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Biomedical subjects

D Young

Publications and source records attributed to D Young.

At least 451 records · Page 25Linked to original sources

Proper cleansing for the face.

Skin type, season, and environmental conditions are factors to be considered when determining a proper cleansing regimen for the face.

Cosmetics↗

Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains.

We have cloned and sequenced a new human oncogene and have named it mas. This oncogene was detected by its tumorigenicity in nude mice using the cotransfection and tumorigenicity assay previously described. The mas oncogene has a weak focus-inducing activity in transfected NIH 3T3 cells. A DNA rearrangement in the 5' noncoding sequence, which occurred during transfection, is probably responsible for activation of the mas gene. The cDNA sequence of the mas oncogene reveals a long open reading frame that codes for a 325 amino acid protein. This protein is very hydrophobic and has seven potential transmembrane domains. In this respect, the structure of the mas protein is novel among cellular oncogene products and may reflect a new functional class of oncogenes.

Animals↗

San Diego suicide study. I. Young vs old subjects.

The suicide rate among people under 30 years of age has nearly tripled in the past several decades. We compared 133 suicides under the age of 30 years with 150 aged 30 years and over. After gathering and reviewing extensive clinical information and postmortem toxicologic data, we assigned diagnoses using DSM-III criteria. A major diagnostic finding was the occurrence of more drug abuse than had been previously reported, significantly more often in the young people. Few other differences were found either between our total sample and previous studies or between our younger and older groups. We conclude that a closer look at the young group is necessary to see what other differences might occur between the drug abusers and other young suicides.

Adolescent↗

San Diego Suicide Study. II. Substance abuse in young cases.

Fifty-three percent of 133 consecutive young suicides had a principal psychiatric diagnosis of substance abuse. Twenty-four percent had an additional principal diagnosis of atypical depression, atypical psychosis, or adjustment disorder with depression. The relationship of the substance abuse to the additional diagnosis was usually obscure, though this subgroup was similar to the group with only substance abuse on a number of factors. Typically, substance abuse was a chronic condition present for nine years. Multiple substance abuse was the norm in these cases, and marijuana, alcohol, and cocaine were the most frequently abused substances. Substance abusers without other principal diagnoses received psychiatric care less frequently than those with additional principal diagnoses.

Adjustment Disorders↗

The relationship of life events and stress to neurosis in China: comparison of 105 neurotic patients to 103 normal controls.

Modified versions of Holmes' Schedule of Recent Experience (SRE) and Social Readjustment Rating Scale (SRRS) are used to compare the stress rating of 43 life events of 105 neurotic patients to 103 normal controls and to compare the quantity of life event changes experienced by the two groups. Life events are divided into three categories on the basis of their frequency of occurrence and the intensity of stress they induce. Significantly higher stress ratings for the neurotic patients are found in 17 of 43 life event items studied. In the year prior to the onset of the neurotic illness, the patient group experienced more life event changes and had significantly higher levels of stress than the control group. The results are compared to Holmes' findings in Japan.

Adolescent↗

Developmental aspects of gastroschisis.

The development of gastroschisis was studied experimentally as well as clinically, particularly concerning the characteristic fibrous coating of the protruding bowel loops, associated intestinal atresia, and postoperative hypoperistalsis without intestinal obstruction. Experimental investigation was carried out in the chicken embryo. The clinical study was a joint one, involving a total of 50 patients with gastroschisis seen at the Sophia Children's Hospital, Rotterdam, and the Royal Hospital for Sick Children, Glasgow, between 1972 and 1985. Some patients were followed antenatally. The results, correlating with previous experiments, were compared with data from the literature. The fibrous coating of the protruding bowel loops appeared to be a late occurrence and directly related to changes of the amniotic fluid secondary to the onset of renal function. Associated intestinal atresia and postoperative hypoperistalsis in the absence of an obstruction both appeared to be due to another late gestational event, consisting of ischemic changes of the bowel wall secondary to the compression of bowel loops and mesentery in the small abdominal wall defect.

Abdominal Muscles↗

Structure-function analysis of murine interleukin 1: biologically active polypeptides are at least 127 amino acids long and are derived from the carboxyl terminus of a 270-amino acid precursor.

