Administration of pyrimethamine/sulfadoxine for prevention of Pneumocystis carinii pneumonia in patients with AIDS.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
L A Miller
Publications and source records attributed to L A Miller.
Blockade of mast cell histamine secretion in response to neurotensin by SR 48692, a nonpeptide antagonist of the neurotensin brain receptor.
1. Pretreatment of rat isolated mast cells with SR 48692, a nonpeptide antagonist of the neurotensin (NT) receptor, prevented histamine secretion in response to NT. 2. This inhibition was rapid in onset (approximately 1 min) and dependent upon the concentration of SR 48692 (IC50 approximately 1-10 nM). 3. SR 48692 (1-1000 nM) did not inhibit histamine secretion elicited by substance P, bradykinin or compound 48/80, or by anti-IgE stimulation of sensitized mast cells. 4. When SR 48692 was injected intradermally (5 pmol in 50 microliters) into anaesthetized rats, 15 min before the intradermal injection of NT, it reduced the effect of NT on vascular permeability. 5. When injected intravenously, SR 48692 attenuated the effects of NT on haematocrit and blood stasis. 6. These results demonstrate that SR 48692 selectively antagonizes the actions of NT on rat isolated mast cells as well as mast cells in vivo. Given the demonstrated specific interaction of SR 48692 with receptors for NT in brain, our results suggest the presence of specific NT receptors on mast cells.
Animals↗
The relative roles of external taurine concentration and medium osmolality in the regulation of taurine transport in LLC-PK1 and MDCK cells.
Taurine is a beta-sulfonic amino acid that serves as a nutrient important for developing brain and retina and as an osmolyte in the medullary collecting duct. The activity of the taurine transport system is regulated by substrate supply and by the external osmolality; these two stimuli induce changes in taurine transport. Increased medium osmolality (500 mosmol) stimulates taurine uptake into MDCK cells but not LLC-PK1 cells. The enhanced taurine uptake that occurs in response to hyperosmolality is localized primarily to the basolateral surface of MDCK cells, whereas the adaptive response to medium taurine concentration is expressed on both the apical and the basolateral surfaces of both cell lines. The response of MDCK cells to medium osmolality requires protein synthesis and RNA transcription and is expressed in the presence of microtubular toxins. When cell monolayers were loaded with taurine by incubation in high-taurine medium before increasing medium osmolality, the expected increase in taurine uptake was blunted. Similarly, increased external beta-alanine (500 microM) also prevented the anticipated increase in taurine accumulation in response to hypertonicity; aminoisobutyric acid and betaine (500 microM) partially prevented the increase in taurine transport after hypertonicity, whereas L-alanine had no effect. The concentration of taurine or structurally similar analogs in the external medium might modify the response of taurine accumulation after exposure to hypertonic medium, in that taurine-replete cells behave differently than taurine-depleted cells. These studies indicate that there are at least tow distinct mechanisms involved in the regulation of taurine transport: external taurine concentration and medium osmolality, with taurine concentration seeming to be the predominant stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
New T47D breast cancer cell lines for the independent study of progesterone B- and A-receptors: only antiprogestin-occupied B-receptors are switched to transcriptional agonists by cAMP.
