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Robert F Miller

Publications and source records attributed to Robert F Miller.

34 records · Page 2Linked to original sources
PubMed2004

Pathology of bone marrow in human herpes virus-8 (HHV8)-associated multicentric Castleman disease.

Human herpes virus-8 (HHV8)-associated multicentric Castleman disease (MCD) is an unusual systemic lymphoid hyperplasia induced by HHV8-infected B cells. Most cases develop in the background of human immunodeficiency virus (HIV) infection. Despite the haematological problems at presentation and the difficulties in the initial diagnosis, the bone marrow appearances of MCD have not been described. In this study we examined the pathology of bone marrow in MCD with a view to identify the features that may be helpful in early diagnosis. Bone marrow aspirates and biopsies from 13 cases of MCD (11 of which were HIV+) and 66 control bone marrow biopsies from HIV-infected cases were studied. The specimens were routinely processed and stained. Immunohistochemistry for HHV8, immunoglobulin light chains, B-cell and plasma-cell markers was performed. The most important features were the presence of characteristic MCD lymphoid follicles containing HHV8+ plasmablasts in three of 13 cases of MCD and scattered interstitial HHV8+ plasmablasts in 11 of 13 cases. In control cases, no such follicles were seen and interstitial HHV8+ plasmablasts were rarely detected (four of 66 cases). Our results suggest that the presence of HHV8+ plasmablasts within lymphoid follicles and/or interstitium of the bone marrow are helpful features for the early diagnosis of MCD.

Adult↗
PubMed2003

Neuroectodermal differentiation from mouse multipotent adult progenitor cells.

We recently showed that a rare cell from murine bone marrow, which we termed multipotent adult progenitor cells (MAPCs), can be expanded for >120 population doublings. Mouse (m)MAPCs differentiate into mesenchymal lineage cells as well as endothelium and endoderm, and, when injected in the blastocyst, mMAPCs contribute to most if not all somatic cell lineages including the different cell types of the brain. Our results, reported herein, demonstrate that mMAPCs can also be induced to differentiate into cells having anatomical and electrophysiological characteristics similar to those of midbrain neurons. Differentiation to a neuronal phenotype was achieved by coculturing mMAPCs with astrocytes, suggesting that neuronal differentiation may require astrocyte-derived factors similar to what is required for the differentiation of embryonic stem cells and neural stem cells to neurons. Differentiation of mMAPCs to neuron-like cells follows similar developmental steps as described for embryonic stem cells and neural stem cells. MAPCs therefore may constitute a source of cells for treatment of central nervous system disorders.

Animals↗
PubMed2003

D-serine and serine racemase are present in the vertebrate retina and contribute to the physiological activation of NMDA receptors.

d-serine has been proposed as an endogenous modulator of N-methyl-d-aspartate (NMDA) receptors in many brain regions, but its presence and function in the vertebrate retina have not been characterized. We have detected d-serine and its synthesizing enzyme, serine racemase, in the retinas of several vertebrate species, including salamanders, rats, and mice and have localized both constituents to Müller cells and astrocytes, the two major glial cell types in the retina. Physiological studies in rats and salamanders demonstrated that, in retinal ganglion cells, d-serine can enhance excitatory currents elicited by the application of NMDA, as well as the NMDA receptor component of light-evoked synaptic responses. Application of d-amino acid oxidase, which degrades d-serine, reduced the magnitude of NMDA receptor-mediated currents, raising the possibility that endogenous d-serine serves as a ligand for setting the sensitivity of NMDA receptors under physiological conditions. These observations raise exciting new questions about the role of glial cells in regulating the excitability of neurons through release of d-serine.

Animals↗
PubMed2003

Calcium oxalate precipitates in a renomedullary interstitial cell tumor.

We report a case of calcium oxalate deposition in a renomedullary interstitial cell tumor (RICT) in a patient dying of full-blown AIDS. The precipitates showed birefringence using a partially polaris ed light and were stained black in Yasue's silver nitrate-rubeanic acid method. The combination of calcium oxalosis and RICT has not been reported before and might possibly be due to systemic biochemical alterations of the glycosaminoglycans as a result of profound metabolic disturbances in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Limited asymptomatic carriage of Pneumocystis jiroveci in human immunodeficiency virus-infected patients.

