Biomedical subjects
Publications and source records attributed to P Miller.
We report 2 patients over the age of 70 who, while on valproate (VPA) for complex partial seizures, developed sensorineural hearing loss. Following discontinuation of VPA for nonaudiologic reasons, the patients reported improved hearing which was confirmed by audiometry. These findings represent VPA-induced sensorineural hearing loss, possibly in preexisting presbycusis.
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Using Barnhill's components of family health functioning, we examined the relationships of spouse anxiety, coping methods, couple responsibility for compliance, and reported compliance with marital couple functioning. Five psychosocial scales were returned by mail by 136 Mended Heart members and spouses from five geographic regions. By multiple regression analysis, confrontive coping strategies and spouse trait anxiety were the two factors predictive of couple marital functioning. When marital functioning scores were examined separately, spouses' confrontive behaviors and patient reported compliance for diet, stress, and smoking prescriptions were predictive of both spouse and patient marital functioning. In addition, spouse marital functioning was predicted by state anxiety and patient compliance, and patient marital functioning by compliance and shared responsibility for compliance. Further studies should evaluate spouse inclusion in rehabilitation programs during hospitalization and convalescence and examine interactional strategies that facilitate confrontive behaviors and patient compliance to promote couple marital functioning after the cardiac event.
In this nonenzymatic colorimetric method, dichlorobenzoquinone chloroimine is used as a color reagent to measure uric acid in urine. This method is less subject to the interferences that make enzymatic methods unreliable and is inexpensive, simple, and fast.
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Acute inflammation was induced in rats by subcutaneous implantation of saline-soaked polyester sponges. Leukocyte depletion with vinblastine leukocyte accumulation and partly inhibited the vascular permeability at 6 h and increased it at 24 h. Complement depletion with cobra venom factor inhibited leukocyte accumulation at 6 h only and had little effect on vascular permeability. The cyclooxygenase inhibitor tiaprofenic acid inhibited leukocyte accumulation with a greater effect at 24 h and also inhibited vascular permeability at this time.
The human cell surface protein CD4 is not only an important accessory molecule in the activation of MHC class-II-restricted T cells, but has also been implicated to be a receptor for the human immunodeficiency virus HIV-I on lymphoid and monocytic cells. We have found that a 24-h treatment of the promonocytic leukemia cell line U937 with rIFN-gamma decreases the expression of the CD4 Ag by 50% as measured by cytofluorographic analysis. The decrease in CD4 expression was dependent on the concentration of rIFN-gamma, with maximal effects occurring at 20 to 200 U/ml. The decrease appeared to be due to actual loss of the CD4 molecule from the cell surface rather than masking of a particular epitope, inasmuch as similar results were obtained with the OKT4 and OKT4A antibodies. The effect of rIFN-gamma to decrease CD4 expression was not due to a general loss of cell surface Ag, because the binding of OKM1 and anti-HLe-1 increased after rIFN-gamma treatment. Treatment of rIFN-gamma also decreased cell surface CD4 expression on the promyelocytic leukemia cell line HL-60, and on the monocytic cell line THP-1, although the extent of the decrease was less than on U937 cells. Freshly isolated normal peripheral blood monocytes treated for 48 h with rIFN-gamma bound much less OKT4 or OKT4A antibody than cells incubated in the absence of rIFN-gamma. Moreover, treatment with rIFN-gamma reduced the percentage of peripheral blood monocytes that were positive for the CD4 Ag. In contrast with the decrease in CD4 levels on rIFN-gamma-treated monocytes, treatment with rIFN-gamma had no effect on CD4 levels on peripheral blood T lymphocytes or T cell lines.
Immunologically-mediated cellular accumulation was measured 24 hours after antigenic challenge using a rat subcutaneous air pouch model. This response was inhibited by treatment with prednisolone, colchicine, anti-thymocyte serum and systemic antigen. In contrast, administration of a range of other pharmacological and clinically active agents had little effect. The profile of inhibitory activity suggested that this response was mainly due to delayed type hypersensitivity with little anaphylactic or Arthus-type component.