Because progesterone antagonists are growth inhibitors, they are in Phase III clinical trials for the treatment of breast cancer. However, when cellular cAMP levels are elevated, some antiprogestins inappropriately activate transcription. We have proposed that hormone "resistance" may result from such unintended stimulation of breast cancer by antagonists. In transient expression systems, the two natural isoforms of human progesterone receptors (PR), B-receptors and truncated A-receptors, have dissimilar effects on agonist-mediated transcription. We show here that in the presence of 8-Br-cAMP, antiprogestin-occupied B-receptors but not A-receptors become transcriptional activators. Therefore, we developed new model systems to study each PR isoform independently in a breast cancer setting: (a) a stable PR-negative monoclonal subline (T47D-Y) of PR-positive T47D breast cancer cells was selected by flow cytometric PR screening. T47D-Y cells are PR-negative by immunoassays, by ligand binding assay, by growth resistance to progestins, by failure to bind a progesterone response element (PRE) in vitro, and by failure to transactivate PRE-regulated promoters; and (b) T47D-Y cells were stably transfected with expression vectors encoding one or the other PR isoform, and two monoclonal cell lines were selected that express either B-receptors (T47D-YB) or A-receptors (T47D-YA) at levels equal to those seen in natural T47D cells. The ectopically expressed receptors are properly phosphorylated, and like endogenously expressed receptors, they undergo ligand-dependent down-regulation. The expected B:B or A:A homodimers are present in cell extracts from each cell line, but A:B heterodimers are missing in both. In the presence of agonists, cAMP-dependent, transcriptional synergism of PRE-regulated promoters is seen in both cell lines. By contrast, in the presence of the antiprogestins RU486 or ZK112993, inappropriate transactivation occurs in YB cells but not in YA cells. The class of antiprogestins represented by ZK98299, which blocks PR binding to DNA, does not activate transcription in either cell line. We propose that these new cell lines are physiological models for the study of PR isoform-specific antiprogestin resistance in breast cancer.
Base Sequence↗
Senile plaques in temporal lobe epilepsy.
Senile plaques (SP) are one of the characteristic pathological lesions of Alzheimer's disease (AD). They are also seen in the brains of some non-demented individuals as an age-related change. Identification of clinical conditions associated with these "incidental" SP could provide insight into AD pathogenesis. We have examined the presence of SP in lobectomy specimens (n = 101) removed in the surgical treatment of temporal lobe epilepsy (TLE). SP were present in 10 specimens from epileptic patients aged 36 to 61 years and the presence of SP correlated positively with patient age. No other significant AD-related pathology was identified and no patients showed any evidence of dementia on neuropsychological testing. When compared with temporal lobe tissue from non-demented, non-epileptic autopsy controls (n = 406), the density and distribution of SP was the same. The age-related incidence of SP however, was significantly greater in the epileptics. This suggests that some aspects of TLE has a positive influence on the formation of SP.
Adult↗
Perceptual flexibility after frontal or temporal lobectomy.
Using stimuli with ambiguous figure-ground relationships, Ricci and Blundo (1990, Neuropsychologia 28, 1163-1173) demonstrated that patients with frontal-lobe lesions are impaired at shifting perspective. No significant difference between right frontal and left frontal groups was found. To investigate this phenomenon further and to look for a possible lateralization-of-lesion effect, 31 patients who had undergone focal cortical excision for the relief of intractable epilepsy and 10 normal control subjects were tested on an expanded version of the original task. It was found that no subjects had any difficulty recognizing at least one aspect in each of the figures and that only patients with right frontal lesions were significantly impaired in recognizing a second. These results indicate that the right frontal region has a particularly important role in the ability to shift visual perspective.
Adult↗
Comparison of three methods for determination of a single MIC of an antimicrobial agent.
Determining a single MIC of an antimicrobial agent that is not included on a routine susceptibility panel can be significantly time-consuming and costly. The UniScept MICRO-MIC, the JustOne, and the E test are single-MIC systems. These systems as well as disk diffusion were compared on the bases of time, cost, and ease of use.
Costs and Cost Analysis↗
Amygdalar sclerosis: preoperative indicators and outcome after temporal lobectomy.
Isolated amygdalar sclerosis (AS) in the presence of an intact hippocampus has been described in a subset of patients who have undergone a temporal lobectomy for the relief of seizures. Clinical observation suggested that these patients might be distinguishable, before and after operation, from those with typical mesial temporal sclerosis, which implies combined amygdalar and hippocampal sclerosis (AHS). From a three year series, all 11 patients classified as having AS were included in this study. These patients were compared with a group of 20 randomly chosen patients with AHS. The groups were found to be well matched in duration of ongoing seizures, full scale IQ, and duration of follow up (mean 19 months). Compared with patients with AHS, patients in the AS group were less likely to have had a seizure in early childhood, a variety of auras, EEG abnormalities localised to one temporal lobe, or an abnormal MRI before operation. They also performed better on preoperative memory tests. At follow up, patients in the AS group were less likely to be seizure free and more likely to have a deterioration in memory after undergoing anterior temporal lobectomy, including part of the hippocampus. The results show that there are preoperative indicators of mesial temporal pathology that are also of prognostic importance given the differences in outcome between the two pathological groups.
