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Biomedical subjects

D Young

Publications and source records attributed to D Young.

At least 271 records · Page 15Linked to original sources
PubMed1995

IGF-1 influences olfactory bulb maturation. Evidence from anti-IGF-1 antibody treatment of developing grafts in oculo.

Recent studies have indicated that both insulin-like growth factor-1 (IGF-1) and IGF-1 receptor mRNA are abundant in developing and adult olfactory bulbs, and that IGF-1 receptor mRNA is abundant in the prenatal cerebral cortex. To examine the potential role of IGF-1 in development of a central nervous system region rich in IGF-1 and its receptor (the olfactory bulb), as compared to one in which IGF-1 is less abundant (the cerebral cortex), tissue pieces of these two central nervous system areas from E15-E17 rat fetuses were transplanted into the anterior chamber of the eye of adult host rats. The transplants were treated with either a total of 300 ng truncated IGF-1, two different IGF-1 polyclonal antisera, two different non-immune sera, a total of 15 micrograms IGF binding protein-1, or vehicle alone. Treatments were administered by preincubation just prior to grafting and by 5 microliters injections into the anterior chamber on days 5, 10 and 15 postgrafting. Olfactory bulb grafts treated with either of the two IGF-1 antisera grew significantly larger than grafts receiving any other treatment. No enhancement of graft size was seen in E16-E17 parietal cortex grafts after IGF-1 antibody treatment. Immunohistochemical studies revealed no difference between the treatments with regard to glial fibrillary acidic protein-, tyrosine hydroxylase- or neurofilament-immunoreactivity within the olfactory bulb grafts. Since, in the olfactory bulb the presumed reduction of endogenous IGF-1 achieved by antibody treatment caused enhanced growth, we suggest that the presence of appropriate endogenous levels of IGF-1 in this area induces maturation. This mechanism is not operative in all brain areas since it was not seen in cortex cerebri grafts. Thus, endogenous IGF-1 appears to influence brain development in a regionally specific manner.

Animals↗
PubMed1995

Harvesting and enrichment of hematopoietic progenitor cells mobilized into the peripheral blood of normal donors by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF: potential role in allogeneic marrow transplantation.

To explore the use of stem/progenitor cells from peripheral blood (PB) for allogeneic transplantation, we have studied the mobilization of progenitor cells in normal donors by growth factors. Normal subjects were administered either granulocyte-macrophage colony-stimulating factor (GM-CSF) at 10 micrograms/kg/d, or G-CSF at 10 micrograms/kg/d, or a combination of G- and GM-CSF at 5 micrograms/kg/d each, administered subcutaneously for 4 days, followed by leukapheresis on day 5. Mononuclear cells expressing CD34 (CD34+ cells) were selectively enriched by affinity labeling using Dynal paramagnetic microspheres (Baxter Isolex; Baxter Healthcare Corp, Santa Ana, CA). The baseline CD34+ cells in peripheral blood before mobilization was 0.07% +/- 0.05% (1.6 +/- 0.7/microL; n = 18). On the fifth day after stimulation (24 hours after the fourth dose), the CD34+ cells were 0.99% +/- 0.40% (61 +/- 14/microL) for the 8 subjects treated with G-CSF, 0.25% +/- 0.25% (3 +/- 3/microL, both P < .01 v G-CSF) for the 5 subjects administered GM-CSF, and for the 5 subjects treated with G- and GM-CSF, 0.65% +/- 0.28% (41 +/- 18/microL, P < .5 v GM-CSF). Parallel to this increase in CD34+ cells, clonogenic assays showed a corresponding increase in CFU-GM and BFU-E. The total number of CD34+ cells collected from the G-CSF group during a 3-hour apheresis was 119 +/- 65 x 10(6) and was not significantly different from that collected from the group treated with G- and GM-CSF (101 +/- 35 x 10(6) cells), but both were greater than that from the group treated with GM-CSF (12.6 +/- 6.1 x 10(6); P < .01 for both comparisons). Analysis of the CD34+ subsets showed that a significantly higher percentage of cells with the CD34+/CD38- phenotype is found after mobilization with G- and GM-CSF. In the G-CSF group, immunomagnetic selection of CD34+ cells permitted the enrichment of the CD34+ cells in the apheresis product to 81% +/- 11%, with a 48% +/- 12% yield and to a purity of 77% +/- 21% with a 51% +/- 15% recovery in the G- and GM-CSF group. T cells were depleted from a mean of 4.5 +/- 2.0 x 10(9) to 4.3 +/- 5.2 x 10(6) after selection, representing 99.9% depletion. We conclude that it is feasible to collect sufficient numbers of PB progenitor cells from normal donors with one to two leukapheresis procedures for allogeneic transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Determinants of bone mass in 10- to 26-year-old females: a twin study.

