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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 415 records · Page 23Linked to original sources

The skin: an immunoreactive target organ during interleukin-2 administration?

Six patients with metastatic malignant melanoma were treated systemically with dacarbazine and interleukin-2 (IL-2). During IL-2 administration all patients developed a macular erythematous rash followed by scaling which began 24-48 h after IL-2 infusion. The dermatological changes were associated with elevated interferon-gamma and tumor necrosis factor alpha serum levels (immunoradiometric assay). Histology revealed nonspecific spongiotic foci in the epidermis and a perivascular mononuclear infiltrate in the dermis. Immunohistochemistry characterized this infiltrate mainly as activated T helper lymphocytes and revealed the expression of intercellular adhesion molecule 1 by endothelial cells and keratinocytes that might have been induced by interferon-gamma. The skin reactions associated with systemic IL-2 administration, show that the skin actually participates as a target organ. They should be differentiated from drug eruptions.

Biopsy↗

Functional, augmented rectal bladder: early clinical experience.

From August 1988 until March 1990, 10 female patients received an augmented, functional rectal bladder according to the technique first described by Kock. Indications were radical cystectomy in 8 and undiversion from a previously wet stoma in 2 patients. There was no perioperative mortality. Postoperative complications were: one obstructive pyelonephritis (treated with a temporary nephrostomy); one obstruction at the ileal intussusception (operative revision), and one slipping at the sigma nippel (no treatment). Intravenous pyelographies taken 2-3 months postoperatively, showed 13 normal and 5 slightly dilated renal units. All patients are completely continent by day, 7 are continent at night, 2 wear sanitary pads during the night due to occasional spotting. The preliminary experience with this new technique is encouraging and warrants further clinical application in patients in whom the external urethral sphincter is not available as continence organ.

Aged↗

[Intra- and postoperative morbidity of radical prostatectomy].

Operation-related morbidity was analyzed in 147 patients, who had undergone radical prostatectomy during the last 3 years. Six major complications (4.1%) had occurred requiring surgical revision. One single postoperative death (0.7%) was caused by a pulmonary embolus. In 51 patients (34.7%) minor complications were noted. Urinary incontinence was severe in 4 patients (3.9%), which was treated by an artificial sphincter in one man during the follow-up period. Twelve patients (11.8%) complained of stress incontinence, grade I-II. Postoperative determinations of serum PSA were below the detectable range in 81% of the patients, including those with a locally advanced tumor stage and adjuvant antiandrogen therapy. Based on our data, it is concluded that radical prostatectomy is today a safe and standardized operative procedure.

Aged↗

[The functional, augmented rectal bladder. Initial clinical experience with 10 patients].

From August 1988 until March 1990, 10 female patients received an augmented, functional rectal bladder, according to the technique first described by Kock. Indications were a radical cystectomy in 8 and a rediversion from a previously wet stoma in 2 patients. There was no perioperative mortality. Postoperative complications were obstructive pyelonephritis (1 case, treated with a temporary nephrostomy), obstruction at the ileal intussusception (1 case; operative revision) and slipping at the sigmoid nipple (1; no treatment). Intravenous pyelography 2-3 months postoperatively showed 13 normal and 5 slightly dilated renal units. All patients are completely continent by day, 7 are continent by night, 2 wear sanitary pads during sleep due to occasional spotting. Preliminary experience with this new technique is encouraging and warrants further clinical application in patients in whom the external urethral sphincter is not available to provide the continence mechanism.

Aged↗

[Experience with ultrasound-guided ESWL].

The ESWL treatment of gallstones has led to the development of ultrasound-guided lithotripters. The interdisciplinary use of these new ESWL systems by urologists, general surgeons and gastroenterologists means that different requirements have to be met. As a result of this development, ultrasound in urology is gaining even more significance. While ESWL treatment of renal calculi under ultrasound guidance has quickly become a routine method, the in situ treatment of ureteral calculi is much more problematic. In our study the validity of diagnostic ultrasound for the localization of ureteral stones was investigated. In an unselected preliminary series only 30% of ureteral calculi could be located by ultrasound. The success rates were 39% for distal stones and 16% for proximal calculi. The treatment results of renal calculi are on a par with those previously obtained under fluoroscopic guidance. Once exact localization is obtained by ultrasound, disintegration rates for ureteral calculi are fully comparable to those performed under fluoroscopic guidance. However, 60% of ureteral stones can not be located by ultrasound. Therefore, retrograde manipulation and ureteroscopic stone disintegration gains more importance in interdisciplinary shock wave centers equipped with ultrasound-guided machines. A real alternative to second-generation lithotripters in the treatment of ureteral stones will thus only be obtained if an X-ray device can be added to the locating system if necessary. With this combination device the treatment of most ureteral calculi will thus be possible.

