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Biomedical subjects

D L White

Publications and source records attributed to D L White.

At least 55 records · Page 3Linked to original sources
PubMed1988

Juvenile hypocalcemia provokes persistent electroencephalographic change in renally compromised rats.

In view of the putative involvement of calcium in uremic encephalopathy and the critical importance of this element in juvenile development, we examined the effect of temporary restriction of dietary calcium intake on serum chemistry and the quantitative electroencephalogram (Q.EEG) in unilaterally 3/4 nephrectomized juvenile male Sprague-Dawley rats. Animals were renally infarcted at 22-26 days of age (50-74 g) and placed on one of two isocaloric dietary regimens: powdered normal rat diet (ND, n = 25) or low calcium diet (LCD, n = 8) for 30 days. At this time, ND animals showed normal serum chemistries, whereas LCD rats were hypocalcemic and azotemic with significantly elevated blood urea nitrogen (BUN) and serum creatinine concentrations and reduced renal creatinine clearance values. All animals thereafter received ND for 25-34 further days, during which time chronic Q.EEG electrodes were implanted. At the end of the common ND feeding period, serum chemistry values were equal and normal in both groups. The average theta/alpha ratio (TAR) of the overnight Q.EEG was assessed for 3 days. We found that the TAR of previously LCD animals was significantly elevated compared with ND rats. This indicates an encephalopathic slowing of the background rhythm of these animals. We conclude that, following restoration of a transient uremic and hypocalcemic episode induced by LCD feeding, the Q.EEG background frequency of juvenile renally impaired rats was abnormally slow after 30 days of ND feeding.

Aging↗
PubMed1987

Hepatobiliary magnetic resonance contrast agents assessed by gadolinium-153 scintigraphy.

A simple method to test new gadolinium complexes potentially useful as enhancement agents for magnetic resonance imaging was developed. Healthy rats underwent scintigraphy with two potential hepatobiliary agents, diethyl IDA and diisopropyl IDA complexed with gadolinium-153. Control products included 153Gd DTPA, 153GdCl3 and technetium-99m diethyl IDA. As shown scintigraphically, 153Gd IDA complexes were partially excreted by urinary and hepatobiliary excretion early after administration. These findings paralleled significant reduction in 1H T1 values of excised livers. However, these agents exhibited prolonged 153Gd whole-body retention. The prolonged tissue distribution of 153Gd activity in animals given 153Gd diethyl IDA did not differ significantly from that observed in animals given GdCl3, and could be attributed to chemical instability or reticuloendothelial uptake. The scintigraphic method permits screening of gadolinium complexes in animals by showing mass balance, kinetics, distribution, and effective stability. Biologic effects of tracer or pharmacologic levels can be compared with those of carrier-free and carrier-added pharmaceuticals.

Animals↗
PubMed1987

The expression of mature myeloid cell differentiation markers in acute leukemia.

Cells from 82 patients with leukemia in acute phase (40 ANLL, 1 AUL, 36 ALL, 5 CGL in blast crisis) were studied for the expression of mature cell markers of the major nonlymphocytic cell lineages (monocytes, granulocytes, erythrocytes and platelets) using monoclonal antibodies. In addition, cells were examined for the presence of HLA-A, B, C antigens, Ia antigens and common ALL antigen, as well as Fc receptors capable of binding murine immunoglobulins. Approximately one-third of ANLL specimens lacked any of the mature-cell differentiation markers studied. These were always in the relatively undifferentiated morphological subgroups (M1 and M2). Some of the specimens in these groups also expressed little or no HLA-A, B, C and/or Ia antigen. Of the lineage-specific MAb, FMC32 and FMC34, which bind to monocytes, and monocytes plus granulocytes respectively, gave the most interesting results. Together with the anti-CALLA antibody J5, they contributed to the differential diagnosis of ANLL and ALL. In addition they detected phenotypic heterogeneity within the FAB types of ANLL, particularly the M1 and M2 groups. Binding of murine IgG2a and IgG3 antibodies, apparently via Fc receptors, was commonly observed with ANLL cells. This is a potentially serious source of "false positives" in studies using murine MAb with human leukemic cells.

Antibodies, Monoclonal↗
PubMed1986

Minimal incision techniques for digital deformities.

