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Biomedical subjects

J Roman

Publications and source records attributed to J Roman.

At least 91 records · Page 5Linked to original sources
PubMed1989

Development of infant reaching in the dark to luminous objects and 'invisible sounds'.

Two studies were conducted to investigate the existence of an unusual U-shaped developmental function described by Wishart et al (1978) for human infants reaching towards invisible sounds. In study 1, 2-7 month olds were presented with four conditions: (i) an invisible auditory stimulus alone, (ii) a glowing visual stimulus alone, (iii) auditory and visual stimuli on the same side (ie combined), and (iv) auditory and visual stimuli on opposite sides (ie in conflict). Study 2 was designed to examine the effects of practice and possible associations made when using the 'combined conflict' paradigm. Infants of 5 and 7 months of age were given five trials with the auditory stimulus, with or without prior visual experience, and five trials with the visual stimulus, with the position of the stimulus varied on each trial. Stimuli were presented individually at the midline, and +/- 30 and +/- 60 degrees from the midline. In both studies testing was conducted in complete darkness. Results indicated that the auditory-alone condition was slower to elicit a reach from the infants, relative to the visual-alone one, and reaches were least frequent to the auditory target. No U-shaped function was obtained, and reaching for auditory targets occurred later in age than for visual targets, but even at 7 months of age did not occur as often and was achieved by fewer infants. In both studies the quality of the reach was significantly poorer to auditory than to visual targets, but there were some accurate reaches. This research adds to our understanding of the development of auditory-manual coordination in sighted infants and is relevant to theories of auditory localization, visually guided reaching, and programming for the blind.

Attention↗
PubMed1989

The fibronectin receptor is organized by extracellular matrix fibronectin: implications for oncogenic transformation and for cell recognition of fibronectin matrices.

Cells interact with extracellular fibronectin (FN) via adhesive fibronectin receptors (FNRs) that are members of the very late antigens (VLAs) subgroup of the integrin family. In stationary fibroblasts, the FNR is highly organized and distributed identically to extracellular FN fibrils. However, in highly migratory neural crest cells and embryonic somatic fibroblasts, this organization is lost and the FNR appears diffuse. Similarly, oncogenic transformation typically leads to disorganization of the FN receptor and loss of matrix FN. Two models can account for these observations. First, the FN matrix may organize the FN receptor at extracellular matrix contacts on the cell surface. Motile cells not depositing FN matrices thus lack organized receptors. Alternatively, as the FNR is required for optimal FN matrix assembly, (McDonald, J. A., B. J. Quade, T. J. Broekelmann, R. LaChance, K. Forseman, K. Hasegawa, and S. Akiyama. 1987. J. Biol. Chem. 272:2957-2967; Roman, J. R. M. LaChance, T. J. Broekelmann, C. J. R. Kennedy, E. A. Wayner, W. G. Carter, J. A. McDonald. 1989. J. Cell Biol. 108:2529-2543) and has putative cytoskeletal links, it could be organized from within the cell helping to position newly forming FN fibrils. To study this question, we developed peptide antibodies specifically recognizing the alpha 5 subunit of the FNR. Using these antibodies, we examined the organization of FN and of the FNR in normal, matrix assembly inhibited, and SV40-transformed human fibroblasts. On FN-coated substrates, the FNR is found in focal contacts rather than diffusely on the basal cell surface, suggesting FNR interaction with intracellular components. However, when FN fibrils are deposited, the FNR is co-distributed with these fibrils. Preventing FN matrix assembly prevents organization of the FNR. Moreover, when fibroblasts with well established FN matrices and co-distributed FNR are incubated briefly with monoclonal antibodies that block FNR binding to FN, the FNR is no longer co-distributed with the FN matrix. Thus, the FN receptor is organized in fibrils on the cell surface in response to extracellular FN. Because exogenous FN restores a FN matrix and receptor organization to SV40-transformed cells, the diffuse FN receptor phenotype appears to be related to loss of the FN matrix rather than to impaired FNR function. These results explain diffusely distributed FNRs in migratory neural crest and embryonic fibroblasts lacking well organized FN matrices and emphasize the existence of separate but related systems controlling FN deposition and recognition by receptor-armed cells.

Cell Adhesion↗
PubMed1987

Peroxidase-catalyzed metabolism of etoposide (VP-16-213) and covalent binding of reactive intermediates to cellular macromolecules.

