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Biomedical subjects

C A White

Publications and source records attributed to C A White.

At least 73 records · Page 4Linked to original sources
PubMed1996

Chronokinetics of liposomal encapsulated ampicillin in fasting and nonfasting rats.

The chronobiological effect on the pharmacokinetics of liposomal encapsulated ampicillin (LEA) was compared at noon (1200) and midnight (2400) after intravenous injection of 50 mg/kg of LEA in rats. The effects of fasting on the circadian rhythms of LEA were also investigated. Serial blood samples were collected for 2 h. Bile and urine were collected during the entire study. Plasma data was analyzed by noncompartmental methods. Dosing of LEA at 2400, when the animals were active, resulted in a 50% decrease in mean residence time (MRT) and a 20% increase in systemic clearance (Cltotal). The increase in Cltotal was reflected by increases in biliary (Clbile) and renal (Clrenal) clearance at 2400. In addition, the steady-state volume of distribution (Vss) at 2400 was also decreased by about 50% as compared to dosing at 1200. Interestingly, no difference in the pharmacokinetic parameters were observed in fasting animals at 1200 and 2400. Since rats consume very little food during their sleep cycle, restriction of food intake did not have any affect on the pharmacokinetics of LEA at 1200. However, fasting rats had an approximately 36% decrease in Cltotal as compared to nonfasting rats at 2400. This decrease in systemic clearance was paralleled by a 60% and 24% decrease in Clbile and Clrenal, respectively. These variations could be attributed to changes in bile composition and/or lipoprotein concentrations in the plasma as a result of "forced" fasting at 2400 when the animals are generally more active and food intake is high.

Ampicillin↗
PubMed1995

SBH-1, a novel Reed-Sternberg-like cell line capable of inducing tumors in SCID mice: immunophenotypic, cytogenetic, and cytokine expression profiles.

A new cell line, SBH-1, with the morphologic, immunophenotypic, and karyotypic features consistent with those of Reed-Sternberg (RS) and Hodgkin (H) cells, has been established from the pleural effusion of a patient. The cytologic appearance of SBH-1 cells is characteristic of multinucleate RS and mononuclear H cells, all containing inclusion-like nucleoli. The SBH-1 cells express CD30, CD15, CD25, CD71, CD45, CD20, CD22, and bcl-2 protein and are negative for epithelial membrane antigen. Cytogenetic analysis showed multiple clonal abnormalities with breakpoints at 14q32, 6q21, and 11q23. The Ig heavy chain genes and both Ig light chain genes were rearranged in SBH-1 cells, whereas the bcl-2 gene was in germline configuration. Messages for the cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha, and transforming growth factor-beta and the cytokine receptors IL-2R, IL-4R, IL-6R, and IL-7R were detected by reverse transcription-polymerase chain reaction analysis. Xenotransplantation of SBH-1 cells into severe combined immunodeficient (SCID) mice led to local and disseminated tumor growth. The cytologic, histologic, and immunohistochemical features of SBH-1 cells in SCID mouse tumors were typical of RS and H cells. The SBH-1 cell line will be useful in the study of RS and H cell biology, inasmuch as it represents a cell line obtained from a previously untreated patient.

Aged↗
PubMed1995

Lymphatic distribution of 3'-azido-3'-deoxythymidine and 3'-azido-2',3'-dideoxyuridine in mice.

