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Biomedical subjects

D Young

Publications and source records attributed to D Young.

At least 433 records · Page 24Linked to original sources
PubMed1988

Characterization of the rat mas oncogene and its high-level expression in the hippocampus and cerebral cortex of rat brain.

The human mas oncogene was originally detected by its ability to transform NIH 3T3 cells. We previously showed that the protein encoded by this gene is unique among cellular oncogene products in that it has seven hydrophobic potential transmembrane domains and shares strong sequence similarity with a family of hormone-receptor proteins. We have now cloned the rat homolog of the mas oncogene, determined its DNA sequence, and examined its expression in various rat tissues. A comparison of the predicted sequences of the rat and human mas proteins shows that they are highly conserved, except in their hydrophilic amino-terminal domains. Our examination of the expression of mas, determined by RNA-protection studies, indicates that high levels of mas RNA transcripts are present in the hippocampus and cerebral cortex of the brain, but not in other neural regions or in other tissues. This pattern of expression and the similarity of mas protein to known receptor proteins suggest that mas encodes a receptor that is involved in the normal neurophysiology and/or development of specific neural tissues.

Amino Acid Sequence↗
PubMed1988

Daytime alertness in patients with chronic insomnia compared with asymptomatic control subjects.

Despite the subjective reports of patients with difficulty initiating and maintaining sleep (DIMS) that they are impaired during the day, consistent differences in daytime functions have not been found between normal sleepers and patients with insomnia. The present study compares polysomnography and Multiple Sleep Latency Test (MSLT) data from 70 clinic patients seeking evaluation for chronic insomnia with data from a group of 45 asymptomatic sleepers. The DIMS group was found to sleep significantly less than the control group; yet they were also significantly more alert than the control group the following day, as measured by MSLT. Within the insomnia diagnostic subgroups, a correlation of -0.67 (p less than 0.05) was found between nocturnal total sleep time and mean MSLT. The results are interpreted as supporting the existence of a tendency towards physiological hyperarousal in patients with chronic insomnia. This tendency may be exacerbated by other factors (e.g., personality disorder, periodic leg movements) also associated with insomnia.

Adult↗
PubMed1988

Some differences between men and women who commit suicide.

Men have persistently had a several-fold higher suicide rate than women. In this study of 204 consecutive suicides, the authors examined three areas in which the men differed from the women. Men used more violent, immediately lethal methods of suicide, were almost three times more likely to be substance abusers, and were more likely to have economic problems as stressors. The authors conclude that while the difference in suicide rate between men and women is complexly determined, the weight of the evidence suggests that more men than women intend to commit suicide.

Adult↗
PubMed1988

Diagnosis of severely ill inpatients in China. A collaborative project using the structured clinical interview for DSM-III (SCID).

The purpose of this project was to investigate any differences in diagnostic practice between Chinese psychiatry and Western psychiatry with regard to severe psychiatric illness among Chinese inpatients. Specifically, the project aimed to look at differences between the Chinese diagnostic system and DSM-III. This study stemmed partly from a desire to investigate the supposed "overdiagnosis" of schizophrenia in China relative to the West. A second objective was to use a structured interview format to obtain clinical data for DSM-III and to decide whether a translated version of such an interview offered promise for future transcultural psychiatric research. Forty-two inpatients on a psychiatric ward in China were interviewed by an American psychiatrist assisted by a Chinese faculty translator and a diagnosis was made using the Structured Clinical Interview for DSM-III. A Chinese professor of psychiatry who was blind to the structured interview results interviewed each patient independently and assigned a diagnosis within the current Chinese system. Follow-up data was obtained on 69% of the patients after 16 months to check for stability of diagnosis. Results of the study pointed to less diagnostic disagreement than previous work had predicted. On cases where there was disagreement, DSM-III diagnoses tended toward affective disorders or atypical forms of psychosis while the Chinese diagnosis tended towards schizophrenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Bipolar Disorder↗
PubMed1988

Ameloblastic odontoma in a cynomolgus monkey (Macaca fascicularis).

An ameloblastic odontoma occurred in an adult cynomolgus monkey (Macaca fascicularis). The neoplasm involved the upper left maxilla as a disfiguring, fleshy growth. The tissue and cellular changes were consistent with an ameloblastic odontoma which is rare in man, nonhuman primates (NHP), and other vertebrate animals. The monkey was one of 50 adult, single-caged housed cynomolgus monkeys. No additional clinical signs of disease were present. Hematology and serum chemistries were within normal limits. There have been three reports in the literature of ameloblastic odontomas in NHP; however, this is the first reported case of an ameloblastic odontoma in a cynomolgus monkey.

Animals↗
PubMed1987

Cholecystokinin mRNA in porcine cerebellum.

