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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 433 records · Page 24Linked to original sources

Mitotic disturbance associated with mosaic aneuploidies.

The association of various unsystematic aneuploidies with premature centromere division (PCD) was observed in a patient with conspicuous clinical features and combined immunodeficiency. Trisomies and monosomies of almost all autosomes and gonosomal aberrations were found separately or in combination in a majority of the proband's lymphocytes and fibroblasts. The chromosome number varied from 44 to 50. A high proportion of the metaphases showed PCD or had the appearance of C-anaphases. These findings probably represent a new mutant affecting mitosis and causing mosaic aneuploidies.

Aneuploidy↗

Clinicopathological findings 11 months after implantation of a functioning aqueous-drainage silicone implant.

An aqueous-drainage silicone device was implanted in a 57-year-old diabetic patient with neovascular glaucoma after failure of conventional therapy. Postoperative intraocular pressure (IOP) was well controlled, ranging between 10 and 20 mm Hg without the use of supplemental agents. Despite the normal IOP, the eye became painful and amaurotic 11 months after implantation due to progression of the retinopathy accompanied by the development of severe tractional retinal detachment. Enucleation was performed and the eye underwent histopathological examination. The filtering bleb around the silicone plate of the implant on the equatorial sclera was lined with a thick layer of collagenous connective tissue. Numerous microcystic spaces could be seen in the bleb wall by light microscopy. Electron microscopy confirmed this finding; in addition, only a meshwork of collagen fibre-like bundles was visible at some areas of the innermost bleb wall. Control of IOP in spite of bleb fibrosis in this particular case may have been due to a loss of matrix components and to the formation of microcystic spaces in the bleb wall, which seem likely to be channels for the passage of aqueous humor.

Anterior Eye Segment↗

Induction of cerebroside synthesis in oligodendroglia.

Oligodendroglia function to produce myelin membranes which surround axons, enhancing saltatory conduction. Myelin consists of a multitude of condensed membranes which are rich in lipids with the major glycolipids, cerebrosides, being 25% of the total lipid. Thus a fully differentiated oligodendroglial cell that is producing myelin membranes would be actively synthesizing cerebrosides. Our laboratory has prepared and analyzed oligodendroglia from mature bovine brain, from neonatal rat brain, and from actively myelinating rat brain. Our studies suggest that the rat oligodendroglia in our culture systems are less differentiated than bovine cells in that they produce lower levels of cerebrosides. Addition of glucocorticoids, thyroid hormone, or retinoic acid all increased synthesis of cerebrosides in rat oligodendroglia. Ketone bodies were also somewhat stimulatory. Having no effect or causing dedifferentiation of the cells were 5-azacytidine and phorbol esters. Thus induction of cerebroside synthesis in oligodendroglia is complex and may involve many factors.

Animals↗

Quantitative, standardized assays for determining the concentrations of bovine lactoperoxidase, human salivary peroxidase, and human myeloperoxidase.

Because of the important biological functions of peroxidases, there is growing interest in the measurement of their concentrations in various secretions. At present, there is no standard method which allows for comparisons in reported activities. This report describes procedures which can be used to measure peroxidase enzyme concentrations by commonly employed assays. Regression equations have been determined which can be used to calculate concentrations of bovine lactoperoxidase (LPO), human salivary peroxidase (SPO), and human myeloperoxidase (MPO) from activities measured with the following donors: pyrogallol, guaiacol, 2,2'-azinobis(3-ethylbenzylthiazoline-6-sulfonic acid), and thiocyanate (SCN-). The peroxidation rates of these donors depend upon the concentrations of hydrogen peroxide (H2O2) used in the individual assays and thus, for accurate, reproducible results, these concentrations must be carefully controlled. The SCN- normally present in human saliva will reduce observed reaction rates by simple competition kinetics in the ABTS, guaiacol and pyrogallol assays and will increase the rates observed when Cl- is used as a donor in NBS assay for MPO. Therefore, SCN- must be removed from saliva samples prior to peroxidase activity determination by all assays except the thionitrobenzoic acid (NBS) assay. LPO cannot be used as a standard for either SPO or MPO because the specific activities of LPO, SPO, and MPO are significantly different.

Animals↗

Onchocerca volvulus: biochemical and morphological characteristics of the surface of third- and fourth-stage larvae.

