Biomedical subjects

R A Brandt

Publications and source records attributed to R A Brandt.

18 recordsLinked to original sources

PubMed1995

Urokinase binding and catabolism by Hep G2 cells is plasminogen activator inhibitor-1 dependent, analogous to interactions of tissue-type plasminogen activator with these cells.

The adherent human hepatoma cell line Hep G2 exhibits receptor mediated endocytosis and catabolism of tissue-type plasminogen activator.plasminogen activator inhibitor type-1 (t-PA.PAI-1) complexes formed when exogenous t-PA combines with endogenous PAI-1 in the extracellular matrix. To determine whether the other major PA, urokinase (u-PA), which also complexes with PAI-1, is metabolised via the same mechanism, 125I-labelled high (hmw) and low (lmw) molecular weight forms of u-PA were incubated with Hep G2 cells at 4 degrees C for 2 hr in the absence and presence of a 100-fold excess of unlabelled ligand in order to detect specific binding. Both hmw and lmw 125I-u-PA formed complexes with PAI-1 and these bound specifically and with high affinity (apparent Kd 3.9 and 4.1 nM, with Bmax 78 x 10(3) and 83 x 10(3) binding sites/cell respectively). Binding by each form of radiolabelled u-PA was inhibited in a dose-dependent fashion by unlabelled t-PA, hmw-u-PA, lmw-u-PA, and by monoclonal anti-PAI-1 antibody. At 37 degrees C, bound hmw and lmw 125I-u-PA.PAI-1 complexes were internalised and degraded rapidly. These findings indicate that the specificity of the previously described receptor which mediates PAI-1 dependent catabolism of t-PA by Hep G2 cells extends to complexes of u-PA with this inhibitor.

Antibodies, Monoclonal↗

PubMed1995

Conservation of energy in competitive swimming.

Energy conservation in swimming is formulated in terms of four functions of the swim speed v: the consumed power K, the mechanical power P used for horizontal propulsion, the remaining expended mechanical power N, and the thermal power loss H. K is well-known (from VO2) and P = FDv, where the drag force FD is not known with certainty but represents a small effect. Estimates of the nonpropulsive components of a swimmer's body motions reveal that N is small, less than 3 watts per kg of body mass. H is estimated by using the theory of convective heat transfer to express the heat loss in terms of the difference between the swimmer's skin temperature and the water temperature. This temperature difference was measured for the NYU men's swim team and found to be 0.033 K per kg of body mass, giving H approximately 34 W kg-1. The results are seen to be in good agreement with the asymptotic (large swim time tf) form of energy conservation. The further requirement that energy conservation is valid to order 1/tf, and use of the 1993 world record race times, is shown to imply that the initial energy available in a swimmer's body is 963 +/- 231 joules per kg of body mass.

Biomechanical Phenomena↗

PubMed1995

[Linear accelerator radiosurgery].

Radiosurgery is the precise radiation of a known intracranial target with a high dose of energy, sparing the adjacent nervous tissue. Technological advances in the construction of linear accelerators, stereotactic instruments and in computer sciences made this technique easier to perform and affordable. The main indications for radiosurgery are inoperable cerebral vascular malformations, vestibular and other cranial schwannomas, skull base meningiomas, deep seated gliomas and cerebral metastases. More recently, the development of fraccionated stereotactic radiotherapy increased the spectrum of indications to bigger lesions and to those adjacent to critical nervous structures. We present our initial experience in the treatment of 31 patients. An adequate control of the neoplastic lesions was obtained and the adequate time of observation is still needed to evaluate the results in arteriovenous malformations.

Adolescent↗

PubMed1992

Stress-induced alterations in autophagic pathway: relationship to ubiquitin system.

