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Biomedical subjects

J Young

Publications and source records attributed to J Young.

At least 361 records · Page 20Linked to original sources
PubMed1991

Neurosteroids: biosynthesis, metabolism and function of pregnenolone and dehydroepiandrosterone in the brain.

Pregnenolone (P) and dehydroepiandrosterone (D) accumulate in the brain as unconjugated steroids and their sulfate (S) and fatty acid (L) esters. The microsomal acyl-transferase activity is highest in immature (1-3 weeks old) male rats. The immunocytochemical and biochemical evidence for P biosynthesis by differentiated oligodendrocytes is reviewed. The importance of P synthesis for its brain accumulation is assessed by the intracysternal injection of the inhibitor aminoglutethimide. Primary glial cell cultures convert P to 20-OH-P, PL, progesterone, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnane-20-one (Polone). Astroglial cell cultures also produce these metabolites, whereas neurons from 17-day mouse embryos only form 20-OH-P. P and D are converted to the corresponding 7 alpha-hydroxylated metabolites by a very active P-450 enzyme from rat brain microsomes. Several functions of neurosteroids are documented. P decreases in olfactory bulb of intact male rats exposed to the scent of estrous females. D inhibits the aggressive behavior of castrated male mice towards lactating female intruders. The D analog 3 beta-methyl-androst-5-en-17-one, which cannot be metabolized into sex steroids and is not demonstrably androgenic or estrogenic is at least as efficient as D. Both compounds elicit a marked decrease of PS in rat brain. The Cl- conductance of gamma-aminobutyric (GABAA) receptor is stimulated by GABA agonists, an effect which is enhanced by Polone and antagonized by PS. Thus, P metabolites in brain as well as steroids of extraencephalic sources may be involved physiologically in GABAA receptor function. The neurosteroids accumulated in brain may be precursors of sex steroid hormones and progesterone receptors have been localized in glial cells. P and D do not bind to any known intracellular receptor. A heat stable P binding protein has been found in brain cytosol with distinct ligand specificity. A binding component specific for steroids sulfates, including Polone S, DS and PS, in the order of decreasing affinity is localized in adult rat brain synaptosomal membranes. Its relationship to the GABAA receptor is under current investigation.

Animals↗
PubMed1991

Prevention of neonatal macrosomia in gestational diabetes by the use of intensive dietary therapy and home glucose monitoring.

This study was undertaken to determine if intensive dietary therapy, home blood glucose monitoring, and the selective use of insulin can be effective in preventing fetal macrosomia. All patients were screened at 24 to 28 weeks' gestation using a modification of O'Sullivan's criteria. The 153 patients diagnosed as gestational diabetics by the study protocol were placed on a 1800 to 2000 Kcal American Diabetes Association diet and taught home glucose monitoring. Insulin therapy was initiated only if blood glucose control was inadequate. There were no significant differences (p greater than 0.05) between the study and reference populations in regard to mean birthweight or the incidence of macrosomia. Since our study criteria for diagnosing gestational diabetes were slightly different from those of the National Diabetes Data Group (NDDG), data from 99 patients meeting the NDDG criteria were analyzed in a similar manner. No significant differences were found between this subgroup and the reference population. Since only 7.2% of our study patients required insulin, we conclude that the incidence of fetal macrosomia in gestational diabetes can be kept equal to that of the general population by a program of intensive dietary therapy and home glucose monitoring, with insulin being used only therapeutically, not prophylactically.

Adult↗
PubMed1991

A multidisciplinary falls consultation service in a nursing home.

A Multidisciplinary Falls Consultation Service made possible a novel interdisciplinary approach to the patient as a faller. A team consisting of members from the medical, nursing, rehabilitation, administration, and activities departments reviewed epidemiological data on 323 falls and evaluated 24 patient referrals. Interventions at all clinical levels of staffing are being developed to reduce the risk of falling.

Accidental Falls↗
PubMed1991

A discrete cis element in the human immunodeficiency virus long terminal repeat mediates synergistic trans activation by cytomegalovirus immediate-early proteins.