The annulated cuticles of third- and fourth-stage larvae of Onchocerca volvulus have the typical structure of other nematodes but the cuticle of fourth-stage larvae was thinner. The surface of the third-stage larva was wrinkled and fuzzy, while that of the fourth-stage was smooth. Intermediate stages in the formation of the new cuticle and epicuticle beneath the old basal layer and of the separation of the cuticles are shown. Monoclonal antibodies specific to the surface of third-stage larvae did not react with the surface of the fourth-stage larvae. Binding of the monoclonal antibodies to the third-stage larvae was abrogated by treatment of the worms with trypsin and proteinase K, but was unaffected by treatment with periodate or the detergents sodium deoxycholate and SDS. The lectins RCA120 and WGA, but not any of the other lectins tested, bound only to the surface of fourth-stage larvae, and not to that of third-stage larvae. The surfaces of third- and fourth-stage larvae were shown to be different and contained stage-specific surface epitopes.

Animals↗

The effect of Biostim (RU-41740) on the expression of cytokine mRNAs in murine peritoneal macrophages in vitro.

The immunomodulatory agent Biostim (RU-41740) was investigated for its ability to induce the expression of cytokine mRNAs in murine peritoneal macrophages in vitro. Northern blot analysis showed that in quiescent macrophage populations, both IL-1 alpha and IL-1 beta mRNA levels were dramatically increased in response to 1 microgram/ml Biostim. Dot-blot analysis showed that in quiescent macrophage populations the expression of mRNAs for IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha could be elevated by concentrations of Biostim as low as 1-10 pg/ml, detectable after 3 h exposure. In parallel experiments LPS was effective only at the higher concentration of 10 ng/ml. Time-course analysis showed that the expression of these cytokine mRNAs was transient, peaking after 1-3 h; only transcripts of IL-1 beta were detectable after 23 h exposure. No effects were seen on the expression of actin, a high-turnover housekeeping gene. We propose that this type of analysis represents a sensitive, specific and reproducible method for assessing the ability of drugs and chemicals to modulate the expression of cytokines that play a pivotal role in the induction of the immune response.

Animals↗

The functional rectal bladder--prevention of hyperchloremic acidosis following vesico-sigmoidostomy in dogs.

Urinary diversion by a vesico-sigmoidostomy was performed in fourteen dogs. The animals were randomly divided into two groups. Group 1 had an isoperistaltic intussusception of the sigma proximal to the vesico-sigmoidostomy. Group 2 was used as control without intussusception. In the postoperative course, serum creatinine, chloride, pH, bicarbonate, base-excess were controlled over a period of four months twice weekly. Additionally, IVPs were taken in all dogs and rectograms performed in the intussuscepted group. While IVPs and creatinine values demonstrated normal postoperative kidney function in all dogs of both groups, acidbase parameters including chloride were significantly (p less than 0.001, Wilcoxon test) better in group 1. Intussusception of the sigmoid colon is a reliable operative way to significantly reduce hyperchloremic acidosis in the course of urinary diversion into the sigmoid colon, while the fecal stream remains undisturbed.

Acidosis↗

The ileal neobladder: experience and results of more than 100 consecutive cases.

The ileal neobladder produces a completely detubularized, low pressure, high capacity reservoir constructed from ileum without any valves. From April 1986 through May 1989, 113 patients underwent this procedure at our institution. Of these patients 99 underwent simultaneous radical cystectomy for bladder cancer and 14 underwent bladder augmentation. The mean postoperative followup was 14.4 months, with a range of 1 to 36 months. There was no perioperative mortality. However, 7 patients died more than 2 months postoperatively: 5 of tumor progression, 1 of pneumonia and severe metabolic acidosis, and 1 of septicemia of unknown cause. Reoperation was necessary in only 13 patients; 10 patients required urethrotomy or dilation of urethral strictures. Day and night continence was preserved in 82.1% of all patients. Stress incontinence, which must be corrected by an artificial sphincter, was found in 4 patients (4.2%) and night-time incontinence that required an external device occurred in 5 (5.3%). Eight patients (8.4%) with mild stress incontinence required no further treatment. Pressure waves exceeding 22 cm. water seldom occurred and then only at maximum capacity. Our experience with this relatively simple system without a nipple is an overwhelming success. The need for reoperation is extraordinarily low and the high reservoir capacity results in continence from the beginning in most patients. The concept is sound and 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↗

Update on quinolone drug interactions.

