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Biomedical subjects

B Weir

Publications and source records attributed to B Weir.

At least 55 records · Page 3Linked to original sources
PubMed1992

Potassium currents of rat basilar artery smooth muscle cells.

Primary isolates of smooth muscle cells from the basilar artery of the rat were studied using whole-cell and single-channel patch-clamp techniques. Two distinct potassium currents were characterized. With low intracellular calcium, depolarization above 0 mV elicited an outward current of a few hundred pA (at +120 mV) with sigmoidal onset and little inactivation during 1.25 s steps. This current was reduced by bath application of 1 mM procaine or 1 mM strychnine, but not by 500 nM charybdotoxin. These are characteristics of the delayed rectifier potassium current in other preparations. With higher intracellular calcium, depolarization above 0 mV elicited a non-inactivating potassium current of several nA (at +120 mV). This current persisted in the presence of 1 mM procaine or strychnine but was reduced by bath application of 100 nM charybdotoxin. In whole-cell recordings in which intracellular calcium was unbuffered with EGTA, spontaneous transient outward currents were manifest and displayed voltage dependence and tail currents similar to the calcium-dependent current. The spontaneous transient current and the calcium-dependent current had similar sensitivity to charybdotoxin. Cell-free membrane patches contained one or more channels of 220 pS (in solutions symmetrical with respect to potassium) with similar voltage and calcium dependence. These are characteristics of the large conductance calcium-activated potassium current in other preparations.

Animals↗
PubMed1992

Vasodilatation of canine cerebral arteries by nicorandil, pinacidil and lemakalim.

1. Nicorandil, pinacidil and lemakalim relaxed precontracted rings of canine cerebral artery. 2. The order of potency was lemakalim greater than nicorandil approximately equal to pinacidil, but all these agents were less effective than nimodipine. 3. The effects of nicorandil were inhibited by methylene blue but not by glibenclamide, while the effects of pinacidil and lemakalim were inhibited by glibenclamide but not by methylene blue. 4. Thus nicorandil probably causes relaxation mostly by effects on guanylate cyclase while lemakalim and pinacidil produce the same effect by action at ATP-dependent potassium channels.

Animals↗
PubMed1992

Relaxant effects on iloprost in canine cerebral artery.

Iloprost caused relaxation of rings of canine cerebral arteries precontracted with prostaglandin F2 alpha or the thromboxane A2 analogue U46619, but it was without effect on arteries precontracted with potassium chloride. Pretreatment with iloprost did not significantly affect the concentration-response curve to any agent. Contractile responses to oxyhemoglobin were completed relaxed by iloprost. In arteries from animals with moderate cerebrovascular spasm, the response to prostaglandin F2 alpha was also reduced by iloprost. The observation that iloprost relaxes the response to oxyhemoglobin to prostaglandin F2 alpha in spastic arteries may be of interest in the management of cerebral vasospasm.

Animals↗
PubMed1992

Pituitary tumors and aneurysms: case report and review of the literature.

A case of acromegaly from a growth hormone-secreting pituitary adenoma associated with dilatation of all major intracranial arteries and bilateral giant, cavernous aneurysms is presented. Although saccular aneurysms are randomly associated with all types of pituitary tumors, the frequency of this happening with growth hormone-secreting or "chromophobe adenomas" is greater than would be expected by chance alone. Intrasellar saccular aneurysms contiguous with tumors have been reported. Bilateral cavernous carotid aneurysms have also occurred in association with pituitary tumors. Both infectious (bacterial and fungal) and traumatic aneurysms can develop as complications of pituitary surgery. A single case of aneurysms due perhaps to actual tumor infiltration of the arterial wall has been reported. Radiation therapy has rarely been associated with aneurysmal dilatation for nonpituitary tumors and has been reported only once after treatment of a pituitary tumor. Aneurysms may mimic pituitary tumors by producing endocrine disturbances, such as hypopituitarism, hyperprolactinemia, and diabetes insipidus, and by compressing adjacent cranial nerves. Anomalous large arteries, such as the trigeminal or transsellar-carotid variants, may run through the sella, and there is a case reported in which the former was associated with a pituitary tumor. A knowledge of these aneurysmal types and vascular anomalies is essential for the pituitary surgeon. Magnetic resonance imaging is now the radiological procedure of choice in the preoperative assessment of patients suspected of having pituitary tumors or recurrences, because, in addition to depicting the tumor, it defines the arterial anatomy and excludes all but very small coexistent aneurysms.

Acromegaly↗
PubMed1991

Effects of K+ channel agonists cromakalim and pinacidil on rat basilar artery smooth muscle cells are mediated by Ca(++)-activated K+ channels.

