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Biomedical subjects

K Weaver

Publications and source records attributed to K Weaver.

At least 37 records · Page 2Linked to original sources
PubMed1994

Enzymatic synthesis of folate and antifolate polyglutamates with Escherichia coli folylpolyglutamate synthetase.

Escherichia coli folylpolyglutamate synthetase was used to synthesize micromole quantities of polyglutamyl conjugates of folic acid, methotrexate, and other analogs of folic acid. The products of the enzymatic reactions were purified by semipreparative C18 HPLC. The position of each amide linkage (gamma or alpha carboxyl) in the polyglutamated products was determined by limited and exhaustive hydrolyses with hog kidney folylpolyglutamate hydrolase and with yeast carboxypeptidase Y. Under standard reaction conditions, the E. coli enzyme added up to five glutamyl residues to each monoglutamated substrate, primarily at the gamma carboxyl position. Thus, an enzyme which naturally adds only two glutamates to naturally occurring folates can be used synthetically to make higher polyglutamates of a wide range of synthetic substrates. The products of the reactions are valuable tools for the study of the metabolism of antifolate drugs as well as metabolic reactions involving folate cofactors.

Escherichia coli↗
PubMed1991

Correlation between cerebral blood flow, somatosensory evoked potentials, CT scan grade and neurological grade in patients with subarachnoid hemorrhage.

Cerebral blood flow (CBF) and central conduction time (CCT) were recorded from 58 subarachnoid hemorrhage patients and from 49 age-matched controls. CBF was calculated following Xenon inhalation and CCT was determined from somatosensory evoked potentials (SSEP's) following median nerve stimulation. Each patient had a CT scan on the day of admission which was graded from I-IV. CBF, CCT and neurological grade (Hunt and Hess classification) were concomitantly recorded 1, 4, 7 and 14 days after subarachnoid hemorrhage. Mean CBF was highest in patients with neurological grades I and II (48.6 +/- 12.3 and 48.1 +/- 10.3 ml/100gm/min respectively) and lowest in patients with neurological grade IV (37.3 +/- 9.6 ml/100gm/min). Patients in neurological grade I or II had mean CBF and CCT measurements that were significantly different from those obtained from patients in neurological grade IV (P less than 0.05). Neurological grade and CT scan grade correlated with CBF (P less than 0.0001) better than CCT (P = 0.015). Unexpectedly low CBF's from patients in neurological grades II and III (less than 37 and less than 31 ml/100gm/min respectively) failed to significantly prolong CCT suggesting CCT is unable to detect marginal ischemia. A significant correlation between CBF and CCT occurred only when CBF was less than 30 ml/100gm/min (R = 0.75, P = 0.05). It appears that prolonged CCT is associated with a drop in CBF only when CBF drops below a certain threshold.

Adult↗
PubMed1990

Agonist-mediated formation of inositol monophosphate isomers in rat cortical prisms.

