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Biomedical subjects

J Bruner

Publications and source records attributed to J Bruner.

At least 37 records · Page 2Linked to original sources

Phase II study of accelerated fractionation radiation therapy with carboplatin followed by vincristine chemotherapy for the treatment of glioblastoma multiforme.

PURPOSE: To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with intravenous carboplatin for patients with previously untreated glioblastoma multiforme tumors. METHODS AND MATERIALS: Between 1988 and 1992, 83 patients received 1.9-2.0 Gy radiation three times a day with 2-h infusions of 33 mg/m2 carboplatin for two 5-day cycles separated by 2 weeks; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. RESULTS: Eighty-three patients were evaluable for analysis. Seventy-four of the 83 patients (89%) received one or more courses of PCV; their median survival was 55 weeks. Total resection was performed in 20% (15 of 74), subtotal resection in 69% (51 of 74), and biopsy in 11% (8 of 74); reoperation (total or subtotal resection) was performed in 28 patients (37%). Survival was worst for those > or = 61 year old (median 35 weeks). Fits of the Cox proportional hazards regression model showed covariates individually predictive of improved survival were younger age (p < 0.01), smaller log of radiation volume (p = 0.008), total or subtotal resection vs. biopsy (p = 0.056), and higher Karnofsky performance status (p = 0.055). A multivariate analysis showed that age (p = 0.013) and extent of initial surgery (p = 0.003) together were predictive of a better survival with no other variables providing additional significance. Only 8.4% (7 of 83) of patients had clinically documented therapy-associated neurotoxicity ("radiation necrosis"). CONCLUSION: When comparable selection criteria were applied, the survival in this study is similar to the results currently attainable with other chemoradiation approaches. The relative safety of accelerated fractionated radiotherapy, as used in this study with carboplatin, enables concomitant full-dose administration of chemotherapy or radiosensitizing agents in glioblastoma multiforme patients.

Adult↗

Glutamate and acetylcholine release from cholinergic nerve terminals, a calcium control of the specificity of the release mechanism.

We describe, in the present work, a continuous procedure for measuring the release of glutamate, and have applied it to analyze the co-release of glutamate and acetylcholine from cholinergic nerve terminals of electric organ synaptosomes. The two substances were measured in similar conditions using the two continuous chemiluminescent assays. The protein "Mediatophore" reconstituted in proteoliposomes was also able to translocate both transmitters with a preference for glutamate when the external calcium was increased between 3 and 10 mM. However, at lower calcium concentrations a clear preference for acetylcholine was found. For a regulated calcium entry as obtained by electrical stimulation of the nerve the release mechanism was fully specific for acetylcholine. Since the specificity of mediatophore depends on the local calcium amounts, the possible role of mediatophore at acetylcholine or glutamate specific synapses may be envisaged and is discussed in relation to the calcium control of specificity.

Acetylcholine↗

The treatment of anaplastic oligodendrogliomas and mixed gliomas.

We evaluated the treatment outcome of 17 patients with anaplastic oligodendroglioma and 17 patients with anaplastic mixed oligodendroglioma-astrocytoma. In the anaplastic oligodendroglioma group, eight patients were treated at the time of the initial admission with radiotherapy and adjuvant chemotherapy, and nine patients were treated at the time of recurrence with salvage chemotherapy. Three patients for whom adjuvant chemotherapy was not successful were also treated with chemotherapy at the time of recurrence. In the initial group, one patient had complete response, three had partial responses, and 4 had stable disease (response and stable disease, 100%), but all except one progressed within 10 months. Of the 12 patients who received chemotherapy during recurrence, there was 1 complete response, 2 partial responses, and 6 stable disease (response and stable disease, 75%), with long response duration and long survival (15-132+ mo). In the anaplastic mixed oligodendroglioma-astrocytoma group, 12 patients were treated at the time of the initial admission and 6 patients treated at the time of recurrence. The initial treatment resulted in two complete responses, three partial responses, and seven stable disease (response and stable disease, 100%), with most responses lasting longer than 12 months. The treatment of the patients with recurrent disease resulted in one partial response and five stable disease (response and stable disease, 100%), with a median time to progression of 6 months. These results suggest that aggressive treatment is beneficial for recurrent anaplastic oligodendrogliomas and mixed gliomas as well as initial mixed gliomas but may offer only minimal advantage over conventional radiotherapy for the initial treatment of anaplastic oligodendrogliomas.