Murine interleukin 1 (IL-1) is initially synthesized as a 270-amino acid precursor protein. Guided by amino-terminal end sequence analyses of mouse macrophage-derived IL-1, it was shown that expression of the carboxyl-terminal 156 amino acids (i.e., amino acids 115-270) of this precursor in Escherichia coli yields biologically active recombinant IL-1 (rIL-1) protein. To answer questions about precursor processing and the size of the smallest biologically active IL-1 fragment, we have engineered deletions of the rIL-1 (115-270) gene to encode two amino-terminal deletion analogs, rIL-1 (131-270) and rIL-1 (144-270), and a carboxyl-terminal deletion analog, rIL-1 (131-257, 270). The analogs were produced in E. coli, purified to homogeneity, and assayed for biological activity on murine thymocytes, human rheumatoid synovial cells, and human dermal fibroblasts and for their ability to bind to IL-1 receptors on murine EL-4 thymoma cells. The amino-terminal deletion analog rIL-1 (131-270) possessed a specific activity in the murine thymocyte proliferation assay equivalent to that of the 115-270 parent protein and exhibited significant biological activity in stimulating the production of collagenase and prostaglandin E2 by synovial cells and fibroblasts. The more extensive amino-terminal deletion analog rIL-1 (144-270) was inactive in all biological assays and failed to compete in the receptor binding assay. The carboxyl-terminal deletion analog rIL-1 (131-257, 270) competed less efficiently (by a factor of 100) in the receptor binding assay, retained weak biological activity on synovial cells and fibroblasts, and only demonstrated full intrinsic activity in the thymocyte proliferation assay when 100-200 times more protein was assayed. These results suggest that biologically active murine IL-1 polypeptides are at least 127 amino acids long and are derived from the carboxyl terminus of the 270-amino acid precursor. Furthermore, it appears that the integrity of the carboxyl terminus of the 270-amino acid precursor is important for activity but that different amino termini can be utilized to generate molecules with equivalent specific activities. This amino-terminal end flexibility supports a processing model for IL-1 maturation that partially explains IL-1 polypeptide heterogeneity.

Amino Acids↗

Schistosomiasis in an American medical investigator.

A 42-year-old American male researcher contracted schistosomiasis from environmental sources in the course of his observations on human behavior in Upper Egypt. After a long asymptomatic period, he developed various symptoms and Schistosoma haematobium was found in a urine examination. After treatment with Metrifonate, urine examination became negative. However, abdominal pain persisted and most diagnostic tests were negative. Colonoscopic examination and biopsy of the mucosa revealed schistosomiasis. Treatment with Praziquantel was thoroughly effective in clearing the persistent Schistosoma haematobium infection. It is necessary to maintain a high index of suspicion in cases of potential schistosomiasis. The availability of nontoxic treatment is discussed.

Adult↗

Correlation of mononuclear phagocyte assay results and in vivo haemolytic rate in subjects with a positive direct antiglobulin test.

A mononuclear phagocyte assay has been used to measure the in vitro interaction of normal donor monocytes with the red cells from subjects with a positive direct antiglobulin test (DAT). The relationship between the in vivo haemolytic rate in these subjects and the results obtained in the assay, expressed as the number of red cells associated with 100 monocytes (ARC value), has been examined. From the results of assays in which normal donor monocytes were incubated with normal (DAT negative) donor red cells it was calculated that ARC values of greater than 2 could be considered significantly elevated. Assays performed on 24 patients with a positive DAT and warm autoimmune haemolytic anaemia resulted in a mean ARC value of 42 (range 1-212). Assay results for two of the patients in this group, however, were not significantly elevated from normal. The red cells from three patients with a negative DAT who were suspected of having autoimmune haemolytic anaemia showed no association with normal donor monocytes in the assay. The mean ARC value obtained for 14 non-haemolysing subjects with a positive DAT was 7 (range 1-47). Assay results for only 10 of the 14 subjects in this non-haemolysing group fell within the normal range. The correlation of assay results and in vivo haemolysis was strengthened when the assays were performed with autologous monocytes. A possible explanation for the unexpectedly low ARC values obtained in some cases of autoimmune haemolytic anaemia is discussed.

Anemia, Hemolytic, Autoimmune↗

San Diego suicide study: comparison of gay to straight males.

Previous large studies of completed suicides have not considered sexual orientation in their data analyses. In this study, data from the known homosexual subpopulation (13 males, aged 21-42) in a series of 283 suicides were examined. They were compared with all other aged male suicides 21-42 (n = 106). Both groups showed considerable substance abuse plus a variety of other psychiatric diagnoses. Both also had a high frequency of relationship difficulties near the time of death. Gays who committed suicide did not have a history of more police trouble and were no more likely to be living alone than the comparison group. They did not have more prior suicide attempts or previous psychiatric treatment. We conclude that, among the factors examined here, there appears to be little difference between gay and heterosexual male suicides.