Whole-cell and cell-free inside-out patch-clamp recording techniques were used to examine the actions of potassium channel openers pinacidil and cromakalim in enzymatically isolated smooth muscle cells of rat basilar artery. Delayed rectifier and calcium-dependent potassium currents were identified from the whole-cell recordings. Only the calcium-dependent potassium current was increased by cromakalim and pinacidil. Recordings from inside-out membrane patches revealed a large conductance voltage- and calcium-dependent potassium channel, which was blocked by charybdotoxin but unaffected by ATP less than 10 mM. Cromakalim and pinacidil increased the open probability of this channel. On the basis of these results, we suggest that such drugs, acting on cerebral arterial smooth muscle cell potassium channels, may be of some benefit in the treatment of cerebral vasospasm following subarachnoid hemorrhage.

Animals↗
PubMed1991

Glibenclamide relaxes vascular smooth muscle constriction produced by prostaglandin F2 alpha.

The present study has demonstrated: (1) glibenclamide can reduce resting tension in canine cerebral arteries but has no effect on resting tension in the rat aorta; (2) glibenclamide can relax prostaglandin F2 alpha-induced contractions in the rat aorta, and in canine femoral, mesenteric, renal, coronary, basilar and middle cerebral arteries; (3) the relaxation produced by glibenclamide in rat aorta is comparable to that of glyceryl trinitrate and stronger than that of papaverine; (4) canine femoral arteries are less sensitive to glibenclamide than the other arteries; (5) in cerebral arteries glibenclamide was as effective as papaverine, but less effective than glyceryl trinitrate; (6) the actions of glibenclamide on cerebral arteries are not mediated by cGMP as they were not blocked by methylene blue, an inhibitor of guanylate cyclase; (7) the effects of glibenclamide are not endothelium-dependent. The mechanism by which glibenclamide produces relaxation is not clear; while the drug is known to block ATP-dependent potassium channels, in vascular smooth muscle this would cause contraction, not dilation. The action of glibenclamide may be at the level of the receptor or the signal transduction process.

Animals↗
PubMed1991

Free radicals mediate actions of oxyhemoglobin on cerebrovascular smooth muscle cells.

Single smooth muscle cells were isolated from the basilar artery of the rat by enzymatic dispersion. The membrane properties of the cells were assessed using the patch-electrode voltage-clamp technique, and cell viability was monitored using fluorescein diacetate uptake. Exposure of the cells to oxyhemoglobin (5 microM) resulted in 1) contraction, 2) the appearance of membrane blebs, 3) an increase in the outward potassium currents, 4) a decrease in the membrane resistance, and 5) cell death. In contrast, no effect of oxyhemoglobin on cultured murine neuroblastoma cells was observed. Methemoglobin (100 microM) had no effects on the smooth muscle cells. Catalase (300 units/ml) or dimethyl sulfoxide (0.5%) protected against the effects of oxyhemoglobin; superoxide dismutase (100-1,000 units/ml) provided only partial protection. Exposure of the cells to superoxide anions generated by xanthine (1 mM) plus xanthine oxidase (10 units/l) or to hydrogen peroxide (500 microM) caused an increase in the outward potassium currents without affecting membrane resistance. Generation of hydroxyl radicals by metal ions plus hydrogen peroxide caused the same effects as oxyhemoglobin, that is, an increase in the potassium currents, followed by a decrease in the membrane resistance and cell death. In conclusion, it appears that oxyhemoglobin exerts its effects on vascular smooth muscle cells by the generation of free radicals, chiefly hydroxyl radicals.

Animals↗
PubMed1990

Absence of IFNA and IFNB genes from human malignant glioma cell lines and lack of correlation with cellular sensitivity to interferons.

We report that 5 of 19 human malignant glioma cell lines have neither interferon alpha (IFNA) nor interferon beta (IFNB) genes that are detectable by Southern blotting. Of 5 other of these malignant glioma lines that have a single IFNB gene copy, 3 lack the IFNA genes entirely and two have one copy. One of the lines that lacks the IFNA genes entirely but has one copy of the IFNB gene has a rearrangement near the IFNB gene that is most easily interpreted as an insertion of a large segment of DNA (at least 50 kilobases) the 3' end of which is less than 1.3 kilobases 5' to the known regulatory sequences of the IFNB gene. In spite of the rearrangement, IFNB-specific RNA is highly inducible in this line by poly(I)-poly(C). The ability of interferon alpha or interferon beta to inhibit cell growth does not depend upon the presence or absence of the respective gene. This finding adds solid tumors to those tumor cell lines (acute lymphocytic leukemia, chronic myelogeneous leukemia) previously determined to lack the IFNA and IFNB genes (Diaz et al., Proc. Natl. Acad. Sci. USA, 85:5259-5263, 1988).

