Biomedical subjects

H S U

Publications and source records attributed to H S U.

At least 37 records · Page 2Linked to original sources

PubMed1992

An assessment of the cerebral protective effects of etomidate in a model of incomplete forebrain ischemia in the rat.

The cerebral protective effects of etomidate were evaluated in a model of incomplete forebrain ischemia. Fourteen Wistar-Kyoto rats were anesthetized with halothane. After preparation, the rats were alloted to either the control group (halothane anesthesia, n = 7) or the etomidate group (n = 7). In the etomidate group, immediately before and during the period of ischemia, the animals received etomidate in sufficient concentration to achieve electroencephalogram burst suppression (loading dose, 7.5 mg/kg; infusion, 0.3-0.5 mg/kg/min). Both groups were subjected to a 10-minute ischemic insult accomplished by bilateral carotid artery occlusion and simultaneous hypotension (mean arterial pressure, 35 mm Hg). Histological evaluation of the brain was performed after a 4-day recovery period. Injury was evaluated in coronal brain sections in five structures: neocortex, striatum, reticular nucleus of the thalamus, and the CA1 and CA3 areas of the hippocampus. The location of the sections in the rostral-caudal axis was chosen to encompass anterior areas within the core of the ischemic territory as well as more posterior regions within the anticipated "watershed" zone between the occluded anterior and the intact posterior circulations. In the animals that received etomidate, statistically significant (P less than 0.05) reduction in the severity of the ischemic injury was observed in the CA3 area and in the ventral portion of the CA1 area of the hippocampus in the more posterior sections. There was an apparent trend toward protection in other structures in both rostral and caudal sections, but these changes were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Neuropsychological sequelae of arteriovenous malformations.

A total of 24 patients harboring arteriovenous malformations (AVMs) in either the dominant hemisphere (n = 12) or the nondominant hemisphere (n = 12) were examined neuropsychologically. When compared with 24 matched normal control subjects, the AVM patients demonstrated differential degrees of impairment in verbal or visuospatial processing, depending on whether the lesion involved the dominant or nondominant hemisphere. As predicted, most compelling were the findings of cognitive deficit associated with the hemisphere contralateral to the AVM relative to matched normal control subjects. Evidence of higher cortical dysfunction contralateral to the residing AVM is discussed in the context of cerebrovascular steal.

Adult↗

PubMed1990

Nerve growth factor infusion in the primate brain reduces lesion-induced cholinergic neuronal degeneration.

NGF is a protein that promotes survival, differentiation, and process extension of selected neuronal populations during development and, in some cases, in the mature organism. Previous lesion and aging studies in the rat have shown that intracerebroventricular NGF infusions can prevent degenerative changes in basal forebrain cholinergic neurons. We sought to determine whether salutory effects of NGF occur in the primate brain. Cholinergic fibers of the septohippocampal projection in the primate were surgically transected, followed by infusion of either a vehicle or an NGF solution into the ventricular system for a 4-week period. Quantification of cholinergic neurons in the medial septal nucleus at the end of the infusion period demonstrated that only 45 +/- 5% of cholinergic neurons could be identified after fornix lesions in vehicle-infused animals, whereas 80 +/- 6% of neurons were visible in NGF-treated animals. Thus, NGF substantially reduced lesion-induced cholinergic neuronal degeneration in the adult primate brain. This finding may be relevant to the hypothesis that NGF has potential use as a cholinergic "neurotrophic-factor therapy," given that loss of basal forebrain cholinergic neurons is common in Alzheimer's disease.

Acetylcholinesterase↗

PubMed1989

Proto-oncogene abnormalities and their relationship to tumorigenicity in some human glioblastomas.