The horseradish peroxidase- and prostaglandin synthetase-catalyzed oxidative metabolism of the highly active anticancer drug, etoposide (VP-16-213), has been studied in vitro. This oxidation of VP-16 resulted in the formation of VP-16 quinone, an aromatic VP-16 derivative and the corresponding aromatic VP-16 quinone. This oxidative metabolism of VP-16 also resulted in the formation of reactive species that covalently bound to exogenously added DNA and heat-inactivated microsomal proteins. The peroxidase-catalyzed binding was time dependent and required the presence of cofactors (hydrogen peroxide or arachidonic acid). The prostaglandin synthetase/arachidonic acid-catalyzed metabolism and binding of VP-16 were inhibited by indomethacin, an inhibitor of the cyclooxygenase, and were shown to involve the peroxidative arm of prostaglandin synthetase. Our studies show that the protein covalent binding species were formed as a result of O-demethylation of the drug as shown by the loss of specifically labeled (O-14CH3) radioactivity from O-methoxy group and by incubating proteins with VP-16 quinones. In contrast, the covalent binding intermediates for DNA appeared to be different and VP-16-derived quinone methides are suggested as DNA binding species. Co-oxidation of VP-16 and the related drug, VM-26, during prostaglandin biosynthesis may be an important pathway for the metabolism of these agents and may play a role in their cytotoxic properties.

Animals↗
PubMed1987

In vitro metabolism of etoposide (VP-16-213) by liver microsomes and irreversible binding of reactive intermediates to microsomal proteins.

We have studied the metabolism of VP-16-213 (etoposide, VP-16), an antitumor agent, by mouse liver microsomes to reactive intermediates and the subsequent covalent binding to microsomal proteins. This metabolism was shown to involve the O-demethylation of VP-16 and resulted in the formation of a 3',4'-dihydroxy derivative (DHVP-16) which was identified by both HPLC and mass spectrometry. The formation of DHVP-16 was cytochrome P-450-mediated as indicated by its dependence on NADPH, its increased production following treatment of mice with phenobarbital, and its marked inhibition by SKF-525A and piperonyl butoxide. Furthermore, DHVP-16 formation required oxygen. Microsomal incubation of VP-16 resulted in an irreversible binding of the drug to the proteins, which was also shown to be cytochrome P-450 dependent. The covalent binding of the VP-16 metabolite(s) was inhibited by DHVP-16 in a dose-dependent fashion, suggesting that the reactive intermediates that bound to proteins were derived from DHVP-16. Electron spin resonance studies indicated that the same semiquinone radical was formed during enzymatic (oxidation or reduction) metabolism of DHVP-16 and the o-quinone derivative of VP-16 (VP-16-Q). VP-16-Q and its semiquinone radical are suggested to be the bioalkylating species.

Animals↗
PubMed1986

Peroxidative free radical formation and O-demethylation of etoposide(VP-16) and teniposide(VM-26).

The peroxidative activation of the antitumor drugs, etoposide (VP-16) and teniposide (VM-26), has been studied in vitro. Both of these drugs, in the presence of horseradish peroxidase or prostaglandin synthetase, formed phenoxy radical intermediates. Furthermore, this activation also resulted in the formation of two metabolites from each of the drugs. Using HPLC and mass spectrometry, one of the metabolites was shown to be the reactive o-quinone derivative of the parent drug which resulted from the peroxidative O-demethylation. It appears that O-demethylation catalyzed by peroxidases may be an important mechanism for the formation of reactive intermediates and may play a role in the mechanism of action of VP-16 and VM-26.

Chromatography, High Pressure Liquid↗
PubMed1986

Nitrosamines and nitrosamine precursors in foods from Linxian, China, a high incidence area for esophageal cancer.

Nitrosamines and precursor secondary amines were assayed in foods from families in four villages of the esophageal cancer high incidence area of Linxian, Henan Province, People's Republic of China. Amines (as tosylamides) and nitrosamines were readily detected at p.p.m. and p.p.b. levels, respectively, in all samples. In this small preliminary survey (25 families, four villages), however, there were no strong correlation between the levels of the carcinogenic nitrosamines or the precursor secondary amines with the incidence of esophageal cancer in the individual families. The success of the analytical procedures suggests that a more extensive study is warranted.

Amines↗
PubMed1985

Immunoglobulin G, A, and M--clonal restriction in multiple sclerosis cerebrospinal fluid and serum--analysis by two-dimensional electrophoresis.