This cross-sectional twin study aimed to quantify the roles of constitutional and lifestyle factors on bone mass in adolescent and young adult women. Areal bone density (BMD) at the lumbar spine, femoral neck, Ward's triangle, and total hip, total body bone mineral content (BMC), and lean mass and fat mass were measured using dual energy X-ray absorptiometry (DXA) in 215 female volunteer twin pairs (122 monozygotic [MZ], 93 dizygotic [DZ]) aged 10 to 26 years. Height, weight, menarchial history, dietary calcium intake, physical activity, current tobacco use, and alcohol consumption were determined by questionnaire. Mean BMD increased with age to around 16 years, when it reached a plateau. Within-pair differences in BMD at the lumbar spine (expressed as a percentage of the pair mean BMD) were univariately associated with pair differences in menarchial status (14 +/- 3%), height (0.7 +/- 0.1% per cm), weight (0.4 +/- 0.1% per kg), lean mass (1.0 +/- 0.1% per kg), and fat mass (0.5 +/- 0.1% per kg). Only menarchial status, height, and lean mass, however, were independent predictors. At the proximal femoral sites, within-pair BMD differences were associated with within-pair lean mass differences (1.0 to 1.1 +/- 0.2%/kg), and no other factor was significant. The same conclusions applied to within-pair differences in BMD/height. Total body BMC was independently associated with menarchial status, height, lean mass, and fat mass; the effects of the latter two variables were stronger in pairs both premenarchial. After adjusting for constitutional factors, no lifestyle factor was independently predictive. By reducing collinearity, the cotwin method clearly identified that lean mass, not fat mass, was the major independent determinant of bone mass at the hip, both pre- and postmenarche.

Absorptiometry, Photon↗
PubMed1995

Neuronal injury following electrically induced status epilepticus with and without adenosine receptor antagonism.

Adenosine is thought to act as an endogenous anticonvulsant and neuroprotective substance in the brain. In the present study we compared neuronal death following status epilepticus (SE) induced in the presence of 8-cyclopentyl-1,3-dimethylxanthine (8-CPT), an A1-adenosine receptor antagonist, with that following SE induced by continuous hippocampal stimulation. Hippocampal damage was characterized using selective nerve and nonnerve cell markers. Six days after SE, both models produced similar patterns of CA1 and CA3 cell loss and selective loss of parvalbumin and hilar somatostatin-immunoreactive interneurons. Calbindin D28K-immunoreactive interneuron numbers and calbindin D28K immunoreactivity in dentate granule cells remained unchanged although calbindin D28K staining was lost in damaged CA1 neurons. Neuronal injury in these areas was also accompanied by reactive gliosis and microglial proliferation, as well as the production of basic fibroblast growth factor and insulin-like growth factor-1 by astrocytes. Although hippocampal damage appeared to be more severe after SE induced in the presence of 8-CPT, this may be due to the increased severity of SE generated in this model.

Animals↗
PubMed1995

Clusterin accumulates in dying neurons following status epilepticus.