Forty-seven bronchoalveolar lavage fluid samples from 16 human immunodeficiency virus (HIV)-infected patients were used to test the latency model of Pneumocystis infection in the human host. Identification of DNA sequence polymorphisms at 4 independent loci were used to genotype Pneumocystis jiroveci from the 35 samples that contained detectable P. jiroveci DNA. Eighteen of those 35 samples came from patients who did not have Pneumocystis pneumonia (PCP) and had confirmed alternative diagnoses. Seven patients had asymptomatic carriage of P. jiroveci over periods of < or = 9.5 months after an episode of PCP, and in all 7 cases, a change in genotype from that in the original episode of PCP was observed. The absence of P. jiroveci DNA in one-fourth of the 47 samples and the observed changes in genotype during asymptomatic carriage do not support the latency model of infection. Asymptomatic carriage in HIV-infected patients may play a role in transmission of P. jiroveci and may even supply a reservoir for future infections.

AIDS-Related Opportunistic Infections↗
PubMed2003

A high-throughput on-line microdialysis-capillary assay for D-serine.

A high-throughput method is described for the analysis of D-serine and other neurotransmitters in tissue homogenates. Analysis is performed by microdialysis-capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection in a sheath flow detection cell. Sample pretreatment is not required as microdialysis sampling excludes proteins and cell fragments. Primary amines are derivatized on-line with o-phthaldialdehyde (OPA) in the presence of beta-mercaptoethanol followed by on-line CE-LIF analysis. Under the separation conditions described here, D-serine is resolved from L-serine and other primary amines commonly found in biological samples. Each separation requires less than 22 s. Eliminating the need for sample pretreatment and performing the high-speed CE analysis on-line significantly reduces the time required for D-serine analysis when compared with traditional methods. This method has been used to quantify D-serine levels in larval tiger salamander retinal homogenates, as well as dopamine, gamma-amino-n-butyric acid (GABA), glutamate and L-aspartate. D-serine release from an intact retina was also detected.

Animals↗
PubMed2003

Polyphenotypic expression of mitochondrial toxicity caused by nucleoside reverse transcriptase inhibitors.

An HIV-infected man taking long-term zidovudine and didanosine presented with a polyphenotypic expression of nucleoside reverse transcriptase inhibitor (NRTI)-induced mitochondrial toxicity. Clinical features included lactic acidosis, myopathy, Fanconi-type proximal tubulopathy, pancreatic dysfunction, pseudo-obstruction, mega-oesophagus, peripheral sensory neuropathy and osteoporosis. A muscle biopsy showed morphologically abnormal mitochondria and respiratory chain biochemistry revealed marked reductions in the activity of respiratory chain enzymes containing mitochondrial DNA-encoded subunits. Southern blotting showed no mitochondrial DNA depletion and long PCR revealed only minor deletions. Following withdrawal of NRTI therapy, the lactic acidosis, pancreatic dysfunction and Fanconi's tubulopathy rapidly improved. Over the next 6 months there was marked improvement in osteoporosis, myopathy and neuropathy. At this stage, dual protease inhibitors and nevirapine were started. A repeat muscle biopsy 14 months after presentation showed normal morphology and respiratory chain biochemistry was almost normal.

Anti-HIV Agents↗
PubMed2002

CD38 expression and NAD+-induced intracellular Ca+ mobilization in isolated retinal Müller cells.

Müller cells of the vertebrate retina are prominent radial glia that provide essential support to sustain homeostasis of the tissue, including redistribution of external potassium, uptake and metabolism of neurotransmitters, and secretion of factors that stabilize the retina. Meeting this diversity of functional supports requires that Müller cells express numerous receptors, transporters, enzymes, and tissue factors. In this study, we provide evidence that adds to the dimensions of Müller cell function by demonstrating a unique relationship between external NAD(+) and the mobilization of internal calcium, expressed in the form of calcium waves. The cellular mechanism that supports internal mobilization of calcium appears to depend on a complex multifunctional ectoenzyme, CD38, which converts NAD(+) into the intracellular Ca(2+)-mobilizing second-messenger cyclic ADP-ribose (cADPR) and could function as a detector for extracellular NAD(+), thus providing a novel signal detection system for evaluating the extracellular environment. Our results are consistent with a model of intracellular Ca(2+) mobilization in which membrane-bound CD38 binds extracellular NAD(+) and triggers intracellular Ca(2+) waves either by direct conversion of NAD(+) to cADPR or by activating intracellular cADPR synthesis. Our preliminary results indicate that the Ca(2+) waves induced by external NAD(+) propagate through an internal pathway that depends on the activation of ryanodine receptors, which appear to be distributed throughout the Müller cell cytosol. Because NAD(+) is likely to be enhanced when cells are stress or damaged, CD38 could enable Müller cells to detect NAD(+) under these circumstances and respond appropriately. Alternatively, NAD(+) could also represent a novel extracellular, paracrine function that mediates signaling between glial cells and/or other cellular elements of the retina.

ADP-ribosyl Cyclase↗
PubMed2002

A new name (Pneumocystis jiroveci) for Pneumocystis from humans.

