Unwanted teenage pregnancies: incidence, interpretation, and intervention.
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Adolescent↗
Biomedical subjects
K Kelley
Publications and source records attributed to K Kelley.
Melatonin interactions with cultured murine B16 melanoma cells.
Both in vitro and in vivo observations have suggested that melatonin modulates malignant cell growth. The present studies aimed to characterize the interactions of melatonin with cultured murine B16 melanoma cells. Time- and temperature-dependent specific melatonin accumulation by B16 murine melanoma cells was observed. B16 cells possessed a high affinity binding site (KD = 1.4 nM) which exhibited structural specificity in its affinity for analogues of melatonin (melatonin > 6-hydroxymelatonin = N-acetyl-5-hydroxytryptamine > 5-methoxytryptamine >> 5-hydroxytryptamine). Evidence for a lower affinity uptake system without structural specificity was also observed. Ninety-five per cent of the specific cell-associated melatonin in B16 cells was present in the soluble subcellular fraction of lysed cells; more than 97% of the cell-associated radioactivity was authentic melatonin. When the solubilized cell extracts from the binding assay were analysed by gel filtration immediately, all of the bound counts eluted at the void volume. Continuous exposure to melatonin for 48-120 h did not affect B16 cell proliferation as determined by cell counts, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay or [3H]thymidine incorporation. After 8-h pulse exposures to melatonin daily for 3 days, a 15% stimulation of B16 cell proliferation (p < 0.02) was observed at melatonin concentrations of 0.1 and 1 nM. The anti-oestrogen, tamoxifen, inhibited B16 cell growth and increased specific melatonin accumulation by B16 cells at 1 x 10(-6) M (p < 0.02). Cultured B16 murine melanoma cells possessed a specific, high affinity uptake system for melatonin which appeared to be altered by anti-oestrogen exposure.
Animals↗
Specific cleavage of the alpha 4 integrin associated with activation of peripheral T lymphocytes.
The heterodimeric VLA-4 integrin has been implicated in lymphocyte migration to inflamed peripheral tissues, lympho-haemopoiesis and autoimmune disease. To determine the structure and function of VLA-4 in physiological processes, molecular forms of the VLA-4 alpha-chain were analysed during T-cell activation. The results showed that prolonged activation of human peripheral T cells was associated with increased cleavage of the 150,000 MW alpha 4 chain into 80,000 and 66,000 MW fragments. Similar-sized alpha 4 fragments could also be generated from 150,000 MW alpha 4 on intact resting T cells by brief trypsinization, whereas trypsin treatment of isolated 150,000 MW alpha 4 resulted in nearly complete protein degradation. Native 80,000 and 66,000 MW alpha 4 chains on activated T cells could not be digested further by trypsin. These results indicated that specific cleavage of 150,000 MW alpha 4 was largely dependent on the tertiary structure of native alpha 4 chains. To determine the specific cleavage site in alpha 4 on peripheral T cells, VLA-4 was isolated and purified from in vitro-activated T cells and the N-terminus of the 66,000 MW fragment was partially sequenced. The sequence SKR/STE was identified as the specific alpha 4 cleavage site on T cells. These results indicate that T cells, upon activation, acquire an enhanced dipeptidase processing activity, which cleaves alpha 4 at a specific site.
Amino Acid Sequence↗
Reduced intracellular drug accumulation in the absence of P-glycoprotein (mdr1) overexpression in mitoxantrone-resistant human MCF-7 breast cancer cells.
A mitoxantrone-resistant human MCF-7 breast cancer subline (MCF/MX) which is approximately 4000-fold resistant to mitoxantrone was isolated by serial passage of the parental wild-type MCF-7 cells (MCF/WT) in stepwise increasing concentrations of drug. MCF/MX cells were also approximately 10-fold cross-resistant to doxorubicin and etoposide but were not cross-resistant to vinblastine. Intracellular accumulation of radiolabeled mitoxantrone was markedly reduced in MCF/MX cells relative to that in the drug-sensitive MCF/WT cells. This decrease in intracellular drug accumulation into MCF/MX cells was associated with enhanced drug efflux, which was reversed when cells were incubated in the presence of sodium azide and 2, 4-dinitrophenol, suggesting an energy-dependent process. Incubation of MCF/MX cells with verapamil did not affect either the accumulation of mitoxantrone or the level of resistance in these cells. Furthermore, RNase protection and Western blot analyses failed to detect the expression of the mdr1 RNA or P-glycoprotein, a drug efflux pump known to be associated with the development of multidrug resistance in vitro. However, a polyclonal antibody directed against a synthetic peptide corresponding to the putative ATP binding domain of P-glycoprotein reacted with two (M(r) 42,000 and 85,000) membrane proteins from MCF/MX cells which were not found in MCF/WT. Functional assays and Western blot analysis for topoisomerase II revealed no differences in topoisomerase II activity or protein levels in MCF/MX cells. Thus, resistance in this cell line is apparently associated with enhanced drug efflux involving a pathway distinct from the mdr1-encoded multidrug transporter P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Differential effects of a murine and chimeric mouse/human anti-interleukin-2 receptor antibody on human T-cell proliferation.