We have presented basic minimal incision approaches to the more common digital deformities. We feel that with proper evaluation of the deformity and the patient, minimal incision surgery techniques give excellent long-term results with several advantages. These advantages include: Less discomfort due to less surgical dissection. Less need for internal fixation by careful use of compression dressings in the immediate postoperative period along with early ambulation. Less disability. Compression dressings allow immediate ambulation in normal footgear. In most instances, the patient is able to return to work sooner and with less discomfort. Better patient acceptance. Procedures may be performed under local anesthesia in the office environment and the patient may usually return to work in normal footgear within 1 to 3 days. Cost containment. Not all digital deformities may be addressed through a minimal incision approach. Internal fixation, multiple procedures with special postoperative shoes, syndactylisms, fusions, transpositional osteotomies, and skin plasties may be necessary in more severe conditions. However, it is equally important to point out that not all digital deformities must be approached in the "traditional" manner, employing large incisions with deep structure dissection, retraction, and visualization. It is up to the podiatric surgeon to develop his skills, and, after carefully evaluating the abnormality, the patient, and his goals, to perform the surgical procedure that will result in the best long-term results with the minimal amount of discomfort, disability, and cost to the patient.

Callosities↗
PubMed1981

The asymmetric transmembrane distribution of phosphatidylethanolamine, phosphatidylserine, and fatty acids of the bovine retinal rod outer segment disk membrane.

The transmembrane distribution of the major aminophospholipids in the bovine retinal rod outer segment disk membrane, phosphatidylethanolamine and phosphatidylserine, was determined using a novel pair of permeable and impermeable covalent modification reagents. The values for the percentages of phosphatidylethanolamine and phosphatidylserine in the outer monolayer were calculated from a simple expression which takes into account the leakage of impermeable reagent into the disk lumen as monitored by the extent of labeling of lysine entrapped in the lumen. We infer from our results that at least 73 to 87% of the disk phosphatidylethanolamine and 77 to 88% of the disk phosphatidylserine are in the outer disk membrane monolayer. The fatty acid composition of the inner aminophospholipids is slightly more saturated than the outer aminophospholipids. Calculations using the lateral surface areas occupied by the disk membrane lipids suggest that 65 to 100% of the disk phosphatidylcholine is on the inner membrane surface. Since the disk phosphatidylcholine is also somewhat more saturated than the phosphatidylethanolamine and phosphatidylserine of the outer monolayer, the total inner membrane monolayer fatty acid composition is more saturated than that of the outer monolayer fatty acid composition.

Animals↗
PubMed1980

Covalent modification of rhodopsin with imidoesters: evidence for transmembrane arragnement of rhodopsin in rod outer segment disk membranes.

The transmembrane disposition of the visual pigment rhodopsin was studied by the covalent labeling of protein amino groups with membrane-permeable and -impermeable imidoesters. A new, highly reactive permeable reagent, 2-(methylsulfonyl)ethyl acetimidate (SAI) was developed for this purpose. The permeabilities of both this compound and the "impermeable" reagent isethionyl acetimidate (IAI) across the rod outer segment disk membrane were directly measured. Our results indicate that rhodopsin contains three classes of amino groups. One class (35--55% of the total) reacts rapidly with the membrane-impermeable reagent and is presumably exposed on the outside surface of the membrane. A second class (35--55% of the total) is located on the internal surface of the disk since its rate of reaction is dependent on the relative permeabilities of the labeling reagents. The remaining 10% of the rhodopsin amino groups are inaccessible to either type of imidate and are largely accounted for by the single lysine residue which specifically binds the chromophore retinal. These findings, taken together with evidence from freeze--fracture electron microscopy, imply that rhodopsin is a transmembrane protein.

Animals↗
PubMed1979

Disaturated and dipolyunsaturated phospholipids in the bovine retinal rod outer segment disk membrane.

Thin-layer chromatography was used to separate the major phospholipid headgroup classes of the rod outer segment disk membrane into subfractions which differ markedly in fatty acid composition. At least 18% of the rod outer segment phosphatidylcholine must contain two saturated fatty acids. Furthermore, two unsaturated fatty acids are found in at least 43% of the phosphatidylserine, 24% of the phosphatidylcholine, and 24% of the phosphatidylethanolamine. The unsaturated acids are predominantly polyunsaturated in all cases. A similar separation, but with less resolution, was achieved with silicic acid column chromatography. The temperature dependence of the polarization of the fluorescence of trans-parinaric acid (9,11,13,15-all-trans-octadecatetraenoic acid) showed that the thermal behavior of aqueous dispersions of the phosphatidylcholine subfractions was consistent with their fatty acid compositions.