Human glioblastomas are highly malignant intracranial tumors, some of which demonstrate amplification of the epidermal growth factor-receptor (EGF-R) gene. Overexpression of this gene is seen in the majority of primary tumors; however, the role of the EGF-R gene in glial tumorigenesis is unknown. The authors explored the relationship between EGF-R gene expression and glioblastoma cell growth in vitro and in vivo and found that this level of EGF-R gene expression did not correlate with tumor cell growth either in soft agar or in the nude mouse. This suggests that the EGF-R gene is not involved in effecting direct growth stimulation in glial oncogenesis. Tumorigenesis involves differentiation arrest; therefore, the expression of several proto-oncogenes in neuroectodermal tumors was investigated to evaluate the potential involvement of the EGF-R gene in glial differentiation. A nonoverlapping expression of the N-myc and EGF-R genes was found in neuronal-derived and glial-derived tumors, respectively. This suggests that the EGF-R gene may be involved in differentiation or its arrest in glia.

Animals↗

PubMed1988

Abnormalities of the human growth hormone gene and protooncogenes in some human pituitary adenomas.

Hypersecretion of human GH (hGH) or PRL by human pituitary adenomas is not under normal homeostatic control despite normal receptor function mediating the regulatory effects of hypothalamic peptides for these trophic hormones. This implies that the defects underlying hormonal hypersecretion may not reside at the plasma membrane of the adenoma cell; instead, dysregulation may reside at the hormone gene level. To investigate this, genomic DNA derived from a prolactinoma and a hGH-secreting adenoma were digested with the restriction endonuclease EcoRI and the methylation sensitive restriction endonuclease HpaII and hybridized with the 32P-labeled genomic hGH (2.6 kilobase) probe. Our data revealed hypomethylation of genes of the hGH family (hGH and chorionic somatomammotropin) in the absence of gross abnormalities such as gene translocation. In a similar analysis using a 32P-labeled probe consisting of the EcoRI-BamHI (500 base pair) fragment in the 5'-flanking region upstream of the first exon of the hGH gene, hypomethylation of this specific site of the hGH genes was observed. These results are consistent with the concept that hypomethylation of genes is involved in gene expression. At the same time, protooncogene abnormalities in these adenomas were investigated to delineate any genetic basis for their neoplastic growth. Genomic DNA of adenomas were subjected to Southern blotting analysis using a panel of protooncogene probes. Amplification of the v-fos gene was observed in one prolactinoma. The significance of this observation is discussed.

Adenoma↗

PubMed1987

Tumorigenicity in the nude mouse of cocultures derived from two nontumorigenic cell types, human pituitary adenomas and mouse C3H 10T1/2 fibroblasts.

Human pituitary adenoma tissues were not tumorigenic in the hormonally manipulated nude mouse. Mouse fibroblast cells (C3H 10T1/2) also did not form tumors when inoculated alone into nude mice. When these two tissues were cocultured and coinoculated into nude mice however, the majority of inocula developed progressively enlarging tumors which could be established in tissue culture and passaged through the nude mouse. These tumors were sarcomatous histologically and thus did not resemble any human pituitary adenoma tissue injected. In order to detect any human cells in these tumors, tumor genomic DNA was subjected to Southern analysis using human repetitive Alu and HGH DNA sequence probes. Southern blot analysis of the nude mouse derived tumor genomic DNA revealed no sizeable human DNA in the mouse tumor cell genome indicating the absence of significant numbers of human cells in the tumors or the transfer of human DNA to the mouse cells. The tumors therefore arose from transformed C3H 10T1/2 cells after coculture with the human pituitary adenoma cells. These results implied that the tumorigenic transformation of susceptible C3H 10T1/2 cells in the cocultures occurred as a result of the secretion by the adenoma cells of transforming substances in the culture media or the induction of tumorigenicity through direct cell-cell contact between the two cell types.

Adenoma↗

PubMed1987

Correction of genetic diabetes insipidus by adult hypothalamic grafts.

Brattleboro rats manifest chronic diabetes insipidus as a result of the genetic deficiency of hypothalamic vasopressin. When basal hypothalamic tissue derived from adult F344 rats was implanted as cell suspensions or tissue blocks in the supraoptic regions of these animals, concentration of urine together with reduced urine output and water intake was observed in some animals. Histologic examination of the grafted brains from the responding animals revealed neuronal cells at the implant sites and vasopressin-staining fibers in the median eminence. This study demonstrates the feasibility of the grafting of adult cerebral tissues to correct a genetic hormonal deficiency.