Recently, it was shown that human immunodeficiency virus (HIV)-infected cells preferentially locate in lymphoid tissue early in the course of infection. Therefore, it is important to characterize the disposition of the anti-HIV agents, 3'-azido-3'-deoxythymidine (AZT) and 3'-azido-2', 3'-dideoxyuridine (AZdU), in the lymphatic system. The disposition of AZT and AZdU in serum and neck, axillary, and mesenteric lymph nodes was studied in mice after intravenous, oral, and intraperitoneal administrations of 50 mg/kg doses. Samples were collected at 0.08, 0.5, 1, 2, 3, 4, and 6 hr after dosing and nucleoside concentrations were determined by HPLC. Pharmacokinetic parameters were estimated using noncompartmental analysis. Maximum concentration, half-life, and area under the serum concentration vs. time curve (AUC) obtained from the serum concentration data were similar for both compounds after intravenous and intraperitoneal administrations; however, a difference in oral bioavailability for AZT and AZdU (49% and 76%, respectively) was noted. Patterns of regional distribution in lymph nodes were similar for both drugs; however, the accumulation of AZdU in the various lymph nodes, according to AUC values, was 3-76% greater than that for AZT. The relative exposure re = AUClymph/AUCserum) of both nucleosides exhibited a dependence on route of administration. Intravenous and oral administrations resulted in a greater distribution of nucleoside into axillary lymph nodes, compared with neck and mesenteric lymph nodes. Following intraperitoneal administration, however, distribution was similar in all three regions. AZT and AZdU distribute into the lymphatic system; however, AZdU accumulation was greater than that of AZT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Frequent p53 gene mutations and novel alleles in familial breast cancer.

Mutations in the p53 gene were detected in 58% of tumor DNAs of patients with a family history of breast cancer (FHBC) compared to 13% with sporadic breast cancer. Seven of 18 FHBC tumors contained the same G to C transversion in codon 156. Novel alleles of altered length were seen in one or more loci on chromosome 17 in 15 of 18 patients with FHBC but only in a single locus in 8 of 14 patients with sporadic breast cancer. The frequency of tumors with mutations in p53, often multiple, accompanied by the appearance of multiple altered-length alleles suggest that DNA replication or repair defects may presage genomic instability in cases with FHBC.

Adult↗
PubMed1993

Neuropeptide Y immunoreactivity identifies a group of gamma-type retinal ganglion cells in the cat.

Ganglion cells within the cat retina have been traditionally grouped by morphological criteria into three major classes: alpha, beta, and gamma. The gamma-type cells have been least well characterized, but the available evidence indicates that this class comprises a relatively heterogeneous population of neurons. In the present study we demonstrate that an antibody for neuropeptide Y (NPY) recognizes a subpopulation of about 2,000 gamma-type ganglion cells. The NPY-immunoreactive (IR) neurons project to the superior colliculus and to the C layers of the lateral geniculate nucleus as demonstrated by retrograde labeling with fluorescent tracers (fluorogold or rhodamine latex microspheres). Virtually all of these cells disappear following lesions of the optic nerve. The NPY-IR ganglion cells were identified as gamma cells on the basis of soma size and dendritic branching patterns. The somas of these neurons are small (8-22 microns in diameter), and each cell is characterized by sparsely branching dendritic processes, usually extending into the middle third of the inner plexiform layer, the physiologically defined ON sublamina. These neurons are distributed across the entire retina, with the highest density at the area centralis. Within local regions of the retina, however, there was no indication that the NPY-IR gamma cells are arrayed in a regular mosaic pattern. These results provide the first evidence that the gamma class of ganglion cells of the cat retina can be subdivided on the basis of immunocytochemical properties.

Animals↗
PubMed1993

Substrate-bound GP130/F11 will promote neurite outgrowth: evidence for a cell surface receptor.

GP130/F11 is a neuronal cell adhesion molecule belonging to the Ig superfamily. Preliminary evidence suggests that it may be important for the fasciculation of axons and cell-cell interactions during synaptogenesis. Previous work has shown that when F3 (the mouse homologue) is transfected into Chinese hamster ovary (CHO) cells it will act as a substrate for neuronal growth and adhesion. In this study we have shown that isolated GP130/F11 will also act as a substrate for the growth of chick dorsal root ganglia cell neurons. The concentration of GP130/F11 on the surface of sympathetic neurons, grown for one day in culture was approximately 40 ng cm-2 which was comparable to the levels required to stimulate neurite outgrowth. Deglycosylation of GP130/F11 or partial denaturation by boiling did not abolish the activity. However, after treatment with dithiothreitol, GP130/F11 was no longer capable of stimulating neurite outgrowth. GP130/F11 will also stimulate neurite outgrowth from forebrain neurons from 7 to 9-day-old embryos. These do not express GP130/F11 until around day 10, providing further evidence that GP130/F11 interacts with an as yet unknown cell surface receptor.

Animals↗
PubMed1992

Membrane and synaptic properties of developing lateral geniculate nucleus neurons during retinogeniculate axon segregation.

