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Biomedical subjects

A R Kraft

Publications and source records attributed to A R Kraft.

At least 19 recordsLinked to original sources

Genome of the bacterium Streptococcus pneumoniae strain R6.

Streptococcus pneumoniae is among the most significant causes of bacterial disease in humans. Here we report the 2,038,615-bp genomic sequence of the gram-positive bacterium S. pneumoniae R6. Because the R6 strain is avirulent and, more importantly, because it is readily transformed with DNA from homologous species and many heterologous species, it is the principal platform for investigation of the biology of this important pathogen. It is also used as a primary vehicle for genomics-based development of antibiotics for gram-positive bacteria. In our analysis of the genome, we identified a large number of new uncharacterized genes predicted to encode proteins that either reside on the surface of the cell or are secreted. Among those proteins there may be new targets for vaccine and antibiotic development.

Bacterial Proteins↗

Interference with murein turnover has no effect on growth but reduces beta-lactamase induction in Escherichia coli.

Physiological studies of a mutant of Escherichia coli lacking the three lytic transglycosylases Slt70, MltA, and MltB revealed that interference with murein turnover can prevent AmpC beta-lactamase induction. The triple mutant, although growing normally, shows a dramatically reduced rate of murein turnover. Despite the reduction in the formation of low-molecular-weight murein turnover products, neither the rate of murein synthesis nor the amount of murein per cell was increased. This might be explained by assuming that during growth in the absence of the major lytic transglycosylases native murein strands are excised by the action of endopeptidases and directly reused without further breakdown to muropeptides. The reduced rate of murein turnover could be correlated with lowered cefoxitin-induced expression of beta-lactamase, present on a plasmid carrying the ampC and ampR genes from Enterobacter cloacae. Overproduction of MltB stimulated beta-lactamase induction, whereas specific inhibition of Slt70 by bulgecin repressed ampC expression. Thus, specific inhibitors of lytic transglycosylases can increase the potency of penicillins and cephalosporins against bacteria inducing AmpC-like beta-lactamases.

Bacterial Proteins↗

Membrane-bound lytic endotransglycosylase in Escherichia coli.

The gene for a novel endotype membrane-bound lytic transglycosylase, emtA, was mapped at 26.7 min of the E. coli chromosome. EmtA is a lipoprotein with an apparent molecular mass of 22kDa. Overexpression of the emtA gene did not result in bacteriolysis in vivo, but the enzyme was shown to hydrolyze glycan strands isolated from murein by amidase treatment. The formation of tetra- and hexasaccharides, but no disaccharides, reflects the endospecificity of the enzyme. The products are characterized by the presence of 1,6-anhydromuramic acid, indicating a lytic transglycosylase reaction mechanism. EmtA may function as a formatting enzyme that trims the nascent murein strands produced by the murein synthesis machinery into proper sizes, or it may be involved in the formation of tightly controlled minor holes in the murein sacculus to facilitate the export of bulky compounds across the murein barrier.

Amino Acid Sequence↗

Outer membrane localization of murein hydrolases: MltA, a third lipoprotein lytic transglycosylase in Escherichia coli.

Lytic transglycosylases are a unique lysozyme-like class of murein hydrolases believed to be important for growth of Escherichia coli. A membrane-bound lytic transglycosylase with an apparent molecular mass of 38 kDa, which was designated Mlt38, has previously been purified and characterized (A. Ursinus and J.-V. Höltje, J. Bacteriol. 176:338-343, 1994). On the basis of four tryptic peptides, the gene mltA was mapped at 63 min on the chromosomal map of E. coli K-12 and cloned by reverse genetics. The open reading frame was found to contain a typical lipoprotein consensus sequence, and the lipoprotein nature of the gene product was demonstrated by [3H]palmitate labeling. On the basis of the distribution of MltA in membrane fractions obtained by sucrose gradient centrifugation, a localization in the outer membrane is indicated. Overexpression of MltA at 30 degrees C, the optimal temperature for enzyme activity, but not at 37 degrees C results in the formation of spheroplasts. Not only a deletion mutant in mltA, but also double mutants in mltA and one of the two other well-characterized lytic transglycosylases (either sltY or mltB), as well as a triple mutant in all three enzymes, showed no obvious phenotype. However, dramatic changes in the structure of the murein sacculus indicate that lytic transglycosylases are involved in maturation of the murein sacculus.