The carbachol and adrenaline-mediated accumulation of inositol monophosphate isomers in rat cortical prisms has been studied using a commonly employed experimental protocol involving preincubation with myo-[2-3H]-inositol and subsequent incubation with agonists in the presence of 10 mM LiCl. Inositol phosphate isomers have been analysed by HPLC and identified by comparison of their elution characteristics with those of commercially available standards and the degradation products of authentic Ins 1,3,4-P3 and Ins 1,4,5-P3. Incubation of prelabelled cortical prisms for 1 hr with 10 mM LiCl alone gives rise to accumulation of radioactivity in two inositol monophosphate peaks which co-elute with Ins 1-P and Ins 4-P and one major bisphosphate peak which co-migrates with Ins 1,4-P2. Most of the monophosphate radioactivity is recovered in the Ins 4-P peak (Ins 1-P/Ins 4-P labelling ratio 0.68). Both carbachol and adrenaline produce dose-dependent increases in the labelling of Ins 1-P and Ins 4-P which are antagonized by atropine and prazosin respectively. However, carbachol produces a larger stimulation of accumulation of both monophosphates and also gives rise to a larger selective increase in the accumulation of Ins 1-P (Ins 1-P/4-P labelling ratio 1.40 in the presence of 1 mM carbachol, 0.98 in the presence of 1 mM adrenaline). Kinetic studies of the carbachol-stimulated increases in inositol mono- and bisphosphate labelling have revealed that, in the early period following carbachol addition (0-5 min), Ins 4-P and Ins 1,4-P2 are labelled more rapidly than Ins 1-P, whereas the reverse is true at later periods (15-60 min) of the incubations. These observations, coupled with the low levels of labelling of the major Ins 1,3,4-P3 breakdown products (Ins 1,3-P2 and Ins 3,4-P2) compared with that of Ins 1,4-P2, suggest that large-scale production of Ins 1-P is a comparatively late feature of carbachol-mediated inositol phospholipid metabolism and that, if the Ins 1-P is derived from breakdown of Ins 1,3,4,5-P4 via Ins 1,3,4-P3, the turnover of Ins 1,3-P2 + Ins 3,4-P2 must be approximately one order of magnitude greater than that of the Ins 4-P precursor, Ins 1,4-P2.

Animals↗
PubMed1990

A CT-based computerized treatment planning system for I-125 stereotactic brain implants.

A computer program has been developed at the University of California, San Francisco, as an aid in planning and evaluating stereotactic brain implants made with 125I seeds. The program allows images of seeds and catheters to be positioned in the target volume revealed by CT. It then generates and displays the resulting isodose distributions. Catheters may be changed interactively until an optimum implant is achieved. From the geometry of a stereotactic implant frame as measured by CT, the program calculates the approach angles of the catheters in the frame coordinate system. After the seeds are implanted, films made with a fiducial marker box can be used to generate true seed positions and hence true isodoses. This paper describes mathematically the geometrical transformations used by the program, and also outlines its many features and options. In its first 2 years of use the program has proved to be a valuable contributor to improved patient care.

Brachytherapy↗
PubMed1989

Effect of magnesium on cocaine-induced, catecholamine-mediated platelet and vascular response in term pregnant ewes.

Ten pregnant ewes were alternated in a study of the blocking effect of parenteral magnesium on the catecholamine response to cocaine. Indirect blood pressures were recorded at 1-minute intervals for 12 minutes before and after a bolus of 2 mg/kg of cocaine. Fetal heart rates were continuously recorded from skin electrodes. Platelet counts were performed before and 12 minutes after cocaine. Control ewes received lactated Ringer's solution, and test animals had 5 mg/kg of elemental magnesium in the form of MgSO4-7H2O in a rapid infusion. A semicrossover was also performed. Platelet counts fell precipitately in controls and rose after magnesium infusions. Fetal heart rates rose in controls at 5-minute intervals and were unchanged in magnesium-treated mothers. Because of disparity of the baseline mean arterial pressure, direct comparisons were not significant before and after cocaine. Alterations from the baseline were different in magnesium-treated versus control animals, with values in the latter rising by 28 +/- 10 mm Hg with lactated Ringer's solution plus cocaine and falling by 3 +/- 5 mm Hg with magnesium pretreatment. Values in test animals originally treated with magnesium rose 4 +/- 11 mm Hg for an overall significance of p less than 0.05. Low beginning serum magnesium levels were associated with ovine hypertension and reduced fetal weight and survival.

Animals↗
PubMed1989

Computer assisted treatment planning for 125I ophthalmic plaque radiotherapy.

This paper describes a computer program for planning the treatment of ocular tumors with 125I plaques. The program permits the input of the tumor configuration into a model eye and facilitates the viewing of the relative geometry of the tumor and various eye structures in different perspectives. Custom-designed 125I plaques can be localized onto the globe, and dose distributions can be calculated and superimposed on the eye structures in any plane or on the inner eye surface. The program allows efficient evaluation of the plaque design in terms of radiation dose distribution relative to the tumor and critical structures.