Apoferritins prepared from horse spleen and heart and rat heart and liver were dissociated by treatment with acetic acid (pH 1.3-3.0). Sedimentation velocity studies showed that apoferritins of spleen and liver (16-17 S) and heart (18-19 S) dissociated into material sedimenting near 3.2 S. Sedimentation equilibrium measurements determined that most of the material had a molecular weight of 38,000-43,000, corresponding to subunit dimers. Failure to dissociate into subunit monomers was confirmed by gel chromatography on Sephadex G-75 and G-150. With the exception of boiling in sodium dodecyl sulfate, further treatments with 0.1-0.4 M KCl, NaCl, 4-9 M urea, 0.01-0.5 M KSCN, 0.1-0.5% Triton X-100, 5-52% dimethylsulfoxide, 10% ethylene glycol, or 0.1% trifluoroacetic acid all failed to cause dissociation into individual subunits, as did exposure to 6 M guanidine-HCl or formic acid, or prior succinylation and/or nitration of the protein. Reassociation occurred between pH 4 and 7 but was not aided by the addition of Fe(II) or reducing agents. It is concluded that ferritins readily dissociate to subunit dimer units and that further dissociation does not occur without full denaturation of the protein.
Oligo(nucleoside methylphosphonate)s complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5 caused specific inhibition of herpes simplex virus type 1 growth. The dodecamer d(TpTCCTCCTGCGG) (deoxynucleoside methylphosphonate residues in italic) caused 50% and 98% decreases in herpes simplex virus type 1 titers at concentrations of 15 microM and 100 microM, respectively. d(TpTCCTCCTGCGG) inhibited viral but not cellular protein synthesis and decreased splicing of immediate early pre-mRNAs 4 and 5. Inhibition was highly sequence specific. A psoralen derivative of d(TpTCCTCCTGCGG) that can covalently bind to complementary sequences after exposure to 365-nm irradiation caused 90-98% inhibition of virus growth in cells treated with oligomer (5 microM) and irradiated at 1-3 hr postinfection. The data suggest that oligo(nucleoside methylphosphonate)s of appropriate sequence and derivatization may be effective as antiviral agents.
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The secretion of cortisol increases in awake dogs after small hemorrhage, with little or no change in plasma immunoreactive (IR) ACTH. To determined if IR-ACTH reflects bioactive (B) ACTH after hemorrhage, changes in B-ACTH and IR-ACTH were determined in awake dogs. Trained dogs were prepared with adrenal venous and femoral arterial and venous cannula. Experiments performed 48-96 h after surgery consisted of blood sampling from the adrenal vein and femoral artery before and after a 7.5-10 ml/kg hemorrhage done over 3 min. Cortisol was assayed by HPLC with UV detection, and adrenal secretory rates were calculated using adrenal blood flow. Arterial B-ACTH was assayed after extraction using rat adrenal cells dispersed with collagenase; corticosterone produced was assayed by HPLC-UV. Arterial IR-ACTH was assayed by RIA using antisera directed against ACTH-(1-24). Dogs in which hypotension occurred (change in mean arterial pressure, -31 +/- 3; n = 6) were compared to dogs in which mean arterial pressure did not change (change in mean arterial pressure, -6 +/- 2; n = 5). In the absence of hypotension, B-ACTH increased by 10 min after the onset of hemorrhage coincident with increased cortisol secretion, whereas IR-ACTH did not increase until 20 min. Resting IR-ACTH was greater than B-ACTH (11 +/- 1 vs. 2 +/- 1 pg/ml), but the peak response of B-ACTH was greater than that of IR-ACTH (13 +/- 4 vs. 8 +/- 3 pg/ml). In the presence of hypotension, B-ACTH increased by 4 min, and IR-ACTH and cortisol secretion increased by 8 min after the onset of hemorrhage. Resting IR-ACTH was greater than B-ACTH (27 +/- 5 vs. 6 +/- 1 pg/ml), and the peak response of B-ACTH was less than that of IR-ACTH (64 +/- 26 vs. 112 +/- 33 pg/ml). In dogs subjected to blood sampling without hemorrhage (n = 4), resting IR-ACTH was greater than B-ACTH (34 +/- 5 vs. 5 +/- 1 pg/ml), but there was no change in B-ACTH, IR-ACTH, or cortisol secretion. The results show that small hemorrhage elicits changes in B-ACTH that are dissociated in time and magnitude from changes in IR-ACTH, are coincident with changes in cortisol secretion, and are greater in dogs that fail to maintain arterial pressure. These data indicate that B-ACTH predicts more accurately the change in cortisol secretion than does IR-ACTH after small hemorrhage.
