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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 541 records · Page 30Linked to original sources

[Chorion biopsy--a new method of prenatal diagnosis].

Chorionic villi are derivates of the trophoectoderm and therefore have the same genetic constitution as the embryo. The recently developed techniques of chorionic villi sampling in the 9th to 11th week of pregnancy and the cytogenetic analysis of this material open a new field in the prenatal diagnosis of chromosomal aberrations. With this method, a result is obtained about 8 weeks earlier than with the classical procedures performed by amniocentesis. This offers major advantages to both patient and physician.

Abortion, Incomplete↗

Molecular analysis of the argB gene of Aspergillus nidulans.

The transcriptional organization and sequence of the Aspergillus nidulans argB gene, encoding ornithine carbamoyl transferase (OCTase; E.C. 2.1.3.3.), was determined. Transcription of the gene begins within a methionine-initiated open translation reading frame, indicating that a second methionine codon of the open reading frame is used for translation initiation. The predicted length of the OCTase precursor peptide is 359 amino acids, and it contains a highly basic amino terminus that is probably involved in mitochondrial targeting. There is extensive homology between Aspergillus OCTase and mammalian and bacterial OCTases and weaker homology between the Aspergillus polypeptide and bacterial arginine carbamoyl transferase.

Amino Acid Sequence↗

Fat clearance method versus manual dissection of lymph nodes in specimens of rectal cancer.

It is essential to submit all lymph nodes from specimens of rectal cancer for histological examination. In a prospective study we compared the traditional method of dissection with the fat clearance technique in 20 operative specimens of rectal cancer. There was no significant difference in the lymph node harvest obtained by either method. The fat clearance technique resulted in a modest saving in dissection time (mean 4 min), but was expensive (pounds 14.00 per specimen) and resulted in an unacceptable reporting delay (mean 3 days). The manual method was cheaper, as effective in identifying nodes and enabled much quicker reporting.

Adipose Tissue↗

Suppression of thymocyte proliferation in vitro by a dioctyltin dichloride-induced serum factor.

Oral administration of dioctyltin dichloride (DOTC) results in the production or release of factors which appear to prevent thymocyte maturation at an early stage. Sera obtained from rats gavaged with 75 mg DOTC/kg on alternate days, significantly inhibited PHA-induced blastogenesis of normal thymocytes. In vitro uptake of tritiated thymidine by thymocytes obtained from DOTC-gavaged rats was markedly reduced. These events occurred 24 to 72 h after commencement of DOTC treatment and preceded overt thymic weight loss. The effects of DOTC may therefore be a consequence of factor(s) capable of blocking the intrathymic differentiation of T cell precursors.

Animals↗

The role of carrageenan in complement activation.

A study has been made of the nature of the interaction between complement and carrageenan, which has been widely reported to inhibit haemolytic complement activity both in vivo and in vitro. Using modified haemolytic complement-fixation tests, the degree of complement consumption by various forms of carrageenan was measured in whole human and rat sera. The median effective concentrations of the carrageenans studied were found to lie in the range 3-300 micrograms/ml for the classical pathway and 500-7800 micrograms/ml for the alternative pathway and were unrelated to sulphate content, as determined by energy dispersive X-ray analysis. It was also found that carrageenan-coated sheep erythrocytes were lysed by complement. This activity was suppressed by ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, which inhibits the classical, but not the alternative pathway, providing conclusive evidence that carrageenan preferentially activates the classical pathway. This finding may help in elucidating the inflammatory reaction induced by carrageenan.

Animals↗

Extravasation assay for the assessment of intestinal reactions to orally presented compounds.

Adverse reactions characteristic of food intolerance are claimed to occur in susceptible individuals following exposure to various chemical additives used to colour, flavour or preserve food. The objective of the present study was to develop a method suitable for investigating the nature and mechanism of these reactions in an animal model. Our results demonstrate that intestinal responses, elicited either specifically following oral challenge by antigen or non-specifically by the direct action of a chemical, can be quantified by evaluating the intestinal extravasation (IEV) of intravenously administered 125I-labelled rat albumin.

Animals↗

Effect of orally administered dioctyltin dichloride on murine immunocompetence.

The immunotoxicological effects of di(n-octyl)tin dichloride (DOTC) in the mouse were measured using a well-defined system to monitor alterations in immune responsiveness towards both self and heterologous cell membrane components. Oral weekly administration of DOTC caused a suppression of the anti-self erythrocyte antibody response. The humoral response against rat erythrocytes was also diminished. Although humoral responsiveness was affected only at a dose level which caused thymic atrophy (500 mg/kg body wt) the delayed type hypersensitivity reaction to oxazolone, a measure of cell-mediated immunity, was not affected. These data indicate that DOTC can suppress specific aspects of murine immunocompetence and may be relevant in designing studies for assessing possible hazards associated with environmental chemicals.