Animals↗
PubMed1979

A chemical mechanism for tissue staining by osmium tetroxide-ferrocyanide mixtures.

The presence of Fe(CN)6(-4) provides sequential, one-electron reduction pathways for OSO4. An equilibrium is established containing OSO4, Fe(CN)6(-4), Fe(CN)6(-3), OSO2(OH)4(-4), and labile cyano-bridged OS-Fe species containing Os in nominal oxidation states of VIII, VII, and VI. These osmium complexes are chelated by appropriately placed donor atoms in the macromolecular tissue matrix, and chelation facilitates the reduction of osmium in situ to lower oxidation states (predominantly IV) that are relatively nonlabile. The greater reactivity and concentration of the Os(VII and VI) intermediates in this system leads to more Os deposition than OsO4 alone; the chelation is responsible for the immobilization of Os and the observed staining pattern in electron micrographs. Chemical data from model systems and electron micrographs of tissue are presented in support of this mechanism.

Animals↗
PubMed1976

The chemical nature of osmium tetroxide fixation and staining of membranes by x-ray photoelectron spectroscopy.

X-ray photoelectron spectroscopy was used to determine the oxidation states of osmium compounds present in erythrocyte ghost preparations and related systems treated with osmium tetroxide. Osmium tetroxide and cholesterol, codeposited at -100 degrees C, began to react at -70 degrees C, and Os(VI) was formed. Similarly, Os(VI) was detected for the known cholesterol-osmate ester prepared and purified chemically. However, osmium tetroxide applied in phosphate buffer (pH 7.2) gave rise to large proportions of Os(IV) and Os(III) species in addition to Os(VI) compounds. Egg phosphatidylcholine likewise produced a mixture of Os(VI), Os(IV), and Os(III), but dipalmitoyl phosphatidylcholine failed to give significant amounts of osmium containing products under identical conditions. Glutaraldehyde gave a mixture of compounds with the same osmium oxidation states when allowed to react with aqueous osmium tetroxide. Unfixed and glutaraldehyde-fixed erythrocyte ghosts also produced mixtures of Ss(VI), Os(IV) and Os(III) under conditions identical to those of normal tissue processing. Additionally, the mixture of adducts initially formed by treatment with osmium tetroxide was further reduced by dehydration of the tissue with ethanol, rpesulting in a final mixture which was 50-60% Os(III). The results support a scheme for the reaction os osmium tetroxide with tissues in which the initial reaction site is the double bonds of unsaturated lipids to form Os(VI) derivatives. Subsequent hydrolysis and further reduction yield complexes of Os(IV) and Os(III). A mixture of these three states is present in membrane specimens during microscopic observation. Os(VI) and Os(IV) could be present as osmate esters and osmium dioxide, respectively; Os(III) could be present as an oxo- or amino complex(es). The photoelectron spectrum of intact erythrocyte ghosts can be synthesized from the spectra of phospholipid and cholesterol only, suggesting the predominance of the reaction with lipids in the fixation process.

Animals↗
PubMed1970

Rabies 1970.

Explore the source record for details and available documents.

Animals↗
PubMedDate not supplied

Detection with echo-planar MR imaging of transit of susceptibility contrast medium in a rat model of regional brain ischemia.

Gradient-refocused echo-planar magnetic resonance (MR) images (TE = 18 msec) were acquired in rats during bolus injection of iron oxide particles, and the first pass of the contrast agent through the brain was monitored. In control rats, contrast agent (0.1 mmol/kg iron) produced significant signal-intensity (SI) reduction over the right hemisphere and similar declines over the left. SI loss occurred first in the cortex and basal ganglia and later in the periventricular regions, along the midline, and in the thalamic zone. Sequential volume-localized proton spectra acquired during transit of 0.02 mmol/kg iron showed substantial reduction in SI, slight asymmetric broadening, and no change in chemical shift of the water resonance. In rats with unilateral occlusion of the middle cerebral artery, peak reduction in ischemic brain SI was to 70% +/- 9% of control, while normal brain SI was reduced to 18% +/- 2% (P less than .01), allowing distinction of the ischemic regions. The presence and location of injury were confirmed with diffusion-weighted imaging and postmortem vital staining. These results demonstrate abnormal transit profiles in a rat model of regional brain ischemia. Evaluation of dynamic contrast delivery patterns may provide unique information in early brain ischemia.