Clusterin is a protein that has been implicated in cell death and remodelling in a number of different tissues. To further investigate the role of clusterin in nerve cell death its expression was measured in the rat brain at various times after status epilepticus (SE) induced by 1 h of hippocampal stimulation, by using in situ hybridization, immunocytochemistry, and immunoblotting. SE lead to a dramatic time-dependent increase in clusterin mRNA in non-nerve cells resembling astrocytes in the hippocampus beginning after 24 h. There was also an earlier induction of clusterin mRNA in dentate granule cells, that survive SE. Only a low mRNA signal was observed over the CA1 pyramidal cells, which die after SE. In contrast to these mRNA results, massive clusterin-like immunoreactivity was observed in CA1 pyramidal cells and dentate hilar neurons (and both of these neuronal populations die after SE), but not in dentate granule cells. We speculate that astrocytes produce clusterin after SE and that the clusterin is then secreted and taken up by hippocampal neurons destined to die. Thus, the role of clusterin in nerve cell death/ regeneration warrants further investigation.

Animals↗
PubMed1995

Psychoactive substance use in three sites in China: gender differences and related factors.

One year prevalence rates for psychoactive substance use are reported based on a community survey in Hunan, Helongjiang and Jiangsu. Data were gathered on more than 14,000 respondents (15-65 years old). The drinking rates ranged from 58.3% to 82.6% for men and from 16.3% to 31.4% for women. Smoking rates ranged from 64.9% to 68.1% for men and from 0.1% to 20.5% for women. Most drinkers were light users and most smokers were heavy users. Illicit drug use was found in the Hunan site. For both frequency and quantity of psychoactive substance use, women are lighter consumers than males (except for the use of minor tranquillizers and analgesics). Psychosocial factors related to drinking and smoking are also investigated in this study.

Adolescent↗
PubMed1995

In vivo effects of interleukin 3 in HIV type 1-infected patients with cytopenia.

OBJECTIVE: To determine the safety, tolerance, and hematological and virological effects of the recombinant hematopoietic growth factor interleukin 3 (IL-3) in HIV-1-infected individuals with cytopenia. DESIGN AND METHODS: A phase I single-center trial was conducted with patients in cohorts of three receiving one of four dose levels of self-administered, subcutaneously injected IL-3 (0.5, 1.0, 2.5, or 5.0 micrograms/kg/day). Toxicities, hematological effects, and virological effects were recorded. Viral studies included serum HIV p24 antigen levels, quantitative plasma and peripheral blood mononuclear cell cultures, and quantitative, competitive polymerase chain reaction of patient plasma. RESULTS: Increases in white blood cell counts (WBC) and absolute neutrophil counts (ANC) were noted at the higher dose levels while absolute eosinophil counts (AEC) increased in all patients. The percent changes in WBC from baseline ranged from 52 to 309 and in ANC from 20 to 262 in the 2.5- and 5.0-micrograms/kg/day groups. The mean AEC change was 17-fold (range, 2- to 59-fold). Hemoglobin, hematocrit, platelets, and CD4 and CD8 counts were generally unaffected although individual patients demonstrated increases in hemoglobin and platelet levels. Toxicities were generally mild, but one patient developed a transient local erythematous rash at the sites of IL-3 injection which pathologically demonstrated hypersensitivity vasculitis. Of note, viral studies did not demonstrate any consistent changes in HIV-1 activity. CONCLUSION: These data demonstrate limited hematological effects of IL-3 monotherapy in HIV-1-infected patients with cytopenia. However, should IL-3 be incorporated into combination cytokine therapies for HIV disease, these data suggest that IL-3 does not enhance in vivo HIV-1 activity.

Adult↗
PubMed1995

Sequence analysis and antigen binding characteristics of Ig SCID Ig+ mice.