Administration, Oral↗

[Chorionic biopsy in prenatal chromosome diagnosis].

This paper reports on 110 chromosome analyses of prenatal diagnosis after chorion biopsy. Normal findings were recorded in 105 cases (51 female, 54 male), and 5 chromosomic abnormalities were found, including triploidy, rarely to be observed in the second trimester, and a trisomy 8. Both direct preparation and long-term cultures were employed for chromosome diagnosis. With long-term cultures, three mosaic findings were recorded that were not confirmed in subsequent examinations of amniotic cells. The observation of certain cells with female karyotype in a long-term culture with otherwise definitely male karyotype illustrates the necessity of polymorphic comparison in order to exclude maternal contamination in the analysis of long-term cultures.

Abortion, Induced↗

[Persistent varicocele following high ligation of the internal spermatic vein. Phlebography and vaso-occlusion with ethibloc].

The importance of phlebography and vaso-occlusion using ethibloc in diagnosis and treatment of the persistent varicocele following ligation ("Bernardis' technique") is demonstrated. We performed 280 surgical ligations of the internal spermatic vein. In 30 patients persistence of the varicocele was found. In 9 patients following phlebography embolisation of a long segment including smaller collaterals was performed using ethibloc. The other 21 patients were treated surgically because of unusual draining of the collaterals into renal capsular veins, into the hemiazygos vein and into renal segmental veins. In all cases following embolisation complete resolution of the varicocele was observed within 3 months.

Diatrizoate↗

Localization of the epidermal growth factor (EGF) receptor within the endosome of EGF-stimulated epidermoid carcinoma (A431) cells.

We have followed the internalization pathway of both epidermal growth factor (EGF) and its receptor in human epidermoid carcinoma (A431) cells. Using EGF conjugated with horseradish peroxidase and anti-receptor monoclonal antibodies (TL5 and EGFR1) coupled either directly or indirectly to colloidal gold we have identified an extensive elaboration of endosomal compartments, consisting of a peripheral branching network of tubular cisternae connected to vacuolar elements that contain small vesicles and a pericentriolar compartment consisting of a tubular cisternal network connected to multivesicular bodies. Immunocytochemistry on frozen thin sections using receptor-specific antibody-gold revealed that at 4 degrees C in the presence of EGF, receptors were mainly on the plasma membrane and, to a lesser extent, within some elements of both the peripheral and pericentriolar endosomal compartments. Upon warming to 37 degrees C there was an EGF-dependent redistribution of most binding sites, first to the peripheral endosome compartment and then to the pericentriolar compartment and lysosomes. Upon warming only to 20 degrees C the ligand-receptor complex accumulated in the pericentriolar compartment. Acid phosphatase cytochemistry identifies hydrolytic activity only within secondary lysosomes and trans cisternae of the Golgi stacks. Together these observations suggest that the prelysosomal endosome compartment extends to the pericentriolar complex and that the transfer of EGF receptor complexes to the acid phosphatase-positive lysosome involves a discontinuous, temperature-dependent step.

Antibodies, Monoclonal↗

Comparison of O6-alkylguanine-DNA alkyltransferase activity based on cellular DNA content in human, rat and mouse tissues.

O6-Alkylguanine-DNA alkyltransferase (alkyltransferase) is the repair protein for O6-alkylguanine, a pre-mutagenic adduct formed by a variety of alkylating agents. Previous comparisons of the repair capacity of O6-alkylguanine in different tissues have expressed the alkyltransferase activity relative to total protein, and have asserted that tissues with low levels of activity were at greater risk for mutagenic damage than tissues with higher levels of activity. Because the alkyltransferase uses DNA as substrate, and because tissues vary greatly in protein content, comparisons of tissue alkyltransferase activity may be more appropriately based on cellular DNA content. We compared alkyltransferase activity relative to tissue DNA content with the activity related to protein content in human, rat and mouse tissues. In each species, liver containing the highest level of activity using either method. In agreement with the findings of others, low levels of alkyltransferase activity relative to protein were seen in human brain, rat brain and small intestine, and mouse kidney. However, based on alkyltransferase activity relative to DNA content, low levels of activity were seen in human bone marrow myeloid precursors, rat bone marrow, brain and intestine, and mouse spleen and bone marrow. The range of activity between tissues was 18-fold in human, 15-fold in rat and 8-fold in mouse. In general, the rank of alkyltransferase activity relative to DNA for each tissue was human greater than rat greater than mouse. These results suggest that the mouse is more susceptible to nitrosoureas than rat or human. In each species, the organs with low levels of alkyltransferase activity relative to tissue DNA content would appear to be targets for mutagenic damage following nitrosourea exposure.

