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Biomedical subjects

N Miller

Publications and source records attributed to N Miller.

At least 163 records · Page 9Linked to original sources
PubMed1988

Delta-9-tetrahydrocannabinol during pregnancy in the rat: effects on development of RNA, DNA, and protein in offspring brain.

Either 15 or 50 mg/kg of delta-9-tetrahydrocannabinol (THC) was administered from Day 2 through Day 22 of gestation. Pair-fed and nontreated groups served as controls and all treated and control litters were fostered at birth to untreated dams. To determine the effects of THC on offspring brain development, DNA, RNA and protein values were determined at 7, 14, and 21 days of postnatal age. DNA and RNA levels appeared unaffected by THC but brain protein levels of the 50 mg/kg offspring were significantly lower than in the other groups at Day 7 and 14. This suggests that the high THC dose inhibited protein synthesis for at least the first 14 days of life. Subsequently, protein levels of the 50 mg/kg offspring increased rapidly so that there were no differences between any of the groups at 21 days of age. These findings for developing CNS parallel the delayed rate of somatic growth previously reported from our laboratory and suggest a transitory rather than a permanent effect of THC on both somatic and brain growth. We also found that THC produces a significant dose-related increase in the sex-ratio of live male-to-female offspring, a finding we have reported previously.

Animals↗
PubMed1988

Positive mood and helping behavior: a test of six hypotheses.

Past research has shown rather consistently that positive mood states lead to increased helpfulness. In an expanded analysis of the published literature, we examined six distinct views about this relation: the focus of attention, objective self-awareness, separate process, social outlook, mood maintenance, and concomitance hypotheses. For each of 61 positive affect conditions in which it was possible to generate an effect-size estimate corresponding to the relative degree of helpfulness exhibited by positive mood subjects (compared with neutral affect subjects), judges assessed the contextual levels of variables relevant to each of the six hypotheses by reading the Method section of each article. Higher-order partial correlation coefficients were then calculated to isolate the independent contribution of each of the theoretically relevant variables to the variation among the 61 effect sizes. The results support the focus of attention, separate process, social outlook, and mood maintenance hypotheses, and partially support the objective self-awareness and concomitance hypotheses.

Affect↗
PubMed1988

A decade of experience with the glutaraldehyde-tanned human umbilical cord vein graft for revascularization of the lower limb.

Between October 1975 and November 1985, 907 lower limb bypasses were constructed in 715 patients (799 limbs) with glutaraldehyde-stabilized umbilical veins (UV-G) used as the predominant, or sole, graft material. Each reconstruction was classified in one of eight categories depending on the site of the distal anastomosis: above- and below-knee popliteal, anterior and posterior tibial, peroneal, trifurcation, sequential, and crural (tibial or peroneal) bypasses with adjunctive distal arteriovenous fistulas. Primary and secondary cumulative graft patency rates were determined for each category as well as cumulative actual palliation that combines end points of graft failure, amputation, and death. Half-life patencies for popliteal, tibial, and peroneal bypasses were 6.5, 2.3, and 1.7 years, respectively. Perioperative graft thrombosis occurred in 11% of popliteal reconstructions compared with 22% for the crural group. Nonocclusive graft failure caused by infection, aneurysm, or progressive foot gangrene occurred in 87 grafts (8%). The overall infection rate was 4.3%. Anastomotic aneurysms (1.4%) and strictures (2.1%) occurred infrequently as isolated phenomena. The incidence of graft dilatation and aneurysms assumed significant proportion after 5 years (36% aneurysms and 21% dilation); the diagnosis was particularly facilitated by B-mode imaging. Nevertheless, the overall clinical impact of graft degradation remained minimal (6% after 5 years). Twenty-two of 26 graft aneurysms were excised with successful graft replacement achieved in 10. During this 10-year period, our attitudes did change with regard to the indication for UV-Gs in relation to the maturation of infrapopliteal reconstructive surgery, appreciation of the superior results attainable with in situ saphenous vein, recognition of morphologic changes in long-term UV-G implants, and the growing documentation of poor results with polytetrafluorethylene in the crural position. We believe that UV-G is an acceptable alternative to the absent or deficient autologous vein, particularly in patients with limited life expectancy and where expediency may be a critical factor.