Amino Acid Sequence↗

The hyperventilation syndrome. A pilot study on the effectiveness of treatment.

The aim of the study was to discover the relative effectiveness of four methods of treating patients suffering from hyperventilation attacks. The methods used were: breathing and relaxation therapy, hyperventilation provocation training, treatment based on influencing the factors which lead to the development of the syndrome, and drug treatment. The first three methods were demonstrated to be effective, whilst the fourth showed no signs of effectiveness. The condition of patients in the control group remained the same or deteriorated.

Adolescent↗

Identification of a parathyroid adenoma by operative ultrasonography.

During surgery, real-time ultrasound scanning accurately localized a parathyroid adenoma posterior to be the superior pole of the right thyroid lobe. This was made feasible because of the ultrasound features of parathyroid tissue and current developments in ultrasound instrumentation.

Adenoma↗

Endoscopic sclerotherapy in acute variceal hemorrhage.

Acute variceal hemorrhage in patients with alcoholic cirrhosis and poor liver function is associated with a high mortality. A nonoperative treatment, endoscopic sclerotherapy, was employed in 22 patients with cirrhosis and poor liver function who had 24 episodes of acute variceal hemorrhage over a 20 month period. Portal hypertension was secondary to alcoholic cirrhosis in 21 patients and cystic fibrosis in 1 patient. Of the 24 patient admissions, 21 were of patients in Child's class C and 3 were class B. Endoscopic sclerotherapy was performed under endotracheal general anesthesia using a modified Negus rigid esophagoscope. The sclerosant (5 percent sodium morrhuate) was injected into all visible varices near the gastroesophageal junction using a MacBeth needle. Definitive control of variceal hemorrhage for the entire hospitalization was achieved in 19 of 24 admissions (79 percent). The in-hospital mortality for acute variceal bleeding was 29 percent; 81 percent of the patients were discharged after control of hemorrhage. There were two major and five minor complications related to sclerotherapy. Based on this preliminary experience it is concluded that injection sclerotherapy controls bleeding and reduces mortality associated with acute variceal hemorrhage in patients with poor liver function.

Adult↗

Colonic complications of acute pancreatitis.

Colonic complications of acute pancreatitis include "pseudo-obstruction," necrosis, hemorrhage, fistula, and ischemic colitis. With the ten cases reported in this article, there are now 75 cases reported in the literature to our knowledge. The fulminating lesions (necrosis and hemorrhage) are usually associated with pancreatic abscess and/or pseudocyst and may occur because of a direct pressure effect with secondary vascular compromise. The lesions are predominant in the transverse colon and at the splenic flexure. Because the risk factor for a colonic complication from pancreatitis is highest in those patients with inflammatory masses in the body and tail of the gland due to colon contiguity, such masses require individualized treatment, including frequent clinical examination with sequential ultrasonography, and probably early surgical intervention.

Adult↗

A rare cause of ischemic colitis: polyarteritis nodosa.

This paper details the first case report of a patient with fulminant, gangrenous, ischemic colitis caused by polyarteritis nodosa which was successfully treated surgically. Ischemic colitis is a rare complication of polyarteritis nodosa. It should be suspected in patients with a past history of polyarteritis nodosa who develop abdominal pain and rectal bleeding. The identification of cutaneous lesions preoperatively and or mesenteric or serosal vascular beading at operation are helpful in establishing this diagnosis. Prognosis is generally determined by the extent of systemic involvement by polyarteritis nodosa, and death is generally associated with renal failure.

Aged↗