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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 469 records · Page 26Linked to original sources
PubMed1989

Receptor-mediated endocytosis and nuclear transport of human interleukin 1 alpha.

In this study we demonstrate that 125I-labelled interleukin (IL) 1 alpha binds specifically to its receptor on the surface of EL4 6.1 cells and is subsequently endocytosed and translocated from the cell membrane to the nucleus, where it progressively accumulates. Two-dimensional polyacrylamide-gel electrophoresis revealed that the internalized 125I-IL1 alpha associated with the nucleus was intact, with negligible breakdown products present. Specific and saturable binding of 125I-IL1 alpha was demonstrated on purified nuclei isolated from these cells. Binding of the radiolabelled ligand showed similar kinetics to that of the plasma-membrane receptor, and was inhibited by both unlabelled IL1 alpha and IL1 beta. Equilibrium binding studies on isolated nuclei revealed a single high-affinity binding site, with a Kd of 17 +/- 2 pM, and 79 +/- 12 binding sites per nucleus. These studies demonstrate that receptor-mediated endocytosis of IL1 results in its accumulation in the nucleus, and this mechanism may play an important role in mediating some of the actions of IL1.

Animals↗
PubMed1989

[Surgical urinary bladder replacement in cancer].

Radical cystectomy, where necessary combined with systemic chemotherapy, is currently regarded to be the treatment of choice in invasive bladder cancer. Compared with such procedures as colonic or ileal conduit the construction of a continent intestinal bladder substitution is not associated with any higher risks but offers a considerably better quality of life without significantly extending the duration of surgery. Our experience with the ileal-neobladder with non-reflux uretero-intestinal implantation described by LeDuc, and Kock's the thoroughgoing application principles to form a low pressure reservoir for bladder substitution, encouraged us to believe that a good long-term prognosis with respect to renal function can be expected. About 90% of all patients with ileal-neobladder are continent day and night. About half of them have sensory function and are capable of voiding urine completely by abdominal straining. For invasive bladder cancer, therefore, continent bladder substitution must be generally regarded to be the superior alternative to urinary diversion by conduit.

Colon, Sigmoid↗
PubMed1989

The t complex polypeptide 1 (TCP-1) is associated with the cytoplasmic aspect of Golgi membranes.

The t complex polypeptide 1 (TCP-1) is a protein of unknown function expressed in large amounts during spermatogenesis. Rat monoclonal antibodies recognizing TCP-1 have been prepared and used to immunoprecipitate and Western blot a 57 kd protein from germ cell and tissue culture cell extracts. In tissue culture cells, indirect immunofluorescent localization of antigen indicated a perinuclear distribution similar to that of the Golgi apparatus. Analysis of the TCP-1 distribution in tissue culture cells showed that the polypeptide was associated with the cytoplasmic aspect of membranes of the trans-Golgi network (TGN). The distribution in spermatids suggested that TCP-1 was localized to structures often associated with the developing acrosome. The TCP-1 antigenic epitopes are highly conserved, allowing the protein to be identified in cells across a wide variety of vertebrate species and tissues. These experiments suggest that TCP-1 may be essential for transport of proteins through the exocytic pathway in all cells and required in large amounts for acrosome formation in developing spermatids.

Acrosome↗
PubMed1989

Effects of reductions in hemoglobin-oxygen affinity and hematocrit level on oxygen consumption and acid-base state in fetal lambs.

To determine whether the high oxygen affinity of fetal blood, compared with that of the adult, is advantageous to the fetus during fetal anemia we studied 16 chronically catheterized fetal lambs. Half of the lambs had hemoglobin-oxygen affinity reduced acutely by isovolemic exchange transfusion with fresh adult whole blood; the other half served as controls. In both groups of fetuses, we measured fetal oxygen delivery, oxygen consumption, and acid-base state at normal fetal hematocrit levels and during reductions in the hematocrit level of 30% (moderate anemia) and 60% (severe anemia) produced by isovolemic exchange transfusions with plasma. At normal fetal hematocrit levels, reductions in hemoglobin-oxygen affinity had no effect on fetal oxygen consumption or acid-base state. During moderate anemia, fetal oxygen delivery decreased in both series of fetuses, but oxygen consumption and base excess fell only in those fetuses whose circulations contained adult hemoglobin. During severe anemia, oxygen consumption and base excess decreased in both groups of fetuses, although these changes were more pronounced in fetuses with adult hemoglobin than in those with fetal hemoglobin. Our data indicate that, even though a high hemoglobin-oxygen affinity may not be essential to a healthy fetus, it is critical for normal metabolism in a fetus subjected to a hypoxic stress such as anemia.

Acid-Base Equilibrium↗
PubMed1989

Effects of thromboxane synthetase inhibition on maternal-fetal homeostasis in gravid ewes with ovine pregnancy-induced hypertension.