Adolescent↗
PubMed1988

A monoclonal antibody to glycoprotein gp85 inhibits fusion but not attachment of Epstein-Barr virus.

Epstein-Barr virus (EBV) codes for at least three glycoproteins, gp350, gp220, and gp85. The two largest glycoproteins are thought to be involved in the attachment of the virus to its receptor on B cells, but despite the fact that gp85 induces neutralizing antibody, no function has been attributed to it. As an indirect approach to understanding the role of gp85 in the initiation of infection, we determined the point at which a neutralizing, monoclonal antibody that reacted with the glycoprotein interfered with virus replication. The antibody had no effect on virus binding. To examine the effect of the antibody on later stages of infection, the fusion assay of Hoekstra and colleagues (D. Hoekstra, T. de Boer, K. Klappe, and J. Wilshaut, Biochemistry 23:5675-5681, 1984) was adapted for use with EBV. The virus was labeled with a fluorescent amphiphile that was self-quenched at the high concentration obtained in the virus membrane. When the virus and cell membrane fused, there was a measurable relief of self-quenching that could be monitored kinetically. Labeling had no effect on virus binding or infectivity. The assay could be used to monitor virus fusion with lymphoblastoid lines or normal B cells, and its validity was confirmed by the use of fixed cells and the Molt 4 cell line, which binds but does not internalize the virus. The monoclonal antibody to gp85 that neutralized virus infectivity, but not a second nonneutralizing antibody to the same molecule, inhibited the relief of self-quenching in a dose-dependent manner. This finding suggests that gp85 may play an active role in the fusion of EBV with B-cell membranes.

Animals↗
PubMed1988

MEDLINE on CD-ROM: end user searching in a medical school library.

End users at the Medical College of Pennsylvania enjoyed searching CD-ROM versions of MEDLINE and judged such searches "extremely useful." To assess the effectiveness of their searches, a sample of 500 search statements from Compact Cambridge (CC) MEDLINE was examined. A high proportion of search statements (224, or 45 percent) retrieved no documents. Over one-third of search statements (185, or 37 percent) contained at least one error, which usually resulted in zero retrieval for that search statement. Searchers attempting to enter Medical Subject Headings were frequently defeated by the elaborate punctuation requirement of CC MEDLINE. "Missed opportunities" were evident in over three-fourths of search statements. One-on-one instruction and library classes may increase search success, but these measures reach a limited audience. Improvement in the search software itself is needed to help searchers improve the effectiveness of their searches.

Computer Literacy↗
PubMed1988

Effects of acebutolol on the serum lipid profile.

Epidemiological and recent interventional studies have emphasised the relationship between plasma lipid parameters and the incidence of coronary heart disease. beta-Blockers, particularly those without intrinsic sympathomimetic activity (ISA), are generally reported to increase triglyceride levels and decrease high density lipoprotein (HDL)-cholesterol levels, both changes theoretically increasing the risk of coronary heart disease. A review of all published trials concerning the effects of acebutolol (a cardioselective beta-blocker with mild ISA) on the plasma lipid profile was carried out, with a particular emphasis on studies reporting a comparison with other beta-blockers. The results indicate that, on average, acebutolol does not have any adverse effects on plasma lipids and may even reduce total and low density lipoprotein (LDL)-cholesterol by 7 and 5%, respectively. In contrast, the other beta-blockers compared under the same conditions (propranolol, pindolol and penbutolol) tended to increase triglyceride levels (+19% when compared with acebutolol) and decrease HDL-cholesterol (-7% when compared with acebutolol) to an extent that was consistent with previous reports in the literature. In interpreting these differences in lipid parameters in the light of epidemiological and interventional study data, the use of acebutolol as opposed to the other beta-blockers could theoretically lead to a relative reduction in coronary risk of 20% or more.