Chromosome Deletion↗
PubMed1990

Standard specimens for stain calibration: application to Romanowsky-Giemsa staining.

Standardized specimens with reproducible staining properties were fabricated from extracts of biological objects (bovine liver, nucleoprotamine and defatted muscle). The standard specimens were stained with two formulations of the Romanowsky-Giemsa stain (RG), using the same azure B and eosin Y. One formulation used methanol and Sorensen's buffer and the other DMSO and Hepes buffer as solvents. The standard specimens were stained either in the composite stain or in the individual dyes dissolved in the same solvents and at the same concentration as the composite stain. Solution spectroscopy demonstrated different spectra for the two formulations with some wavelength regions varying by more than an order of magnitude. The RG spectra were also very different from those of the individual dyes dissolved at the RG concentration in the respective solvents. The stained standard specimens were analyzed by microspectrophotometry and were found to have spectra similar to those of cell smears. Furthermore, the standard specimens were shown to be a repeatable substrate for stain uptake. The transmitted light intensity from random fields of the same standardized specimen varied +/- 5%. When specimens were stained at the same time, the specimen-to-specimen variation depended on preparation conditions and the measurement wavelength, but was as good as +/- 5% for some conditions. The quantitative stain performance of both formulations was studied and compared. The standardized specimens provide a tool for the quantitative study of staining processes and specimen preparation procedures and for stain calibration.

Animals↗
PubMed1990

The history of cerebral vasospasm.

In summary, over a period of approximately four decades, an important new pathologic process was identified. There is no longer any doubt that the deposition of the subarachnoid clot in the basal cisterns can, over the course of a few days, lead to a progressive, severe vasoconstriction. This, in turn, can reduce cerebral blood flow to the distal brain, which, depending on a multitude of factors, can result in cerebral infarction. It is highly likely that the erythrocyte is the most important blood element in the pathophysiology of this process. The exact mechanism by which the blood vessel is forced into this destructive spasm remains to be elucidated. Significant steps have been taken to avoid the consequences of vasospasm by using hypertension and hypervolemia (or at the very least avoiding iatrogenic hypotension and hypovolemia). These measures have resulted in a reduced incidence of delayed ischemia. Because clot has been shown to cause vasospasm, it has seemed only logical that the early removal of clot would be efficacious in its prophylaxis. Experimental and clinical evidence to support this view has been gathered. Therapeutic measures based on it have been shown to be effective in the experimental situation but await controlled clinical evaluation. In the past decade, thanks to such trials, one of the calcium antagonist drugs has been shown to be effective in improving the outcome following subarachnoid hemorrhage, probably on the basis of reducing the frequency and extent of infarction by small vessel dilatation or neuronal protection. Although patients still die from this lethal complication of subarachnoid hemorrhage, it is difficult not to have some measure of optimism, based on the history just reviewed, that cerebral vasospasm will be a treatable disease within a few decades.

Animals↗
PubMed1990

The effect of clot removal on cerebral vasospasm.

There seems to be no doubt that periarterial clot causes vasospasm and that vasospasm is a significant cause of delayed ischemic neurologic deficits and infarcts. It is to be hoped that a way can be found to remove such clots effectively and rapidly before they do their deadly damage.

Animals↗
PubMed1989

Trends in blood pressure, osmolality and electrolytes after subarachnoid hemorrhage from aneurysms.

Daily trends in blood pressure, osmolality and electrolytes were analyzed in a series of 173 operated aneurysm cases who had subarachnoid hemorrhage (SAH) and were admitted within 4 days of the ictus. High blood pressure was associated with a greater risk of mortality and the development of clinically significant vasospasm (VSP). High osmolality shortly after admission was related to mortality but not VSP. Changes in sodium and potassium had no obvious relationship to mortality or VSP.

Adolescent↗
PubMed1989

Transcranial Doppler studies in aneurysm patients.

Fifty patients with ruptured intracranial aneurysms and 8 patients with elective clipping of unruptured aneurysms had daily transcranial Doppler (TCD) measurements performed. The highest mean middle cerebral artery velocity (MCA-Vel) was considered to be the best single parameter for judging a patient's susceptibility to clinically significant vasospasm (VSP). Surgery for the clipping of unruptured aneurysms by itself does not lead to an increase in MCA-Vel. There is a progressive increase in MCA-Vel after subarachnoid hemorrhage (SAH) from aneurysms which peaks between 7 and 10 days. The MCA-Vel is higher on the side of the ruptured aneurysm and the degree of rise is greater if blood is seen on the initial CT scan. It is highly unlikely that a patient whose MCA-Vel remains under 100 cm/sec has a degree of angiographic VSP which causes clinical symptomatology. Patients whose MCA-Vel is greater than 200 cm/sec are at great risk of developing clinical symptomatology of VSP and are very likely to have significant angiographic VSP. There is a transitional zone in between these two levels.