Animals↗

PubMed1986

Polarity of neutral amino acid transport and characterization of a broad specificity transport activity in a kidney epithelial cell line, MDCK.

The Madin-Darby canine kidney (MDCK) cell line was investigated with respect to the cellular polarity of amino acid transport in early confluent versus late confluent cultures. Early confluent cultures could take up amino acids from the apical and the basolateral sides of the cell layer via amino acid transport Systems A, ASC, and L. However, in late confluent cultures the activities of Systems A and L were clearly localized to the basolateral surface of the cell monolayer. In addition to the presence of systems A, ASC, and L, a novel activity, measurable under conditions used for quantitating System ASC, was found to be active in the apical membrane of these cells. This transporter, termed System G (for general), recognized basic and neutral amino acids with high affinity and acidic amino acids with lower affinity. System G exhibited broad substrate specificity, strict cation specificity, and a broad pH optimum with maximal activity at acidic pH. The activity of System G was relatively low after growth in serum-containing medium but was induced in a defined medium. Induction of System G activity was dependent upon the presence of prostaglandin E1. The broad substrate specificity, low pH optimum, and Na+ dependence suggest that System G may function in apical membranes as an energy-dependent transport route during reabsorption of amino acids from the kidney tubule lumen.

Alanine↗

PubMed1986

Sodium entry pathways in renal epithelial cell lines.

Na+ entry into kidney epithelial cells occurs by a multiplicity of pathways. Established cell lines such as the A6 cells, derived from the collecting duct of the kidney of Xenopus laevis, MDCK cells, from the distal tubule of a dog kidney, and the LLC-PK1 cells, originating from the proximal tubule of a pig kidney, provide excellent model cell systems for the detailed characterization and isolation of the proteins which comprise these entry pathways. Major pathways of Na+ entry include the amiloride-sensitive Na+ channel, the amiloride-sensitive Na+/H+ antiporter, and the loop diuretic-sensitive NaCl/KCl symporter. While the former two systems have been shown to exhibit an apical location in epithelial cells so far examined, the last system may be localized to either the basolateral or apical surface, depending on the transport function of the cell. Nutrient/Na+ symporters such as the glucose, phosphate, and p-aminohippurate symporters may all be localized to the apical surfaces of proximal tubular cells, but other systems, including those specific for neutral amino acids, may predominate in the basolateral surface or be distributed between the two membranes. Studies concerned with the catalytic, structural, and regulatory properties of these transport systems serve not only to characterize the individual translocators in established cell lines, but also to suggest their physiological functions in intact kidney tissues.

Aldosterone↗

PubMed1985

Characterization of chemically and virally transformed variants of Madin-Darby canine kidney (MDCK) epithelial cells.

Oncogenic derivatives of Madin-Darby canine kidney (MDCK) cells were isolated in the nude mouse, and nononcogenic anchorage-independent transformants were isolated in vitro following chemical mutagenesis in vitro. These transformed cell lines as well as a Moloney sarcoma virus (MSV) transformed line were characterized with respect to their serum and anchorage requirements, growth rates, final saturation densities, and sensitivities to contact inhibition. None of these in vitro growth characteristics were found to correlate with tumorigenicity in nude mice. One tumorigenic clone, MDCK-T1, was characterized with respect to serum-free growth requirements, cAMP production, and ornithine decarboxylase (ODC) activity. These cells exhibited a significant reduction in the PGE1 requirement for growth, they produced higher levels of cAMP, and they expressed a reduced level of ODC activity relative to the parental MDCK cells. These findings may reflect changes in growth control mechanisms which accompany kidney epithelial cell tumorigenesis and suggest that the study of transformed lines derived in this manner could lead to the identification of in vitro properties which are associated with malignancy.

