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J Roby

Publications and source records attributed to J Roby.

18 recordsLinked to original sources
PubMed1999

Alpha-galactose based neoglycopeptides. Inhibition of verotoxin binding to globotriosylceramide.

Solution and solid phase strategies for the synthesis of alpha-galactose based neoglycopeptide derivatives 2-13 were developed. Neoglycopeptides generated were tested for the inhibition of verotoxin binding to globotriosylceramide (Gb3) using ELISA. Among all of the compounds tested, only the lipid derivatives of neoglycopeptides, 11, 12 and 13 were found to be inhibitors, IC50 = 2.0 mM (11b and 12c) and 0.2 mM (11c and 13c). All of the inhibitors (11b, 11c, 12c and 13c) have a similar branching of the two alpha-galactosyl units at the N-terminal glycine residue of a short peptide and a lipid moiety attached at the C-terminal site. Both of these factors seem to be crucial for the inhibition. It is interesting to note that the inhibitors have only a portion of the natural trisaccharide ligand. The secondary groups either may contribute in sub-site oriented interactions with the protein receptors or may mimic the internal sugar units of the cell-surface ligand, Gb3.

Anti-Infective Agents↗
PubMed1998

Diversity of C-linked neoglycopeptides for the exploration of subsite-assisted carbohydrate binding interactions.

Diversity of alpha-galactose based C-linked neoglycopeptides (1b, 2b, 3c, 4d, and 5d) has been developed to explore the importance of subsite-assisted carbohydrate binding interactions. Deprotected C-linked neoglycopeptides (1b, 2b, 3c, 4d, and 5d) were synthesized and tested in competitive inhibition assays using a model enzyme-linked lectin (e.g., Maclura pomifera). Compound 2b, with two alpha-galactoside units on the side chain of the lysine residue of the dipeptide backbone, exhibited a remarkable effect with a 2.82-fold increase in its inhibitory properties (IC50 1.48 mM) in comparison to 1b (IC50 4.18 mM).

Binding Sites↗
PubMed1997

Imaging human intra-cerebral connectivity by PET during TMS.

Non-invasive imaging of human inter-regional neural connectivity by positron emission tomography (PET) during transcranial magnetic stimulation (TMS) was performed. The hand area of primary motor cortex (M1) in the left cerebral hemisphere was stimulated with TMS while local and remote effects were recorded with PET. At the stimulated site, TMS increased blood flow (12-20%) in a highly focal manner, without an inhibitory surround. Remote covariances, an index of connectivity with M1, were also focal. Connectivity patterns established in non-human species were generally confirmed. Excitatory connectivity (positive covariance) was observed in ipsilateral primary and secondary somatosensory areas (S1 and S2), in ipsilateral ventral, lateral premotor cortex (M2) and in contralateral supplementary motor area (SMA). Inhibitory connectivity (negative covariance) was observed in contralateral M1.

Brain Mapping↗
PubMed1997

Longitudinal relaxation and diffusion measurements using magnetic resonance signals from laser-hyperpolarized 129Xe nuclei.

Methods for T1 relaxation and diffusion measurements based on magnetic resonance signals from laser-hyperpolarized 129Xe nuclei are introduced. The methods involve optimum use of the perishable hyperpolarized magnetization of 129Xe. The necessary theoretical framework for the methods is developed, and then the methods are applied to measure the longitudinal relaxation constant, T1, and the self-diffusion constant, D, of hyperpolarized 129Xe. In a cell containing natural abundance 129Xe at 790 Torr, the T1 value was determined to be 155 +/- 5 min at 20 degrees C and at 2.0 T field. For a second cell at 896 Torr, at the same field and temperature, the T1 value was determined to be 66 +/- 2 min. At a higher field of 7.05 T, the T1 values for the two cells were found to be 185 +/- 10 and 88 +/- 5 min, respectively. The 129Xe self-diffusion constant for the first cell was measured to be 0.057 cm2/ s and for the second cell it was 0.044 cm2/s. The methods were applied to 129Xe in the gas phase, in vitro; however, they are, in principle, applicable for in vivo or ex vivo studies. The potential role of these methods in the development of newly emerging hyper-polarized 129Xe MRI applications is discussed.

Animals↗
PubMed1996

Collagenase-I, stromelysin-I, and matrilysin are expressed within the placenta during multiple stages of human pregnancy.