SCID mice as they age may develop a limited number of functional B and T cell clones. VH and VL gene sequences of hybridoma antibodies derived from the spleens of five adult SCID Ig+ mice revealed nine clonally unrelated, i.e. derived from different precursor lymphocytes, groups of Ig. Of these, four used the VH7183 family, one Q52, three J558 and one VH3609. VH7183 was seen in excess over J558 despite a 5-fold larger number of J558 family members in the mouse genome. Preferential use of D proximal VH genes along with reduced N region addition in the heavy chain VDJ joins of these antibodies suggest derivation from a population of lymphocytes with characteristics of the perinatal repertoire. All of the hybridomas produced kappa light chains of several different VL family groups. Sequences of 23 VH and 22 VL genes of hybridomas derived from one mouse (no. 45) showed that they were all clonally related, differing only in somatic mutations. Autoreactivity of these antibodies to cellular antigens [including (U1)RNP-specific A protein and SmB] was analyzed, and shown to correlate with the geneology and specific mutations within members of the clone. The geneological tree derived from sequence data permitted a study of the microevolution of a clone of B cells and showed that as it developed there was a tendency toward increased strength of self-reactive binding as well as alterations in specificity toward these autoantigens. Analysis of replacement:silent mutation ratios within members of this clone reflected limited affinity maturation in mouse 45 and none for another mouse, no. 58. These data are consistent with the progressive differentiation of B cells in an immunodeficient state in the absence of clonal competition with B cells of similar antigen specificities as they populate the spleen.

Amino Acid Sequence↗
PubMed1995

Synergism between gonadotrophins and vinblastine relative to the frequencies of metaphase I, diploid and aneuploid mouse oocytes.

Ovulated oocytes are used to obtain estimates of germ cell aneuploidy following in vivo treatment with various chemicals. Such studies commonly use exogenous gonadotrophins to increase the number of ovulated oocytes and to induce ovulation during specific time periods. However, the gonadotrophin dosages have not been evaluated relative to the possibility that synergistic and antagonistic interactions may exist between the hormones and the chemical being studied. We, therefore, studied the interactions of different hormone dosages (5 IU pregnant mare's serum (PMS) and 2.5 IU human chorionic gonadotrophin (HCG), 7.5 IU PMS and 5 IU HCG, and 10 IU PMS and 7.5 IU HCG) alone (controls) and in combination with 0.2 mg/kg of the aneugen vinblastine sulfate (VBS) relative to the number of oocytes ovulated, the frequencies of metaphase I (MI), diploid and aneuploid oocytes. The results indicated that the proportions of oocytes ovulated were not significantly (P > 0.05) different among the various control and VBS groups. VBS, however, resulted in significantly (P < 0.01) higher levels of MI oocytes than in controls. In the VBS-treated females, higher frequencies (P < 0.05) of MI oocytes were found in the 7.5 IU PMS and 5 IU HCG and 10 IU PMS and 7.5 IU HCG groups as compared to the 5 IU PMS and 2.5 IU HCG group. The frequencies of diploid oocytes did not differ significantly (P > 0.05) within the control of VBS groups; whereas, when comparisons were made between each control and VBS group, only the difference between the 5 IU PMS and 2.5 IU HCG groups was significant (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗
PubMed1995

Neurokinin receptors subserving plasma extravasation in guinea pig airways.

In the respiratory system the tachykinins substance P and neurokinin A exhibit a variety of effects on airway function that include bronchoconstriction, vasodilatation, and plasma extravasation. Increased microvascular permeability with accompanying plasma extravasation is a principal cause of tissue edema observed in asthma. In guinea pig airways it has been suggested that neurogenic plasma extravasation is mediated by tachykinins, released from sensory nerve terminals, acting via neurokinin (NK) receptors. We have characterized NK receptor mediated plasma extravasation in guinea pig airways, using 125I-labelled human fibrinogen as a marker for leakage. Extravasation was induced using selective NK1 and NK2 receptor agonists, capsaicin, or nonadrenergic, noncholinergic nerve stimulation. The inhibitory effects of the selective nonpeptide NK receptor antagonists (CP 99,994 for NI1 and SR 48,968 for NK2) were also examined. Results from our studies demonstrate conclusively that only NK1 receptors subserve plasma extravasation in the trachea and large airways of the guinea pig. In start contrast, extravasation in the lower airways (secondary bronchi and intraparenchymal airways) of the guinea pig is mediated by both NK1 and NK2 receptors.