Adult↗

Immunological activity of a 38-kilodalton protein purified from Mycobacterium tuberculosis.

A 38-kilodalton (kDa) protein antigen from Mycobacterium tuberculosis was purified by monoclonal antibody TB71-based affinity chromatography. This molecule carries two nonoverlapping epitopes recognized by monoclonal antibodies TB71 and TB72, which are expressed substantially more strongly by M. tuberculosis than by Mycobacterium bovis. However, cross-reactive determinants between these two species were revealed on the 38-kDa protein by a rabbit anti-BCG serum. An immunoradiometric assay based on the TB71 and TB72 antibody pair specifically determined 38-kDa-antigen concentrations in mycobacterial extracts. Antibodies in sera from tuberculosis patients estimated by binding to 38-kDa-antigen-coated microtiter plates were positively correlated with TB72 competing titers. Unlike antibodies, T-cell proliferative responses to the 38-kDa protein were expressed equally by 60% of tuberculosis patients and healthy BCG-vaccinated subjects. Similarly, delayed-type hypersensitivity skin reactions were elicited in both M. tuberculosis- and M. bovis-sensitized guinea pigs. The results suggest the immunodominance of the species-specific B-cell and cross-reactive T-cell stimulatory epitopes.

Animals↗

A comparison of mitoxantrone and doxorubicin in breast cancer.

Ninety patients with breast cancer refractory to cyclophosphamide/fluorouracil/methotrexate (CMF) have been randomized in their treatment, receiving either doxorubicin or mitoxantrone. Seventy-nine have received two full courses of therapy. Twelve of the 40 (30%) who initially received doxorubicin responded, whereas eight of the 47 (17%) who received mitoxantrone responded. These rates are not statistically different. The degree of myelosuppression was equivalent. Patients who received mitoxantrone had less nausea, vomiting, alopecia, and fatigue. Controllable clinical congestive heart failure developed in seven patients, and four others had a deterioration of noninvasive measures of cardiac function without clinical failure. One patient with clinical heart failure developing received only doxorubicin and one, only mitoxantrone, whereas the others received both agents. The duration of remission and time lapsed before disease progression were almost identical for the two regimens. This study included a crossover design. Two of 22 (10%) patients receiving doxorubicin and five of 24 (21%) receiving mitoxantrone as secondary therapy responded. This suggests that there is not absolute cross-resistance between these agents. We conclude that the efficacy of these two drugs is comparable in patients refractory to CMF, though the nonhematologic side effects of mitoxantrone are less.

Adult↗

Phase I/II trial of human recombinant interferon gamma in renal cell carcinoma.

Recombinant interferon gamma (IFN-gamma) was given to 13 patients with metastatic renal cell carcinoma in a Phase I/II trial. Patients were treated twice weekly by a 4-h intravenous infusion. Three patients were each entered at escalating dose levels. Doses were also escalated in each patient until an individual maximum tolerated dose was reached. Pharmacokinetics, toxicity, and tumor response are reported. Blood levels were related to dose and were detected in 6/7 patients receiving 30-75 MU/m2. The t1/2 was approximately 60 min in the higher dose patients, although detectable serum levels in some patients were observed at 24 h. The maximum tolerated dose was 75 MU/m2. Toxicity was limited to the symptom complex of anorexia, fever, and malaise. The latter two were dose-related and quite severe in high-dose patients. No minor or partial responses were observed in any patient.

Adult↗

Effects of recombinant human GM-CSF on proliferation of clonogenic cells in acute myeloblastic leukemia.

Proliferation of acute myeloblastic leukemia (AML) cells in vitro is limited in most cases to a small subset of blasts that have several properties of stem cells. These leukemic colony-forming cells (AML-CFU) generally require addition of exogenous growth factors for proliferation in agar or methylcellulose. These factors can be supplied by media conditioned by phytohemagglutinin-stimulated normal leukocytes or by CSF-secreting tumor cell lines. However, the exact factor or factors required for stimulation of AML-CFU growth have not been defined. We compared the AML-CFU stimulatory activity of a human recombinant GM-CSF with that of GCT-CM, Mo-CM, and the PHA-leukocyte feeder system in 15 cases of AML. In each of the 12 cases that required exogenous growth factors for maximum AML-CFU growth, recombinant GM-CSF could replace either GM-CSF or Mo-CM, and could partially replace the PHA-leukocyte feeder system. These results indicate that this GM-CSF is a growth promoter of AML-CFU in these culture systems.

Adult↗