The preference for interleukin-2 receptor (IL-2R) expression on activated, compared with resting T lymphocytes makes the IL-2R a promising target for selective immunosuppressive therapy. To increase the potential therapeutic effectiveness of anti-IL-2R monoclonals, a chimeric mouse/human variant was constructed from Ig genes isolated from a murine anti-human IL-2R hybridoma cell line, designated AHT54. AHT54 binds to the same or spatially related epitope as IL-2 on the p55 protein that constitutes the low- and high-affinity forms of IL-2R. Although the murine and chimeric AHT54 antibodies inhibited cell-surface binding of IL-2 to the same extent, the chimeric antibodies containing a human IgG1 constant region had substantially more anti-proliferative activity than their murine IgG1 counterparts. Our results indicated that the human constant region of the chimeric antibodies interacted more efficiently than the murine constant region with effector components present in peripheral blood mononuclear cells (PBMC).
Animals↗
Isolation of the bombesin/gastrin-releasing peptide receptor from human small cell lung carcinoma NCI-H345 cells.
Purification of the gastrin-releasing peptide (GRP) or bombesin receptor has proved elusive in part due to technical difficulties. In the present studies, the problem of oxidized radioligand was avoided by the use of 125I-GRP, which was verified to be not oxidized by high performance liquid chromatography. Specific 125I-GRP binding (at 0 degrees C) to intact human small cell lung carcinoma NCI-H345 cells which had been subjected to a dilute acid wash was 6 fmol/10(6) cells. Inhibition of GRP degradation by human H345 cell membranes through the use of phenanthroline or phosphoramidon permitted the development of binding assays for the GRP receptor in detergent-solubilized crude membrane preparations. The solubilized GRP receptor exhibited saturable, high affinity (KD = 1.3 nM), temperature-dependent specific binding averaging 402 +/- 65 fmol/mg protein (mean +/- S.E. for eight separate membrane preparations with 125I-GRP concentration = 3 nM), with a Bmax = 434 fmol/mg protein using a gel filtration binding assay. That the GRP receptor had been solubilized was demonstrated by its failure to pellet when centrifuged at 100,000 x g for 60 min, its passage through a 0.22-micron filter without loss of binding activity, and its elution in the void volume of a Sephadex G-50 gel filtration column, but within the inclusion volume of a Sephacryl S-200 column (Ve/V0 = 1.1). Isolation of the GRP receptor from human H345 cell-solubilized membranes was achieved by ligand affinity chromatography. A unique 70-kDa band on silver-stained reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis was reproducibly eluted from GRP14-27 affinity columns by an acidic high salt buffer, but binding activity was denatured by these conditions. The protein nature of the GRP receptor was demonstrated by its sensitivity to proteases after isolation. In addition, two unique bands of 65 and 70 kDa were eluted from the GRP14-27 affinity column with GRP14-27 in neutral buffer, and this eluate possessed specific 125I-GRP binding with a stoichiometry of approximately 1:1. Thus, reported here is the isolation of a functional membrane-associated, saturable, high affinity GRP receptor with temperature-dependent binding from the solubilized membranes of human H345 cells.
Bombesin↗
Is ST elevation the only electrocardiographic response of the ischemic right ventricle?
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Angioplasty, Balloon, Coronary↗
Results of revision total knee arthroplasty performed for aseptic loosening.
One hundred thirty-seven revision total knee arthroplasties (TKA) performed in 117 patients with failed aseptic metal-to-plastic knees over ten years (1974-1984) were studied to determine the long-term clinical and roentgenographic results and were compared to primary TKA. The mean age was 65 years (range, 32-90 years). Fifty-three percent had rheumatoid arthritis, and 47% had osteoarthritis. The mean interval from initial to revision TKA (129 knees) was four years (range, three months to 11 years) and from the first to second revision (seven knees) was 2.4 years (range, seven months to 5.5 years). The most common reasons for failure were loosening (73%), patellar complications (13%), and instability (10%). The mean follow-up time was 5.2 years (range, two to 12 years). Function, instability, motion, and pain all improved after revision TKA, but these improvements were significantly less than those seen after primary TKA. One-third of the patients still ambulated with crutches, a walker, or not at all. While mean postoperative flexion was 100 degrees, 24% could not flex to 90 degrees. Most patients (90%) were malaligned at the time of failure and remained so after revision (78%). The increased incidence of radiolucent lines (tibial, 61%; femoral, 24%) was not related to increased failure. Complications were not increased over primary TKA. The failure rate was 5.8% at 5.2 years, or approximately 1% per year. A successful clinical result was defined as a knee with mild or no pain, mild or no instability, and flexion to at least 90 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Infection as a complication of total knee-replacement arthroplasty. Risk factors and treatment in sixty-seven cases.