Concurrent administration of both ciprofloxacin and norfloxacin with sucralfate leads to a decrease in quinolone bioavailability. It is unknown whether this decrease is clinically significant because studies have focused primarily on pharmacokinetics and not therapeutic outcomes. A reasonable recommendation may be to avoid using sucralfate and norfloxacin concurrently, or avoid administration of norfloxacin and ciprofloxacin within two hours of sucralfate administration. Magnesium- and aluminum-containing antacids may also interfere with quinolone absorption. Calcium carbonate and H2 receptor antagonists do not appear to interact with quinolones and may be considered as an alternative to sucralfate or magnesium- and aluminum-containing antacids when quinolones are administered. Concurrent administration of ciprofloxacin and theophylline may precipitate theophylline toxicity if not monitored carefully. Some clinicians recommend a 30% empiric reduction in theophylline dosage when ciprofloxacin therapy is initiated. Because the drug interaction is not completely predictable, the patient's theophylline levels should be monitored and signs and symptoms of toxicity noted, adjusting the dose as needed. Decreased theophylline clearance may persist for as long as five days following discontinuation of ciprofloxacin. Some potential for slight increases in serum theophylline concentrations secondary to norfloxacin administration may exist. However, it is unlikely to be clinically significant, based on currently available information.

Ciprofloxacin↗

Gastrin- and somatostatin-immunoreactive cells of the antral mucosa in patients with duodenal or gastric ulcers. An immunocytochemical study.

Gastrin- and somatostatin-immunoreactive cells in biopsies taken from the prepyloric portion of the antrum from 15 patients with duodenal ulcer, 16 patients with gastric ulcer, and a control group of 19 patients without histopathological alterations of the antral mucosa were studied using peroxidase anti-peroxidase and immunogold-silver staining methods in combination with morphometry. Numerical densities and sizes (immunoreactive areas) of the cells demonstrated were measured and compared between all three groups. Gastrin- and somatostatin-immunoreactive cells were located most frequently in the lower midzone of the gastric crypts. None of the parameters measured showed a correlation with age or sex. The group with duodenal ulcer tended to exhibit gastrin- and somatostatin-cell-hyperplasia whereas the size of both cell types remained unchanged. In comparison with the control group, the numerical density of gastrin-immunoreactive cells was significantly increased in gastric ulcer patients, whereas the numerical density of somatostatin-immunoreactive cells was decreased in this group. Immunoreactive areas of both cell types were significantly increased in patients with gastric ulcer.

Adult↗

Effects of counselling on knowledge about HIV-1 among transfusion recipients and their partners. Transfusion Safety Study Group.

The present study determined how much HIV-1-positive persons knew about AIDS, and HIV-1 transmission and prevention, in comparison with HIV-1-negative controls in a predominantly heterosexual cohort. The subjects were blood donors, blood recipients, hemophiliacs, and their sexual partners. A 16-item questionnaire about AIDS, HIV-1 transmission, and knowledge of safe sexual practices was administered to 228 subjects to determine background information. The HIV-1-positive cohort answered more questions correctly (mean = 8.5) than did the HIV-1-negative cohort (mean = 6.5), largely as a result of general information about AIDS among those with steady sexual partners. All persons, however, were poorly informed about HIV-1 transmission and safe sexual practices. Thus, there is a great need for effective counselling.

Acquired Immunodeficiency Syndrome↗

Role of the human transferrin receptor cytoplasmic domain in endocytosis: localization of a specific signal sequence for internalization.

Wild-type and mutant human transferrin receptors have been expressed in chicken embryo fibroblasts using a helper-independent retroviral vector. The internalization of mutant human transferrin receptors, in which all but four of the 61 amino acids of the cytoplasmic domain had been deleted, was greatly impaired. However, when expressed at high levels, such "tailless" mutant receptors could provide chicken embryo fibroblasts with sufficient iron from diferric human transferrin to support a normal rate of growth. As the rate of recycling of the mutant receptors was not significantly different from wild-type receptors, an estimate of relative internalization rates could be obtained from the distribution of receptors inside the cell and on the cell surface under steady-state conditions. This analysis and the results of iron uptake studies both indicate that the efficiency of internalization of tailless mutant receptors is approximately 10% that of wild-type receptors. Further studies of a series of mutant receptors with different regions of the cytoplasmic domain deleted suggested that residues within a 10-amino acid region (amino acids 19-28) of the human transferrin receptor cytoplasmic domain are required for efficient endocytosis. Insertion of this region into the cytoplasmic domain of the tailless mutant receptors restored high efficiency endocytosis. The only tyrosine residue (Tyr 20) in the cytoplasmic domain of the human transferrin receptor is found within this 10-amino acid region. A mutant receptor containing glycine instead of tyrosine at position 20 was estimated to be approximately 20% as active as the wild-type receptor. We conclude that the cytoplasmic domain of the transferrin receptor contains a specific signal sequence located within amino acid residues 19-28 that determines high efficiency endocytosis. Further, Tyr 20 is an important element of that sequence.