Animals↗
PubMed1995

The health care seeking behavior of schizophrenic patients in 6 East Asian areas.

The patterns of health care seeking behavior of 1061 schizophrenics and the factors that affect the determination of the patterns were studied in 6 areas of 5 nations in east Asia: Hunan and Sichuan Provinces in China, Japan, Korea, Malaysia and the Philippines. The information was gathered through a structured questionnaire developed by the authors. The subjects generally favored psychiatry-oriented health care, but with frequent interruptions or combination with other types of managements. Most Japanese subjects sought care in western medicine, while subjects from Hunan, Sichuan and Korea alternated between western medicine and magicoreligious therapies or traditional herbal medicine. In the Philippines and Malaysia, the majority of the subjects sought magicoreligious therapies first, then later sought western psychiatric care. The choice of western psychiatric care was mostly influenced by the decision maker's knowledge and interpretation of the patient's illness. In determining the choice of management among various types of non-psychiatric management, cost, location, and societal attitudes played substantial roles as well as knowledge and interpretation. Suggestions and opinions were discussed to improve health care services for schizophrenic patients in each community.

Adult↗
PubMed1995

Comparison of a gonadotropin-releasing hormone agonist and a low dose oral contraceptive given alone or together in the treatment of hirsutism.

Chronic GnRH agonist therapy lowers androgens and decreases androgen-dependent hair shaft diameter, but the resulting induction of hypoestrogenemia has limited its usefulness as a single agent. Estrogen- and progestin-containing oral contraceptives also reduce circulating androgen levels and are commonly used empirically for the treatment of hirsutism, but have not been evaluated in a blinded randomized controlled fashion. The present study is the first double masked trial to evaluate the combination use of a GnRH agonist and an estrogen-containing oral contraceptive and tests our hypothesis that these could synergistically reduce androgen levels and suppress hormone-dependent hair growth while avoiding the symptoms and risks of agonist-induced hypoestrogenemia. We enrolled 64 women in a 24-week blinded randomized controlled trial to compare placebo, nafarelin (NAF; 400 micrograms, intranasal spray, twice daily), norethindrone (1 mg), and ethinyl estradiol (NOR 1/35; 0.035 mg, daily, for 3 of 4 weeks), or combined use of NAF and NOR 1/35 for 24 weeks. At baseline and every 8 weeks, we measured gonadotropins, estrogens, androgens, and hair growth. Bone density was assessed by dual energy x-ray adsorptiometry, and hot flashes were measured objectively. Baseline total testosterone (T), free T, percent free T, and sex hormone-binding globulin-binding capacity were similar among groups. With treatment, significant reductions (P = 0.01) in total T were seen with combination and NAF only therapy. Significant increases (P < 0.001) in the sex hormone-binding globulin-binding capacity were seen in women given NOR 1/35 alone or in combination with NAF. Free T levels decreased to approximately half of baseline levels with combination treatment (17.9 to 6.4 nmol/L; P < 0.001) and NOR 1/35 alone (20.8 to 10.2 nmol/L; P < 0.001). There was a significant decrease in hair shaft diameter after combination therapy (P < 0.05) that was not seen with either agent alone. Combination therapy also prevented the hot flashes and bone loss that occurred with agonist alone. In summary, our results demonstrate that combination GnRH agonist and low dose oral contraceptive therapy is more effective than either agent alone in the treatment of hirsutism and avoids the hypoestrogenic complications that occur with agonist only therapy.