Animals↗

PubMed1985

The effect of high dose sodium thiopental on brain stem auditory and median nerve somatosensory evoked responses in humans.

Median nerve somatosensory evoked potentials (MnSSEPs), brain stem auditory evoked responses (BAERs), and the cortical electro-encephalogram (EEG) were recorded in six patients during a 62-min infusion of sodium thiopental (STP) at a rate of 1.25 mg X kg-1 X min-1 (total dose, 77.5 mg/kg). The EEG became isoelectric after 22 +/- 8 (SD) min of STP infusion. Dose-related changes in the latencies and amplitudes of various evoked response wave forms were observed. However, in no instance was any component of either the MnSSEP or the BAER rendered unobtainable by STP administration. For the MnSSEP, progressive increases in the central conduction time (5.33 +/- 0.41 ms preinduction vs. 7.46 +/- 1.2 ms at t = 60 min) and in the latency of the cortical primary specific complex were observed simultaneously with significant reductions in the amplitude of the latter (2.10 +/- 0.85 muV preinduction vs. 0.85 +/- 0.55 muV at t = 60 min). Changes in the latency and amplitude of the response recorded over the upper cervical spine (C2) were not statistically significant in this small population. For the BAER, progressive and significant increases in the latencies of Waves I, III, V (e.g., Wave V latency: 6.16 +/- 0.24 vs. 6.87 +/- 0.31 ms) and in the I-III, III-V, and the I-V interwave latencies were observed. The amplitudes of the BAER components were not significantly altered. The authors conclude that the administration of a dose of STP in excess of twice that required to produce EEG isoelectricity can be compatible with effective monitoring of MnSSEPs and BAERs. However, STP produces dose-related changes in both evoked response wave forms, which must be considered in the interpretation of responses elicited during STP anesthesia.

Adult↗

PubMed1985

Microsurgical excision of paraventricular arteriovenous malformations.

Periventricular arteriovenous malformations (AVMs) have often been deemed inoperable because of their location in critical structures. Furthermore, the excision of large lesions may be complicated by the potential for serious brain swelling and hemorrhage due to "autoregulation breakthrough." Nonetheless, the unfavorable natural history of the untreated disease in a symptomatic young patient has induced us to approach these lesions using staged microsurgical excision combined with elective barbiturate coma for maximal cerebral protection. Between 1979 and 1983, six patients (four female, aged 12 to 60 years, and 2 male, aged 14 and 29) who harbored large AVMs in the basal ganglia, thalamic, and hypothalamic areas presented with subarachnoid hemorrhage (2 cases), progressive neural deficits (3 cases), and intractable headache (1 case). Nineteen staged operations were performed for the complete excision of these lesions. Among the first three patients, there was one death due to "autoregulation breakthrough" hemorrhage into the lateral ventricle during the excision of a lesion approached through the sylvian fissure using standard anesthesia techniques. This led to the adoption of the transventricular surgical approach and elective barbiturate coma to facilitate exposure of the lesion and to protect the adjacent vital structures from potential ischemia. Three patients were treated in this fashion uneventfully. Of the five successfully treated patients, two have returned to their preoperative status and one has completely recovered from global hemispheric ischemia and hemiplegia. The hemiparesis in one patient worsened as a result of postoperative hypertensive intraventricular hemorrhage, and one patient developed mild dysphasia and hemiparesis. This experience suggests that this approach offers a valid therapeutic regimen for the treatment of this disease. During the same period, three patients--one man (age 23) and two women (aged 29 and 22)--harboring four intraventricular AVMs presented with intraventricular hemorrhage. After the acute effects of chemical ventriculitis and hydrocephalus were overcome with cerebrospinal fluid diversion, all four lesions were excised microsurgically using the transtemporal approach. One patient demonstrated significant and progressive improvement of her preoperative memory deficit. The remaining two patients have both returned to their preoperative employment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1985

The hemodynamic consequences of high-dose thiopental anesthesia.

