A novel protein complex distinct from mismatch repair binds thioguanylated DNA.

To elucidate molecular mechanism(s) of cellular response to mercaptopurine, a widely used antileukemic agent, we assessed mercaptopurine (MP) sensitivity in mismatch repair (MMR) proficient and MMR deficient human acute lymphoblastic leukemia (ALL) cells. Sensitivity to thiopurine cytotoxicity was not dependent on MMR (i.e., MutSalpha) competence among six cell lines tested. Using electrophoretic mobility shift assay analysis, we found that the incubation of nuclear extracts from ALL cells with synthetic 34-mer DNA duplexes containing deoxythioguanosine (G(S)) within either G(S).T or G(S).C pairs, resulted in formation of a DNA-protein complex distinct from the DNA-MutSalpha complex and unaffected by ATP. Isolation and sequence analysis of proteins involved in this DNA-protein complex identified glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a component. Western blot analysis of nuclear extracts from a panel of human lymphoblastic leukemia cell lines revealed markedly different basal levels of GAPDH in nuclei, which was significantly related to thiopurine sensitivity (p = 0.001). Confocal analysis revealed markedly different intracellular distribution of GAPDH between nucleus and cytosol in six human ALL cell lines. Redistribution of GAPDH from cytosol to nucleus was evident after MP treatment. These findings indicate that a new DNA-protein complex containing GAPDH and distinct from known MMR protein-DNA complexes binds directly to thioguanylated DNA, suggesting that this may act as a sensor of structural alterations in DNA and serve as an interface between these DNA modifications and apoptosis.

Repair of giant occipital encephaloceles with microcephaly secondary to massive brain herniation.

Giant occipital encephaloceles rarely contain large amounts of neural tissue that cannot be replaced in the abnormally small calvarium. Resection of neural elements is therefore often necessary in order to accomplish a closure. A technique is described wherein an extracranial compartment is prepared utilizing fine tantalum mesh to enclose the neural contents. The mesh is attached to the periphery of the skull defect providing a rigid extracranial compartment for the encephalocele. As intracranial pressure increases, the calvarium is forced to expand. The tantalum mesh is gradually imbricated into the calvarium by daily digital compression. If ventriculomegaly occurs, an interval ventriculoperitoneal shunt is placed. The encephalocele repair is reopened and the tantalum is surgically imbricated at that time. This allows for a satisfactory cosmetic result with preservation of all neural elements.

Hospital ethics committees: a pediatric neurosurgical perspective.

The Pediatric Neurosurgical Section of the American Association of Neurological Surgeons was polled regarding the status of hospital ethics committees. Twenty-four committees were identified in 74 pediatric neurosurgical centers in the United States. (Thirteen of these were formed between October 1983 and February 1984.) In addition, 21 are in the planning stages. Physicians predominate, with nurses, hospital administrators, the clergy, social workers, attorneys and lay persons usually represented. Functions include review of ethical and patient care decisions and providing counsel and support primarily to physicians and nurses. Rarely do committees make policy, determine prognosis or make final decisions regarding life-support systems. Approximately one case per year is reviewed. Committee formation frequently appears to be a crisis response to highly publicized pediatric cases and recent positions of the Department of Health and Human Services. Their purpose, construct, function and utilization raise serious questions as to their usefulness and necessity.

Intracranial extension of nasal dermoids.

Nasal dermoid cysts with intracranial extension have been thought to be a rare entity. Seven new cases of nasal dermoid cyst with intracranial involvement were treated from 1975 through 1982 by combined otolaryngological-neurosurgical management. Preoperative radiological studies were helpful in predicting intracranial extension in only three cases. The extracranial lesion was resected by the otolaryngologist using surgical hemoclips to tag the dermoid remnant entering the cranium. These hemoclips were a helpful landmark for the neurosurgeon when resecting the intracranial extension through a bifrontal craniotomy approach. In four cases, the dermoid cyst entered the cranium through a persistent foramen cecum and lay within the falx in association with a bifid crista galli. We think that this entity is more common than was previously appreciated. Patients with a diagnosis of nasal dermoid should undergo polytomography or computed tomography of the glabellar area. Even when all x-ray studies are negative, neurosurgical preoperative evaluation and operative standby should be obtained before the otolaryngologist attempts the resection of a nasal dermoid cyst.

Fluctuation of intracranial pressure associated with the cardiac cycle.

Within the intensive care setting, a portable microcomputer system was used to extract three parameters from the intracranial pressure fluctuation associated with the cardiac cycle. One parameter, the mean of sampled intracranial pressure, was defined as the average value of pressure for a 1.08-second interval following the R wave of the electrocardiogram. Another parameter, the amplitude of intracranial pressure, was defined as the difference between the mean and the peak value of the sampled intracranial pressure for the interval considered. The third parameter, a latent interval, was defined as the time period between the occurrence of the R wave and the occurrence of the peak value of the subsequent intracranial pressure fluctuation. Six adults and one pediatric patient were monitored. Both the amplitude and the mean of sampled pressure tended to vary inversely with the latent interval. For the adult patients, the latent interval varied between 503 and 804 ms; the mean pressure ranged between 2.4 and 19.0 mm Hg and the amplitude pressure ranged between 0.6 and 7.2 mm Hg. The latent interval for the child was much shorter (ranging between 269 and 325 ms), and both the mean and the amplitude pressures were much higher (ranging between 38.4 and 57.3 mm Hg and 14.2 and 16.5 mm Hg, respectively). Statistical correlation between hourly pulse rates and the latent interval among the adult cases revealed little association (r = -0.20). For all patients considered, the correlation between the amplitude and the mean of sampled intracranial pressure was quite high, with an r value of +0.91. These reported observations support a conceptual model in which blood volume changes associated with the cardiac cycle occurring within the semirigid craniospinal sac are assumed to underlie the fluctuation of intracranial pressure.

Intracranial and extracranial neurogenic hamartoma.

A case of neurogenic hamartoma involving the middle cranial fossa, nasopharynx, and left anterior cervical region and presenting at birth as an obstructive oropharyngeal mass is described. Special management included Gelfoam embolization of the vascular supply, control of airway and feeding, assessment of biological activity of the mass, and appropriate staging of the procedure with neurosurgical, head and neck surgical, and radiological support.

Retest reliability of the Halstead Impairment Index in a normal, a schizophrenic, and two samples of organic patients.

In a 1974 study Matarazzo, et al. reported the test-retest reliability of the Halstead-Reitan Neuropsychological Battery for a sample of normal young men and a comparison group of older Ss with cerebrovascular disease. The present study extended this earlier one by addition of comparable test-retest findings from two additional comparison groups: a sample of chronic schizophrenic Ss and a sample of organic patients who underwent endarterectomy. Despite the lack of comparability across the four samples on many dimensions, including age and test-retest interval, the results again reveal a high degree of clinical as well as purely psychometric reliability for most of the tests in the neuropsychological battery and the additional suggestion for further research that the test-retest instability found for some of the Ss in the schizophrenic sample may, itself, hold promise of differential clinical significance in the diagnosis of a "schizophrenic" vs. "organic" process.