Antineoplastic Combined Chemotherapy Protocols↗

Long-lasting decrease in the crayfish giant motoneuron soma excitability induced by Ca2+ influx.

After a single Ca-dependent action-potential or a 300 ms clamp pulse to 0 mV in the motor giant somata of the crayfish abdominal nerve cord, a decrease in input resistance, an afterhyperpolarisation and a shortening of the test action potentials were observed during 10-15 min. These effects were due to a novel type of long-lasting outward current, triggered by a single influx of Ca2+, resistant to TEA+ and blocked by Ba2+.

Action Potentials↗

Transthyretin immunoreactivity in choroid plexus neoplasms and brain metastases.

Although choroid plexus papillomas (CPP) and primary choroid plexus carcinomas (CPC) are rare neoplasms of the central nervous system, they have been the subject of a number of immunohistochemical studies. To date, no unique or specific marker for these neoplasms has been found, however. Normal choroid plexus is a major site of transthyretin (TTR) synthesis, and recently this protein has been proposed as a possible specific marker of choroid plexus differentiation in tumors. In this study, we performed immunohistochemistry for TTR on 13 choroid plexus tumors (six CPP and seven CPC) and on 23 carcinomas metastatic to the brain, four of which had a papillary architecture. We also included four ovarian teratomas that contained choroid plexus elements. Two of the CPP had diffuse staining for TTR, while the four others stained only focally. Five of the CPC stained only focally and less intensely than the control, while one case was negative. Only one CPC stained as strongly and diffusely as normal choroid plexus. Two of the papillary and six of the nonpapillary metastases had focal staining similar to that seen in the five focally positive CPC. The choroid plexus elements of the ovarian teratomas stained as strongly as the positive control. These findings indicate that TTR immunoreactivity is not restricted to primary choroid plexus tumors. Furthermore, most choroid plexus carcinomas stain only weakly or not at all. This limits the usefulness of TTR immunohistochemistry in the diagnosis of primary choroid plexus neoplasms and in the distinction of CPC from metastatic carcinoma.

Adenocarcinoma↗

Sodium-dependent depolarizing potentials in veratrinized crayfish muscle fibres.

In the slow abdominal flexor muscle fibers of the crayfish Procambarus clarkii, veratrine or veratridine applied during several minutes produced the persistent transformation of the muscle fibre from a nonspiking into a Ca-dependent spiking one and spikes were followed by a long-duration depolarization. The long-duration potential depends on external Na+ but is not blocked by 30 microM tetrodotoxin (TTX). In solutions containing normal concentrations of Na+ (207 mM) the absence of Ca2+ or the presence of calcium channel blockers abolished both potentials. The results show that alkaloid toxins reveal a Ca2+-dependent, TTX-resistant Na+ conductance in crayfish tonic muscle fibres.

Action Potentials↗

Arsenazo III transients and calcium current in a normally non-spiking neuronal soma of crayfish.

Arsenazo III was used to investigate Ca2+ transients in the normally non-excitable soma of the motor giant neurones of the crayfish Procambarus clarkii. Two kinds of regenerative potentials could be obtained depending on membrane potential conditioning: a fast spike after a pre-hyperpolarization to -90 mV and a slow action potential after a pre-depolarization to -50 mV. Only the second of these was accompanied by an Arsenazo III transient. In voltage-clamped, somata injected, with tetraethylammonium chloride, an absorbance change could be obtained by pulsing the membrane potential above -44 mV. The relationship between absorbance change and potential peaked between 0 and +10 mV then fell off to zero at ca. +150 mV. Changes in light absorbance studied using double-pulse protocols suggested that the inactivation of Ca2+ entry was predominantly mediated by the intracellular free Ca2+ concentration. External application of 1 mM-CdCl2 abolished both the absorbance changes and the (Ca2+) inward current. The voltage dependence of this current was similar to that of the absorbance change. For positive membrane potential the current-voltage relationship showed a voltage-dependent conductance property, the origin of which is discussed.

Action Potentials↗

Treatment-related leukoencephalopathy. A study of three cases and literature review.