Adolescent↗
Characterization of antigenicity and immunogenicity patterns of native and recombinant zona pellucida proteins in the white-tailed deer (Oidocoileus virginianus).
The effectiveness of zona pellucida antigens in immunizing white-tailed deer to reduce fertility was evaluated by analysing the constituent deer zona pellucida proteins and their immunogenicity. Does were immunized with porcine zona pellucida antigens. The antibodies were characterized using immunohistochemical and immunoblot analysis, in which zona pellucida proteins were separated by one-dimensional and two-dimensional PAGE. Deer anti-porcine zona pellucida antibodies were found to recognize all the major proteins of the porcine zona pellucida. These antibodies also recognized several proteins of deer zona pellucida, indicating that it is possible to break immune tolerance in the deer using such a protocol. The antibodies were also found to recognize peptides of 55 and 75 kDa that were produced by expressing cDNA clones containing antigens of major glycoproteins of rabbit zona pellucida. Furthermore, antibodies against rabbit zonae pellucidae recognized antigens in zonae of paraffin-embedded deer ovaries. Taken together, these experiments demonstrate the crossreactive nature of a number of zona pellucida epitopes found in deer and in several other species. They also illustrate the immunogenicity possible in such an immunization protocol, and provide valuable probes for the investigation of follicular development in this and other species.
Animals↗
Electronic fetal monitoring competency--to validate or not to validate: the opinions of experts.
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Clinical Competence↗
Risk factors for delayed immunization against measles, mumps, and rubella in Colorado two-year-olds.
OBJECTIVES: 1) To examine a wide range of potential risk factors for delayed childhood immunization against measles, mumps, and rubella and 2) to determine the parental response to proposed solutions regarding the problem of delayed childhood immunization. DESIGN: A case-control study in which subjects had (controls) or had not (cases) received measles, mumps, and rubella vaccine (MMR) by 2 years of age. Parents of subjects were also surveyed to find out whether they thought selected proposals to improve immunization rates would be successful. RESULTS: Maternal education of high school or less at the time of the child's birth, more than or equal to two moves between birth and age 2, maternal age < 21 years of age at the time of the child's birth, more than or equal to two older siblings, participation in The Special Supplemental Food Program for Women, Infants, and Children (WIC), participation in the federal food stamp program, and incorrect knowledge of the recommended age for MMR significantly elevated the odds ratio (OR) for delayed immunization. At least two older siblings (OR = 3.2), maternal age < 21 years of age at the time of the child's birth (OR = 2.8), and incorrect knowledge of the recommended age for MMR (OR = 2.7) remained significant risk factors in a multivariate logistic regression model. Insurance status and cost factors were not significant risk factors for delayed immunization. Parents though that reminders for immunization and a central record system would have made obtaining immunizations easier. CONCLUSIONS: Based on our findings of the importance of immunization knowledge and demographic characteristics as risk factors for delayed immunization, we suggest that a message (the recommended age for immunizations) and a target group for that message (families who move frequently, have older children, and are headed by younger parents) be evaluated as an intervention to improve immunization rates.
Adult↗
Inhibition of epidermal growth factor-like growth factor secretion in tracheobronchial epithelial cells by vitamin A.