The major immediate-early (IE) promoter of human cytomegalovirus directs the expression of several differentially spliced and polyadenylated mRNAs that encode isoformic proteins with apparent molecular masses of 55, 72, and 86 kDa. All of these proteins are potent transcriptional regulatory proteins. We are interested in the collateral interactions between human cytomegalovirus and human immunodeficiency virus (HIV) in the context of dual infection of a cell. The roles of the specific IE protein isoforms and their respective response elements involved in trans activation of the HIV long terminal repeat (LTR) are not known. Here we present evidence that major IE proteins IE86, IE72, and IE55 are capable of trans-activating the HIV LTR in a T-cell line, HUT-78. The IE55 isoform noncooperatively stimulates the HIV LTR in the presence of either isoform IE72 or IE86. Interactions between isoforms IE72 and IE86, however, result in strong synergistic activation of the LTR. Our results suggest that a specific 155-amino-acid protein domain that is unique for the IE86 protein participates in this synergic interaction. Point mutational analysis of the LTR identified a distinct cis-acting target site, located between nucleotide positions -174 and -163, that mediates exclusively synergistic trans activation by the IE72 and IE86 proteins. Finally, this study underscores the role of a cellular intermediate(s) for communicating the synergic interactions between two IE trans activators.

Amino Acid Sequence↗
PubMed1991

[Inhibition by dehydroepiandrosterone of aggression responses of spayed female mice towards lactating intruders is potentiated by neonatal androgenization].

Female mice of an inbred Swiss strain were injected subcutaneously (s.c.) with either testosterone propionate or oil-vehicle on the day of birth. Once adult (8 week-old), they were spayed, and then treated either with dehydroepiandrosterone (80 micrograms/day s.c. for 15 days) or with solvent. The decrease of biting attacks by dehydroepiandrosterone was definitely more prominent in neonatally imprinted females than in controls.

Animals↗
PubMed1991

Intraperitoneal doxorubicin in combination with systemic cisplatinum and cyclophosphamide in the treatment of stage III ovarian cancer.

Recent concepts and technical development have led to the successful application of the principles of intraperitoneal chemotherapy in the management of advanced epithelial ovarian cancer. In a pilot study we treated five patients with Stage III ovarian cancer after maximal cytoreductive effort (residual tumor less than or equal to 2 cm) with combination chemotherapy consisting of intraperitoneal doxorubicin and intravenous cisplatinum and cyclophosphamide. Although intraperitoneal doxorubicin demonstrates a pharmacologic advantage over the intravenous administration of this drug, its use is limited by severe abdominal pain requiring narcotic analgesics. Chemical peritonitis and extensive peritoneal adhesions are frequent complications. The role of combination intraperitoneal and systemic chemotherapy in ovarian cancer warrants further study.

Aged↗
PubMed1990

Peptide inhibitors of enveloped virus infection inhibit phospholipid vesicle fusion and Sendai virus fusion with phospholipid vesicles.

Small hydrophobic peptides that are capable of inhibiting Sendai virus infection of cells (Richardson, C. D., Scheid, A., and Choppin, P. W. (1980) Virology 105, 205-222) are also capable of inhibiting membrane fusion in a pure lipid vesicle system. Large unilamellar vesicles of N-methyl dioleoylphosphatidylethanolamine containing encapsulated 1-aminonaphthalene-3,6,8-trisulfonic acid and/or p-xylene bis (pyridinium bromide) were formed by extrusion. Vesicle fusion (contents mixing) and leakage were then monitored with the 1-aminonaphthalene-3,6,8-trisulfonic acid/p-xylene bis(pyridinium bromide) fluorescence assay. Sendai virus fusion with lipid vesicles was measured by following the relief of fluorescence quenching of virus labeled with octadecylrhodamine B chloride, a lipid mixing assay for fusion. The efficiency with which the peptides carbobenzoxy-D-Phe-L-PheGly, carbobenzoxy-L-Phe-L-Tyr, and carbobenz-oxy-Gly-L-Phe inhibit fusion of N-methyl dioleoyl-phosphatidylethanolamine large unilamellar vesicles directly paralleled their previously known effectiveness in blocking virus infectivity of cultured cells. In addition, above a certain concentration threshold, the inhibitory peptides decreased the initial rate of leakage from lipid vesicles. The inhibition by these peptides of virus-vesicle fusion followed the same order of potency as for vesicle-vesicle fusion. The observation of the same relative potency of these peptides toward inhibition of virus-cell infection, and virus-vesicle and vesicle-vesicle membrane fusion suggested that these peptides inhibited virus-cell infection by inhibiting the ability of the virus to fuse with the cell. Furthermore, these results suggest that the mechanism of inhibition of all three fusion events may have steps in common.