Animals↗
PubMedDate not supplied

Comparison of Fe-HBED and Fe-EHPG as hepatobiliary MR contrast agents.

The authors studied the biodisposition and hepatobiliary transport of two potential magnetic resonance imaging contrast agents, the iron (III) chelates of N,N'-bis(2-hydroxybenzyl)ethylene-diamine-N,N'-diacetic acid (HBED) and diastereomeric N,N'-ethylenebis(2-hydroxyphenylglycine) (EHPG). Fecal and urinary excretion (mean +/- standard deviation), respectively, of FE-59 over 7 days in rats given tracer doses of the contrast agents were 67% +/- 2% and 22% +/- 1% for Fe-59-HBED and 22% +/- 2% and 26% +/- 5% for Fe-59-EHPG. In bile duct-cannulated rats given 0.05-mmol/kg doses labeled with Fe-59, 52% +/- 8% of Fe-59 from Fe-59-HBED but only 17% +/- 3% of that from Fe-59-EHPG was excreted into the bile within 90 minutes. Bromosulfophthalein, but not taurocholate or oxyphenonium, was shown to compete with both agents for hepatobiliary transport. Enterohepatic recirculation of both agents was less than 1%.

Animals↗
PubMedDate not supplied

The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease.

Neurofibrillary tangles and senile plaques, together with cells immunoreactive for the Alz-50 antibody (A50-ir cells) or for an antibody against paired helical filaments (PHF-ir cells), and amyloid deposits stained with antibodies against beta-(or A4)-amyloid, have been mapped throughout the ventral forebrains of 25 old people. The cognitive status of each individual was assessed and a "Clinical Dementia Rating" (CDR) assigned, either before death in the Memory and Aging Project of Washington University, or by a postmortem interview, with an appropriate collateral source. The cases studied included 13 nondemented cases (CDR = 0), six very mildly to mildly demented cases (CDR = 0/0.5 to 1) and six more severely demented cases (CDR = 2 to 3). Because even the very mildly demented brains showed substantial pathological change, emphasis was placed on examining the nondemented cases for the earliest changes that could be associated with Alzheimer's disease. Different distributions were found for tangles and plaques. Tangles (and A50-ir and PHF-ir cells) were present in all of the brains examined. In the younger nondemented cases (aged 54 to 63) there were a few affected cells in the anterior olfactory nucleus and the parahippocampal gyrus. In older nondemented cases (aged 73-89) more tangles were found in the same areas, and also in hippocampal field CA1. The very mildly demented cases had many more tangles, but their distribution was similar. Only in the severely demented cases were large numbers of tangles present in the neocortex. In contrast, no plaques (or beta-amyloid immunoreactivity) were found in any of the younger nondemented cases or in four of the eight older nondemented cases. In three older nondemented cases there were a few primitive plaques, which were restricted to localized regions of the neocortex (e.g., a portion of the inferior temporal cortex). In one nondemented case and all of the very mildly to mildly demented cases there were very large numbers of mostly primitive plaques, particularly in the neocortex. With greater severity of dementia there is a shift from primitive to mature plaques. These results were interpreted to imply that the first development of tangles and plaques occurs in different parts of the brain. Tangles appear during aging in the anterior olfactory nucleus, the parahippocampal gyrus and the hippocampus, but are rare in the neocortex except in demented brains. Conversely plaques may develop first in the neocortex. Unlike tangles, plaques are not a consistent feature of aging, at least up to age 80.

Aged↗
PubMedDate not supplied

Hepatic metastases: rat models for imaging research.

Improved rat liver tumor models with solitary or multiple metastatic tumors were developed for radiological imaging research. Unlike previous studies which employed trocar inoculation of tumor fragments, an enzymatically disaggregated cell suspension of mammary cancer was injected by fine needle either directly into the liver to produce solitary cancer nodules, or indirectly via the spleen or mesenteric vein to produce multiple liver metastases. Tumor size was proportional to the time elapsed after implantation. The operative mortality of direct liver, splenic parenchymal, and mesenteric inoculations were 8%, 4%, and 27%, respectively. MR tissue characteristics, image contrast, and pharmaceutical enhancement of these tumors closely resembles human hepatic metastases. The availability of reproducible, inexpensive animal models of metastatic cancer allows efficient evaluation of new liver imaging techniques.

Adenocarcinoma↗