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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 19 recordsLinked to original sources
PubMed1992

Monoclonal antibodies against defined epitopes of the human transferrin receptor cytoplasmic tail.

Three murine monoclonal antibodies (mAbs) against the 61-residue amino-terminal cytoplasmic tail of the human transferrin receptor (TR) have been produced by immunization of mice with recombinant human TR produced in a baculovirus expression system. Mutant human TRs expressed in chick embryo fibroblasts (CEFs) with point mutations or deletions in their cytoplasmic tails have been used to map the epitopes defined by each of the mAbs. One mAb, H68.4, previously shown to block receptor internalization, binds proximal to the carboxy-terminal side of the YTRF internalization signal of TR. The second mAb, H73.2, binds near to the carboxy-terminal side of the H68.4 epitope, whereas the third mAb, 160.1, binds closer to the transmembrane region. H68.4 and H73.2 are auto-antibodies consistent with their epitopes mapping to a region of the human TR that has an identical amino acid sequence to the mouse TR. All three mAbs crossreact with the cytoplasmic tail of Chinese hamster TR. Double labelling of recombinant human TRs on chick embryo fibroblast (CEF) cell membrane preparations with B3/35 and H68.4 antibody-gold conjugates established that receptors in clathrin-coated pits were not labeled with H68.4, implying that associated coated pit proteins may block binding of this mAb.

Amino Acid Sequence↗
PubMed1992

A human serotonin 1D receptor variant (5HT1D beta) encoded by an intronless gene on chromosome 6.

An intronless gene encoding a serotonin receptor (5HT1D beta) has been cloned and functionally expressed in mammalian fibroblast cultures. Based on the deduced amino acid sequence, the gene encodes a 390-amino acid protein displaying considerable homology, within putative transmembrane domains (approximately 75% identity) to the canine and human 5HT1D receptors. Membranes prepared from CHO cells stably expressing the receptor bound [3H]serotonin with high affinity (Kd 4 nM) and displayed a pharmacological profile consistent, but not identical, with that of the characterized serotonin 5HT1D receptor. Most notably, metergoline and serotonergic piperazine derivatives, as a group, display 3- to 8-fold lower affinity for the 5HT1D beta receptor than for the 5HT1D receptor, whereas both receptors display similar affinities for tryptamine derivatives, including the antimigraine drug sumatriptan. Northern blot analysis revealed an mRNA of approximately 5.5 kilobases expressed in human and monkey frontal cortex, medulla, striatum, hippocampus and amygdala but not in cerebellum, olfactory tubercle, and pituitary. The 5HT1D beta gene maps to human chromosome 6. The existence of multiple neuronal 5HT1D-like receptors may help account for some of the complexities associated with [3H]serotonin binding patterns in native membranes.

Amino Acid Sequence↗
PubMed1992

The local lymph node assay: results of a final inter-laboratory validation under field conditions.

The local lymph node assay (LLNA) assesses the sensitizing activity of chemicals by measurement of primary lymphocyte proliferation in lymph nodes draining the site of application. In this final inter-laboratory study the consistency of LLNA results between laboratories and with guinea pig maximization test (GPMT) data was examined under 'field' conditions. Nine chemicals were evaluated independently by each laboratory according to guidelines for test concentration and vehicle selection developed during previous validation studies to ensure assay optimization. Equivalent predictions of sensitization potential were obtained by all laboratories for eight chemicals. Five of seven chemicals identified as sensitizers in the GPMT were correctly identified in the LLNA--four by all laboratories and 1 (4-chloroaniline) by one laboratory only--although in this latter case, two other laboratories obtained clear dose responses, suggestive of sensitization. The LLNA identified correctly those chemicals predicted to be extreme or strong sensitizers in the GPMT. The remaining two chemicals were non-sensitizers in the guinea pig and failed to elicit positive proliferative responses in the LLNA. These data demonstrate that sensitivity and reliability of the LLNA is retained when chemicals are evaluated independently, and that it provides a reliable pre-screen for the identification of chemicals with significant sensitization potential.

Animals↗
PubMed1992

Membrane-bound and solubilized brain 5HT3 receptors: improved radioligand binding assays using bovine area postrema or rat cortex and the radioligands 3H-GR65630, 3H-BRL43694, and 3H-LY278584.