Human pregnancy is associated with extensive growth and remodelling of the uterus and placenta, and restructuring of these tissues during specific stages of gestation likely involves the degradative activity of various matrix metalloproteinases (MMPs). In this investigation, we used in situ hybridization and immunohistochemistry to identify the sites and cell source of collagenase-1 (MMP-1), stromelysin-1 (MMP-3), matrilysin (MMP-7), and 92 kDa gelatinase (MMP-9), a subgroup of MMPs with the combined ability to degrade essentially all matrix proteins. Human tissues were recovered from uncomplicated pregnancies at various gestational ages and from pregnancies complicated by chorioamnionitis, pre-eclampsia, and placenta accreta. Our results show prominent expression of all four MMPs in specific cells of human placentae involved in trophoblast invasion and placental maturation. Collagenase-1 and stromelysin-1 were detected in cells of the amnion, decidua, and chorionic villi at all stages of pregnancy. Ninety-two kilodalton gelatinase was present in granulocytes whenever present. Matrilysin was seen in cytotrophoblasts and syncytiotrophoblasts during early pregnancy but only in cytotrophoblasts by the third trimester. In addition, we found that matrilysin is over expressed and is produced by more cell types in placentae from pregnancies complicated by pre-eclampsia suggesting that the proteolytic activity of this MMP contributes to the pathology of this condition. We conclude that certain MMPs produced by resident cells of the human placenta, and in particular trophoblasts, participate in the physiological progress human gestation and parturition.

Amnion↗
PubMed1993

In situ localization of parathyroid hormone-like protein and mRNA in intraepithelial neoplasia and invasive carcinoma of the uterine cervix.

Parathyroid-like protein (PLP), or parathyroid hormone-related peptide, is a well-recognized mediator of paraneoplastic hypercalcemia (humoral hypercalcemia of malignancy syndrome). In this study we examined the expression of PLP by 40 invasive squamous cell carcinomas (SCCs) of the cervix and selected carcinomas of nonsquamous histology. Using a polyclonal antibody to human PLP, 93% of SCCs, including two tumors from patients with humoral hypercalcemia of malignancy syndrome, showed moderate to strong cytoplasmic immunoperoxidase staining for PLP. The strongest staining often was observed in areas of invasion associated with stromal desmoplasia. The small number of weak or negatively stained SCCs were all poorly differentiated tumors. Although native uninvolved squamous epithelium showed weak to moderate staining of the superficial layers, there was variable or full-thickness immunostaining in areas of dysplasia. Normal endocervical glands and stroma as well as cervical adenocarcinomas and neuroendocrine carcinomas were negative. In situ hybridization studies showed abundant PLP mRNA within SCC in patients with hypercalcemia. However, PLP mRNA was of relatively low abundance in tumors of normocalcemic patients. Ultrastructural studies showed cytoplasmic, membrane-bound, granular inclusions in tumor cells from the hypercalcemic patients. Our data suggest that increased PLP gene transcription contributes to the increased production of PLP and the pathogenesis of humoral hypercalcemia of malignancy syndrome.

Adult↗
PubMed1993

Neointimal macrophages colocalize with extracellular matrix gene expression in human atherosclerotic pulmonary arteries.

Vascular remodeling in adult atherosclerotic pulmonary arteries is characterized by discrete areas of neointimal extracellular matrix gene expression, suggesting regulation by local factors. Though the factors responsible for inducing matrix gene expression in atherosclerotic lesions are largely unknown, several observations suggest macrophages may be a focal source of those factors. Immunohistochemistry confirmed the presence of macrophages in the neointima of atherosclerotic elastic pulmonary arteries from patients with unexplained pulmonary hypertension. Areas of neointima containing dense clusters of macrophages were separated by sparsely populated areas. Foamy macrophages resided more deeply within the neointima than nonfoamy macrophages, which were found more often subjacent to the endothelium or within the lumenal one-third of the neointima. Combined immunohistochemistry-in situ hybridization indicated neointimal fibronectin and type I procollagen gene expression was intimately associated only with nonfoamy neointimal macrophages. These observations suggest that: (a) nonfoamy neointimal macrophages participate in the local regulation of extracellular matrix gene expression in atherosclerotic pulmonary arteries; (b) foamy macrophages, which are not associated with matrix gene expression, have undergone modulation of their secretory phenotype.