Of 4171 total knee arthroplasties that were performed at our institution from 1973 to 1987, sixty-seven were followed by infection. The risk of infection was significantly increased in patients, particularly men, who had rheumatoid arthritis; in patients who had ulcers of the skin; and in patients who had had a previous operation on the knee. Infection was also associated with obesity, recurrent urinary-tract infection, and oral use of steroids, although the correlation was not statistically significant. Of the various treatment options that were studied, removal and delayed replacement of the knee prosthesis resulted in the best functional results.
Aged↗
Natural killer (NK) activity and interferon (IFN) production by a fraction of spleen and blood lymphocytes in swine.
After carbonyl iron treatment and gradient isolation, spleen and blood pig lymphocytes exhibited NK activity and produced IFN after viral induction. Removal of plastic-adherent cells, including the majority of B cells, did not change these activities. The plastic-non-adherent cells were further separated into two subsets of roughly similar size by panning using a monoclonal, anti-T, and anti-null cell antibodies (81 + cells). NK activity and IFN production were found in the 81 - cell fraction. A significantly higher proportion of null lymphocytes from blood and of splenic Fc-gamma receptor-bearing lymphocytes was also found among the 81 - cell fraction as compared to the 81 + fraction, without any change among other subsets. Similar proportions of helper (PT4+), cytotoxic (PT8+) and total T cells (MSA4+) were found among lymphocytes bound to target K562 cells and among the whole lymphocyte population. In contrast, lymphocytes that bound K562 cells demonstrated a striking increase in the proportion of Fc-gamma receptor-positive cells of high affinity. These results show that NK cells and IFN-producing cells are mainly included in the same blood and spleen fraction, and suggest that among 81 - cells only those expressing an Fc-gamma receptor of high affinity are active.
Animals↗
Spectra of G ratio, myelin sheath thickness, and axon and fiber diameter in the guinea pig optic nerve.
The spectra of fiber and axon diameter, myelin sheath thickness, fiber density, and g ratio of the optic nerve were analyzed for the strain-13 guinea pig, an animal extensively utilized in the investigation of experimental disorders of demyelination. Our detailed analytical study of the normal guinea pig optic nerve provides the basis for comparison to disease states and the morphology of other species. As in the rat, mouse, and chipmunk, fiber diameters in the guinea pig were unimodal, but dissimilar to the trimodal fiber spectra of the cat and primate. The predominance of medium-sized fibers (0.80-2.00 microns), common to most species, contributed to the larger mean fiber diameter (1.45 microns) of the guinea pig optic nerve, in which small fibers (0.50 microns or less) were infrequent and fibers larger than 5.00 microns in diameter, seen in the cat and primate, were absent. While myelin sheath thickness increased with axon diameter in the guinea pig, as in other species, a g ratio of 0.81 in the guinea pig was greater than in most mammals. Since conduction velocity is dependent on axon size, as well as myelin properties, the relatively larger mean axon diameter of the guinea pig optic nerve (1.18 microns) may compensate for the decrease in its myelination.
Animals↗
Development of a bacteria-independent model of the multiple organ failure syndrome.
Criteria that allow definition of the multiple organ failure syndrome include pulmonary, hepatic, renal, and gut barrier dysfunction along with characteristic histopathologic changes. It has been difficult to study multiple organ failure due to lack of a satisfactory experimental model that would reproduce the pathophysiologic and histopathologic characteristics, would be stable enough to allow study over several days, and would be free of exogenous primary bacterial infection. We have studied pathophysiologic and histopathologic alterations in a potential model of multiple organ failure. Wistar rats received one of the following solutions by intraperitoneal injection: 4 mL of saline, 4 mL of mineral oil, or 1 mg per gram of body weight of zymosan A in 4 mL of mineral oil. Animals that received zymosan developed hypoxia, decreased creatinine clearance, and changes in hepatic microsomal cytochrome P450 content and aniline hydroxylase activity. Bacterial translocation occurred in the zymosan group. The lungs, liver, and kidneys of the animals that received zymosan exhibited histopathologic changes. We conclude that this model fulfills our criteria for a model of multiple organ failure.
Animals↗
Cough-cardiopulmonary resuscitation in the cardiac catheterization laboratory: hemodynamics during an episode of prolonged hypotensive ventricular tachycardia.