Using previously cloned cDNAs to pig brain prepro-cholecystokinin mRNA and slot blot and S1 nuclease protection assays, the relative cholecystokinin mRNA levels in different regions of the pig brain were measured. The relative amounts of cholecystokinin mRNA generally correlated well with the levels of cholecystokinin-immunoreactive peptides in the various regions tested. One clear exception was noted in the cerebellum; in this region, levels of cholecystokinin mRNA were about 20% of the levels in brain cortex (or second highest level in all areas tested) whereas the mature forms of cholecystokinin peptides (cholecystokinin 58, cholecystokinin 8) were undetectable (less than 3 pmol/g). In vitro translation of cerebellar and cortical cholecystokinin mRNA indicated that there was no difference in the efficiency with which these two RNAs were translated into immunoreactive prepro-cholecystokinin. DNA sequence analysis confirmed that a cloned full-length cerebellar cholecystokinin cDNA was indistinguishable from its cortical counterpart and, therefore, must encode an identical prepro-cholecystokinin. We conclude that there are pronounced regional differences in cholecystokinin expression in pig brain. The apparent discrepancy between levels of immunoreactive cholecystokinin peptides and cholecystokinin mRNA in the cerebellum could be explained by a high turnover rate for the peptides, differential processing of the peptides, or tissue-specific inhibition of cholecystokinin mRNA translation.

Animals↗
PubMed1987

Phase I/II trial of interferon-beta-serine in patients with renal cell carcinoma: immunological and biological effects.

Interferon-beta-serine (IFN-beta ser) is a recombinant genetically altered interferon with extensive in vitro antiproliferative, antiviral, and immunological effects. We undertook a Phase I/II trial of this agent in patients with untreated metastatic renal cell carcinoma with good performance status. IFN-beta ser was given twice weekly (Monday/Thursday) by a 4-h i.v. infusion. Three patients were entered at increasing drug levels until the maximum tolerated dose was determined. Moreover, if individual patients tolerated the initial IFN treatment, the dose was escalated one level at the next treatment. Preliminary studies with normal donor cells demonstrated that IFN-beta ser in vitro enhanced activity in a mononuclear-MBL-2 growth inhibition, NK-cell, and monocyte antibody-dependent cellular cytotoxicity assay. Therefore, prior to therapy these in vitro tests were performed utilizing each patient's mononuclear cells in an attempt to predict tumor response with in vitro immunological response to IFN. In general, there was no difference in IFN responsiveness in vitro between patients who developed tumor response (3) and those who did not (12). After initiation of treatment blood was taken from patients at frequent intervals for assessment of biological response. The following parameters were not altered at any dose or time interval: T-cell number, T-H/S ratio, % Leu 11a-positive cells, percentage or intensity of staining with anti-HLA-DR, and concanavalin A driven T-cell proliferation. Monocyte antibody-dependent cellular cytotoxicity was significantly depressed 4 h after doses of 30-150 million units/m2 but returned to base line at 24 h. Activity in three assays was significantly increased in patients receiving therapy: MBL-2/growth inhibition assay, NK-cell, and 2',5' oligonucleotide synthetase activity. In general changes in these assays were observed at low levels of IFN-beta ser, increased at 4-48 h, then returned toward base line. We conclude that IFN-beta ser is an active biological agent in vitro and significantly modulated the biological responses in patients with renal cell carcinoma.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

T cell activation by anti-idiotypic antibody: mechanism of interaction with antigen-reactive T cells.

It has been shown that the activation of T cells by an anti-idiotypic antibody (anti-Id) TB71 containing an internal image of the corresponding mycobacterial antigen (38 kDa) was achieved by the interaction of anti-Id TB71 with the T cell receptor complex (CD3/Ti). The accessory cell requirement in this response could not be replaced by anti-Id TB71 coupled to Sepharose beads and was not inhibited by Fc receptor blockade. When taken together with the finding that anti-Id TB71-induced proliferation of a T cell clone was restricted by determinants encoded by the major histocompatibility complex, these findings suggested that anti-Id TB71 was presented to 38-kDa antigen-reactive T cells by the same mechanisms as conventional antigenic determinants. That is, both stimulated T cells through the CD3/Ti complex and had to be presented in the context of class II molecules on accessory cells. The finding that the disruption of the integrity of the anti-Id TB71 combining site did not affect T cell responsiveness although antibody binding was ablated implied that anti-Id TB71 may be partially degraded and re-expressed with MHC class II determinants.

Antibodies, Anti-Idiotypic↗
PubMed1987

Comparison of recombinant human immunodeficiency virus gag precursor and gag/env fusion proteins and a synthetic env peptide as diagnostic reagents.

Diagnostic reagents for detection of human immunodeficiency virus (HIV) exposure with improved reliability may be provided by viral encoded proteins produced by recombinant DNA techniques or by synthetic peptides corresponding to appropriate viral epitopes. We have expressed at high levels in E. coli a gag gene segment corresponding to approximately 97% of the p55 gag precursor protein, as well as a novel gag/env fusion protein that contains antigenic determinants in common with gag p24, env gp41, and env gp120. The gag and gag/env proteins were purified from insoluble inclusion bodies by sequential extraction with increasing concentrations of urea. These components were tested for reactivity with antisera to HIV proteins and peptides. We have also chemically synthesized a peptide corresponding to env residues 578-608, representing a portion of env gp41. The final preparation of gag and gag/env proteins in 8 M urea reacted with sheep anti-HTLV-III p24 gag antibodies and acquired immune deficiency syndrome (AIDS) patient sera. The gag/env fusion protein also reacted with rabbit anti-HIV env 500-511 peptide antibody. Both recombinant proteins and the env peptide were suitable as reagents for evaluation of serum samples by enzyme-linked immunosorbent assay (ELISA). Results of ELISA assays utilizing the recombinant viral proteins and synthetic peptide were in good agreement with results obtained using disrupted virus as antigen in ELISA assays and immunoblotting.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Effect of dietary protein and food restriction on milk production and composition, maternal tissues and enzymes in lactating rats.