Acebutolol↗
PubMed1988

Adoptive immunotherapy of diabetes in autologous nonobese diabetic mice with lymphoid cells ex vivo exposed to cyclosporin plus interleukin 2.

Between 12 and 26 wk of age, approximately 80% of female nonobese diabetic (NOD) mice from the inbred Sansum colony develop lymphocytic insulitis and become overtly diabetic. The disease in this animal model is similar to human insulin-dependent diabetes mellitus (IDDM) in both genetics and autoimmune pathogenesis. Cyclosporin A (CsA) has been used for immunosuppression in IDDM of recent onset in humans but has several limiting side effects. Therefore, a different regimen for CsA immunosuppression was investigated. Autologous splenic lymphoid cells from 12-wk-old not-yet-diabetic female NOD mice were cultured for 72 h with CsA plus interleukin 2 (IL-2) before reinfusion into the animal from which they were isolated. After this treatment, only 2 (18%) of 11 mice became overtly diabetic during an observation period of 19 wk, while 18 (86%) of 21 age-matched control mice developed diabetes during the same observation period (P less than .001). These data suggest an ex vivo preferential IL-2 activation of specific suppressor cells for the autoimmune process with CsA blockade of cytolytic/helper activities. Because the in vivo concentrations of CsA with this procedure would be negligible, these findings have implications for the potential nontoxic use of CsA in human protocols as well.

Animals↗
PubMed1987

Prolongation of cell cycle transit time and the presence of non-cycling cells in human lymphoblastoid cells cultured under adverse conditions.

The growth characteristics of B lymphocytes infected with Epstein-Barr virus (lymphoblastoid cells) have been investigated by flow cytometric analysis of DNA content and by estimation of cell culture doubling times. It was found that the manipulative procedures involved in the cell cycle analysis resulted in a slowing of the growth rate. This slowing of growth was brought about by the prolongation of cell cycle transit times and by the entry of cells into a short-lived non-cycling pool. The entry of a proportion of the cells into the non-cycling pool may be the normal response of lymphoblastoid cells to non-optimal conditions. The non-cycling cells survived in culture with a T 1/2 of approximately 30-60 hr and continued to secrete immunoglobulin. Their surface transferrin receptors were considerably reduced, which suggests that the failure to divide may have resulted from a failure of growth factor receptors to reach a threshold value following mitosis.

B-Lymphocytes↗
PubMed1987

Effects of low-dose cyclosporine prophylaxis in nonobese diabetic mice.

Among female nonobese diabetic mice, ketotic insulin-dependent diabetes mellitus (IDDM) develops spontaneously in 80% between 12 and 26 weeks of age. This condition resembles human type I diabetes. IDDM developed in 0 of 11 (0%) mice prophylactically treated with 10 mg of cyclosporine A (CyA) per kg s.c. every 4th day from 8 to 26 weeks of age; 8 of 10 (80%) of sex- and age-matched controls developed IDDM; 2 of 8 (25%) followed up to 5 months beyond the time of drug administration developed IDDM. The distribution of specific radioactivity ([3H]CyA) was used to calculate the concentrations of CyA in serum, blood cells and various organs. Serum values of CyA produced by radioimmunoassay were higher than those estimated by the [3H]CyA method. Pancreata of CyA-treated mice were histologically normal. Pancreata of control mice showed lymphocytic infiltration of the islets of Langerhans. Neither hepatotoxicity nor nephrotoxicity assessed by biochemical and histological data was detectable in CyA-treated mice. The insulin secretory capacity of trypan blue viable functional pancreatic islets isolated post-treatment; was significantly lower in controls than in CyA-treated mice; islet content of insulin was not statistically different between controls and CyA-treated mice. We conclude that low nontoxic doses of CyA abrogate completely the development of diabetes in the female nonobese diabetic mouse and abolish lymphocytic infiltration of the islets of Langerhans against which there is autoimmunity. The effect of CyA persists well past the duration of therapy.

