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Biomedical subjects

M Kellett

Publications and source records attributed to M Kellett.

At least 19 recordsLinked to original sources

Plaque abrasion and intra-aortic balloon leak.

STUDY OBJECTIVE: To determine and correct cause of high incidence of intra-aortic balloon leaks (ruptures). DESIGN: Epidemiologic investigation of factors associated with intra-aortic balloon leak, and sequential application of corrective measures evaluated by continued concurrent data collection. SETTING: Thirty-four-bed ICU in 598-bed tertiary care medical center. INTERVENTIONS: Procedure changed to place smaller balloons (34 mL instead of 40 mL) in patients less than 163 cm in height. MEASUREMENTS AND RESULTS: Demographic and clinical data on all patients showed no change after initial interventions, followed by significant drop (8 to 2%) in incidence of balloon leak when smaller, shorter balloons were placed in shorter patients. CONCLUSIONS: Placement of larger, longer balloons in patients increases risk of perforation of balloon by calcific plaque in the distal thoracic and abdominal aorta.

Aged

Measurement of in vivo proliferation in human colorectal mucosa using bromodeoxyuridine.

In vivo bromodeoxyuridine (BrdUrd) labelling of the human large bowel was performed and a detailed histochemical localisation of label in sections of crypts was undertaken using a monoclonal antibody to BrdUrd containing DNA. Flow cytometric studies on extracted nuclei were also performed (data presented elsewhere). The average crypt in the human large bowel (excluding the rectum) was 82 cells in height and 41 cells in circumference, with a total of about 2000 cells (assuming a topographical correction factor of 0.6). Ten per cent of the cells were replicating their DNA--that is, were in the S phase of the cell cycle--and 0.4% were in mitosis. The median position for the labelling index versus cell position frequency plot is at the 20th cell position--at a quarter of the crypt height. The lower and upper limits of the cell proliferation are given by the 5th and 95th percentiles at cell positions 4 and 43 respectively. The peak labelling index is about 30% and it occurs at cell position 15. The labelling index at the crypt base, the probable stem cell zone, is about 14%, suggesting that these cells have a longer cell cycle. Taking a value of 8.6 hours for the duration of the S phase (deduced from the flow cytometric data) and assuming a growth fraction of 1.0 for the mid-crypt, these data provide an estimate of about 30 hours for the cell cycle time. The rectal crypts are about the same size but contain about 30% fewer S phase cells. The data also yielded a per cent BrdUrd labelled mitosis curve.

Aged

Proliferation in human gastrointestinal epithelium using bromodeoxyuridine in vivo: data for different sites, proximity to a tumour, and polyposis coli.

The distribution of DNA synthesising cells in the crypts of the epithelium in human small and large bowel after injection of bromodeoxyuridine into patients has been studied in relation to the position of the cells in the crypt using immunohistochemistry. Different sites of normal epithelium have been studied. The ileum has a shorter crypt and a very significantly smaller total cell population size. However, it has similar peak labelling index (LI) values to the colon, while the rectum has a lower peak LI value. The mean position of the label occurs at the 17th cell position in the ileum and at about the 22nd position in both the colon and rectum. The overall mean LI is significantly higher in the ileum at 17.8%, intermediate in the colon at 10.3%, and lowest in the rectum at 8.5%. There is thus an inverse relation between the likelihood of developing a tumour and the rate of cell proliferation as measured by the LI. Assuming a value of 8.6 hours for the duration of S, the data suggest that the cell cycle time in the mid crypt region is about 30 hours for the ileum and colon and about 37 hours for the rectum. Samples taken adjacent (within 1 cm) to a tumour show a general dampening of proliferative activity at all cell positions compared with samples taken more than 5 cm from a tumour. This is illustrated by the average LI, which is about 5.4% in the colon adjacent to a tumour compared with 10% distant; comparable values for the rectum are 4.6% and 8.5%. Samples taken from two patients with polyposis coli show distributions with a significant difference in skewness compared with normal colon and a general shifting of the distribution to the right, that is to higher cell positions. There is a significant increase in the mean cell position and the position of the peak LI in the polyposis coli samples.

Adenomatous Polyposis Coli

A comparison of in vivo cell proliferation measurements in the intestine of mouse and man.