The etiology and pathogenesis of treatment-related leukoencephalopathy remain obscure. The evidence is substantial, however, that radiation therapy in combination with higher cerebral concentrations of certain chemotherapeutic agents such as MTX increases the likelihood of permanent damage. There is no therapy of apparent benefit for treatment-related leukoencephalopathy, but reasonable alternatives include 1) withholding chemotherapy and/or radiation, 2) administering calcium leucovorin in high doses intravenously in methotrexate-induced leukoencephalopathy (26), or 3) perfusing the subarachnoid space (2) from above through an Ommaya reservoir and out from below through a lumbar puncture needle or lumbar subarachnoid catheter. Because CT scan abnormalities and subtle mental or intellectual changes are often noted before the full-blown clinical presentation, a prospective study involving periodic CT scanning as well as formal neuropsychologic testing appears worthwhile in all patients who are to receive cranial irradiation and/or chemotherapy in the prophylaxis or active treatment of CNS disease in order to detect and perhaps even to prevent this adverse side effect of cancer therapy.

Adolescent↗

Gap-like junctions between neuron cell bodies and glial cells of crayfish.

Data reported up to now on neuron-glia relationships, show that neuron cell bodies and glial cells are separated by a narrow intercellular cleft which is considered as the microenvironment of the nervous system, and where neuron-glia exchange occurs. We present here evidence that neuron perikarya and ensheathing glial cells of the abdominal ganglia of the crayfish communicate through gap-like junctions. These junctions could constitute short circuits for ionic exchange between neuron perikarya and glial cells, probably with some degree of electrotonic coupling between neurons and glia. In the preparation described here, the intercellular cleft would play only a secondary role in neuron-glia communication.

Animals↗

Guillain-Barré syndrome with cytomegalovirus infection of peripheral nerves.

Cytomegalovirus (CMV) infection involving multiple organ systems is a common finding in the acquired immunodeficiency syndrome. Acute CMV neuritis was a complication in two patients with acquired immunodeficiency syndrome. The diagnosis was made in both patients at autopsy, where typical CMV inclusions in the lumbar dorsal roots were noted in one patient and the same inclusions were found in the retroperitoneal peripheral nerves in a second patient. Electron microscopy confirmed the presence of viral particles in affected nerve segments. Patient 1 was hospitalized for ascending motor paralysis that remained unexplained at the time of death. In patient 2 the finding of CMV neuritis was incidental. Although CMV infection has been cited as an event antecedent to acute inflammatory polyradiculopathy (Guillain-Barré syndrome), to our knowledge morphologic evidence of the presence of virus has not been documented in this disease previously.

Acquired Immunodeficiency Syndrome↗

Tonic muscle fibres of crayfish after gangliectomy: increase in excitability and occurrence of sodium-dependent spikes.

Under normal conditions crustacean muscles consist of a mixed population of muscle fibres, some show only delayed rectification upon depolarization, while others display graded or all-or-none action potentials. It is now well documented that these action potentials are due to a tetrodotoxin (TTX)-insensitive voltage-dependent Ca2+ influx. Here we present evidence that several weeks after axonotomy of the motor nerve and removal of an abdominal ganglion in crayfish there was an increase of the number of slow flexor muscle fibres showing action potentials. Some of these action potentials were dependent on Na ions and were TTX-sensitive. These results suggest that after operation voltage-dependent Na+ channels become apparent in the muscle fibre membrane of the crayfish.

Animals↗

Effects of high calcium solutions on glutamate sensitivity of crayfish muscle fibres.

Crayfish neuromuscular preparations were studied after 18--36 h exposure to high calcium solutions. As previously reported for frog neuromuscular preparations the treatment damaged the nerve terminals and decreased junctional potentials. The resting potentials and input resistances of the muscle fibres were not affected; but their sensitivity to glutamate was significantly decreased when compared to that of control muscles. After exposure to high calcium, the sensitivity to gamma-aminobutyric acid, the putative transmitter at inhibitory synapses, was increased. Apparently normal twitches were elicited by direct stimulation, and calcium spikes could still be observed in the fibres. A decreased sensitivity to glutamate was also noted in experiments carried out on denervated muscles 8 months after section of the motor axons. Possible relations between nerve terminal damage and the decrease in sensitivity to glutamate are discussed.

Animals↗