Simultaneous maternal indirect blood pressure measurements, electronic fetal heart rate monitoring, and ultrasonographic biophysical profile testing were used to assess maternal-fetal homeostasis in gravid ewes during gestational days 127 to 134 (term 146), during a 72-hour fast, and during treatment with thromboxane synthetase inhibitors CGS13080 and CGS12970. Seventy-five percent of the ewes (12 of 16) developed clinical signs of ovine pregnancy-induced hypertension, including maternal hypertension and fetal depression. In three untreated hypertensive ewes, pregnancy was terminated by spontaneous premature delivery, and one maternal death occurred after an eclamptic seizure. All nine ewes treated with one of the two thromboxane synthetase inhibitors responded to therapy with decreases in blood pressure and resolution of fetal depression. These nine ewes completed gestation, and were delivered at term. These data indicate that therapy with thromboxane synthetase inhibitors in this animal model of preeclampsia results in profoundly beneficial effects and suggest that further studies of thromboxane synthetase inhibitors are warranted in preeclampsia.

Animals↗
PubMed1989

Cellular and molecular effects of di-n-octyltin dichloride on the rat thymus.

Experiments have been performed to characterise early changes in the proliferative capacity and phenotypic makeup of thymocytes obtained from DOTC-treated PVG rats. The analysis of density gradient-separated thymocytes demonstrated that within 72 h of oral dosing, spontaneous in vitro thymocyte proliferation was markedly suppressed. A concomitant depletion of an MRC OX18 positive thymocyte population was also observed. These events occurred prior to both overt thymic weight loss and characteristic, treatment-induced histopathological changes. Since recent evidences suggest that the growth factor interleukin-2 (IL-2) may play an important role in thymocyte proliferation, additional molecular biological studies were performed to evaluate whether DOTC may exert its anti-proliferative effects by compromising IL-2 production. Using a mRNA cytoplasmic dot blot technique, the examination of thymocyte lysates from treated and control animals revealed that DOTC markedly down regulated and at high doses abolished, the normal expression of the IL-2 gene. The high turnover gene alpha-actin was, however, unaffected by its action, thus demonstrating the selective effects of DOTC.

Animals↗
PubMed1989

VAT-1: an abundant membrane protein from Torpedo cholinergic synaptic vesicles.

Expression screening was used to isolate cDNA clones encoding a synaptic vesicle membrane protein, VAT-1, which is specifically expressed in the electric lobe of marine rays. The predicted protein has a molecular weight of 41,572 daltons and contains several hydrophobic regions. An antibody raised against a fusion protein synthesized in E. coli recognizes an abundant 42 kd protein that copurifies largely with synaptic vesicles. Trypsin digestion of intact and lysed vesicles as well as membrane extractions suggests that VAT-1 is an integral membrane protein. The VAT-1 RNA is localized to the electromotor nucleus, and the fusion protein antibody stains the electric organ, demonstrating that the protein is transported to nerve terminals. These studies define a novel synaptic vesicle protein that is likely to play a central role in the functions mediated by specific classes of synaptic vesicles.

Acetylcholine↗
PubMed1989

What's new in urology?

Urology has undergone remarkable growth and a variety of clinical substantial therapeutic concepts have changed within the last few years. The following short summary incorporates the most actual advances in basic science and clinical medicine as well as surgical technique. Spectacular new concepts have been developed according to therapy of bladder substitution using bowel. Therapy of stone formation in the urinary tract is possible by using extracorporal shockwave therapy in more than 2/3 of the patients. Additionally, promising aspects in the treatment of hypernephroma with immune response modifiers are actually of great interest. The evaluation of prostatic specific antigen (PSA) as a specific marker in prostatic carcinoma and the conflict between indication for lymphadenectomy or surveillance therapy in testicular cancer stage I, as well as tumor regression under chemotherapy influences clinical trials (e.g. surgical debulking). The brief review of diagnostic and therapeutic approaches including some aspects of andrology hopefully may help to understand clinical problems and demonstrate the effectiveness of standard urologic diagnosis and therapy.

Humans↗
PubMed1989

Studies of the mechanism of tolerance induced by short-term immunosuppression with cyclosporine in high-risk corneal allograft recipients. I. Analysis of CTL precursor frequencies.

Transplantation of unmatched allogeneic corneas into highly vascularized recipient eyes under the cover of short-term immunosuppression with cyclosporine enables permanent engraftment. The aim of this study was to further elucidate the mechanism(s) underlying this tolerant state. In eight "high-risk" cornea recipients the clone sizes of donor-specific and third-party reactive cytotoxic T cell precursors were assessed by limiting dilution analyses before and at three and six months after transplantation. Acquired allograft tolerance in these patients was not accompanied by clonal reduction of donor-specific CTL-p, whereas in the case of an irreversible rejection the donor-specific CTL pool size was significantly enlarged. This donor-specific CTL-p increase could already be seen two months before clinical manifestation. These patterns differed from that of tolerant renal transplant patients, in whom marked and donor-specific reduction of CTL-p was observed. During rejection identical patterns with increasing donor-specific CTL-p frequencies were seen in both groups of patients. We conclude that induction of tolerance by short-term CsA to unmatched cornea grafts is not caused by clonal reduction of the effector precursor cell pool.