Adult↗
PubMed1995

The role of the tymbal in cicada sound production

1. The tymbal of Cyclochila australasiae consists of a biconvex membrane bearing alternating long and short ribs anteriorly and an irregularly shaped tymbal plate posteriorly. These sclerotised regions are coupled together by the surrounding highly flexible cuticle, which contains resilin. Dorsally, there is a thick pad of resilin, which functions as a spring, returning the tymbal to the out position and maintaining the stress on the long ribs. 2. Contraction of the tymbal muscle causes the tymbal plate to swing inwards, acting as a lever so that the surface of the tymbal moves through more than twice the distance of muscle shortening. This produces an inward movement and twisting of the dorsal ends of the long ribs, which then buckle in sequence, with each rib undergoing a sudden deformation from a convex to a V-shaped profile. Buckling takes place at the rib's weakest point, which is the narrow, highly sclerotised mid-region. 3. Inward buckling of the tymbal generates a loud click with a dominant frequency around 4 kHz. Resonances close to 4 kHz can be demonstrated in a buckled-in tymbal when driven by internal sound or by vibration at the tymbal plate. These resonances occur in sealed cicadas and those in which the abdominal air sac has been opened at both its anterior and posterior ends, which shows that the resonances are not due to the air sac; the tymbal itself is a resonant system. The maximum amplitude of tymbal vibration occurs at the V-shaped dimples in the centre of the long ribs. 4. When the tymbal plus abdominal air sac system is driven by vibration at the tymbal plate, the Q3dB of the sound radiated through the tympana is about 12.5, which is approximately the sum of those of the tymbal (Q=9.3) and of the air sac (Q=3.4) resonators. When the tymbal is not loaded by the air sac, i.e. in the sealed cicada and open cicada preparations, the Q3dB of its resonance is higher, between 13 and 20. 5. The click produced as the tymbal pops out is over 20 dB quieter than the in-click and has a dominant frequency around 6 kHz. When driven in the resting position, resonances are found close to 6 kHz but there is only a weak general vibration of the ribs and tymbal plate. When the tymbal is pushed in gradually, the resonant frequency changes from about 5.5 kHz to about 4.3 kHz as the tymbal buckles inwards. The left and right tymbals of the same insect may differ slightly in their acoustic properties. 6. As the tymbal buckles inwards, it displaces a volume of approximately 6 &micro;l into the abdominal air sac volume of about 2 ml. The resulting sound pressure inside the air sac attains peak values of 155&shy;159 dB SPL; the root mean square values are 141&shy;144 dB SPL. The mean peak value just outside the tympana is 148.5 dB SPL. 7. Overall, the present work supports and extends our earlier model of cicada sound production: the tymbal click provides a coherent resonant source that drives the abdominal resonator, from which sound is radiated via the tympana. At the same time, the system provides the pressure transformation between muscle power and sound power that is desirable for efficient sound radiation.

Journal Article↗
PubMed1995

Comparison of hard- and soft-copy digital chest images with different matrix sizes for managing coronary care unit patients.

OBJECTIVE: This study was to determine whether different digital display formats for portable chest radiographs of coronary care unit patients would provide comparable information for clinical care. In particular, we tried to ascertain whether 1024 x 1024 pixel (1K) images on a picture archiving and communication system (PACS) workstation would be comparable to 1760 x 2140 pixel (2K) images on workstations or to digital films. If comparability could be proved, we hypothesized that 1K workstations could considerably lower equipment and film costs and facilitate image transmission from point to point. MATERIALS AND METHODS: Four chest radiologists read a panel of chest studies assembled from 98 coronary care unit patients, comparing 1K and 2K soft-copy images with digital hard copies. For all three image types for the 98 patients, the readers evaluated nine image parameters that the cardiologists deemed essential for clinical decision making. Two other chest radiologists reviewed each patient's three image types, historical chest images, current and prior radiologic reports, and medical record to determine the consensus, or "truth findings." RESULTS: With one exception (small pleural effusions), the receiver operating characteristic analysis showed no significant differences in the clinical information derived from the three image types. CONCLUSION: For clinical management in a coronary care unit, comparable information can be obtained from digital radiologic chest studies using a 1K x 1K soft-copy format, a 2K x 2K soft-copy format, or a hard copy (film). Substantial savings in cost and time are therefore possible by using soft-copy images and lower resolution (1K x 1K) workstations and, when necessary, by transmitting images on regular telephone lines.

Coronary Care Units↗