During the first postnatal month in the ferret (Mustela putorius furo), the projections from the retina to the lateral geniculate nucleus (LGN) become segregated into eye-specific layers and ON and OFF sublayers, a process that is thought to depend in part on neuronal activity. Remarkably, virtually nothing is known about the physiological features of LGN neurons during this period. We have recorded intracellularly from 46 A-layer neurons in slices of the ferret LGN between the ages of postnatal days 7 and 33. The passive membrane properties and current-voltage relationships of the developing neurons were similar in many, though not all, respects to those of adult LGN neurons. Action potentials in younger animals were smaller in amplitude and longer in duration than in older animals, but cells at all ages were capable of producing spike trains whose latency and spike number varied with stimulus intensity. In addition, cells at all ages responded with low-threshold potentials upon release from hyperpolarization. Slightly more than half of the LGN neurons responded to optic tract stimulation with excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), or EPSP-IPSP pairs, beginning with the youngest ages. Thus, as early as the second postnatal week, and much before the onset of pattern vision, LGN neurons have many of the membrane and synaptic properties of adult thalamic neurons. These data are consistent with LGN cells playing a significant role in activity-dependent reshaping of the retinogeniculate pathway.

Action Potentials↗
PubMed1992

Ontogeny of somatostatin immunoreactivity in the cat retina.

In the ganglion cell layer of the adult cat retina, subgroups of displaced amacrine cells and alpha ganglion cells are immunoreactive for somatostatin or a somatostatinlike substance. Both types of immunoreactive cells are found preferentially in inferior retina. We studied the development of somatostatin immunoreactivity in the prenatal and postnatal cat retina to determine how such unusual distributions of immunoreactive cells arise. Somatostatin-immunoreactive profiles were first observed at embryonic day (E) 30, within the inner retina in a central region that included the optic disk and the area centralis. By E36, immunoreactivity had virtually disappeared from the central retina but was present throughout the periphery. The immunoreactive profiles could not be classified morphologically because of their immaturity but were most likely retinal ganglion cells, the earliest born cells of the inner retina. Of the two types of immunoreactive cell observed in the adult, the first to be recognized morphologically was the displaced amacrine cell, at E45. These cells were virtually adultlike in morphology and number by E51, two weeks before birth. In contrast, immunoreactive alpha ganglion cells were not apparent until five days after birth and did not achieve their mature numbers and immunoreactive staining characteristics until more than a month later. From the time they could initially be recognized, both immunoreactive displaced amacrine cells and alpha cells were distributed mainly in the inferior retina. A third type of somatostatin-immunoreactive cell was transiently observed in the superior and inferior retina during prenatal and early postnatal development. These cells were characterized by granular staining in irregular shapes and few, if any, faintly stained processes. Injections of retrograde tracers into retinorecipient targets revealed that many of these cells were retinal ganglion cells. They disappeared by postnatal day 38. Our results indicate that somatostatin immunoreactivity initially follows a central-to-peripheral pattern of development, as is typical of other developmental events in the mammalian retina. They also indicate that the two types of somatostatin-immunoreactive neurons present in the adult cat retina (displaced amacrine and alpha ganglion cells) attain their mature immunocytochemical properties with very different timecourses. Finally, the observation that somatostatin immunoreactivity appears transiently in the granular-staining ganglion cells, distributed throughout the superior and inferior retina, suggests that the peptide may play a regulatory role in the development of the retina and/or retinofugal pathways.

Animals↗
PubMed1992

Cadmium-Sulfide Crystallites in Cd-(gammaEC)(n)G Peptide Complexes from Tomato.

Hydroponically grown tomato plants (Lycopersicon esculentum P. Mill. cv Golden Boy) exposed to 100 micromolar cadmium sulfate produced metal-(gammaEC)(n)G peptide complexes containing acid-labile sulfur. The properties of the complexes resemble those of the cadmium-(gammaEC)(n)G peptide complexes from Schizosaccharomyces pombe and Candida glabrata known to contain a cadmium sulfide crystallite core. The crystallite is stabilized by a sheath of peptides of general structure (gammaGlu-Cys)(n)-Gly. The cadmium-peptide complexes of tomato contained predominantly peptides of n(3), n(4), and n(5). spectroscopic analyses indicated that the tomato cadmium-sulfide-peptide complex contained CdS crystallite core particles smaller than 2.0 nanometers in diameter.

