A Burkholderia pseudomallei colony variant necessary for gastric colonization.

UNLABELLED: Diverse colony morphologies are a hallmark of Burkholderia pseudomallei recovered from infected patients. We observed that stresses that inhibit aerobic respiration shifted populations of B. pseudomallei from the canonical white colony morphotype toward two distinct, reversible, yet relatively stable yellow colony variants (YA and YB). As accumulating evidence supports the importance of B. pseudomallei enteric infection and gastric colonization, we tested the response of yellow variants to hypoxia, acidity, and stomach colonization. Yellow variants exhibited a competitive advantage under hypoxic and acidic conditions and alkalized culture media. The YB variant, although highly attenuated in acute virulence, was the only form capable of colonization and persistence in the murine stomach. The accumulation of extracellular DNA (eDNA) was a characteristic of YB as observed by 4',6-diamidino-2-phenylindole (DAPI) staining of gastric tissues, as well as in an in vitro stomach model where large amounts of eDNA were produced without cell lysis. Transposon mutagenesis identified a transcriptional regulator (BPSL1887, designated YelR) that when overexpressed produced the yellow phenotype. Deletion of yelR blocked a shift from white to the yellow forms. These data demonstrate that YB is a unique B. pseudomallei pathovariant controlled by YelR that is specifically adapted to the harsh gastric environment and necessary for persistent stomach colonization. IMPORTANCE: Seemingly uniform populations of bacteria often contain subpopulations that are genetically identical but display unique characteristics which offer advantages when the population is faced with infrequent but predictable stresses. The pathogen Burkholderia pseudomallei is capable of forming several reversible colony types, and it interconverted between one white type and two yellow types under certain environmental stresses. The two yellow forms exhibited distinct advantages in low-oxygen and acidic environments. One yellow colony variant was the only form capable of chronic stomach colonization. Areas of gastric infection were marked by bacteria encased in a DNA matrix, and the yellow forms were able to produce large amounts of extracellular DNA in vitro. We also identified the regulator in control of yellow colony variant formation. These findings demonstrate a role in infection for colony variation and provide a mechanism for chronic stomach colonization-a frequently overlooked niche in melioidosis.

PANORAMA: an integrated Web-based sequence analysis tool and its role in gene discovery.

As the exponential growth of DNA sequence information in databases continues, the task of converting this deposited information into knowledge becomes more dependent on integrative sequence analysis and visualization tools. PANORAMA is an Internet-accessible software package that performs a variety of informatics analyses on a given DNA sequence and returns a visual and interactive representation of the results. Its design is modular, so that further sequence analysis tools can be integrated with minimal effort. The utility of PANORAMA is demonstrated in the analysis of 650 kb of human genomic DNA from chromosome region 3p21.3, a region of potential tumor suppressor genes involved in lung cancer, breast cancer, and other forms of cancer. PANORAMA aided in the discovery of genes and alternate splice forms of known exons, in the demarcation of intron-exon boundaries, and in the identification of promoter regions and polymorphisms, all of which contributed to a better understanding of the region. PANORAMA is available on the World Wide Web at http://atlas.swmed.edu.

Posterior amorphous corneal dystrophy. An ultrastructural study of a variant with histopathological features of an endothelial dystrophy.

Posterior amorphous corneal dystrophy (PACD) is a rare autosomal-dominant disease, generally classified with the pre-Descemet's dystrophies. It is characterized by deep stromal corneal opacification, flat corneas with low keratometry values, and central thinning. To our knowledge, only one previous ultrastructural study has been published on this disease. This 5-year-old white boy presented with best corrected vision (20/50 right and 20/60 -2 left). The corneas had dense opacities, bilaterally, deep in the corneal stroma. Keratometry was 39.50/40.50, bilaterally. The patient's father had 20/20 vision, bilaterally, with minimal opacifications in the deep corneal stroma. A penetrating keratoplasty was performed. In contrast to the previously reported case of PACD, in which the abnormalities were largely limited to the stroma, our patient had subepithelial deposits, only mild stromal abnormalities, and a thick collagenous layer posterior to Descemet's membrane, thus suggesting that this variant of PACD is a generalized corneal disease including endothelial and epithelial abnormalities, rather than a pure stromal dystrophy.

Simulated superior oblique tendon sheath syndrome.

Three patients with simulated Brown's superior oblique tendon sheath syndrome are presented. With the use of computed tomographic (CT) findings, the site of the pathology could be demonstrated. In all three patients, there were definite abnormal findings in the anterior sheath of the reflected tendon of the superior oblique. The abnormal findings in one case were confirmed at the time of surgery. Therapy in two of the cases was determined by the abnormal findings on the CT scan.

Transection of the inferior rectus muscle.

Four cases of isolated inferior rectus transection secondary to trauma are presented. The clinical and CT scan findings are illustrated. The CT scan findings are very useful in the surgical management and prognosis of these cases.