Bovine area postrema tissue was used as a convenient source of tissue for studies of brain 5HT3 receptors. 5HT3 receptor density was determined to be 97 +/- 5 fmol/mg and 124 +/- 10 fmol/mg of protein using the commercially available 5HT3 radioligands, 3H-GR65630 and 3H-BRL43694, respectively. The equilibrium dissociation constants (KD) for 3H-GR65630 and 3H-BRL43694 were 0.5 +/- 0.1 nM and 1.7 +/- 0.3 nM, respectively. The affinities of a series of drugs for the 5HT3 receptor using the two radioligands were essentially identical; the Ki values and order of affinities of agonists and antagonists were very similar to data published in studies on radiolabeling of 5HT3 receptors in rat brain. 3H-LY278584 also labeled 5HT3 receptors in bovine area postrema homogenates with a KD of 3.1 +/- 0.1 nM and a Bmax of 84 +/- 6 fmol/mg. In rat cortical homogenates, 3H-LY278584 produced the most reliable specific signal of 72%, with a KD of 2.6 +/- 0.3 nM and a Bmax value of 10.5 +/- 1 fmol/mg. At 1 nM, 3H-GR65630 or 3H-BRL43694 specific binding represented 28 and 50% of total radioligand binding, respectively. These data in bovine and rat brain tissues indicate that bovine area postrema can be used with 3H-GR65630, 3H-BRL43694, or 3H-LY278584 for drug screening or molecular investigations of the brain 5HT3 receptor: only 3H-LY278584 can be used for studies on the regulation and/or the molecular properties of 5HT3 receptors in rat cortical homogenates. 5HT3 receptors were solubilized from bovine area postrema and characterized using 3H-GR65630.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effect of platelet activating factor on different phases of murine in vitro fertilization.

PURPOSE: Our purpose was to examine the effect of platelet activating factor (PAF) in different phases of mouse in vitro fertilization and optimal parameters that would enhance the fertilization rate. DESIGN AND SETTINGS: Various PAF concentrations (10(-7) to 10(-5) M) were selected to investigate its effect on three phases of mouse in vitro fertilization (i.e., sperm capacitation, sperm/oocyte coincubation, and preimplantation embryo growth) in three experimental groups: (I) with PAF treatment in the first phase, (II) with PAF treatment adopted in the first and second phases, and (III) with PAF treatment implemented in all three phases. RESULTS: The improvement of the fertilization rate in PAF treatment groups over the control group ranges from 6.5 to 19.0% (P < 0.05-P < 0.001). The highest enhancement of fertilization rate was achieved under the condition of PAF treatment (10(-6) M) through sperm capacitation and sperm/oocyte coincubation phases. CONCLUSION: The PAF concentration of 10(-6) M in sperm capacitation and sperm/oocyte coincubation yielded the greatest improvement in fertilization. However, continuing PAF treatment after sperm/oocyte coincubation had no beneficial effect on fertilization and preimplantation development.

Animals↗
PubMed1992

[Judgement of prognosis in multiple trauma of patients with blunt abdominal injuries based on different useful trauma scores].

The use of trauma indices for characterisation of polytraumatized patients concerning prognoses is being discussed for nearly 30 years. In the seventies a couple of trauma indices were developed. Some of them are in use all over the world. In the Department for Trauma surgery in the General Hospital of Salzburg three of the common trauma scores were analysed and compared with one another: Injury Severity Score (Baker), Polytraumascore of the University Clinic of Hannover, Trauma index (Schreinlechner and Eber). As a rule most studies presently published are based on the Injury Severity Score. In a retrospective analysis of 62 polytraumatized patients we could show that the Trauma index of Schreinlechner and Eber is more practicable for classification of polytrauma because it shows a good correlation of score, fatality and prognoses.

Abdominal Injuries↗
PubMed1992

Adverse reactions to synthetic food colours: interactions between tartrazine and muscarinic acetylcholine receptors in isolated guinea-pig ileum.

The ability of selected food colours to interact with isolated guinea-pig ileum was investigated using a gut bath system. Studies revealed that guinea-pig ileum was specifically sensitive to tartrazine. Intestinal contraction occurred dose-dependently down to a minimum effective dose of 10 microM. All other colours examined proved negative. Studies investigating the biological activity of structural analogues of tartrazine revealed the ability to initiate intestinal contraction was associated with the presence of the carboxylic acid residue at the R1 position of the pyrazole ring. Blocking studies showed that tartrazine contraction was inhibited by atropine alone but not by any other blocking agent tested, implying that tartrazine acts either directly or indirectly upon the muscarinic acetylcholine receptor associated with parasympathetic innervation.

Animals↗
PubMed1992

Female fertility following extracorporeal shock wave lithotripsy of distal ureteral calculi.

This study was prompted by a spontaneous abortion in a 21-year-old woman following extracorporeal shock wave lithotripsy (ESWL ) of a distal ureteral calculus. To our knowledge, it is the first clinical retrospective study on the possible adverse effects of ESWL to the female reproductive tract. We analyzed treatment data and radiation exposure of 84 women in the reproductive period, and surveyed the patients by questionnaire, to which 67 (79.8%) responded. After ESWL 57 women (85.1%) practiced some form of contraception, while 10 childless women attempted to become pregnant. Overall 7 children with no malformations or chromosomal anomalies were born to 6 patients. Miscarriages were noted in 3 patients (4.5%) but they occurred at least 1 year after ESWL. Our data suggest that ESWL of lower ureteral calculi is a safe and effective procedure, and does not affect female fertility or lead to increased teratogenic risk.