Amino Acid Sequence↗
PubMed1990

Diffuse bony metastases at presentation in a child with glioblastoma multiforme. A case report.

At initial diagnosis, an 11-year-old girl with glioblastoma multiforme (GBM) presented with diffuse osteoblastic metastases. Primary brain tumors rarely metastasize outside of the central nervous system (CNS) without prior neurosurgery. Extracranial spread at diagnosis has been previously documented in just two adults. Extracranial metastasis of a childhood glioma without prior neurosurgery at any time during the course of the disease is exceedingly rare. Spread to bone by gliomas is also infrequent, and when they occur, bony metastases are usually isolated to one or two sites in any given patient. The widespread osseous metastases in our patient have been reported in three prior cases of high-grade gliomas. This child's GBM likely reflects a highly aggressive variant with the potential to spread outside the CNS and with a predilection for bone. Oncologists should be aware that GBM may present in this fashion during childhood.

Bone Neoplasms↗
PubMed1990

Cancer in Jewish migrants to Israel.

Data on the incidence of 15 cancers in the Jewish population of Israel from the period 1961-1981 have been studied with emphasis on the risk of disease in relation to birthplace, calendar time, and duration of residence in Israel. The results show wide variations in incidence by birthplace, from less than 2-fold for pancreatic cancer to a 40-fold difference for oesophageal cancer in females; the reasons for these are often little understood. The potential importance of environmental agents in aetiology for different migrant groups is discussed in relation to the size and rapidity of changes in risk related to the duration of residence in Israel.

Africa, Northern↗
PubMed1990

The purification and characterization of 3-dehydroquinase from Streptomyces coelicolor.

The enzyme 3-dehydroquinase was purified over 4000-fold to homogeneity from Streptomyces coelicolor. The subunit Mr estimated from polyacrylamide-gel electrophoresis in the presence of SDS was 16,000. The native Mr estimated by gel filtration on a Superose 6 column was 209,000, indicating that the enzyme is a large oligomer. The enzyme was found to be extremely thermostable. This stability, along with the structural and kinetic properties of the enzyme, suggest that it is very similar to the quinate-inducible 3-dehydroquinase found in Neurospora crassa and Aspergillus nidulans. This similarity was confirmed by direct N-terminal sequencing.

Amino Acid Sequence↗
PubMed1990

Isolation, sequence and biosynthetic significance of a novel fragment of gastrin-releasing peptide from chicken proventriculus.

The isolation of bombesin-related peptides in chicken proventriculus was monitored by radioimmunoassay using a C-terminal specific bombesin antibody. Two peptides were identified, one corresponded to the 27-residue, chicken gastrin-releasing peptide (GRP-27) previously identified; the other corresponded to its C-terminal hexapeptide. Chicken GRP-27 stimulated pancreatic and gastric acid secretion in anaesthetized turkeys, but the hexapeptide was inactive. No evidence could be found to suggest that the hexapeptide was an artifact of degradation generated during extraction or isolation. It is proposed that the hexapeptide is produced either by chymotryptic-like cleavage of GRP-27 or by trypsin-like cleavage followed by two cycles of dipeptidylaminopeptidase cleavage. This type of biosynthetic processing may be more common than formerly supposed.