The role of retinal cryopexy in the management of experimental perforation of the eye during strabismus surgery.

In order to investigate the role of retinal cryopexy in the management of accidental perforation of the globe during strabismus surgery, the retinas of 30 rabbit eyes were perforated with a needle simulating the clinical incident. Ten of these eyes received no further treatment, ten eyes were treated with moderate transscleral cryopexy of the surrounding retina, and the remaining ten eyes were treated with excessively heavy cryocoagulation. The incidence of secondary retinal detachment was identical in the first two groups of rabbits, while it was markedly increased in those rabbits treated with excessively heavy transscleral cryopexy (P less than .01). Based on these findings and a review of the literature, recommendations are made for the management of accidental perforation of the globe during strabismus surgery.

Anterior segment anomalies associated with the fetal alcohol syndrome.

Anterior segment anomalies were noted in eight children diagnosed as having the fetal alcohol syndrome. Peters' and Axenfeld's anomalies were among the specific defects noted. Four children have maintained clear corneal grafts. A teratogenic action of alcohol during a critical period of development of anterior chamber structures is suggested as an etiologic factor. It is proposed that the varied types and severity of abnormalities noted might result from differences in blood alcohol levels, timing of the insult, and genetic background of the fetus. The observation of various types of malformations thought to share a similar pathogenesis lends additional support to the assumption that there is an interrelationship among these types of congenital segment pathology.

The relationship of blood transfusions to retrolental fibroplasia.

The medical records of 53 premature infants weighing less than 1,360 g at birth were examined. The retinas of 32 infants remained normal, while mild active retrolental fibroplasia developed in 17 babies, and severe active retrolental fibroplasia developed in four babies. The birth weight, duration of exposure of supplemental oxygen, and the amount of blood they received as transfusions were recorded. There was no significant difference in these values for those babies whose retinas remained normal and for those babies in whom mild retinopathy of prematurity developed. However, the infants in whom severe retrolental fibroplasia developed were significantly smaller in weight at birth and received more supplemental oxygen and transfused blood. There was a close correlation between the amount of blood transfused and days of exposure to supplemental oxygen. In addition, the ratio of transfused blood to days of supplemental oxygen exposure was greater in those infants in whom no retrolental fibroplasia developed and least in those infants in whom severe active retrolental fibroplasia developed.

The surgical treatment of overcorrected esotropia.

The medical records of 33 consecutive patients who developed secondary exotropia following surgery for esotropia were reviewed. Only six patients (18%) had normal medial rectus function. Lateral rectus recession proved to be an excellent procudure for correcting the deviation in these patients, provided the surgery was limited to the eye with the narrower palpebral fissure. Twenty-seven patients (82%) exhibited limitation of adduction secondary to medial rectus underaction. Of these patients, 75% were successfully corrected following a 12 mm advancement and resection of the underacting medial rectus muscle. The details of the surgical technique performed are discussed.

Recurrent "non-Hodgkin's lymphoma presenting with gingival enlargement. Report of a case.

A 66-year-old white woman with recurrent "non-Hodgkin's lymphoma" is discussed. Her initial manifestation of recurrent disease was gingival enlargement. We reviewed the oral manifestations of lymphoma and discussed the course of this patient's disease, with particular attention to the local treatment of the gingival enlargement.

Use of the astigmatism correction device on the Zeiss fundus camera for peripheral retinal photography.

High quality photographs of the peripheral retina are made possible by the proper positioning of the astigmatism correction device on the Zeiss fundus camera. Using a plus cylinder, axis perpendicular or a minus cylinder, axis parallel to that around which the eye is rotated will eliminate the astigmatism induced by viewing the retina obliquely through the optical surfaces of the eye, resulting in a sharply focused image at the film plane. Proper use of this instrument can be helpful in evaluating and diagnosing retinal lesions that occur in the peripheral fundus.

The surgical treatment of undercorrected esotropia: an evaluation of the effect of recession of the medial rectus muscle 13.5 mm from the limbus.

Nineteen patients with residual esotropia following conventional maximum horizontal recess-resect surgery were treated by further recession of the medial rectus muscle to a point 13.5 mm from the limbus. Six of these patients also underwent an 8-mm resection of the ipsilateral lateral rectus in addition to the medial recession. Eighteen of the patients achieved a good to excellent cosmetic result in the primary position. One patient was markedly overcorrected probably secondary to an unwarranted lateral rectus resection. Most of the patients showed some mild limitation of adduction, but this was generally not a significant cosmetic or functional defect. The degree of limitation seen was no greater than that which has been observed in similar patients treated by marginal myotomy. Recession of the medial rectus muscle 13.5 mm from the limbus seems to be a safe and effective method of treating surgically undercorrected esotropia.