Journal Article↗
PubMed1992

Solubility and posttranslational regulation of GP130/F11--a neuronal GPI-linked cell adhesion molecule enriched in the neuronal membrane skeleton.

GP130 (renamed contactin) has previously been identified by its detergent insolubility and retention with the actin-containing "membrane skeleton" isolated from chicken neurons and brain. The contactin sequence predicted a transmembrane and cytoplasmic domain for the molecule. Recently, F11 was shown to have an identical sequence except for the C terminus, and it was predicted to be linked to the plasma membrane by a glycosylphosphatidylinositol (GPI) group. Here we describe that GP130 can be released both from brain membranes and the detergent-insoluble membrane skeleton by a phosphoinositol-specific phospholipase C (PI-PLC) indicating that F11 and GP130/contactin are probably identical and that surprisingly the lipid anchor is partly or totally responsible for its non-ionic detergent insolubility. The "membrane skeleton" is a rich source of GPI-linked glycoproteins as judged by 1) most glycoproteins can be released by a PI-PLC and 2) most [3H]ethanolamine-labeled glycoproteins are present in, or enriched in the membrane skeleton. Thus, detergent insolubility appears to be a characteristic of GPI-anchored glycoproteins. No evidence has been obtained that GP130/F11 is released or secreted in vivo or in culture. In addition, GP130/F11 has an unusually long half-life in culture of greater than 3 days. The structure of the neuronal membrane skeleton and the potential function of GPI-anchored glycoproteins is discussed.

Animals↗
PubMed1991

Subgroup of alpha ganglion cells in the adult cat retina is immunoreactive for somatostatin.

We have previously shown that two types of cells in the ganglion cell layer of the adult cat retina are immunoreactive for somatostatin (White et al., '90). One of the types was identified by morphological criteria as a wide-field amacrine cell. The other cell type had a large, angular soma that resembled the alpha ganglion cell, but evidence was not available to identify it definitively as a ganglion cell. Both cell types were distributed preferentially in the inferior retina. In this report, we demonstrate that the two types of cell are, indeed, displaced amacrine cells and alpha ganglion cells. First, when retrograde tracers were injected into central visual targets, the immunoreactive large cells but not the displaced amacrine cells were found to be labeled. Second, after unilateral section of the optic nerve, the immunoreactive large cells disappeared from the retina on the lesioned side, but the displaced amacrine cells occurred in the same numbers in both retinae. In the periphery, the large cells ranged in diameter from 33 to 47 microns, comparable only to alpha ganglion cells (Boycott and Wässle, '74). An antiserum to parvalbumin was used to visualize the dendrites (Röhrenbeck and Wässle, '88) of somatostatin-immunoreactive large cells. Based on dendritic stratification within the inner plexiform layer (Famiglietti and Kolb, '76), the somatostatin-immunoreactive large cells were found to include both on-center cells and off-center cells, but were predominantly of the off-center type. Within a local region, they were found to be arrayed with greater regularity than the overall population of alpha ganglion cells. These results indicate that alpha ganglion cells of the cat retina can be subdivided on the basis of their immunoreactive staining for somatostatin and suggest that the diversity of ganglion cells in the cat retina may be greater than has been recognized on the basis of morphological criteria alone.

Animals↗
PubMed1990

Somatostatin-immunoreactive cells in the adult cat retina.