Amino Acid Sequence↗
PubMed1990

Regulation of alkaline phosphatase by 1,25-dihydroxyvitamin D3 and ascorbic acid in bone-derived cells.

The bone, liver, and kidney isozyme of alkaline phosphatase (ALP) has been measured in MG-63 human osteosarcoma cells after treatment with ascorbic acid (AA) and/or 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Both compounds were required to achieve maximum ALP activity. When grown in the absence of 1,25-(OH)2D3 cells had low basal ALP activity regardless of whether media contained AA. In AA-free medium, 1,25-(OH)2D3 (10 nM) increased ALP activity fourfold. Addition of AA further increased levels of ALP activity induced by 1,25-(OH)2D3 to 10-15 times those found in -AA controls. The earliest effects of 1,25-(OH)2D3 were seen after 24-48 h, and ALP activity continued to increase for 6-8 days. AA and 1,25-(OH)2D3 had similar effects on ALP activity in ROS 17/2.8 rat osteosarcoma cells. In MG-63 cells the effects of AA and 1,25-(OH)2D3 could not be simply explained by the ability of these compounds to inhibit cell growth because another mitotic inhibitor, hydroxyurea, had a minimal effect on ALP activity. 1,25-(OH)2D3-specific induction of ALP +/- AA was totally blocked by inhibitors of protein and RNA synthesis. Maximal ALP induction was obtained when cells were plated at low density. Consistent with our previous report (Franceschi et al. 1988 J Biol Chem 263:18938-18945), 1,25-(OH)2D3 rapidly stimulated type I collagen synthesis and acid-precipitable hydroxyproline production in MG-63 cells and this stimulation was further increased by AA. These results suggest that induction of the osteoblast marker, ALP, is directly or indirectly coupled to collagen matrix synthesis and/or accumulation.

Alkaline Phosphatase↗
PubMed1990

Pharmacokinetics of intraperitoneal doxorubicin in combination with systemic cyclophosphamide and cis-platinum in the treatment of stage III ovarian cancer.

The pharmacokinetics of intraperitoneal doxorubicin in three previously untreated patients with ovarian cancer are described. All patients were maximally cytoreduced (largest residual tumor less than or equal to 2 cm). The average total body clearance (TBC) was 16.3 ml/kg/min (range 10.6-20.4 ml/kg/min) and the mean volume of distribution (VD) was 42.4 liter/kg (range 27.6-46.9 liter/kg). Half-life of elimination (t 1/2 beta) was 2.6 hr. In spite of a therapeutic advantage of 60 when administered intraperitoneally, prohibitive local toxicity limited the use of doxorubicin via the intraperitoneal route in patients with ovarian cancer.

Aged↗
PubMed1990

Cholesterol dynamics in membranes.

Time-resolved fluorescence anisotropy of the sterol analogue, cholestatrienol, and 13C nuclear magnetic resonance (NMR) spin lattice relaxation time (T1c) measurements of [13C4] labeled cholesterol were exploited to determine the correlation times characterizing the major modes of motion of cholesterol in unsonicated phospholipid multilamellar liposomes. Two modes of motion were found to be important: (a) rotational diffusion and (b) time dependence of the orientation of the director for axial diffusion, or "wobble." From the time-resolved fluorescence anisotropy decays of cholestatrienol in egg phosphatidylcholine (PC) bilayers, a value for tau perpendicular, the correlation time for wobble, of 0.9 x 10(-9) s and a value for S perpendicular, the order parameter characterizing the same motion, of 0.45 s were calculated. Both tau perpendicular and S perpendicular were relatively insensitive to temperature and cholesterol content of the membranes. The T1c measurements of [13C4] labeled cholesterol did not provide a quantitative determination of tau parallel, the correlation time for axial diffusion. T1c from the lipid hydrocarbon chains suggested a value for tau perpendicular similar to that for cholesterol. Steady-state anisotropy measurements and time-resolved anisotropy measurements of cholestatrienol were used to probe sterol behavior in a variety of pure and mixed lipid multilamellar liposomes. Both the lipid headgroups and the lipid hydrocarbons chains contributed to the determination of the sterol environment in the membrane, as revealed by these fluorescence measurements. In particular, effects of the phosphatidylethanolamine (PE) headgroup and of multiple unsaturation in the lipid hydrocarbon chains were observed. However, while the steady-state anisotropy was sensitive to these factors, the time-resolved fluorescence analysis indicated that tau perpendicular was not strongly affected by the lipid composition of the membrane. S perpendicular may be increased by the presence of PE. Both steady-state anisotropy measurements and time-resolved anisotropy measurements of cholestatrienol were used to probe sterol behavior in three biological membranes: bovine rod outer segment (ROS) disk membranes, human erythrocyte plasma membranes, and light rabbit muscle sarcoplasmic reticulum membranes. In the ROS disk membranes the value for S perpendicular was marginally higher than in the PC membranes, perhaps reflecting the influence of PE. The dramatic difference noted was in the value for tau perpendicular. In both the ROS disk membranes and the erythrocyte membranes, tau perpendicular was one-third to one-fifth of tau perpendicular in the phospholipid bilayers. This result may reveal an influence of membrane proteins on sterol behavior.