Abortion, Spontaneous↗
PubMed1992

Experimental 6 log10 white cell-reduction filters for red cells.

White cell (WBC) reduction of blood components has been receiving increased attention as a way of reducing transfusion-related complications such as WBC-associated HLA alloimmunization and transmission of cell-associated viral diseases. Currently available filters are limited to removing approximately 3 log10 (99.9%) of WBCs from red cells (RBCs). The performance of two experimental filters that were designed to remove 6 log10 WBCs from fresh RBCs during component preparation was evaluated. Both filters were able to meet this objective in less than 40 minutes with RBC losses of less than 15 percent under nonoptimized conditions. Filtered RBCs showed storage parameters within the normal range over a 42-day period. The use of these filters, if combined with a sterile docking device or if incorporated into a collection set, should provide the means to supply highly WBC-reduced RBCs with a normal shelf life.

Blood Specimen Collection↗
PubMed1992

The selective use of AMSA following high-dose cytarabine in patients with acute myeloid leukaemia in relapse: a Leukemia Intergroup study.

This clinical trial was designed to evaluate the role of high-dose cytarabine (ara-C) in the treatment of adults with acute myeloid leukaemia (AML) in first relapse. We also tested the hypothesis that the selective use of AMSA (100 mg/m2/d on days 7, 8 and 9) would increase the complete remission (CR) rate when leukaemia cells remained in the bone marrow immediately following 6 d of Ara-C (2-3 g/m2/12 h) alone. Of 155 patients evaluable for response, 115 (74%) experienced marked cytoreduction by day 6 and received no further induction chemotherapy; 53 (45%) of these patients achieved CR after one course and 45 (38%) had resistant disease. The 36 patients (23%) with inadequate cytoreduction after the 6 d of ara-C alone were randomly assigned either to no further chemotherapy (21 patients) or to 3 d of AMSA (15 patients). The CR rates after one course were 14% and 53%, respectively (P = 0.01), and the fractions with resistant disease were 76% and 40%, respectively. The fractional reduction of leukaemia cells in the day 6 bone marrow aspirate specimen (P < 0.0001) and the reduction in the leukaemia cell mass measured in the day 6 marrow biopsy (P = 0.001) were the strongest predictors for achieving CR versus having residual disease in univariate analyses. The median duration of remission was 5 months, but seven patients (10%) remain in CR after 30-92 + months. Among the 140 patients who received only the 6 d of ara-C, the pretreatment albumin (P = 0.002) and lactate dehydrogenase (P = 0.01) levels were the strongest predictors of response in univariate analyses, but only the albumin remained significant (P = 0.01) in a stepwise logistic regression analysis. Those patients with albumin > 4.0 mg/dl and LDH < 125% of normal had a 71% CR rate, and only 16% had resistant disease. Thus, pretreatment characteristics and rapid cytoreductin in the day 6 bone marrow sample identified a favourable subset of patients with AML in first relapse, some of whom responded quite well to 6 d of ara-C alone and have had long disease-free remissions.

Acute Disease↗
PubMed1992

Secretory and accessory cell functions of the alveolar macrophage.

We have attempted to address the requirements necessary for alveolar macrophage accessory cell function. We have also examined the in vitro and in vivo factors that must be taken into account when interpreting results from experimental studies. Differences in phenotypic expression by rat alveolar pleural and peritoneal macrophages are noted, as well as the differing expression of major histocompatibility complex (MHC) class II molecules. Furthermore, alveolar macrophages, harvested from rat lung, do not express the interleukin (IL)-1 cytokines, and lipopolysaccharide (LPS) treatment of quiescent cells (after 24-hr in vitro culture) induces low levels of expression of IL-1 alpha and IL-1 beta. Short-term inhalation of refractory ceramic fibers, however, results in markedly increased IL-1 beta expression after stimulation with LPS. We suggest that, in vivo, IL-1 beta may be involved in the initial recruitment and activation of inflammatory cells rather than in induction of immune responses. We also postulate, based on recent published evidence, that alveolar macrophages activate the dendritic cells within the respiratory epithelium. Thus alveolar macrophages would release cytokines critical for the activation of dendritic cells during the afferent limb of the immune response, and they would respond to products of sensitized T-cells such as interferon-gamma and IL-4 to interact with T-helper cells in an antigen-specific MHC-restricted manner during the efferent limb of the response.