Peptides have been found in the retinas of all mammalian species studied to date, but little is known about their localization and function in the cat. Using two mouse monoclonal antibodies directed to somatostatin 14, we have observed two sparse groups of somatostatin-immunoreactive neurons in the cat, both distributed preferentially in the inferior retina. The more numerous cell type is characterized by a small- to medium-sized soma (mean diameter = 16.3 +/- 9.0 microns; n = 186) with sparsely branching, far-reaching varicose processes that ramify mainly in the inner plexiform layer. The majority of these cells are located in the ganglion cell layer, with the remainder in the proximal inner nuclear layer and the inner plexiform layer. They are in especially high density at the retinal margin. In morphology and soma size, these cells resemble wide-field amacrine cells. The second cell type has a large, granular-staining soma (mean diameter = 29.7 +/- 14.8 microns; n = 145) with poorly stained primary processes and is found only in the ganglion cell layer. Cells of this type are most similar in their size and morphology to alpha ganglion cells. In contrast to the location of somatostatin-immunoreactive somata, a dense meshwork of immunoreactive processes was observed at all eccentricities within the inner plexiform layer, adjacent to the inner nuclear layer and to the ganglion cell layer. Labeled processes arising from the inner plexiform layer were also occasionally detected in the outer plexiform layer and the nerve fiber layer. Additional processes of unknown origin were observed in the nerve fiber layer and the optic nerve head. The extensive distribution of immunoreactive processes suggests that somatostatin-immunoreactive somata located preferentially in the inferior half of the retina have a widespread influence on neural activity.

Animals↗
PubMed1990

Effect of concurrent sucralfate administration on the absorption of erythromycin.

To determine the influence of sucralfate on the absorption of erythromycin, prior to evaluating its efficacy in decreasing erythromycin-associated gastrointestinal (GI) intolerance, we assessed pharmacokinetic parameters in six healthy adult volunteers. Erythromycin ethylsuccinate administered alone or with sucralfate as a single dose was compared. Sucralfate did not significantly alter the elimination rate constant, half-life, or area under the curve for erythromycin ethylsuccinate. It is therefore unlikely that efficacy of erythromycin ethylsuccinate will be altered when sucralfate is coadministered.

Adult↗
PubMed1990

Effect of sulfhydryl-deficient diets on hepatic metallothionein, glutathione, and adenosine 3'-phosphate 5'-phosphosulfate (PAPS) levels in rats.

Low dietary concentrations of methionine and cysteine are known to decrease hepatic glutathione content. However, it is not known if restricting the dietary content of these sulfur containing amino acids also affects hepatic levels of adenosine 3'-phosphate 5'-phosphosulfate (PAPS), the cofactor for sulfation, or metallothionein, a protein rich in sulfhydryl groups. Rats were fed diets lacking cysteine and containing various concentrations of methionine (0.15, 0.3, or 0.6%) for 8 days. Control diet contained 0.3% each of methionine and cysteine. Hepatic glutathione levels were decreased approximately 75% in rats fed diets containing 0.15 or 0.3% methionine. In contrast, PAPS and hepatic metallothionein concentrations were not decreased by the low sulfhydryl diets. Additionally, rats on the various diets were challenged by the administration of ZnCl2 (3 mmol/kg. sc). In both control rats and rats maintained on sulfhydryl-deficient diets, ZnCl2 increased hepatic metallothionein to the same level. However, significantly lower levels of PAPS were observed after ZnCl2 in rats receiving sulfhydryl-deficient diets than in controls. In summary, restriction of dietary sulfhydryl markedly decreases the hepatic content of glutathione and has a minor effect on PAPS concentration, but does not decrease the basal hepatic concentration of metallothionein or its induction by ZnCl2.

Adenine Nucleotides↗
PubMed1989

In vitro evaluation of the determinants of bactericidal activity of ampicillin dosing regimens against Escherichia coli.

An in vitro flow model was used to examine the influence of peak concentration (Cmax), the area under the antibiotic concentration-time curve (AUC), the magnitude of AUC above the MIC, and the aggregate time the antibiotic concentration exceeds the MIC (TMIC) on the bactericidal effect of ampicillin against Escherichia coli ATCC 12407. Bacteria in the log phase were exposed to therapeutically realistic drug regimens. Ampicillin concentration and bacterial density (CFU per milliliter) were measured over time. Four parameters reflecting bactericidal activity were quantitated: difference between initial and minimum and initial and final bacterial densities, area under the bacterial density-time curve, and a fourth parameter, sigma, which is a function of these three. Multiple regression analysis confirmed AUC as the major factor in predicting bactericidal activity. An AUC of greater than 70 micrograms.h/ml correlated with the lack of emergence of resistance.

Ampicillin↗