Amino Acid Sequence↗

Continence after total bladder replacement: urodynamic analysis of the ileal neobladder.

Since April 1986 we have carried out 103 bladder substitutions with the ileal neobladder; 91 of these were performed after radical cystectomy in males (group 1) and 12 after subtotal bladder resection (group 2); 55 patients in group 1 and 8 in group 2 were followed up by long-term urodynamic investigations and by a questionnaire concerning micturition patterns and continence at home 3 months post-operatively. The maximum bladder capacity was approximately 770 ml with an absolute intravesical pressure of 23 to 30 cm H2O. Intravesical pressure waves with a mean amplitude of 20 cm H2O were found in 38% of patients in group 1 and 25% in group 2; 61% of these patients were asymptomatic. The results showed that 85% of patients were continent by day and by night. We attribute this to our operative technique: the ileal loop is folded 4 times in a "W" or "M" shape to achieve complete detubularisation of the bowel and the external urethral sphincter is carefully preserved. Altogether, these data show the ileal neobladder technique to be a reliable and safe method of bladder substitution.

Cystectomy↗

Cell proliferation in chorionic villi at different gestational ages, as analyzed by premature chromosome condensation.

The technique of premature chromosome condensation (PCC) was adapted to human first-trimester chorionic villi cells to analyze the cell-cycle kinetics of interphase chromatin. Uncultured cells of the cytotrophoblast (CT) and the mesenchymal core (MC) were obtained by a two-step digestion. PCC was induced by fusion of the chorionic interphase cells with mitotic Chinese hamster ovary or HeLa cells. Cells showing PCC in G1 (classes 1-6), S, and G2 were found. To analyze further the proliferation stages of chorionic G1 interphases, the proliferation potential index (PPI) of 34 placentae recovered between the 8th and 12th week of gestation was determined. The mean PPI found in the CT and MC cells ranged from 18% to 73%, values similar to those described for intensely proliferating tissues. The highest mean PPI value (73%) was observed in CT cells from placentae recovered at the 9th week of gestation, indicating a high specific proliferative activity of CT cells at this developmental stage.

Animals↗

IgA pemphigus foliaceus: a case report.

An 84-year-old male with a 4-week history of vesiculobullous eruptions was diagnosed clinically and pathologically to suffer from pemphigus foliaceus. Amazingly, direct immunofluorescence demonstrated intercellular IgA deposits in the whole epidermis. The patient did not respond to a regimen of fluocortolone and azathioprine but rapidly improved under dapsone. The few reported dermatoses with intraepidermal IgA deposits do not form a homogeneous group. In the following, their spectrum will be outlined. It is important to distinguish these dermatoses from IgG pemphigus, since they require a different therapy.

Aged↗

ESWL monotherapy for large stones and staghorn calculi.

From December 1986 through March 1988, 52 renal units (RU) with large stone burden have been treated by ESWL monotherapy. In all patients a ureteral stent was placed prior to lithotripsy, to provide drainage of the kidney during the period of stone passage. Data of 43 RU were collected for the present report. Complications ; following treatment were infrequent (2%), whereas auxiliary measures became necessary in 32% of the patients. After a mean follow-up of 9.1 months, 54% of the patients were found stone-free. Stratification according to different stone types and compositions revealed that none of the 7 patients with complete staghorns could be completely cleared and that struvite stones had a significantly better outcome than calcium oxalate stones (75 vs. 25%). Consequently, for a large but not excessive stone burden in a normal or only slightly dilated renal collecting system, ESWL monotherapy under the protection of a ureteral stent may be a comparably safe alternative to percutaneous surgery.

Adult↗