Vitamin A deficiency of respiratory tract epithelium results in the phenomenon of squamous cell metaplasia. The mechanisms by which vitamin A regulates airway epithelial cell growth and differentiation are not completely understood. In this study, we focused on the effects of vitamin A (retinol) on growth of human and non-human primate tracheobronchial epithelial (TBE) cells in culture. Retinol and its derivatives have little growth-stimulatory effect on TBE cells that are maintained in primary culture in a serum-free medium supplemented with 6 hormonal supplements: insulin, transferrin, epidermal growth factor (EGF), hydrocortisone, cholera toxin, and bovine hypothalamus extract. However, it was observed that retinol exhibited dose-dependent inhibition of TBE cell growth when EGF was removed from this serum-free culture condition. This inhibition can be reversed if EGF or the conditioned medium of primary TBE cells that are maintained in vitamin A-deficient condition is added. This type of EGF-retinol interacting phenomenon was not observed with the 5 remaining hormonal supplements. Analysis of 125I-labeled EGF binding shows a down-regulation of the high affinity binding sites (Kd = 0.09 nM) on TBE cells grown in the absence of vitamin A. These results suggest that TBE cells are capable of secreting an EGF-like growth factor in the absence of vitamin A. The possibility that transforming growth factor-alpha (TGF-alpha) is involved in this phenomenon is further examined by antibodies specific to TGF-alpha and its binding to an EGF-receptor. Using the TGF-alpha antibody, the presence of a TGF-alpha-specific antigen was found to be 3-fold higher in the conditioned medium obtained from the vitamin A-deficient cultures than that derived from retinol-treated cultures. Furthermore, the antibody neutralizing the TGF-alpha binding to an EGF receptor was able to reduce the DNA synthesis associated with the vitamin A deficiency. These results suggest that vitamin A plays an important regulatory role in the paracrine/autocrine secretion of EGF/TGF-alpha-like mitogen in TBE cell cultures.
Animals↗
Hippocampal sclerosis and human memory.
OBJECTIVE: To study the effects of hippocampal sclerosis on preoperative neuropsychological memory tests. DESIGN: Analyses of variance and chi 2 tests were used to compare patient groups (divided retrospectively) with a control group. SETTING: Hospital epilepsy unit. PATIENTS AND OTHER PARTICIPANTS: All patients who underwent a temporal lobectomy for intractable seizure relief during the preceding 18 months were included if the following criteria were met: (1) age was between 15 and 55 years; (2) IQ was 80 or greater; (3) the left hemisphere was dominant for speech; (4) there had been no previous brain surgery; (5) sufficient hippocampal tissue had been supplied for pathologic study; and (6) there was no hippocampal abnormality other than sclerosis. The 40 patients who met all of these criteria were divided into groups based on pathological classification (presence or absence of hippocampal sclerosis) and side of excision. Ten normal control subjects, matched to the patients based on age and education, were also asked to perform the memory tests. All subjects approached gave their informed consent to participate in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: None. RESULTS: No group demonstrated impairments on measures of attention or recognition memory. A deficit in learning paired-word associates was found for the left hippocampal sclerosis, right hippocampal sclerosis, and left no-hippocampal sclerosis groups, but on tests requiring the delayed recall of information, only patients with hippocampal sclerosis were impaired. For verbal tasks, the delayed recall deficit was limited to patients with left-sided sclerosis. CONCLUSIONS: Hippocampal sclerosis impairs the ability to learn associations and to retain information over a delay interval. For the learning and retention of verbal material, the left hippocampus is more important than the right.
Adolescent↗
Inhibitory effects of the neurotensin8-13 analogs Asp13-NT8-13 and Asp12-NT8-13 on mast cell secretion.
Pretreatment of isolated mast cells with analogs of neurotensin 8-13 (NT8-13), in which the amino acids Leu13 or Ile12 are replaced with an aspartic acid (Asp13-NT8-13 or Asp12-NT8-13), inhibits the secretion of histamine in response to NT. A 10 min pretreatment with either analog (10 microM) inhibited NT-induced histamine release by 90% (Asp13-NT8-13) or by 98% (Asp12-NT8-13). At concentrations that are inhibitory, Asp13-NT8-13 and Asp12-NT8-13 alone elicit very little release (< 5% at 10 microM). In the continued presence of the analogs, the inhibitory effect lasts for more than 45 min; removal of the analogs resulted in restoration of sensitivity to NT within 10 min. Pretreatment with analog Asp13-NT8-13 resulted in a 39% inhibition of stimulation by substance P and a 52% inhibition of stimulation by histamine-releasing peptide (HRP). In contrast, pretreatment with analog Asp12-NT8-13 gave no inhibition of release by SP or HRP. Neither analog inhibited histamine release in response to bradykinin (BK), NT1-12, compound 48/80 (48/80), the calcium ionophore A23187, or anti-IgE stimulation of passively sensitized mast cells. Although Asp12-NT8-13 and Asp13-NT8-13 differ slightly in regard to the peptides they inhibit, both probably act at a step early in the stimulus-secretion coupling sequence; most likely before the rise in the level of free intracellular calcium that has been shown to accompany secretion in mast cells. It is suggested that these analogs exert their inhibitory effect on NT by competing with NT for a binding site on the mast cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Neonatal HIV seroprevalence studies. A critique of national and international practices.
