PubMed Health⌕ Search

Biomedical subjects

J F Ross

Publications and source records attributed to J F Ross.

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

Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications.

BACKGROUND: Despite significant differences in ligand binding between the two known isoforms of the human membrane folate receptor (FR), designated herein as FR-beta (placenta) and FR-alpha (placenta, KB cells), little is known about their tissue specificities, and there is no report on the relative expression of FR-beta in any tissue other than in placenta. METHODS: The mRNA for each FR isoform in a wide variety of normal fetal and adult tissue explants, primary normal cell cultures, malignant tumor explants, and established tumor cell lines was estimated by a polymerase chain reaction assay. Total receptor levels were estimated by a [3H] folic acid binding assay. RESULTS: Both the FR isoforms were expressed in fetal as well as adult tissues. Normal tissues generally expressed low to moderate amounts of FR-beta. FR-alpha alone was expressed in normal epithelial cells and was frequently strikingly elevated in a variety of carcinomas, with the exception of squamous cell carcinomas of the head and neck. In contrast, a variety of malignant tissues of nonepithelial origin generally expressed elevated levels of FR-beta alone. Established tumor cell lines expressed FR-alpha virtually alone and did not reflect FR expression patterns in vivo. KB cells and JEG-3 cells grown at low folate concentrations further up-regulated FR-alpha but not FR-beta. CONCLUSIONS: Although FR-beta is the more common isoform, FR-alpha and FR-beta are differentially regulated in normal tissues, carcinomas, nonepithelial malignancies, and immortalized cells or in response to changes in extracellular folate concentrations. The tissue specificity of FR isoforms and their elevation in malignant tissues may be a significant factor in FR-mediated folate uptake, in tissue responsiveness to promising novel antifolates, and in FR-related immunodiagnosis/immunotherapy.

Adult↗
PubMed1994

Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity.

The expression of a membrane-associated folate receptor (FR) was elevated in spleen samples from patients with chronic (CML) and acute (AML) myelogenous leukemias compared with normal spleen. Contrary to earlier reports, antibodies to a purified FR from placenta cross-reacted quantitatively with this protein in solution radioimmunoassays. Similar to FR-alpha (KB cells) and FR-beta (placenta), the protein was released from the membrane by phosphatidylinositol-specific phospholipase C, indicating a glycosylphosphatidylinositol (GPI) membrane anchor. Screening of a cDNA library from CML spleen with a heterologous murine FR cDNA and also amplification of FR cDNAs from spleen and bone marrow in CML, AML, chronic lymphocytic leukemia (CLL), and acute lymphocytic leukemia (ALL) by polymerase chain reaction (PCR) using degenerate oligonucleotides yielded cDNA clones representing FR-beta, a novel FR (type gamma), and an aberrant transcript of FR-gamma with a 2 base pair deletion resulting in a truncated 104-residue polypeptide; FR-alpha was not detected in these tissues. The cDNA for FR-gamma predicts a 243-residue polypeptide with an amino acid sequence homology of 71% and 79% with FR-alpha and FR-beta, respectively, a 23-residue amino-terminal signal peptide, and 3 potential sites for N-linked glycosylation. Transfection of COS-1 cells with the cDNA for FR-gamma resulted in low expression of a [3H]folic acid binding protein on the cell surface that was GPI-anchored. PCR analysis of total RNA from a number of normal and malignant tissues and cell lines indicated a limited tissue specificity of FR-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Highest brain bismuth levels and neuropathology are adjacent to fenestrated blood vessels in mouse brain after intraperitoneal dosing of bismuth subnitrate.