Lactating rats have been fed either a protein-restricted diet (10 vs. 20% casein in the control diet) or the control diet at 80, 60 and 40% of the voluntary intake for 7 d from d 7 of lactation. Food consumption, changes in maternal live weight, litter live weight gain and the mass of several maternal tissues were determined together with the activity of several mammary and liver enzymes, including 10 that are essential for fatty acid and complex lipid synthesis. Milk production was estimated from the litter weight gain and litter weight. Lactating rats fed the 20% protein diet ad libitum consumed three times that of nonlactating rats; their liver and kidney masses were significantly higher and their adipose mass was lower. The livers of the lactating rats were fatty, containing 118 mg lipid/g compared with 42 mg/g for the nonlactating rats. Lactating rats fed either the protein-restricted diet or the control diet at 40 and 60% of the ad libitum intake of the control diet had lower mammary, liver and kidney masses than rats consuming the control diet ad libitum. Both protein and food restriction led to lower rates of milk production than those of ad libitum-fed control rats as evidenced by the decrease in litter live weight gains. The concentrations of total lipid, total protein and lactose in milk were not affected by these dietary treatments. The concentration of alpha-lactalbumin in milk of rats fed the low protein diet was, however, lower than that in the milk of all rats receiving the control diet, irrespective of intake. Consumption of the restricted diets resulted in only small changes in specific activities (mu/mg protein) of 15 mammary enzymes. In the livers, lactation led to higher specific activities of all four soluble lipogenic enzymes examined but did not affect the particulate enzymes involved in complex lipid synthesis. The dietary restrictions resulted in lower specific activities of the soluble enzymes compared with those of the lactating rats consuming the control diet ad libitum without affecting the particulate enzymes. Total activities of these enzymes were, however, lower than those for the control rats as a result of the smaller liver mass in the rats receiving the restricted diets.

Animals↗
PubMed1987

T-cell activation by anti-idiotypic antibody: evidence for the internal image.

Human lymphoproliferative responses to a rabbit anti-idiotypic antibody (anti-Id TB71) and the corresponding mycobacterial protein antigen [38,000 molecular weight (MW)] have been investigated in a number of donors. It was found that responsiveness to anti-Id TB71 correlated with responder and non-responder (four subjects each) status to the 38,000 MW antigen. Furthermore, the induction of T-cell proliferation by both the 38,000 MW antigen and the anti-Id TB71 was dependent on accessory cells. When taken together with the concordance between the 38,000 MW antigen and anti-Id responsiveness, this implies that the 38,000 MW antigen and anti-Id TB71 stimulate related, or at least partially overlapping, repertoires of T cells. This was confirmed by the finding that cloned T cells reactive with the 38,000 MW antigen also proliferated in response to the anti-Id TB71. These observations are readily explained if the anti-idiotypic antibody contains an internal image of, and can therefore mimic, the antigen.

Animals↗
PubMed1987

Phase I/II trial of recombinant gamma-interferon in patients with renal cell carcinoma: immunologic and biologic effects.

Thirteen patients with metastatic renal cell carcinoma were entered on a Phase I/II trial of recombinant gamma-interferon (gamma-IFN). Patients (3) were entered on escalating dose levels, and each patient was escalated to the next dose until an individual maximum tolerated treatment dose (MTD) was established. Multiple parameters of biologic response were measured. Patients were studied twice baseline and at frequent intervals after the initial treatment and every treatment until the patient's individual MTD was reached. The MTD for most patients was less than 75 X 10(6) U/m2. Small, but statistically significant, enhancement of monocyte antibody-dependent cellular cytotoxicity and mononuclear cell inhibition of MBL-2 growth were noted in vitro at gamma-IFN concentrations greater than 250 U/ml. Clinically obvious biologic effects were observed: fever, chills, hypotension, and malaise. However, laboratory assays of peripheral blood mononuclear cell natural killer cell activity, tumor (MBL-2) growth inhibition, antibody-dependent cellular cytotoxicity, lymphoblastic T-cell subsets, and 2'5'-oligonucleotide synthetase were not altered in vivo.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

Human ros1 and mas1 oncogenes located in regions of chromosome 6 associated with tumor-specific rearrangements.

Oncogenes have been implicated in tumorigenesis based on their localization to chromosomal sites associated with tumor-specific structural rearrangements. We have mapped the human ros1 (formerly mcf3) and mas1 oncogenes to the distal half of chromosome 6q, within a region frequently rearranged in malignant cells. Chromosomal mapping of these two new human transforming genes may help elucidate the involvement of the long arm of chromosome 6 in diverse tumor types.

Cell Line↗