Run-on gene transcription in human neocortical nuclei. Inhibition by nanomolar aluminum and implications for neurodegenerative disease.

The incorporation of [alpha-32P]-uridine triphosphate into DNA transcription products was examined in short post-mortem interval (PMI) human brain neocortical nuclei (n, 22; PMI, 0.5-24 h) using run-on-gene transcription. Reverse Northern dot-blot hybridization of newly synthesized RNA against either total cDNA or Alu repetitive DNA indicated that human brain neocortical nuclei of up to 4-h PMI were efficient in incorporating radiolabel into new transcription products, after which there was a graded decline in de novo RNA biosynthetic capacity. To test the effects of 0-3000 nM concentrations of ambient aluminum on RNA polymerase I (RNAP I) and RNA polymerase II (RNAP II) transcription, dot blots containing 0.5, 1.0, 2.0, and 5.0 micrograms of DNA for (1) the human-specific Alu repetitive element (2) the neurofilament light (NFL) chain, and (3) glial fibrillary acidic protein (GFAP) were Northern hybridized against newly synthesized radiolabeled total RNA. These DNAs represent heterogeneous nuclear RNA (hnRNA), neuronal-, and glial-specific markers, respectively. We report here a dose-dependent repression in the biosynthetic capabilities of brain RNAP II in the range of 50-100 nM aluminum, deficits similar to those previously described using a rabbit neocortical nuclei transcription system and at concentrations that have been reported in Alzheimer's disease (AD) euchromatin. Transcription from RNAP II and the neuron-specific NFL gene in the presence of aluminum was found to be particularly affected. These findings support the hypothesis that brain gene transcription in the presence of trace amounts of ambient aluminum impairs mammalian brain DNA to adequately read out genetic information.

Computed tomographic findings in Wernicke-Korsakoff syndrome.

An unconscious patient had a differential diagnosis of coma. Traumatic, metabolic, and infectious origins were considered, but none explained her condition satisfactorily. Clinical features on examination were compatible with Wernicke-Korsakoff syndrome. Her condition improved with supportive treatment and thiamine hydrochloride administration. A computed tomographic scan showed large, symmetric, low-density thalamic lesions, the condition of which improved after three months.

Intracranial extension and spontaneous hemorrhage of a sphenoid plasmacytoma.

A 71-year-old woman with IgG multiple myeloma presented initially with a compression fracture of the thoracic spine. She responded to radiation therapy and chemotherapy with melphalan and prednisone. One year later, she died from a plasmacytoma eroding intracranially from the greater wing of the sphenoid bone with an associated subdural hematoma. Uncal herniation had been preceded for several weeks by facial numbness. Cranial and intracranial plasmacytomas may occur as isolated lesions or as part of multiple myeloma and can present clinically in a variety of ways, most frequently with cranial nerve palsies. Large intracranial extensions may produce cerebral compression and spontaneous hemorrhage similar to that seen with other malignant intracranial neoplasms. The differential diagnosis of changes in level of consciousness in myeloma patients should include increased intracranial extension and spontaneous hemorrhage.

Pellet-gun brain wound complicated by Clostridium Perfringens meningitis.

A ten-year-old male was hospitalized for a pellet-gun wound to the brain. He developed Clostridial meningitis within eighteen hours in spite of radical debridement and prophylactic antibiotics. However, successful recovery was obtained with high levels of penicillin and chloromycetin antibiotic therapy.

Spinal cord potentials evoked by peripheral nerve stimulation.

Lumbar, thoracic, and cervical spinal cord responses evoked by sciatic nerve stimulation were measured in 20 cats at the skin level and directly from the dorsal surface of the cord. Computer averaging techniques were used for both skin level recordings and cord surface recordings at all levels. Recordings made directly from the cord surface at lumbar levels were large and were characterized by a large, initial, negative transient, followed by a more complicated and variable waveform. As recording electrodes were moved rostrally, the initial large spike decreased in amplitude and the duration and latency of the response increased. At cervical levels were large and were characterized by a large, initial, negative transient, followed by a more complicated and variable waveform. As recording electrodes were moved rostrally, the initial large spike decreased in amplitude and the duration and latency of the response increased. At cervical levels the responses were polyphasic, of long duration and small amplitude. Deafferentation by posterior rhizotomy of all lumbar and sacral roots ipsilateral to sciatic nerve stimulation abolished the response at all levels. Thoracic cord section also abolished the response over the cervical cord. Skin level recordings were of shorter latency than direct recordings, especially at cervical levels. Response configurations were similar for both recording techniques at lumbar levels, but had different waveforms at both thoracic and cervical levels. Clinical implications of the techniques and possible explanations of the waveforms recorded are discussed.

Survival following gunshot wound of the pons: neuroanatomic considerations. Case report.

The successful treatment of a civilian gunshot wound of the vermis and pons is described. A large missile fragment was removed from a depth of 2 cm within the pons at the level of the facial colliculus. Despite initial coma and subsequent irregular respiration with sleep apnea, the patient survived. Neurological, radiographic, and operative findings are correlated with the anatomy of the pons.