Alkylating Agents↗

Interventions in high-risk occupational cohorts: a cross-sectional demonstration project.

In 1980, the Workers' Institute for Safety and Health began a demonstration project designed to develop a model program of community-based intervention in three cohorts with different workplace exposures and target cancer sites. Program components included identification, notification, medical surveillance, education, social support services (eg, psychosocial, legal, financial, etc), and evaluation. The three cohorts included the Augusta cohort, a group at risk for bladder cancer due to workplace exposure to beta-naphthylamine; the Port Allegany cohort, a group at high risk of cancer associated with a workplace exposure to asbestos; and the Pattern Makers cohort, a group shown to be at increased risk of colorectal cancer. Together, these three projects give a cross-sectional view of possible approaches to educational and medical intervention strategies in diverse situations.

Asbestosis↗

Chromosomal mosaicism and maternal cell contamination in chorionic villi cultures.

In a series of 110 chromosome analyses, after chorionic villus sampling, mosaics were found in 3 out of 106 long term cultures. In all 3 cases, subsequent amniotic fluid cell cultures showed normal karyotypes. Maternal cell contamination was encountered in one long term culture derived from carefully dissected chorionic villi.

Amniocentesis↗

Assessment of the ability of mice fed on vitamin A supplemented diet to respond to a variety of potential contact sensitizers.

The contact sensitizing potential of various compounds was tested in mice maintained on a diet supplemented with vitamin A acetate. Substances were applied epicutaneously. After challenge, increases in ear thickness were measured and the differences in response between control and treated groups determined by the Mann Whitney test. A number of sensitizers, including Dowicil 200, cinnamaldehyde, hydroxycitronellal and Kathon CG gave positive sensitivity responses.

Allergens↗

Value of mucin histochemistry in follow up surveillance of patients with long standing ulcerative colitis.

It has been suggested that diffuse changes in epithelial mucins may help to identify a subgroup of patients with ulcerative colitis who are at increased risk of developing colorectal cancer. Colonoscopic biopsy specimens were taken from 11 colitic patients shortly before colectomies were performed, in which cancer was identified. These patients were matched to colitic patients without cancer for age, sex, and duration of disease. Sections were stained with high iron diamine and alcian blue (HID-AB), mild periodic acid Schiff, and for peanut lectin binding sugar sequences. The sections were assessed blindly and graded semiquantitatively. Most showed ulcerative colitis in remission or mild active disease. There were no differences between the study and control groups. Metaplastic foci were more common in the group who had cancer. These showed increased staining of mucus by mild periodic acid Schiff and increased binding by peanut lectin to the supranuclear (Golgi) zone. Epithelial dysplasia (detected in four of the patients with cancer showed focal intense binding by peanut lectin to cytoplasm, mucus, and glycocalyx. Although dysplasia differed histochemically from normal tissue, special techniques did not facilitate its diagnosis.

Adult↗

Experimental basis of angioinfarction for the treatment of renal hypertension.

Collateral circulation and recanalization represent the main problems of organ-ablating renal embolization. Different animal models were used to study the influence of central, peripheral, and capillary occlusion on organ necrosis. The first laboratory experiments were performed to optimize transcatheteral application of the embolization media tested (Gelfoam powder, Histoacryl, Ethibloc). Experiments with the model of a normal rat kidney (n = 400) showed that only capillary embolization homogeneously occluding the entire arterial system resulted in complete organ necrosis, while following central (renal artery ligation) or peripheral (Gelfoam powder) occlusion, areas of intact parenchyma remained. Ethibloc/glucose proved to be the embolization medium best suited for capillary embolization (radiopaque, inert, slow resorption). Studies with the model of unilateral renal hypertension of the rat (n = 146) demonstrated the equivalent therapeutic efficiency on blood pressure of Ethibloc embolization (57% cured, 21% improved) compared to surgical nephrectomy (50% cured, 29% improved), whereas renal artery ligation (85% failed) resulted in minor improvement only. In order to adapt capillary embolization with Ethibloc/glucose to clinical angiographic techniques, we performed angioinfarction of canine kidneys (n = 15): the use of a balloon catheter is mandatory. This guarantees blood stasis during the embolization procedure and avoids embolic reflux. Possible clinical indications of capillary embolization in renal hypertension as a less invasive method are, e.g.: malignant nephrosclerosis; renovascular or glomerulonephritic contracted kidneys, and renal dysplasia. Indications for super-selective vaso-occlusion are renal aneurysms, a-v malformations, and segmental hypoplasia.

Angioplasty, Balloon↗