The disease known as Pneumocystis carinii pneumonia (PCP) is a major cause of illness and death in persons with impaired immune systems. While the genus Pneumocystis has been known to science for nearly a century, understanding of its members remained rudimentary until DNA analysis showed its extensive diversity. Pneumocystis organisms from different host species have very different DNA sequences, indicating multiple species. In recognition of its genetic and functional distinctness, the organism that causes human PCP is now named Pneumocystis jiroveci Frenkel 1999. Changing the organism's name does not preclude the use of the acronym PCP because it can be read "Pneumocystis pneumonia." DNA sequence variation exists among samples of P. jiroveci, a feature that allows reexamination of the relationships between host and pathogen. Instead of lifelong latency, transient colonization may be the rule.

AIDS-Related Opportunistic Infections↗
PubMed1999

Oropharyngeal samples for genotyping and monitoring response to treatment in AIDS patients with Pneumocystis carinii pneumonia.

A nested PCR, amplifying a portion of the gene encoding the mitochondrial large subunit ribosomal RNA (mt LSU rRNA) of Pneumocystis carinii sp. f. hominis was applied to oropharyngeal samples obtained on repeated occasions from 12 HIV-infected patients with P. carinii pneumonia (PCP) to monitor response to anti-P. carinii treatment. Genotyping of P. carinii sp. f. hominis was also performed on paired samples of oropharyngeal and broncho-alveolar lavage samples before the start of treatment, and on oropharyngeal samples during the course of treatment, by analysis of sequence variation at the internal transcribed spacer (ITS) regions of the nuclear rRNA operon. When a simple dilutional method was used, a reduction in the amount of amplification product was observed in samples from all patients during the course of treatment. In eight of the 12 patients, a single ITS sequence type was found in the oropharyngeal samples and also in the paired broncho-alveolar lavage sample. A mixed infection was identified in the samples from three patients. In eight patients, the ITS sequence types identified in the oropharyngeal sample were the same as in the broncho-alveolar lavage sample. Nested PCR amplifying the mt LSU rRNA on oropharyngeal samples provides a non-invasive method of monitoring response to treatment of PCP. ITS sequence typing of P. carinii sp. f. hominis from oropharyngeal samples appears to be a reliable alternative to broncho-alveolar lavage samples and provides a non-invasive tool for further epidemiological studies.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Evidence for low-voltage-activated (LVA) calcium currents in the dendrites of tiger salamander retinal ganglion cells.

We have evaluated the spatial distribution of low-voltage-activated calcium currents in ganglion cells of the tiger salamander retina. Whole-cell recordings were obtained from ganglion cells in a retinal slice preparation and from acutely dissociated ganglion cells that were identified through retrograde dye injection. In single dissociated cells, we estimated the magnitude (pA) and current density (pA/pF) of LVA currents in ganglion cells, both with and without dendritic processes. Ganglion cells that retained a portion of their dendritic arbor had larger LVA calcium currents and higher LVA current densities than those which lacked processes. When cell capacitance measurements were used to derive the surface area of the soma and dendritic processes, we concluded that a higher LVA current density was present in the dendrites; we estimate that, on average, the current density in the dendrites is approximately five times that of the soma. The presence of a significant density of LVA calcium channels in the dendrites of ganglion cells suggests that they could be involved in a number of cellular functions, including dendritic integration of synaptic currents, impulse generation, and homeostatic functions related to changes in the intradendritic calcium concentration.

Ambystoma↗
PubMedDate not supplied

N-methyl-D-aspartate receptors contribute to the baseline noise of retinal ganglion cells.

Whole-cell recordings of tiger salamander ganglion cells were obtained using a superfused retinal slice preparation. Membrane current fluctuations were recorded under voltage-clamp conditions with cells usually held at -70 mV. Current fluctuations at rest (Mg2+ = 1 mM) were reduced by adding D-2-amino-7-phosphonoheptanoate (D-AP7). Resting fluctuations were increased by adding N-methyl-D-aspartate (NMDA) or by removing extracellular Mg2+. These increased fluctuations were blocked by D-AP7. Blocking NMDA receptors under control conditions also reduced a tonic inward current by -1 to -15 pA. Fluctuation analysis of current noise shows that the noise power spectrum measured in the presence of NMDA is similar to that measured under Mg(2+)-free conditions. We conclude that NMDA receptors are active in cells held at -70 mV even in the presence of 1 mM Mg2+. We believe this activation is due to the presence of endogenous glutamate in the retina. The observations of this study strongly suggest that NMDA receptors contribute to the resting noise and conductance properties of retinal ganglion cells. Our results suggest NMDA receptors are activated by an ambient level of extracellular glutamate whose source has yet to be determined.

Ambystoma↗