Cough-CPR, a deep rhythmic forceful cough repeated 30-60 times per minute, can be an effective resuscitative technique during emergencies occurring in the cardiac catheterization laboratory. We provide documented evidence on the potential of cough-CPR to maintain adequate systemic arterial blood pressure and consciousness during malignant ventricular arrhythmias, including the longest cough-CPR episode (75-90 sec), with continuous hemodynamics recorded. Results in three patients disclose that 1) mean arterial pressure during cough-CPR was 47-66% of nonarrhythmic baseline at a cough rate of 38-46% of normal sinus rhythm heart rate; 2) mean arterial pressure during hypotensive ventricular tachycardia was 17-60 mm Hg higher with than without cough-CPR; 3) at comparable diastolic pressures (33 vs. 31 mm Hg), systolic arterial pressure during cough-CPR was 40 mm Hg higher than basic CPR; and 4) consciousness can be maintained with cough-CPR during prolonged malignant ventricular arrhythmias. Thus cough-CPR can be a valuable adjunct in maintaining patient stability while definitive therapy for the malignant ventricular arrhythmia is administered.
Aged↗
Quantitative analysis of labelled inner retinal proteins in experimental optic neuritis.
In order to determine if axonal transport changes in chronic experimental allergic encephalomyelitis (EAE) were due to blockade or increased discharge of fast transported proteins from the inner retina, we examined the presence of pulse labeled proteins in autoradiograms of the optic nerve head, retinal ganglion cell and nerve fiber layers of juvenile strain-13 guinea pigs with chronic EAE and normal controls. Quantitative analysis of silver grains, performed six and twenty-four hours following the intravitreal injection of tritiated leucine, showed a decrease in inner retinal radioactivity in those with EAE, whereas no difference was detected between the two groups after three days. Grain counts within the optic nerve heads of guinea pigs with EAE were reduced at all time intervals studied. These results are consistent with an increase in discharge of fast transported proteins from retinal ganglion cells into optic nerve axons and support our previous observations of increased radioactivity at the foci of optic nerve demyelination.
Animals↗
Clinical and electroencephalographic features of simple partial seizures.
The clinical and electroencephalographic features of 87 simple partial seizures in 14 patients were studied with video-EEG telemetry. The patients were able to respond to verbal stimuli during all seizures and, later, could clearly recall ictal events. To determine whether the EEG changes in simple partial seizures could be reliably observed, a reader blindly reviewed four EEGs of equal duration for each seizure. These EEGs consisted of one ictal and three nonictal recordings obtained at predetermined times before the seizure. There were 27 motor seizures (mean duration, 86 seconds; range, 2 to 250 seconds), all involving clonic movements of the head and/or upper extremities; 8 (30%) of these had a sensory component (pain in 6, paresthesia in 2). An EEG change, usually localized spikes or sharp waves over the contralateral or both rolandic regions, was identifiable in nine (33%) of the motor seizures. The 60 nonmotor seizures (mean duration, 63 seconds; range, 8 to 375 seconds) involved a variety of symptoms, including somatosensory/special sensory (3 seizures), autonomic (26 seizures), cognitive (1 seizure), affective (14 seizures), and mixed, or more than one category of nonmotor symptoms (16 seizures). In only nine (15%) of the nonmotor seizures was there an ictal EEG change, usually localized spikes or paroxysmal theta activity over the temporal region. Overall, among the 87 simple partial seizures, only 18 (21%) revealed ictal EEG changes. Thus, a normal EEG is common during simple partial seizures and does not exclude the diagnosis.
Adolescent↗
Long-term results of total hip arthroplasty in protrusio acetabuli.
Ninety-three total hip arthroplasties were examined radiographically and clinically to investigate the best method of correction in protrusio acetabuli. Fifty-three percent were treated with cement alone, 36% with mesh or protrusio shell, and 11% with bone graft. Long-term follow-up study revealed a high percentage of immediate and late radiolucent lines. The highest rate of loosening, 50%, occurred in the cement alone group, which had not been corrected to within 10 mm of anatomic position. Sex, cause of protrusio, age at operation, and degree of osteopenia were not significantly different between the groups. The follow-up period was longer in the cement alone group, but this did not account for the excessively high rate of loosening. Correction of the anatomic position in protrusio deformity is vital, whether accomplished with cement, mesh, protrusio shell, or bone graft. Late radiolucent lines are common and do not reliably indicate loosening.
Acetabulum↗
Sexual attitudes and contraception among females across five college samples.
The relationships among sexual attitudes, sexual and contraceptive behavior, and responses to statements about sexual topics are explored using data obtained in the Sexual Opinion Survey concerning 772 women attending four midwestern U.S. universities in the period 1977-1979. "Associations generally occurred between the expression of more positive sexual attitudes and the reporting of behaviors and attitudes supportive of effective contraceptive activity."
Adolescent↗