A small fraction of humans ingesting bismuth (Bi)-containing medications develops neurotoxicity in which neuropsychiatric signs precede motor dysfunction. Large ip doses of Bi subnitrate (BSN) produce similar signs in mice, but little is known about the pathogenesis of neurotoxicity in either species. Adult female Swiss-Webster mice received a neurotoxic dose (2500 mg/kg ip) of BSN. Bi distribution and neuropathology were determined as follows: (1) Regions of central and peripheral nervous system were assayed for Bi by atomic absorption spectrometry (AAS) 28 days after dosing, (2) regional brain Bi distribution was demonstrated in histologic sections by autometallography 28 days after dosing, and (3) blood/brain barrier status and neuropathologic effects were evaluated by light and electron microscopic techniques 1, 3, and 7 days and 2, 3, 4, and 5 weeks after dosing. By AAS, Bi levels were highest in olfactory bulb (approximately 7 ppm), hypothalamus (approximately 7 ppm), septum (approximately 3 ppm), and brain stem (approximately 3 ppm). Striatum and cerebral cortex had the least Bi (approximately 1 ppm). Regional distribution by autometallography showed that high Bi levels were associated with diffusion of Bi from fenestrated blood vessels of circumventricular organs and olfactory epithelium. All treated mice had hydrocephalus, but no other pathology was demonstrable by light microscopy. By electron microscopy, dramatic expansion of the extracellular space between choroid plexus epithelial cells was observed. Dendrites in the neuropil of the hypothalamus and septum exhibited vacuoles and membranous debris. Based on the Bi distribution and lesions, we propose that diffusion of Bi from fenestrated blood vessels contributes to pathogenesis of neurotoxicity in mice. This proposal is consistent with the clinical features of Bi-related neurotoxicity in humans.

Animals↗
PubMed1989

Applications of electrophysiology in a neurotoxicity battery.

Electrophysiology encompasses a multifaceted group of diagnostic tests which have been validated through clinical use. These evaluate not only CNS and PNS function, but also the function of the cardiovascular system, which affects the nervous system indirectly. As the many positive attributes of these tests become more widely recognized, it seems likely that the use of electrophysiologic tests will expand in the future.

Animals↗
PubMed1988

Characterization of a murine model for human bismuth encephalopathy.

An epidemic of bismuth (Bi)-related neurotoxicity in France remains poorly understood, partly because no satisfactory animal model exists. We have now characterized such a model. Single or multiple intraperitoneal injections of Bi subnitrate into female mice produced neurologic signs (myoclonus, ataxia, tremors, convulsions) and blood (1.2 micrograms/g) and brain (8.4 micrograms/g) Bi levels like those in human cases. Hydrocephalus and axonal swellings in spinal cord were the major neuropathologic lesions.

Animals↗
PubMed1982

Growth-rate-dependent adjustment of ribosome function in chemostat-grown cells of the fungus Mucor racemosus.

The dimorphic fungus Mucor racemosus was grown as a yeast in a chemostat. Cellular growth rates were varied over a fourfold range under an atmosphere of N2 and over an eightfold range under CO2. Under either atmosphere, an increase in the cellular growth rate resulted in increases in (i) the cellular ribosome concentration, (ii) the percentage of ribosomes active in protein synthesis, and (iii) the rate of polypeptide chain elongation. The rate of protein synthesis in this organism can therefore be regulated by adjustment of all of these mechanisms.

Carbon Dioxide↗
PubMed1981

Relationship of internal cyclic AMP levels, rates of protein synthesis and mucor dimorphism.

Changes in the intracellular pools of cyclic AMP and specific rates of protein synthesis have been described as correlates of the yeast-to-hypha conversion in Mucor racemosis. A further examination of the relationship between these physiological parameters and the cellular morphogenesis was conducted in the present study. The levels of intracellular cyclic AMP consistently varied as a function of the cell morphology rather than the CO2 tension, oxygen tension or growth rate. The specific rate of protein synthesis failed to change during a N2-to-air-induced yeast-to-hypha transition. Previously reported changes in this parameter during CO2-to-air- and CO2-to-N2-induced yeast-to-hypha shifts may be a consequence of growth rate changes rather than development per se.

Carbon Dioxide↗
PubMed1979

A review of the mortality in the burns units at the Victoria General Hospital and the Izaak Walton Killam Hospital, January, 1967, to April, 1977.