Arteriosclerosis↗
PubMed1992

Extracellular matrix protein gene expression in atherosclerotic hypertensive pulmonary arteries.

Lobar pulmonary arteries from patients with unexplained pulmonary hypertension were obtained at the time of single-lung transplantation to determine the response of large elastic vessels to increased intraluminal pressure. Specifically, human pulmonary arteries were examined to determine if remodeling remained active at the time of surgery and whether remodeling was similar to previously reported remodeling observed in several animal models. Grossly, the hypertensive vessels appeared atherosclerotic. Histochemical stains revealed a thick, diffuse neointima in hypertensive vessels compared with normal vessels. Immunohistochemistry demonstrated elastin protein in the neointima and in situ hybridization studies demonstrated tropoelastin mRNA largely in the neointima. Similarly, immunohistochemistry and in situ hybridization detected cellular fibronectin, thrombospondin and type I collagen protein and mRNA within the thickened intima from hypertensive vessels. These studies provide evidence that hypertensive vessels in patients with severe chronic pulmonary hypertension are actively remodeling but that the pattern of remodeling is different from previously described animal models.

Adult↗
PubMed1991

Lack of linkage to chromosome 5q11-q13 markers in six schizophrenia pedigrees.

We examined linkage between schizophrenia and five genetic markers on chromosome 5 in six pedigrees. Analyses were run considering the affected phenotype to be schizophrenia, schizophrenia plus a spectrum of related disorders, and these disorders plus any axis I diagnosis. None of the analyses were suggestive of linkage at any of the markers, either considering the pedigrees individually or in the aggregate. In our pedigrees, multipoint linkage analyses excluded much of the region that had supported linkage in an earlier study. These findings are consistent with other attempts to replicate the chromosome 5 linkage finding.

Chromosome Mapping↗
PubMed1985

EEG and evoked potential changes during gas- and liquid-breathing dives to 1000 msw.

To test the hypothesis that compression in helium gas and compression without gas (hydrostatic compression) both produce the same neurological symptoms of high pressure nervous syndrome (HPNS), groups of 4 to 5 dogs were exposed to one of the following: (a) a 2-h surface control breathing He-O2 gas; (b) compression to 700-1000 msw breathing He-O2 gas; (c) a 2-h liquid-breathing control [ventilation with warmed (38 degrees C), oxygenated fluorocarbon liquid, FC-80]; and (d) "near hydrostatic" compression to 700-1000 msw while being ventilated with liquid from a sealed reservoir. Power spectra obtained from scalp-recorded EEG signals revealed a significant compression-related shift of power from the normally dominant 5-8 Hz band to the 8-11 Hz band. This effect was greatest at 600 msw and occurred equally in both dive groups. At very high pressures (greater than 900 msw) power in this 6-10 Hz range became reduced whereas 16-22 Hz activity increased as the EEG flattened. Somatosensory evoked potentials (SEPs) were elicited by subdermal electrical stimulation in the foreleg (n = 120). The latency of P1 (approximately 31 ms) did not change in any group; transmission time to cortex was unaltered by time or pressure. However, the "late-wave" P4 (approximately 250 ms) was slowed by 32-35 ms at 1000 msw in both groups (P less than 0.003 in He-O2). Since these main symptoms were provoked equally in both He-O2 and FC-80 dive groups, helium pressure did not play a significant role in the etiology of HPNS in this animal model. It is concluded that the HPNS is primarily a result of excessive pressure per se or rate of change of pressure per se.

Animals↗
PubMed1983

Liquid ventilation in dogs: an apparatus for normobaric and hyperbaric studies.

A liquid-breathing apparatus is described for remote surface studies and for use in experiments of near-hydraulic compression in dogs. It consists of a flexible tank sealed against chamber gas, containing a supply of clean warmed (38 degrees C) fluorocarbon (FC-80) equilibrated with 1 bar O2 and an electronically controlled means of delivering the liquid to the dog. Each breath (tidal volume 290 ml) was "weighed" into the animal by the signal from a force platform supporting the dog and a digital control unit that automatically actuated inspired-and expired-line solenoid valves. The apparatus was successfully used to remotely maintain liquid ventilation in awake dogs for 2 h during surface studies (5 dogs) and in dives to 1,000 m seawater (5 dogs). During liquid breathing, mean arterial O2 partial pressure was always adequate (congruent to 300 Torr) and mean arterial CO2 partial pressure was normal (less than or equal to 40 Torr). An uncompensated metabolic acidosis was indicated by low pH values and a decrease in arterial base excess to--4.5 meq x 1(-1). O2 uptake and CO2 output appeared to be significantly lower (42 and 35%, respectively) during liquid ventilation.