Endoscopes↗

The ileal neobladder. Operative technique and results.

Bladder substitution by continent bowel reservoirs has been one of the real advancements in modern urology. Short-term experience with and patients' acceptance of the ileal neobladder have been excellent. As do others, we consider this technique to date the procedure of choice in male patients requiring radical cystectomy.

Adult↗

Identification of a serum protein polymorphism via two-dimensional electrophoresis. Family and population studies in two genetically isolated groups: North American Hutterites and Australian aborigines.

We report the identification and initial family and population studies of a previously undescribed serum protein polymorphism with two allelic forms. It was discovered in Hutterites, a reproductively isolated religious sect, and is also present in Australian aborigines and a sample of Chicago residents. A two-allele model is consistent with the segregation pattern observed in five kindreds within our initial study group. This polymorphism, provisionally designated SPPM-158, appears as a horizontal (charge-based) doublet in silver-stained ISO-DALT high-resolution two-dimensional electrophoresis gels. It is a low-concentration polypeptide (approximately 1 mg/dL) that has an apparent MWSDS of 43.6 kD and an isoelectric point of approximately 5.5. We infer that it circulates as a multimer or in a high-molecular-weight (greater than 200 kD) complex with other proteins because it is not observed in normal body fluids derived from physiologically ultrafiltered plasma such as amniotic fluid, urine, or cerebrospinal fluid; however, it is present in urine of patients with glomerular proteinuria. The high heterozygosity rates imply utility of this new serum protein marker for both forensic and population studies.

Australia↗

Halogenated inhalation anesthetic agents decrease transepithelial electrical measurements across the isolated iris-ciliary body.

Transmembrane electrical measurements were performed on the isolated rabbit iris-ciliary body (I-CB) to study the direct effects of halogenated inhalation anesthetic agents on the ciliary epithelium. Addition of either halothane, enflurane, or isoflurane to the control 95% O2:5% CO2 gas mixture resulted in a dose-dependent decrease in the short-circuit current (SCC) and potential difference (PD). This response was reversible after the anesthetic gas was discontinued. Pretreatment with either alpha-adrenergic or beta-adrenergic antagonists (phentolamine or timolol) had no effect on the halothane-induced decrease in SCC. Delivery of the analgestic gas N2O did not alter baseline electrical measurements across the isolated I-CB.

Analysis of Variance↗

[Local treatment of disseminated granuloma anulare with a vitamin E emulsion].

The treatment of granuloma annulare is still unsatisfactory. A number of topical and systemic therapies have been tried, some of which can improve the condition, but serious side effects are possible with those reported so far. We treated a patient with disseminated granuloma annulare by local application of a vitamin E emulsion and achieved a marked improvement within as little as 12 days.

Administration, Oral↗

[Complex cyanotic heart defect in a newborn infant with cat eye syndrome].

In a cyanotic newborn with characteristic features of Cat-Eye-Syndrome, cytogenetic examination disclosed a supernumerary small bisatellited chromosome. Angiography showed Tetralogy of Fallot with pulmonary atresia and a narrow patent ductus arteriosus with additional stenosis of the bifurcation of the pulmonary artery. At an age of 14 weeks, the patient died after the attempt of corrective cardiac surgery. Congenital cardiac malformation is present in more than one third of patients with cat-eye-syndrome and is usually the lifelimiting malformation in this syndrome.

Abnormalities, Multiple↗

Interactions of methylmercury with rat primary astrocyte cultures: inhibition of rubidium and glutamate uptake and induction of swelling.