Using tritiated thymidine (3HTdR) labelling in vivo in the mouse we have determined the labelling index (LI%) at each cell position along the sides of sections of crypts in the small and large bowel. We have compared LI versus cell position frequency plots obtained in this way with those obtained using bromodeoxyuridine (BrdUrd) in vivo in the small intestine. Both thymidine analogues give identical patterns and similar levels of labelling: for example, the overall LI is 29.1% after 3HTdR and 34.7% after BrdUrd in the mouse ileum. Similar data have been obtained following in vivo labelling in humans with BrdUrd prior to gastrointestinal surgery for cancer and in mouse colon following 3HTdR labelling. Comparisons between the mouse and human data show that the spatial distribution of label within the crypts occurs at the same relative positions in the two species. However, the intestinal crypts are between 2-fold and 4-fold larger, particularly in their length, in the human: for example, 250 and 450 cells per crypt for ileum and 590 and 2000 cells per crypt for the colon in mouse and human respectively. The absolute value of the maximum LI in the mouse small intestine (56.5%) is higher than it is in the human (26.3%). However, the patterns of proliferation are similar in the two species under steady-state conditions.

Animals

A topographical study of the circadian rhythm in labelling index of mouse gingival and floor-of-mouth epithelium, including changes in labelling activity with individual cell position on the epithelial ridges.

A continuous strip of epithelium from the mandibular teeth to the ventral surface of the tongue of B6D2F-1 mice was examined autoradiographically after tritiated thymidine flash-labelling. Five areas were defined: area 1, the gingival sulcus epithelium adjacent to tooth enamel; area 2, the free gingival margin epithelium; area 3, the attached gingiva; area 4, the floor of mouth with undulating basement membrane; area 5, the floor of mouth with flat basement membrane. Data for the circadian variation in the proportion of DNA synthetic cells were recorded into a microcomputer, which enabled a large number of cells to be scored. The topographical position of each basal cell along the rete ridges and the incidence of labelling were noted. In each of the five areas a statistically significant circadian variation in labelling index (LI) was demonstrated, with a peak at 04.00-06.00 h and a trough at 20.00 h, although area 1 was slightly out of phase with the rest. The 24-h average LI values were almost double those obtained from a single flash-labelling at 10.00 h. The peak to trough ratio in LI was greatest in area 5 and fell towards area 1. Within the attached gingiva, cells deepest in the epithelial ridges had a larger peak to trough ratio than more superficial basal cells. For a group of mice labelled at 10.00 h the mean LI of the basal epithelial cells in areas 1-5 was 7.5 +/- (3.0)% (SD). Various aspects of the distribution of DNA synthesis in relation to topography were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ro 22-5417, a new clavam antibiotic from Streptomyces clavuligerus. I. Discovery and biological activity.

Streptomyces clavuligerus NRRL 3585, a culture which produces a variety of beta-lactam antibiotics in the penicillin, cephalosporin and clavam families, was found to produce a new beta-lactam antibiotic, Ro 22-5417. The compound, which was neither a substrate for nor inhibitor of several beta-lactamases, showed antimicrobial activity in defined minimal medium but little or no inhibitory activity in nutrient-rich medium. The activity was bacteriostatic against Bacillus species ATCC 27860 and was antagonized by D- and L-methionine, L-cystathionine, L-homocystine and O-acetyl-L-homoserine but not by L-homoserine, L-aspartate, L-cysteine or other common amino acids, vitamins and nucleosides. Our results are consistent with Ro 22-5417 acting as an inhibitor in methionine biosynthesis.

Anti-Bacterial Agents

Antimetabolites produced by microorganisms. XIII. The synthesis and microbiological production of a novel amino acid, L-2-amino-4-(2-aminoethoxy) butanoic acid.

A novel amino acid, L-2-amino-4-(2-aminoethoxy-)-butanoic acid, was isolated from a fermentation broth of Streptomyces sp. X-11,085. It was shown to be identical with the chemical reduction product of an antimetabolite antibiotic, L-2-amino-4-(2-aminoethoxy)-trans-3-butenoic acid, a co-product in the fermentation. Addition of the title compound to the fermentation led to an enhanced yield of the antimetabolite suggesting that the saturated amino acid serves as a precursor for the antimetabolite.

Aminobutyrates

Antimetabolites produced by microorganisms. XII (S)-alanyl-3-[alpha-(S)-chloro-3-(S)-hydroxy 2-oxo-3-azetidinylmethyl]-(S)-alanine, a new beta-lactam containing natural product.

(S)-Alanyl-3-[alpha-(S)-chloro-3-(S)-hydroxy-2-oxo-3-azetidinylmethyl]-(S)-alanine was isolated from a fermentation broth of an unidentified Streptomyces species 372 A. The structure was determined by single crystal X-ray diffraction analysis. The substance inhibits the growth of several strains of gram-positive and gram-negative bacteria in a chemically defined medium but growth inhibition is relieved by addition of L-glutamine to the medium.

Alanine