Antisense methylphosphonate-modified oligomers (ONMP) complementary to 8 nucleotides spanning the twelfth amino acid codon of human c-Ha-ras have been synthesized to explore their inhibitory effect on ras p21 translation. The ONMP Ras 0, perfectly complementary to the specific target region in normal c-Ha-ras, inhibits cell-free translation of p21 from a normal c-Ha-ras mRNA template in a dose-dependent manner. At 200uM Ras 0, p21 translation is inhibited by almost 90% in a rabbit reticulocyte lysate; at 100uM, p21 is reduced by over 60%. Ras I and Ras II contain, internally, a single and double base mismatch, respectively. The inhibitory activity of these ONMPs is reduced in proportion to the number of mismatches. When the target mRNA encodes the activated c-Ha-ras differing by a single nucleotide at the twelfth amino acid codon from normal c-Ha-ras, the magnitude of the inhibitory effect of Ras I increased significantly because Ras I is now perfectly complementary to its target mRNA. In turn, Ras 0, now only partially complementary, is considerably less effective at the same concentrations. Therefore, the inhibitory effect is exquisitely sensitive to the extent of the sequence complementarity between the antisense ONMP and the targeted mRNA.
Anti-ras oligodeoxyribonucleoside methylphosphonates (ONMP's) complementary to the initiation codon region have been synthesized to explore their efficacy and specificity on ras-p21 translation. ONMP (IC-0) precisely complementing the first initial 11 nucleotides of the Balb-ras initiation codon region acts in a dose-dependent manner to inhibit p21 translation by a rabbit reticulocyte lysate. At 100 microM, IC-0 inhibits the cell-free translation of p21 close to completion. The two control oligomers containing one or two nucleotide mismatches were significantly less effective than IC-0 at the equivalent concentration. In living cells, a perfectly matched ONMP directed against the initiation codon region inhibited Ha-ras p21 expression by 90% at a concentration of 50 microM.
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The relationship of attitudes and perceived beliefs of others to regimen compliance and personal psychologic and social adjustments of patients with myocardial infarction was investigated 1 year after the infarction. Eighty-one patients (39 in the experimental group, 42 in the control group) who participated in a prior study on the effect of a nursing intervention on regimen compliance, completed scales that assessed attitudes toward regimen prescriptions (diet, medications, activity, smoking, and stress response), perceived beliefs of others concerning compliance, personal adjustments, and regimen compliance. At 1 year, no differences were found between experimental and control groups for regimen compliance or personal adjustments. There was a significant decrease in mean scores for all variables from the time the patient was in the hospital to 30 days afterward, but no change at 1 year from the 30- or 60-day visit. At 1 year, attitudes were predictive of compliance for all regimen prescriptions. Perceived beliefs of others were predictive of diet, activity, and medication prescriptions.
Inflammation was induced in the 6-day subcutaneous air pouch of the rat by injection of carrageenin. The model was characterized in terms of exudate volume, leucocyte accumulation, granuloma, vascular permeability and protein clearance up to 7 days after injection of carrageenin. From days 2-3 rapid and reproducible changes in these responses were observed which indicated a change from polymorphonuclear (PMN) leucocyte-dominated to mononuclear (MN) leucocyte-dominated inflammation. A second injection of carrageenin on day 3 gave increases in exudate formation and PMN accumulation on day 4. Administration of carrageenin mixed with 3 day inflammatory exudate gave an increased exudate volume and decreased leucocyte accumulation at 6 h. Reduction of 6-h cellular accumulation by use of a lower dose of carrageenin or a I-day air pouch gave complete inhibition of exudate formation on day 3. In contrast, inhibition of the 6-h cell response with prednisolone had no effect on the 3-day response. Daily treatment with indomethacin gave increased PMN accumulation on day 3. Similar treatment with prednisolone additionally reduced exudate volume. Treatment on day 2 with prednisolone gave similar effects whereas indomethacin, BW755C and protease inhibitors had no effect. Administration of colchicine at this time gave inhibition of exudate volume on day 3 whereas complement depletion gave increases in volume and PMNs.