The ability of astrocytes to sequester MeHg may indicate an astrocyte-mediated role in MeHg's neurotoxicity. Hence, studies were undertaken to assess the effects of MeHg on metabolic functions in cultured astrocytes. MeHg (10(-5) M) significantly inhibited the initial rate (5 min) of uptake of 86RbCl, used as a tracer for K+. 86RbCl uptake was also sensitive to the omission of medium Na+. MeHg (10(-5) M) also markedly inhibited the initial rate of uptake (1 min) of the Na(+)-dependent uptake of [3H]L-glutamate. A second neurotoxin, MnCl2 (0-5 x 10(-4) M), did not alter [3H]glutamate or 86RbCl uptake. MeHg, but not MnCl2, also stimulated the release of intracellular 86Rb+ in a dose-dependent fashion. This effect could be prevented by the administration of MeHg as the glutathione conjugate. These observations support the hypothesis that the astrocyte plasma membrane is an important target for MeHg's toxic effect and specifically that small concentrations of this organometal inhibit the ability of astrocytes to maintain a transmembrane K+ gradient. This would be expected to compromise the ability of astrocytes to control extracellular K+ either by spatial buffering or active uptake, resulting in cellular swelling. We therefore studied volume changes in astrocytes using uptake of [14C]3-O-methyl-D-glucose, in attached cells in response to exposure to MeHg. Exposure to MeHg (0-5 x 10(-4) M) caused a marked increase in the cell volume that was proportional to concentrations of MeHg.

3-O-Methylglucose↗

Movement of internalized ligand-receptor complexes along a continuous endosomal reticulum.

Complexes of cell-surface receptors and their ligands are commonly internalized by endocytosis and enter a prelysosomal endosomal pathway for further processing. Fluorescence microscopy and video recording of living cells to trace the passage of ligand-receptor complexes has identified the endosomal compartment as an extensive network of tubular cisternae. Endocytosed material entering this reticulum enters discrete swellings, identified as multivesicular bodies by electron microscopy, which move along the reticulum towards the pericentriolar area.

Biological Transport↗

Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body.

We compared the internalization and intracellular sorting of epidermal growth factor receptor (EGF-R) and point mutant kinase-negative EGF-R separately expressed in NIH 3T3 cells lacking endogenous receptor. Both EGF-Rs internalized rapidly, but kinase-negative receptor was surface down-regulated only with monensin or at 20 degrees C. Furthermore, EGF internalized by mutant receptor alone was, in significant proportion, returned to the cell surface undegraded. Hence unlike wild-type receptor, kinase-negative EGF-R recycles. By electron microscopy the early pathways of endocytosis for the two receptors were identical; however, after 10-20 min the pathways diverged at the multivesicular body (MVB). Wild-type EGF-R, destined for degradation, localized to internal vesicles, while kinase-negative EGF-R, destined for recycling, localized to surface membranes of the MVBs and moved to small tubulovesicles. We conclude that sorting of internalized receptor for degradation or recycling can occur through spatial segregation within the MVB, and sorting of EGF-R is controlled by tyrosine kinase activity.

Animals↗

Hydrocortisone induction during oligodendroglial differentiation.

Steroid hormones are important for the normal development of brain. The addition of hydrocortisone to oligodendroglia in culture increases the level of mRNA for proteolipid protein, increases the synthesis of cerebrosides, and provides an induction of activities for the ketone body metabolizing enzymes. While proteolipid protein and cerebrosides are major components of myelin membranes, ketone bodies serve as precursors for lipid synthesis during development. Thus, hydrocortisone is important during the differentiation of oligodendroglia and during initial myelin production.

Animals↗

Tissue limited mosaicism in a patient with tetrasomy 9p.

Cytogenetic analysis of an abnormal newborn girl showed an extra chromosome with the characteristics of an isodicentric 9p chromosome [idic (9)(pter----q12----pter)] in 98% of peripheral lymphocyte metaphases examined. This cytogenetic interpretation was substantiated by quantitative measurement of erythrocyte galactose-1-P-uridyltransferase (GALT) activity, which is consistent with the expression of 4 normal GALT genes. Cytogenetic results from skin fibroblasts showed mosaicism with only 11% of the metaphases having the extra chromosome. Selective genetic pressure based on a functional disadvantage of tetrasomy 9p in the skin is proposed. The in vivo establishment of cytogenetically normal cells in various tissues may be necessary for in utero survival of tetrasomy 9p infants.

Abnormalities, Multiple↗

Discordant findings in chorionic villus direct preparation and long term culture--mosaicism in the fetus.

Prenatal cytogenetic study of chorionic villi showed a discrepancy between a normal female karyotype 46,XX in the direct preparation after short-term incubation, and a 45,X karyotype in the long-term culture. The subsequent amniocentesis revealed a normal karyotype in three cultures and a 45,X/46,XX mosaicism in one culture. Cytogenetic analysis of chorionic villi after termination of the pregnancy showed a normal karyotype in the direct preparation and a 45,X/46,XX mosaicism in the long-term culture. Fetal lymphocytes showed normal karyotypes, whereas fibroblast cultures revealed a 45,X/46,XX mosaicism.

Chorionic Villi Sampling↗