Animals↗
PubMed1990

The uptake and metabolism of cyclophosphamide by the ovary.

The uptake of cyclophosphamide (CTX) and its metabolites was evaluated by injecting adult female rats with 14C-CTX on the morning of metestrous or proestrus. Rats were sacrificed 1 and 5 hours after 14C-CTX injection. The ovary, uterus, spleen, thymus, liver, kidney, anterior pituitary, duodenum, skeletal muscle and whole blood were isolated from each rat. Samples were combusted using a biological material oxidizer and the resulting CO2 was absorbed and counted. Liver and kidney had the highest uptake of 14C-radioactivity. The ovary appears to have 14C uptake comparable to the thymus and other tissues. Metabolism of CTX by the ovary was investigated by incubating 14C-CTX with human and rat granulosa cells and other ovarian cells obtained from pregnant mares' serum gonadotropin (PMSG)-primed immature rats, in separate experiments. The conversion of CTX to two marker metabolites, 4-ketocyclophosphamide and 4-hydroxycyclophosphamide was negligible and did not change in the presence of luteinizing hormone (LH). It is concluded that 1) following 14C-CTX injection, the ovary takes up a proportion of 14C-radioactivity comparable to other target tissues (e.g. thymus) and 2) the ovary is not capable of activating CTX in vitro in our system.

Animals↗
PubMed1990

Pancreatic secretory trypsin inhibitor in gastrointestinal mucosa and gastric juice.

We studied the distribution of pancreatic secretory trypsin inhibitor (PSTI) in the epithelia of the gastrointestinal tract and determined whether PSTI is secreted into gastric juice. PSTI was measured by a specific radioimmunoassay in biopsy specimens taken from the upper (n = 8) and lower (n = 7) gastrointestinal tract of patients with normal endoscopies. PSTI was present in the stomach, small intestine, and colon. Concentrations (micrograms/g protein) were highest in the stomach, and significantly higher in the antrum (1240, 670-1700, median and range) than in the gastric body (370, 350-570) (p less than 0.01). Concentrations were similar in the duodenum (180, 80-210) and colon (160, 130-360). PSTI determined by immunohistochemistry was present in mucus secreting gastric foveolar cells, duodenal Paneth cells, and colonic non mucus cells. PSTI was present in gastric juice. The median (range) concentration of PSTI in basal gastric juice from 13 patients with duodenal ulcers was 9 (3-21) micrograms/l and did not change during stimulation with pentagastrin. The rate of secretion, however, did increase significantly (p less than 0.05) from 1430 (180-2810) ng/h to 4500 (1250-12,770) ng/h during pentagastrin stimulation. PSTI was labile in acid pepsin but stable in the neutral conditions present in the mucus layer. The presence of pancreatic secretory trypsin inhibitor throughout the gut and its secretion into the lumen suggests a hitherto unrecognised mechanism protecting gastrointestinal epithelia against luminal proteases.

Adult↗