day was followed by a dramatic improvement within 10 days. Muscle function was normal at 8 months and has remained so during 3 subsequent years of L-carnitine 3 grams per day. Pretreatment muscle biopsy had documented low levels of free carnitine and short-chain acylcarnitine compounds. Carnitine palmityltransferase was slightly elevated. The asymptomatic parents had low-normal muscle carnitine levels, slight increase in muscle fiber lipid droplets, osmiophilic lipid-laden Schwann's cell vacuoles, and myelin lamellae with different periodicities.

Adult↗
PubMed1977

Perfusion and molecular modification of idoxuridine to alter its cerebrospinal fluid metabolism.

Two methods to deter the rapid intrathecal degradation of idoxuridine were investigated: (a) rapid drug perfusion through the ventricular system, and (b) modification of the molecule to its uronic acid derivative, 2'-deoxy-5-iodo-5'-uridinecarboxylic acid, to make it less susceptible to enzymatic digestion. Perfusion of idoxuridine through the ventricular system (ventriculocisternal) of dogs at 0.97 ml/min saturated the metabolic pathway so that the outflow solution yielded a single spot (Rf 0.76) on TLC indicative of the intact molecule. The 125I-labeled uronic acid was synthesized from the 125I-labeled parent compound, and the labeled compounds were compared after their individual intracisternal injection in dogs. Since there was no difference in the disappearance rates, the stability of the uronic acid was, in fact, no greater than that of the parent compound in vivo. Ventricular perfusion of idoxuridine, however, seems a suitable means for increasing the amount of active drug delivered to central nervous system tumors and viral infections.

Animals↗