Immunoglobulin G, A, and M (IgG, IgA, and IgM) were purified from multiple sclerosis (MS) cerebrospinal fluid (CSF) and sera and analyzed by two-dimensional electrophoresis. The light (L)-chains of MS CSF IgG were of limited diversity and dominated by about 30 major spots and many less intense spots. CSF IgG of patients with subacute sclerosing panencephalitis (SSPE) was dominated by 10 to 20 intense L-chain spots. L-chains from patients with fungal, syphilitic, and tuberculous infections of the central nervous system (CNS) ranged from 70 to in excess of 300 spots. The patterns of L-chains in MS CSF and autologous sera were different, indicating amplified synthesis of particular L-chains in MS CNS. Cathodic IgG fractions differing in isoelectric point by 0.1 to 0.3 pH units were isolated. SSPE CSF IgG fractions were dominated by a few L-chain spots, MS CSF fractions contained less than 20 spots, and MS serum fractions contained about 200 spots. MS CSF mu-chains were similar in isoelectric point range to serum but fractionated into discrete spots compared with a diffuse pattern in serum. MS CSF IgA alpha-chain spot overlapped in mobility with serum alpha-chains except a portion of the alpha-chain complex in CSF was shifted cathodically forming discrete spots. The CSF L-chains of both IgM and IgA were completely dissimilar to serum. These studies indicate major limited diversity and compartmentalized CNS synthesis of IgG, IgA, and IgM in MS. The restricted clonal pattern is proposed as consequent to B-cell stimulation by disease-related antigen(s) with limited epitope complexity. The dominance of a small number of L-chains supports results from idiotypic analysis suggesting finite clonal complexity of MS CSF IgG and indicates the feasibility of structural analysis of MS CSF L-chains, particularly amino acid sequence determinations.

Humans↗
PubMed1982

The middle ear in long-term dialysis.

When fluctuating middle ear fluid was observed in patients receiving long-term dialysis, the dialysis was suspected as the potentiating factor. In a statewide survey, a significant number of ear, nose, and throat specialists were undecided about etiology. They were also uncertain about treatment choice and delivering services without consulting the managing nephrologist. Tympanograms obtained on an equal number of patients receiving hemodialysis and peritoneal dialysis throughout two treatment sessions indicated measurements of middle ear impedance remain within the normal range. It was concluded that effusion in the middle ear of patients receiving dialysis is not related to dialysis procedures.

Acoustic Impedance Tests↗
PubMed1979

Opsonization of antitumor reactive lymphocyte in SJL/J mice bearing spontaneous or transplanted reticulum cell sarcomas (RCS).

Radiolabelled antitumor reactive T lymphocytes (ARC) were prepared in vivo by immunization of SJL/J mice with mitomycin C inactivated syngeneic LA-6 tumor cells followed by injection of 125IUdR to label dividing cells. These ARC were specifically diverted to the liver when injected in LA-6 tumor-bearer serum and injected i.v. into normal SJL/J mice. Likewise, SJL/J anti-Balb/c ARC were diverted to the liver of SJL/J mice bearing spontaneous reticulum cell sarcomas (RCS) carrying Balb/c cross-reactive antigens but not in mice with Balb/c negative neoplasms. Mice with Balb/c positive tumors also had circulating ARC opsonizing factors. These results suggest a mechanism for the survival of antigenic tumors involving macrophages and ARC opsonizing (ARCO) factors. A novel approach to immunotherapy is discussed.

Animals↗
PubMed1978

Severe electrolyte disturbances associated with metolazone and furosemide.

In two patients with severe hypertension and moderately severe renal insufficiency, metolazone and furosemide were used in combination with propranolol, methyldopa, and hydralazine to augment control of blood pressure. This combination of diuretics also was used in five patients with refractory congestive heart failure. The patients developed severe electrolyte disturbances with a general pattern of hyponatremia. disproportionate hypochloremia, alkalosis, and phyokalemia. These abnormalities were transient in the patients with severe hypertension and moderately severe renal insufficiency. Effective long-term control of blood pressure was obtained. In the patients with heart failure, edema persisted. Due to the severity of the electrolyte derangements, metolazone and furosemide were discontinued. Because of potential untoward effects, this combination of diuretics should be used with caution.

Adult↗
PubMed1976

Subcutaneous arteriovenous fistula for hemodialysis.

Arteriovenous fistula is now an accepted method of vascular access for hemodialysis in chronic end-stage renal disease. The arteriovenous fistula constructed is based on the status of the forearm vessels. Our results were satisfactory and comparable to other dialysis centers.

Adolescent↗
PubMed1975

Fosfomycin in treatment of chronic urinary tract infection.

A study was made of fosfomycin in the treatment of chronic urinary infection in 51 patients. 72% of the 67 bacteria isolated and tested in the laboratory with discs containing 50 mug of fosfomycin were found to be sensitive to the antibiotic. The majority of E. coli, Klebsiella, P. mirabilis and Ps. aeruginosa strains were sensitive to the antibiotic. Generally, 60 mg of fosfomycin/kgbody weight was administered intramuscularly 6-hourly for 7-15 days. A clinical and bacteriological cure was obtained in 39 patients (76%), and after 4-6 weeks in 31 patients (61%). Blood and urine fosfomycin levels were determined in seven patients, three with normal renal function, three with moderate renal insufficiency, and one with severe renal insufficiency. The antibiotic levels and elimination time maintained a clear relation with the degree of renal insufficiency.

Adolescent↗