Cerebrovascular Circulation↗
PubMed1989

Daily trends in white blood cell count and temperature after subarachnoid hemorrhage from aneurysm.

A retrospective analysis of the cases of 173 patients operated on for aneurysms and admitted to a neurosurgical service early after subarachnoid hemorrhage was conducted with respect to white blood cell (WBC) count and highest daily temperature. Daily trends for the development of clinically significant vasospasm (VSP) as well as mortality during the hospitalization were analyzed. An admission WBC count greater than 15 x 10(9)/l was associated with 55% mortality as opposed to 25% mortality for those with a lower WBC count. The mortality of those with a temperature greater than 37.5 degrees C on Day 0 was 60%, compared with 35% for those with a lower temperature. A WBC count greater than 15 x 10(9)/l on Day 0 was associated with a VSP rate of 40%; a lower WBC count was associated with a VSP rate of 30% Day 0 temperatures greater than 37.5 degrees C were associated with a VSP rate of 40%, while patients with lower temperature had a VSP rate of 30%. By Day 6, the patients with temperatures greater than 37.5 degrees C had a VSP rate of 60%, double that of the VSP rate of those with temperatures less than 37.5 degrees C. WBC count was apparently more closely linked to the chance of dying than the chance of developing VSP. The development of fever after a few days is related to both increased mortality and increased chance of developing VSP.

Adolescent↗
PubMed1988

Pathway of nerves with vasoactive intestinal polypeptide-like immunoreactivity to the major cerebral arteries of the rat.

The pathway of nerves with vasoactive intestinal polypeptide (VIP)-like immunoreactivity to the major cerebral arteries was studied in rats by means of the indirect immunofluorescent method. The fibers are densely distributed in the ethmoidal nerves and in the adventitia of both the external and internal ethmoidal arteries. Section of both ethmoidal nerves and external ethmoidal arteries before they enter the cranial cavity induced a marked reduction of VIP-like immunoreactive fibers in the walls of the vessels of the circle of Willis and its major branches. However, section of the external ethmoidal artery alone did not result in visible changes of the nerves around major cerebral arteries. The present study suggests that VIP-like immunoreactive fibers surrounding major cerebral arteries of the rat arise from fibers in the ethmoidal nerve showing immunoreactivity to VIP.

Animals↗
PubMed1988

Effects of vasospasm on levels of prostacyclin and thromboxane A2 in cerebral arteries of the monkey.

To determine whether cerebral arteries in spasm have an altered capacity to synthesize the vasoactive substances prostacyclin and thromboxane A2, we measured levels of these arachidonic acid metabolites using a primate model of vasospasm. Twenty-four cynomolgus monkeys were assigned at random to one of three groups designated sham, clot, or clot-removal. All animals underwent base line cerebral angiography and bilateral dissection of the major cerebral arteries from the arachnoid. The clot and clot-removal groups had autologous hematomas placed around the vessels to simulate subarachnoid hemorrhages. The sham group had a similar volume of saline instilled into the subarachnoid space. Twenty-four hours later, the clot-removal group underwent a second craniotomy to remove the hematomas. Seven days after the initial operation, angiography was repeated on all animals. The animals were then killed, and the cerebral arteries were removed. Basal levels of prostacyclin and thromboxane in the cerebral vessels were measured after incubation in vitro by radioimmunoassay. No detectable leukotriene C4 release by these arteries was measurable using radioimmunoassay. Angiography revealed severe cerebral vasospasm in the clot group, but not in the clot-removal or sham groups. There were no statistical differences among the groups in thromboxane release, but prostacyclin levels were significantly lower in the clot group than in the clot-removal group (P less than 0.05). It thus seems that, if an imbalance in constrictor and dilator eicosanoids occurs in association with vasospasm, this is more likely to arise from a relative lack of the vasodilator component prostacyclin than from a surplus of the vasoconstrictor thromboxane.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

The American centennial of brain tumor surgery.

Early in 1887 the first well-documented total removal of an unequivocal brain tumor in America was carried out in New York City by Robert F. Weir. The patient died during the immediate postoperative period. Later in the same year in Philadelphia, W.W. Keen also removed a large meningioma; his patient lived many years. In 1886, a Dr. Morse in California had probably performed a partial removal of a glioma from a patient who died shortly after the operation. To celebrate the centennial of Keen's triumph, it is worthwhile as well to contemplate the efforts of his contemporaries.

Brain Neoplasms↗