The hemodynamic and electroencephalographic effects of a 60 min infusion of thiopental, given at the rate of 1.25 mg X kg-1 X min-1 (total dose 75 mg/kg), were studied in 10 patients without cardiorespiratory disease undergoing surgery for the removal of large and/or deeply seated arteriovenous malformations. Data on heart rate, arterial, right atrial, pulmonary arterial, and pulmonary capillary wedge pressures, thermodilution cardiac output (expressed as cardiac index), the electroencephalogram, arterial blood gases, and serum thiopental concentrations were collected during a sedated, resting control period, and then every 15 min during drug infusion. Lactated Ringer's solution (total volume 1-2 liters) was infused throughout the study period at rates sufficient to maintain pulmonary capillary wedge pressure at control values. In doses sufficient to render the electroencephalogram isoelectric [t approximately equal to 30 min, 37.5 mg/kg cumulative dose, serum concentration 51 +/- 17 micrograms/ml (mean +/- SD)], drug infusion resulted in significant increases in heart rate (to 116% of control), and decreases in arterial pressure (to 87% of control), stroke volume index (to 87% of control), systemic resistance (84% of control), and both left and right ventricular stroke work indices (66% and 69% of control, respectively). Cardiac index was unchanged (following a transient increase at t = 15 min). There were no changes in pulmonary vascular resistance, or blood gases. A large total dose of thiopental (8-11 gm) was needed to maintain electroencephalogram suppression for the remainder of these 10-20 hr procedures, and emergence was slow (48-72 hr). The resultant prolonged ICU support may have contributed to serious postoperative complications in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1984

Neuronotrophic activities in cerebrospinal fluid of head trauma patients.

Neuronotrophic factors (NTFs) are agents required for neurons to survive in tissue culture. In this study, we investigated the presence of NTFs in cerebrospinal fluid (CSF) of patients with central nervous system (CNS) injury. Cerebrospinal fluid was collected from 15 patients with acute CNS lesions in whom ventricular catheters had been placed to monitor and to facilitate the control of intracranial pressure. Neuronotrophic activity within the CSF was assayed using cultures of neurons derived from fetal rat hippocampus and embryonic chick cerebral cortex. Cerebrospinal fluid from all 15 patients contained NTFs which supported the survival of rat hippocampal neurons. Survival of chick cortex neurons was supported by eight of nine CSF samples. In the 11 patients from whom consecutive CSF samples were available, NTF activity assayed in rat hippocampal cultures tended to decrease during the first several days after CNS injury. In CSF collected from three patients by lumbar puncture for diagnosis of "nontraumatic" conditions, no NTFs were detectable. NTFs supporting hippocampal neurons were also detected in extracts of blood clot obtained from normal volunteers. Neuronotrophic activity in the CSF was heat sensitive, nondialyzable, and macromolecular, suggesting its association with a protein(s). These observations suggested that (i) NTFs are detectable in human CSF after CNS injury, (ii) NTFs appear in response to the injury itself, and (iii) at least some human NTFs can support the survival in culture of nonhuman CNS neurons.

Animals↗

PubMed1984

Metastatic prolactin-secreting pituitary adenoma.

A 62-year-old man had a malignant prolactin-secreting pituitary adenoma. The tumor was initially resected through a transfrontal approach. Recurrence six years later was manifested by an occipital metastasis, which was excised. Progressive clinical deterioration ensued despite irradiation and chemotherapy of the intrasellar and occipital recurrence, and the patient died. Pathologic examination of tumor tissue obtained from the occipital metastasis showed increased cellular pleomorphism and mitotic rate in comparison with the original surgical specimen. The only true indication of malignant transformation, however, was the invasion of tumor capsule by adenoma cells, observed in the autopsy specimen. These findings support the contention that the diagnosis of a malignant pituitary adenoma rests ultimately on the demonstration of local invasive growth and/or distant metastasis. Since prolactinomas are usually non-aggressive, malignant degeneration of adenomas is decidedly rare. Its occurrence underlines the need for aggressive follow-up and treatment.