Brachytherapy↗
PubMed1989

Kinetic analysis of A23187-mediated polyphosphoinositide breakdown in rat cortical synaptosomes suggests that inositol bisphosphate does not arise primarily by degradation of inositol trisphosphate.

The kinetics of polyphosphoinositide breakdown and inositol phosphate formation have been studied in rat cortical synaptosomes labelled in vitro with myo-[2-3H]inositol. Intrasynaptosomal Ca2+ concentrations have been varied by the use of Ca-EGTA buffers or by adding the ionophore A23187 in the presence and absence of 1 mM Ca2+. The former studies have revealed that, at very low (20 nM) intrasynaptosomal free Ca2+ levels, inositol bisphosphate, but not inositol monophosphate levels are reduced. Addition of A23187 in the absence of added Ca2+ gives rise to greatly enhanced inositol bisphosphate accumulation, which is further enhanced if 1 mM Ca2+ is present in the extrasynaptosomal medium. At all time points examined (down to 2 s after adding ionophore), the ratio of inositol trisphosphate/inositol bisphosphate accumulation does not exceed 0.2, and calculations based on inositol bis- and trisphosphate breakdown rates in synaptosomal lysates suggest that only a minority of the inositol bisphosphate arises from degradation of inositol trisphosphate. Addition of ionophore in the presence (but not in the absence) of 1 mM Ca2+ leads to rapid breakdown of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) and ATP and slower breakdown of phosphatidylinositol 4-phosphate (PtdInsP). The rates of loss of PtdinsP2 and ATP are very highly correlated, suggesting that polyphosphoinositide resynthesis may be limited by ATP availability at high Ca2+ levels. Analysis of 32P-labelled synaptosomes also reveals that A23187 produces Ca2+-dependent losses of PtdInsP2, PtdInsP, ATP, and GTP radioactivity and a marked increase in the radioactivity of a compound distinct from nucleotides or any of the lipid breakdown products tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1988

Is inositol bisphosphate the product of A23187 and carbachol-mediated polyphosphoinositide breakdown in synaptosomes?

Synaptosomes have been isolated from rat cerebral cortex and labelled in vitro with [32P]orthophosphate and myo-[2-3H]inositol. Subsequent addition of the Ca2+ ionophore A23187 in the presence of 2 mM extrasynaptosomal Ca2+ raised intrasynaptosomal free [Ca2+] to greater than 2 microM from a resting level of 200 nM and led to rapid breakdown of polyphosphoinositides. This was accompanied by a small increase in the level of inositol monophosphate, greatly enhanced accumulation in inositol bisphosphate, but no detectable increase in inositol trisphosphate. Depolarising (25 mM) extrasynaptosomal K+ produced a smaller increase in intrasynaptosomal free [Ca2+] (to around 400 nM) and a proportional increase in inositol bisphosphate radioactivity. Carbachol (1 mM) alone elicited only limited polyphosphoinositide breakdown and inositol mono- and bisphosphate formation, but this was greatly increased in the presence of 25 mM K+. The effect of carbachol in the presence of depolarising K+ was time- and dose-dependent and was antagonised by atropine (10 microM). There was no detectable accumulation of inositol trisphosphate in the presence of carbachol, K+, or carbachol plus K+, even after short (30 s.) incubations. The lack of inositol trisphosphate accumulation does not appear to result from rapid formation of inositol tetrakisphosphate or from enhanced breakdown of the trisphosphate in synaptosomes.

Animals↗
PubMed1987

Subcellular distribution of beta-adrenoceptors in brain following administration of antidepressant drugs.