The autophagic response of the cell to nutrient deprivation or heat stress is characterized by an increase in the rate of cellular protein degradation. Using temperature-sensitive mutant cell lines that harbor a mutation in the ubiquitin pathway, we have recently shown that this response is dependent on a functional ubiquitin-activating enzyme E1. The ubiquitin pathway is involved in a multitude of cellular events including protein degradation, the best understood of these. Herein the activation of the ubiquitin molecule via E1 is followed by its covalent conjugation to acceptor proteins followed by proteolysis. It is therefore important to study the linkage between the autophagic response and E1. Using these same cell lines, CHO E36 and CHO ts20, we demonstrate that after heat stress or nutrient deprivation there is a rapid and reversible decrease in the buoyant density of subcellular vesicles containing lysosomal hydrolases, a characteristic found to accompany autophagy. This stress-induced change is found in all cell lines examined, independent of the activity of the E1. The light-density vesicles, which comigrate with endosomes on colloidal silica gradients, are not accessible to the endocytic marker transferrin-horseradish peroxidase (HRP) after cellular uptake and subsequent HRP-mediated density shift analysis. Furthermore, morphology of the isolated fractions from control and stress-induced cells was similar. These results thus demonstrate the changes in hydrolase-containing intracellular vesicles that accompany nutritional deprivation or heat stress and support the notion that the linkage of the autophagic response to the ubiquitin system is at a step in autophagy which does not affect the formation of autophagic vesicles.

Animal Nutritional Physiological Phenomena↗

PubMed1991

The ubiquitin-activating enzyme, E1, is required for stress-induced lysosomal degradation of cellular proteins.

ts85, a cell line that harbors a mutant thermolabile ubiquitin-activating enzyme, E1, fails to degrade short lived proteins at the restrictive temperature (Ciechanover, A., Finley, D., and Varshavsky, A. (1984) Cell 37, 57-66). However, the involvement of the ubiquitin system in the degradation of long lived proteins (most cellular proteins fall in this category) has not been addressed. In the present study we show that upon shifting the mutant cells to the restrictive temperature, there is no change in the rate of degradation of long lived proteins. In contrast, shifting the wild-type cells (FM3A) to the high temperature is accompanied by a 2-fold increase in the rate of proteolysis of this group of proteins. This heat-induced accelerated degradation can be inhibited completely by NH4Cl and chloroquine. Similarly, exposure of the cells to starvation, a stimulus that activates the autophagic-lysosomal pathway, has no effect on the degradation of long lived proteins in the mutant cells after inactivation of E1. Under the same conditions, the degradation rate in the wild-type cells increases almost 4-fold. Analogous results were obtained using a different cell line that also harbors a thermolabile E1 (ts20 (Kulka, R. G., Raboy, B., Schuster, R., Parag, H. A., Diamond, G., Ciechanover, A., and Marcus, M. (1988) J. Biol. Chem. 263, 15726-15731)). Cycloheximide and 3-methyladenine, known inhibitors of formation of autophagic vacuoles, inhibit the heat-induced accelerated degradation of long lived proteins in wild-type cells. Taken together, the results suggest that 1) heat stress induces enhanced degradation of intracellular proteins; 2) the process occurs most probably in autophagic vacuoles; and 3) activation of ubiquitin is required for the formation of these vacuoles. As there is no change in the basal rate of degradation of intracellular proteins in the mutant cells at the restrictive temperature, it appears that the ubiquitin system is not involved in their breakdown.

Adenine↗

PubMed1988

Immunoelectron microscopic localization of ubiquitin in hepatoma cells.

Ubiquitin, a 76 amino acid protein, is covalently attached to abnormal and short-lived proteins, thus marking them for ATP-dependent proteolysis in eukaryotic cells. Free (unconjugated) ubiquitin was localized in hepatoma cells using affinity purified anti-ubiquitin antibodies and colloidal gold immunoelectron microscopy. The anti-ubiquitin antibodies recognize only unconjugated ubiquitin. Ubiquitin is found within the cytoplasm, nucleus, the microvilli, autophagic vacuoles and lysosomes.

Antibody Specificity↗

PubMed1980

[Reversal of fixed neurological deficits after extra-intracranial arterial anastomosis].

Four patients with fixed neurological deficits due to occlusion of the middle cerebral or the internal carotid arteries, and with collateral circulation to their territory diagnosed by angiography, recovered after extra-intracranial arterial anastomosis. Functional recovery was seen since the first hours after bypass in three cases and the first few days in the other. Angiographic demonstration of collateral circulation to the territory of an occluded cerebral artery seems to be useful in the selection of patients with fixed neurological deficits for extra-intracranial arterial anastomosis, mainly when other methods are not available.

Adult↗

PubMed1980

Chronic spinal subdural haematoma.