We reviewed the mortality experience in Halifax burn units over the ten-year period January, 1967, to April, 1977. Major complications leading to death were examined and related to initial injury, length of survival, and preexisting disease. When possible, antemortem diagnoses were compared with postmortem pathological findings. Renal failure, sepsis, and pulmonary complications were the most frequent causes of death in burn patients. The patients who died from renal failure tended to expire soon after being burned, and tended to have been inadequately hydrated during the long journey to Halifax. Patients with sepsis did not die within the first 48 hours of being burned. Early excision of the burn wound with homograft replacement might have prevented some of these deaths. Pulmonary complications early in the postburn course appeared related to closed-space and possibly to inhalation injury. However, pneumonia tended to predominate later.

Acute Kidney Injury↗
PubMed1978

The general surgeon in the management of patients with multisystem trauma in a community hospital.

The general surgeon in a community hospital must assume the role of leader of the trauma team in managing patients with multisystem trauma. Initial resuscitative measures must be instituted to assure cardiopulmonary stability. Following this a complete assessment of the various body systems must be undertaken. The general surgeon will then be in a position to decide whether definitive treatment in the community hospital is possible or whether transfer is required. The basis resources of such a hospital in terms of medical expertise, support staff, laboratory and radiology facilities are all important considerations in making this decision. Most individuals with multisystem trauma can be managed in the community hospital.

Decision Making↗
PubMed1977

Transections of stria medullaris or stria terminalis in the rat: effects on aversively controlled behavior.

Surgical transection of the stria medullaris (SM) reliably interfered with the acquisition of a one-way avoidance response but had no effect on two-way shuttle box avoidance, passive avoidance, intake of palatable fluids, or locomotor activity. Transection of the stria terminalis (ST) selectively interfered with the animals' reactions to punishment in a passive avoidance situation but had no effect on one-way or two-way active avoidance or on locomotor activity. This pattern of effects complements the results of earlier investigations from our laboratory that showed that two-way avoidance learning (but not one-way avoidance or passive aboidance behavior) was impaired after fornicotomy and after transection of the ventral connections of the septum with the lower brain stem. The latter cut, but not fornicotomy or transection of ST or SM, reproduced the effects of septal lesions on water intake, body weight, and preferential intake of palatable solutions. The results of this investigation provide support for the hypothesis that the septum exercises a number of separate functions that are mediated by different pathways.

Animals↗
PubMed1975

Some behavioral effects of transecting ventral or dorsal fiber connections of the septum in the rat.

The behavioral effects of large electrolytic lesions in the septal area were compared with those of knife cuts that severed the ventral or dorsal connections of this structure. Rats with septal lesions lost weight and were transiently hyperdipsic. Ventral cuts produced similar effects, but dorsal cuts did not. All three operations decreased the latency to eat in a novel environment, increased the intake of sweetened milk, enhanced acquisition of a food-rewarded running response, and facilitated acquisition of a shuttle box avoidance response, The lesion, but neither of the knife cuts, reduced the effects of punishment and impaired the acquisition of a one-way avoidance response.

Animals↗
PubMed1975

Septal influences on operant responding in the rat.

The afferent and efferent connections of the septum with the hippocampus (fornix) of with the hypothalamus and lower brain stem (medial forebrain bundle) were transected by means of an encephalotome near the point where these pathways enter or leave the septal area. A transection of the fornix that produced minimal direct damage to cellular components of the septum of hippocampus reproduced the effects of large septal lesions on responding in several temporally defined paradigms that involve periods of response suppression (differential reinforcement of low rates, discriminated Sidman avoidance, fixed interval). Transection of the medial forebrain bundle fibers that interconnect the septum with the hypothalamus and lower brain stem did not affect behavior in any of these paradigms. These observations should be veiwed in the context of the results of earlier investigations which demonstrated that transection of the medial forebrain bundle reproduces several other components of the septal lesion syndrome.

Animals↗