Adenoma↗

PubMed1984

The hemodynamic consequences of high-dose methohexital anesthesia in humans.

The hemodynamic, electroencephalographic (EEG), and metabolic effects of a high-dose methohexital anesthetic were examined in eight neurosurgical patients. The patients were studied at rest and at 15-min intervals during a 60-min infusion of the drug, given at a rate of 0.40 mg . kg-1 . min-1 (total dose 24 mg/kg). Ventilation was controlled with oxygen:air (FIO2 = 0.50), and fluid was infused at a rate sufficient to maintain pulmonary capillary wedge (PCW) pressures at control values (8 +/- 2 mmHg, mean +/- SD). Serum methohexital concentrations increased progressively, reaching values of 11.7 +/- 2.9 micrograms/ml at t = 30 min and 18.1 +/- 10.8 micrograms/ml at t = 60 min. Characteristic barbiturate-induced EEG changes were noted, with isoelectricity achieved at t = 28 +/- 13 min. Methohexital infusion resulted in significant reductions in arterial pressure (84% of control at t = 60 min), systemic vascular resistances (83% of control at t = 60 min), right and left ventricular stroke work indices (65% and 68% of control, respectively at t = 60 min), and total body O2 consumption (76% of control at t = 60 min). In addition, a progressive dose-related decrease in stroke volume index was noted (50.1 +/- 90 ml X beat-1 X m-2 at t = 0, 40.1 +/- 10.2 ml X beat-1 X m-2 at t = 60 [80% of control]). This occurred in spite of unchanged ventricular filling pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1984

Radical removal of lipomas of the conus and cauda equina with laser microneurosurgery.

Ten patients with ages ranging from 4 weeks to 21 years presented with a subcutaneous lumbosacral mass noted at birth. After spinal high resolution ultrasonography or computed tomography to determine the extent of neural involvement and the length of the tumor mass in the spinal canal, the patients underwent operation. Rectal electromyographic continuous monitoring was used in all for assessment of the S-2 and S-3 function during dissection. Carbon dioxide laser microneurosurgery was used in all operations. Radiating energy was used for the subcutaneous mass removal (40 to 60 W), the intracanalicular dissection (1 to 5 W), and the intraconus dissection (1 to 3 W). A radical removal was obtained in all. Postoperative cerebrospinal fluid fistula occurred in 1 patient and was successfully treated. Wound dehiscence that healed with secondary closure occurred in 2 patients. Would infection that required treatment with systemic antibiotics and topical therapy occurred in 1 patient. Paraplegia occurred in 1 patient. This was the single very significant complication of this series. It was thought to have occurred because of the polymer used to seal the tenuous dura mater at the time of closure. We conclude that, with carbon dioxide laser microneurosurgery, the lipomatous tumors can be removed safely from the neural structures of the conus and cauda.

Adolescent↗

PubMed1983

Polar redistribution of Na+K+ATPase in aggregating MDCK cells.

The distribution of Na+K+ATPase was examined immunoelectronmicroscopically along the plasma membranes of aggregating MDCK cells grown in tissue culture. Na+K+ATPase was localized with the use of affinity-purified antibodies employing the double-antibody immunoperoxidase technique. Na+K+ATPase-like immunoreactivity was uniformly distributed along the plasmalemma of cells grown in suspension. Once attached to the substratum, individual MDCK cells exhibited Na+K+ATPase immunoreactivity limited to the microvilli-laden mucosal surface. This exclusive mucosal distribution of Na+K+ATPase disappeared and a basolateral immunoreactivity became apparent once intercellular contacts and the formation of tight junctions occurred between neighboring cells. Thus, both cellular attachment to the substratum, and tight junction formation between aggregating MDCK cells are essential to the genesis of Na+K+ATPase polar distribution. These two events, however, appear to induce opposing distribution patterns for Na+K+ATPase.

Animals↗