The distribution of specific binding of [3H]dihydroalprenolol([3H]DHA) in sucrose gradients (0.2-1.75 M), containing homogenates of the cortex of rat brain, centrifuged to equilibrium (110,000 g/16 hr), was examined in controls and after treatment with antidepressant drugs. There were no significant changes in the specific binding of [3H]DHA after acute administration of desipramine (DMI, 50 mg/kg) or clorgyline (20 mg/kg), either in terms of the number of receptors or distribution in the sucrose gradient. There was a significant decrease (29%) in the number of beta-adrenoceptors after the chronic regimen with DMI, but again no apparent alteration in the density of the receptor-containing membranes, both samples having a maximum distribution at approximately 1.1 M sucrose. Non-specific binding was maximal at 0.65 M sucrose. Electron microscopy showed that the non-specific binding was largely to myelin and the fraction containing most specific binding was composed of membrane fragments. The activity of Na+ K+ ATPase had a single broad peak (maximum at 1.1 M sucrose). Thus, at the times studied, in vivo desensitisation/internalisation of cortical beta-adrenoceptors did not apparently occur following large acute doses of antidepressant drugs and furthermore the down-regulation which followed the chronic regimen with DMI did not involve migration of receptors into "light density fractions" which are reported to be present after acute exposure to agonists in vitro.

Animals↗
PubMed1986

Pregnancy-induced hypertension and low birth weight in magnesium-deficient ewes.

The fetal and maternal morbidity and mortality from the hypertensive disease states of pregnancy is a major problem. While much is known about the syndrome, the cause has been elusive. The ewe was chosen to test a hypothesis that depletion of magnesium may be involved. Twelve Finnish ewes were subjected to low magnesium diets with half given magnesium in the water. Tests included measurement of blood pressure in the waking state and by noninvasive technique. Magnesium levels were measured by atomic absorption spectrophotometry in the plasma and tissue of the ear tips. Findings included significant elevation of arterial blood pressure, reduction in fetal weight with pathologic confirmation of placental and renal lesions which were similar to those seen in the human condition. Significant lowering of both plasma and tissue of magnesium was noted. The hypothesis was supported and extended to include possible interaction with prostacyclin and thromboxane as intermediaries in a hypomagnesic coagulative angiopathy. This entity would also explain the association of migraine in the eclamptic and preeclamptic syndrome reported by previous authors. The success of parenteral magnesium in the treatment of these human conditions is therefore more than purely empiric.

Animals↗
PubMed1985

Radiation therapy for thyroid eye diseases.

Sixty-two patients (28 men and 34 women, 26 to 84 years old) with thyroid ophthalmopathy were treated with approximately 20 Gy of fractionated photon irradiation. Eight of 14 patients with motility problems improved after treatment. Ten of 14 with thyroid optic neuropathy improved or stabilized, but four had recurrences within five months after completion of irradiation. Generally, patients who had disease durations of less than six months responded better than those with more long-term ocular changes.

Adult↗
PubMed1983

Rhytidectomy in male patients.

We have reviewed the face lifting procedures performed in twenty-seven of our male patients performed during the years, 1979-1980. Their pre-operative and post-operative appearances have been carefully analyzed as to the best method of treatment as well as the risks and complications of these operations. This discussion includes an explanation of our current operative techniques for male face lifting.

Dermatologic Surgical Procedures↗
PubMed1982

Volume averaging limitations of computed tomography.

A simple volume averaging model was shown to be inadequate for predicting effective computed tomographic attenuation values of mixtures of bone or air with soft tissue. Computed tomographic values derived from scanning stratified sub-slice thickness objects were shown theoretically and experimentally to have a non-linear dependency on relative fractional content and a surprisingly large dependency on spatial extent of the stratified substances. The mode was applied to the problem of computed tomographic values in thin, flat structures such as pools of blood in the subarachnoid space. The results show only small deviations from simple volume averaging theory for layers of low contrast substances such as blood and soft tissue, but potentially large deviations for layers of substances with high contrast differences such as bone, air, and tissue. This phenomenon explains certain artifacts and demonstrates rather fundamental problems in the accuracy of analytic reconstruction techniques. It may justify postprocessing correction or iterative approaches.

Mathematics↗