Animals↗
PubMed1986

The significance of supraclavicular fossa node recurrence after radical mastectomy.

The clinical and pathologic features of 35 patients who had ipsilateral supraclavicular node (SCF) recurrence after radical mastectomy were reviewed. These were compared with the features of 70 patients who had a local skin recurrence after radical mastectomy, 48 of whom had a single nodule and 22 of whom had multiple skin nodules. There were no significant differences between age at diagnosis, disease-free interval, menstrual status, tumor type and grade, and extent and location of axillary node metastases in the three groups. Survival of the SCF group was intermediate between those of the single-nodule and multiple-nodule groups. SCF recurrence is an almost invariable signal of micrometastatic disease; thus, such patients are ideal candidates for trials of adjuvant therapy.

Actuarial Analysis↗
PubMed1986

Hereditary antithrombin III deficiency: case report and review of recent therapeutic advances.

We report on a newly diagnosed family with hereditary antithrombin III deficiency, with thromboembolic complications in the propositus. Both the propositus and his asymptomatic sister had decreased plasma levels of antithrombin III antigen and activity (28-52% of normal with good agreement between functional and immunologic assays). The propositus developed deep venous thrombosis, followed by massive pulmonary emboli despite heparin therapy and was treated with streptokinase and heparin with excellent results. Shortly thereafter, small bowel obstruction required surgical intervention, and antithrombin III concentrate, recently available in the United States as an investigational new drug (I.N.D.), was administered with no postoperative thrombotic complications. He was subsequently asymptomatic while on warfarin prophylaxis but twice developed venous thrombosis when he failed to take warfarin. The addition of danazol therapy led to a sustained rise in the antithrombin III level. Each of these therapeutic approaches is discussed and the literature reviewed with emphasis on the newer agents--streptokinase, antithrombin III concentrate, and danazol.

Adult↗
PubMed1986

Increased dietary leucine changes the rhythm of prolactin secretion.

As we have recently shown that prolactin secretion in vitro is regulated by extracellular leucine, we wanted to determine whether leucine had a similar regulatory action on prolactin secretion in the intact animal. Leucine was administered to cycling female rats by way of their drinking water (0.5%) for a period of 24 days. At daily intervals during this time, six control and six leucine-treated rats were killed and their trunk blood subsequently assayed for prolactin content. On days 7, 14, and 21 during this period, pituitaries from the sacrificed rats were fixed and processed for electron microscopy. Leucine treatment resulted in an alteration in the normal four-day cyclicity in serum prolactin levels and a stimulation of prolactin synthesis as evidenced by ultrastructural changes in the pituitary mammotrophs. In a parallel set of experiments, daily vaginal smears were taken from nonsynchronized animals for 24 days before and 24 days during leucine administration. Leucine treatment resulted in variable alterations in the estrus cycle depending upon the stage of the cycle when the leucine was first administered. The changes in serum prolactin and the disturbances of the estrus cycle in the leucine-treated animals persisted for approximately 20 of the 24 days. In a shorter control experiment (seven days), alanine treatment (0.5%) was found to have no effect on prolactin levels. It is concluded that a mild elevation in dietary leucine can affect prolactin synthesis and release and the normal progression of the estrus cycle.

Animals↗
PubMed1986

The relation between popularity and achievement: a longitudinal test of the lateral transmission of value hypothesis.

Data from a longitudinal study of school desegregation were used to examine the relation between normative social influence processes and academic achievement in order to test theoretical models of how school desegregation produces benefit. Subjects were white, Mexican-American, and black elementary school children who were measured once prior to and twice after desegregation of their schools. For all groups, analyses using structural equation techniques showed that, contrary to the lateral transmission of values hypothesis, which views social influence processes as shaping academic achievement, "causal influence" did not flow from social acceptance to academic achievement; instead, achievement appeared to affect subsequent social acceptance.

Achievement↗