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Anonymous Testing↗
Use of polymerase chain reaction in an epidemiologic investigation of Pontiac fever.
In June 1992, 13 (38%) of 34 resort guests experienced illness that met a symptom-based case definition of Pontiac fever. Each ill guest reported using an indoor hot tub compared with 6 (29%) of 21 nonill guests (P < .001). Water samples from the indoor hot tub were culture-negative for legionellae using standard techniques, coculture with amebae, and intraperitoneal inoculation of guinea pigs. However, polymerase chain reaction (PCR) testing of the water samples indicated the presence of Legionella pneumophila. Direct fluorescent antibody testing identified the organism as serogroup 6. Seroconversion to L. pneumophila serogroup 6 occurred in 7 (64%) of 11 ill guests and none of 5 nonill guests (P = .03). These results suggest that in certain circumstances, culture of environmental samples should be supplemented with additional tests such as PCR. These results are also consistent with the concept that Pontiac fever can be caused by nonviable legionellae.
Animals↗
Immunoelectron microscopic localization of testicular and somatic cytochromes c in the seminiferous epithelium of the rat.
Somatic and testis-specific cytochromes c were localized ultrastructurally in the seminiferous epithelium by immunocytochemistry using monospecific antibodies. Cytochrome cS was lost from the mitochondria as spermatogenesis advanced, while there was a relative increase in cytochrome cT during the zygotene-to-pachytene transition; this was in agreement with other studies that have suggested activation of the cytochrome cT gene during prophase of the first meiotic division. Cytochrome cT was highly concentrated in mitochondria that were being degraded within cytoplasmic lobes of spermatids and in residual bodies that were phagocytized by Sertoli cells. The two isoforms were found to coexist within the same mitochondrion during the transitional period from cytochrome cS to cytochrome cT predominance. In addition, both cytochromes c were present in the chromatoid bodies of spermatocytes and round spermatids; this suggests that the chromatoid body may be involved in the storage of these isozymes and possibly in their differential expression within germ cell mitochondria. Apocytochrome c was concentrated in mitochondria and chromatoid bodies of the germ cells and also scattered in the cytoplasm. The presence of the holoprotein and apoprotein immunoprobes within the chromatoid bodies of spermatocytes and spermatids was an interesting observation that raises questions regarding the precise location of the synthesis of cytochromes c in spermatogenic cells.
Animals↗
Polarity of taurine transport in cultured renal epithelial cell lines: LLC-PK1 and MDCK.
We characterized taurine transport in two continuous renal epithelial cell lines: LLC-PK1, derived from the proximal tubule of the pig, and the Madin-Darby canine kidney (MDCK), which was originated from the distal tubule of the dog. In the LLC-PK1 cell line, taurine transport is greatest at the apical surface of the cell, whereas in the MDCK cell line taurine transport is greatest at the basolateral surface. Both apical and basolateral surfaces of LLC-PK1 and MDCK cells exhibit an adaptive response to the extracellular taurine concentration (medium taurine concentration). Only the basolateral surface of the MDCK cell responded to hyperosmolality with increased taurine accumulation. This indicates differential control of the beta-amino acid transport system by substrate and external tonicity. The function of the beta-amino acid transport system may be different depending on the cell. In the LLC-PK1 cell, there is net transepithelial movement of taurine and changes in transporter activity in response to supply of substrate. In contrast, taurine accumulation by the MDCK cell appears to be a mechanism for adaptation to osmotic stress.
Amino Acid Transport Systems↗