Animals↗
PubMed1981

Control of HPNS in humans during rapid compression with trimix to 650 m (2131 ft).

In 1978 a series of deep trimix (He-N2-O2) dives was initiated to establish the relationship between a given nitrogen percentage and the rate of compression required to prevent the high pressure nervous syndrome (HPNS) at 460 m (1509 ft) and to determine the effects of inspired gas density, hydrostatic pressure, and narcosis o various circulatory and respiratory parameter, including the presence of dyspnea. In 1979, three human subjects were compressed to 460 m in 12 h 20 min with 5% N2 in He-O2. This resulted in nausea, vomiting, fatigue, tremors, and other signs and symptoms of HPNS that were especially prominent on arrival at that depth but had much improved by Day 2. In March 1980 the same profile was repeated but with 10% N2 in He-O2. The divers arrived at 460 m with virtually no symptoms of HPNS, but the psychometric performance, as for Atlantis I, still was decreased by some 40% on Day 1 and recovered to some 15% by Day 2. After 5-6 days at 460 m further extension of the dive to 650 m (2132 ft) with a 7.7% N2 mixture for 24 h showed similar control of symptoms of HPNS, although inspiratory resting dyspnea was present in one subject. The results are discussed in relation to the interactions of nitrogen percentage and rate of compression.

Air↗
PubMed1980

Lithium effects: protection against nitrogen narcosis, potentiation of HPNS.

The effect of either 10, 8, or 6 meq/kg of intraperitoneal lithium chloride or sodium chloride on the loss of righting response (RR50) produced by 18.2 ATA N2-ATA O2 was examined in rats. Results were compared to the effects of 10, 8, 6, or 4 meq/kg of intraperitoneal lithium chloride given 24 h before determination of the convulsion pressure (PC) in 40 rats compressed with He-O2 at 160 atm/h at 37 +/- 0.5 degrees C. Lithium (10 meq/kg) prevented the nitrogen-narcosis-induced loss of righting response but significantly potentiated the pressure (depth) at which convulsions and tremors occurred.

Animals↗
PubMedDate not supplied

Fast spin-echo characteristics of visual stimulation-induced signal changes in the human brain.

A fast spin-echo (FSE) technique used in a conventional MR imaging scanner has been successfully developed for obtaining functional MR images with high spatial resolution and multiple slices. Our preliminary visual stimulation studies using the FSE technique show that the nuclear MR signal increases by 2.6% during activation in the primary visual cortex. These results provide evidence that the diffusion of tissue water molecules plays a key role in determining functional MR signal amplitude. Because the FSE functional MR imaging signal is extremely sensitive to microvascular (brain capillaries) hemodynamics, the FSE technique can be a powerful tool for studying the neuronal activity of the human brain.

Adult↗
PubMedDate not supplied

In situ hybridization of human erythropoietin in pre- and postnatal kidneys.

Due to the transient transcription of the gene of erythropoietin (EPO) in response to hypoxic stimuli, localization within the cell of origin in humans has not been possible. Under acutely induced transcription of the EPO gene, through severe bleeding (hematocrit < 10%), EPO transcripts were detected within renal interstitial cells in rodents. However, by immunohistochemistry or tissue culture, human tubular epithelial cells or glomerular mesangium have been shown to produce EPO, suggesting a species difference. Aiming to investigate the precise location of EPO in intact human kidneys, 38 fetal, infant, and adult kidneys were examined by in situ hybridization. Kidneys from patients with conditions predisposing to severe hypoxia and/or induced polycythemia were utilized, because under these conditions active EPO mRNA synthesis is expected. We found specific EPO mRNA transcripts within a small population of cortical interstitial cells of near-term or postnatal kidneys.

Adult↗
PubMedDate not supplied

Flying for life.

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Aircraft↗