Animals↗
PubMed1992

Drug therapy for nocturnal enuresis. Current treatment recommendations.

It is estimated that enuresis occurs in 5 to 7 million children in the United States. The treatment approach for enuresis is controversial, in large part due to a lack of consensus as to the exact cause of enuresis. Several factors either alone or together may contribute to this syndrome. In addition, there is strong evidence of a genetic component to enuresis. Pharmacotherapy continues to be the preferred treatment for both physicians and families. The most widely used drugs include antidepressants, anticholinergics, and desmopressin. The tricyclic antidepressant imipramine has been used extensively since the 1960s. The exact mechanism of action in enuresis is unknown although it appears to be related to the anticholinergic and antispasmodic effects of the drug. The most common adverse effects reported with imipramine include personality changes, insomnia, anorexia and anxiety. There has been renewed interest in antidiuretic treatment of enuresis. Researchers have found that enuretic children do not have the ability to reduce urine volume at night or concentrate the urine they produce during the night. Clinical trials with desmopressin administered by nasal inhalation report a marked reduction in enuretic episodes. Adverse effects were limited to nasal complaints, rhinitis, or epistaxis. Additional long term studies are needed to delineate desmopressin's role in therapy. Although the number of options for treatment of enuresis is expanding, criteria to predict patient response need to be defined.

Adolescent↗
PubMed1992

[Itching following therapy with hydroxyethyl starch (HES) in otoneurological diseases].

It is generally assumed, that a disturbance of microcirculation is the common pathogenetic end factor in various cochleovestibular disorders of different etiology. Therefore improvement of microcirculation is an important therapeutic goal. Several studies demonstrated, that hydroxyethylstarch (HES) has better haemorheological effects than Dextran and less side effects. For this reason we have changed the therapy with Dextran since 1987 to hydroxyethylstarch in several oto-neurological disorders (as sudden hearing loss, neuronopathia vestibularis, idiopathic facial palsy). As after the therapy with HES--generally after dismissal from the ENT-department--some patients complained of general pruritus, so we performed a retrospective study with a standardized interview-protocol. Of 481 treated patients we investigated 237 (49%): of 149 patients treated with HES 200/0.5, 43 patients (28.8%) complained of pruritus; from 88 patients treated with Dextran 40, only 5 patients (5.7%) reported pruritus. The difference is significant (p less than 0.0001). In nearly half of the patients (more than 40%) the pruritus started in normal skin 1 to 3 weeks after the HES-therapy and lasted for 6 weeks to 6 months; the itching was very resistant to therapy (f.e. with antihistaminics). We want to draw the attention to this possible, in the literature until now quite neglected, for some patients extremely uncomfortable and socially embarrassing side effects after HES-therapy when given in relatively high doses. It is therefore suggested therapeutic recommendations should be developed to prevent this undesired side effect.

Cochlear Diseases↗
PubMed1992

[Ileal neobladder].

Since April 1986, 227 patients received an ileal neobladder at our institution. Of these patients 206 underwent simultaneous radical cystectomy for bladder cancer, and 21 received a bladder augmentation. The mean postoperative follow-up ranges from 3-71 months. Perioperative mortality was 2.55 percent, 15 percent of the patients died later than 2 months postoperatively, 13.4 percent due to tumor progression, 1.5 percent because of pneumonia, severe metabolic acidosis, myocardial infarction and apoplexia. Day and night continence was preserved in 77 percent of the patients with a follow-up of more than 2 years; severe stress incontinence was found in 2 patients, and night time incontinence needing some external device in 4.6 percent. 11.5 percent with mild stress incontinence do not require further treatment. Our experience with this relatively simple procedure is excellent: the need for re-operation is low and the high reservoir capacity results in early continence in most cases. This concept offers a genuine alternative to any form of cutaneous urinary diversion with an incidence of complications not higher than after standard supravesical urinary diversion.

Adult↗
PubMed1992

An immunohistochemical study of mesothelial cell seeding for knitted Dacron.

Six greyhounds underwent bilateral femoral artery replacement with knitted Dacron, one side seeded with omental digest at graft preclotting, the other acting as an unseeded control. Grafts were removed at 24 hours and two months. Tissue was examined using a monoclonal antibody (MNF116) directed against a broad range of human cytokeratins to differentiate mesothelial cells (MC) from microvascular endothelial cells (MEC), which stained only with a polyclonal antibody directed against von Willebrand Factor (anti-vWF). Cells released from omentum by collagenase stained with MNF116 and reacted poorly with anti-vWF. Identical cells were observed to be within the interstices of seeded but not control knitted Dacron. Few remained in seeded grafts (n = 2) removed at 24 hours and none at two months (n = 4).

Animals↗