Chronic spinal subdural haematomas are uncommon. This is the report of a 62-year-old hypertensive and diabetic white female, with progressing paraparesis and sensory loss in the lower limbs for six months. There was no history of trauma to the spine. Ascending myelography disclosed a complete block at the first lumbar vertebra. At operation, a characteristic chronic subdural haematoma was found and removed. Postoperative course was uneventful, and nine months after surgery she was asymptomatic. Spontaneous chronic subdural haematoma, although rare, should be considered in the diagnosis of spinal cord compression. Surgical treatment may lead to complete recovery of the neurological deficit.

Diabetic Angiopathies↗

PubMed1979

[Prophylactic antibiotics in neurosurgery].

The post-operative infection-rate in neurosurgical patients who received prophylactic antibiotics was compared to the infection-rate of patients who received no antibiotics. None of the 73 studied patients had pre-operative infection. Infections occured in 26,4% of the patients in the first group and in none of the second group (p less than 0,2); 27,5% of the patients with intracranial lesions and 9% of the patients with spinal lesions in the frist group had post-operative infections, and none in the second group (p less than 0,05 and 0.05 less than p less than 0.1). 67% of all the patients had severe neurological lesions; 27% of these had post-operative infections; only 4% of the patients with mild lesions had infections (p less than 0.05). Post-operative infections were severe and fatal in most of these cases. Prophylactic broad-spectrum antibiotics were of no value in preventing post-operative infections in these neurosurgical patients and those who received no antibiotics had a significantly lower rate of infections.

Adolescent↗

PubMed1978

[Neurocutaneous melanosis. Report of a case].

The clinical, laboratorial and radiological features of a 3-month-old child with neurocutaneous melanosis are described. The patient was born with multiple disseminated benign cutaneous nevi, proven by skin-biopsy, and presented with drug-resistant seizures and psycho-motor retardation. Serial cerebrospinal fluid studies showed high protein and low glucose levels, with pleocytosis and malignant cells in the fluid. Pneumoencephalogram showed mild non-obstructive hydrocephalus. Immunological studies showed normal immunological activity at three months of age and very poor activity at one year. The patient died at 16 months of age, after the sudden onset of intracranial hypertension and meningeal signs. Immunotherapy and chemotherapy were suggested but not accepted by the family. Some comments are made based on this and other 43 cases described in the literature; the value of laboratory studies in detecting malignant transformaiton in the meninges in patients with benign skin nevi is stressed.

Anticonvulsants↗

PubMed1976

Cervical spondylosis. Prognostic value of preoperative signs and symptoms.

One hundred and forty-one patients with cervical spondylosis were studied, looking for a possible prognostic value in preoperative signs and symptoms. Duration of symptoms lasting from one month to five years until surgical treatment and spinal fluid protein level had no prognostic value in these patients. In those with radiculopathy, the degree of upper limb pareses, muscle atrophy, absent or diminished reflexes, sensory involvement, number of myelographic defects and age had prognostic value. In those with myelopathy, the degree of lower limbs pareses and spasticity, sensory involvement, number of myelographic defects and age had prognostic value. Surgery is a definite method of treatment for patients with progressive signs and symptoms due to cervical spondylosis; some of the preoperative signs and symptoms are valuable in establishing their prognosis.

Cervical Vertebrae↗

PubMed1976

[Cerebrovascular diseases of the "moyamoya" type].

The case of a 34-year-old caucasian male with subarachnoid hemorrahge is reported. The right carotid arteriogram shows the typical internal carotid artery occlusion at the syphon, whith an abnormal vascular network at the base of the brain; the right anterior and middle cerebral arteries fill from the vascular network and through meningocortical anastomoses; the right posterior communicating and cerebral arteries are tortuous and hypertrophic. The left carotid arteriogram shows hypertrophy of the common and internal carotid arteries; both anterior and middle cerebral arteries fill from this side; the anterior communicating artery is thick (foetal type) and a median anterior cerebral artery to the corpus callosum is present. It is the authors' view that the "moyamoya" disease is a congenital one, since the abnormal vascular network at the base of the brain would not be necessary, in this case, to preserve good collateral circulation to the right cerebral hemisphere. No other case with the typical findings of "moyamoya" disease on one side and hypertrophy of the carotid arteries on the other was found in the literature.

Adult↗

PubMed1974