Adult↗
PubMed1989

[Role of extracorporeal shockwave lithotripsy without anesthesia in the treatment of ureteral calculi].

With anesthesia-free lithotripsy recently being available, the discussion upon the treatment of choice of ureteral calculi has been renewed: is a preliminary retrograde manipulation still preferable for proximal calculi? Is ureteroscopy the better treatment for stones in the lower ureter? The retrospective evaluation of our patients with ureteral calculi (January-August 1988) failed to reveal a significantly compromised efficiency with the modified HM-3 lithotripter (40 nF. generator, 17 cm. ellipsoid): 70% (including 11% with repeated sessions) of the patients with proximal stones and 90% (including 28% with repeated sessions) of the patients with distal calculi were successfully treated in situ without the need for anesthesia, auxiliary measures, or ureteroscopy. These results do not substantially differ from those obtained with the old HM-3 in 1987, and confirm, that the majority of patients with ureteral calculi can bypass the discomfort of retrograde manipulation or the risks of ureteroscopy.

Anesthesia↗
PubMed1989

Paracentric inversion 11.

A new familial case of paracentric inversion of chromosome 11 inv(11)(q21q23.3) ascertained by multiple abortions in a female carrier is presented. A review of the literature shows 19 further cases of paracentric inversion 11. According to the different breakpoints, the inversions of the long arm of chromosome 11 may be classified into three types.

Abortion, Habitual↗
PubMed1989

Converting nursing care cost to revenue.

The authors describe the process that bridges the gap between concept and reality by developing a successful system of charging for nursing services. By determining the cost of nursing services and extracting the nursing charge from the traditional room rate, nursing units are converted to revenue producers, with the ability to negotiate for managed care contracts, justify budgets and staffing, equate nursing with other revenue producing centers, and eliminate opinion about perceptions of the cost of nursing services.

Costs and Cost Analysis↗
PubMed1989

[Current therapy of ureteral calculus].

Since lithotripsy requiring no anesthesia recently became available, the discussion revolving around the treatment of choice for ureteral calculi has been renewed: is a preliminary retrograde manipulation still preferable for proximal calculi? Is ureteroscopy the better treatment for stones in the lower ureter? The retrospective evaluation of our patients with ureteral calculi (January to August 1988) failed to reveal a compromised efficiency with the modified HM3 Lithotripter (40 nF generator, 17 cm ellipsoid): 70% (including 11% with repeated sessions) of patients with proximal stones and 90% (including 28% with repeated sessions) of patients with distal calculi were successfully treated by in situ ESWL with no need for anesthesia, auxiliary measures, or ureteroscopy. These results do not significantly differ from those obtained with the old HM3, and they confirm that the majority of patients with ureteral calculi can bypass the discomfort of retrograde manipulation and the risks of ureteroscopy.

Combined Modality Therapy↗
PubMed1989

[3 years' experience with the ileum neobladder--the first 108 patients].

Between April 1986 and April 1989, each of 108 patients received an ileum neobladder, 94 patients for total bladder substitution after radical cysto-prostatectomy and 14 for augmentation of a fibrotic and contracted bladder following tuberculosis, interstitial cystitis or radiotherapy of the pelvis. The operative technique is standardized, relatively simple and safe, and it prevents upper urinary tract deterioration and reflux. Continence is preserved in more than 80% of all patients by the function of the external urethral sphincter and by the high capacity and the low internal pressure of the intestinal reservoir. Follow-up of more than 3 months postoperatively was possible in 96 patients, the evaluation including micturition behavior at home and a urodynamic investigation. Stress incontinence requiring correction by an artificial sphincter was found in 3 and nocturnal incontinence necessitating some external device in 6 patients. There was no perioperative mortality. Local tumor recurrence and/or metastases occurred in 14 patients; 7 patients died postoperatively, 5 owing to tumor progression, 1 of pneumonia and serve metabolic acidosis, and 1 owing to septicemia of unknown cause. Re-operation was necessary in 13 patients, in 6 because of mechanical ileus or intra-abdominal abscess, in 3 because of stenosis of the uretero-ileal anastomosis, in 1 because of tumor progression, in 1 because of vesico-vaginal fistula, in 1 patient because of incisional hernia, and in 1 because of wound dehiscence. Urethrotomy or dilatation of urethral strictures was necessary in 8 patients. All other early and late complications were rare and could be managed by conservative means.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