Progressive spatial restriction of Sek-1 and Krox-20 gene expression during hindbrain segmentation

After segmentation of the vertebrate hindbrain, expression of the zinc-finger gene Krox-20 and the receptor tyrosine kinase gene Sek-1 is precisely restricted to rhombomeres (r) 3 and 5. This precise segmental expression is likely to reflect a critical requirement for these rhombomeres to acquire a distinct and homogeneous identity and raises the question as to how this relates to the intermingling and restriction of cell movement during segmentation. We have analysed Krox-20 and Sek-1 expression in the mouse and chick hindbrain at single-cell resolution using whole-mount in situ hybridisation and immunocytochemistry. We find that, in the mouse, the presumptive r3 and r5 expression domains each arise as narrow stripes that then broaden, suggestive of a recruitment of cells to an r3/r5 identity and/or a segmental regulation of cell proliferation. In addition, we find that expression of these genes initially occurs in fuzzy domains, and that these are progressively restricted to segmental domains, although occasional "violating" cells are observed even after segmentation. We propose that the establishment and maintenance of these segmental domains may involve both a dynamic regulation of r3/r5 identity and the restriction of cell movement across rhombomere boundaries.     

Helicobacter pylori does not migrate from the antrum to the corpus in response to omeprazole

BACKGROUND: Omeprazole is known to have an effect on Helicobacter pylori in vivo. One opinion is that H. pylori "migrates" from the antrum to the corpus in response to omeprazole therapy. METHODS: To determine whether H. pylori migrates in response to omeprazole, we assessed the presence of H. pylori in the antrum and corpus in duodenal ulcer patients receiving omeprazole for 4 wk. Culture and histological examination of antral biopsies (Genta stain) were performed before patients received omeprazole, at the end of therapy, and 4-6 wk later. The end points were presence or absence of H. pylori and the number of H. pylori colonies per biopsy. RESULTS: Seventy-two patients had H. pylori in both the antrum and corpus at entry and 4-6 wk after ending therapy. Three general patterns were prevalent at the end of omeprazole therapy: antrum- and corpus-positive (54%), antrum-negative and corpus-positive (24%), both antrum- and corpus-negative (21%), and one patient had antrum-positive with corpus-negative (1%). Evaluation of the number of colonies per biopsy in those who remained H. pylori-positive in both the antrum and corpus throughout showed that the number of H. pylori decreased in both the antrum and corpus during therapy (507 +/- 60 vs. 225 +/- 51, p < 0.01 and 415 +/- 58 vs. 290 +/- 46 0.1) for antrum and corpus, respectively, and tended to return to pre-therapy levels 4-6 wk later. The number of H. pylori in the corpus also decreased in the antrum-negative and corpus-positive group during therapy with omeprazole (433 +/- 87 vs. 185 +/- 61, p < 0.05). In most of the patients studied, the number of H. pylori in the corpus was less posttreatment than it was pretreatment. The decrease in H. pylori load was also reflected in the development of false-negative urea breath tests. CONCLUSIONS: Omeprazole is detrimental to H. pylori in both the antrum and the corpus; migration from the antrum to the corpus in response to omeprazole is a myth.     

Displaced fractures of the middle third of the forearm in children. The therapeutic considerations]

There been studied 100 cases of fractures of the middle third of both bones of forearm in child for to assess the correctitude of the therapy, based on the analysis of results. The most correct surgical techniques consist of osteosynthesis with Kirschner wire of the both bones, knowing the particularities of the fracture linea in child and the minimal tissues' damages. In the child younger then 10 years old, the open reduction is rarely necessary. Any displaced fracture of middle third of both bones of forearm, whatever the age of the child would be orthopedically reduced, before performing the surgical therapy. The unstable osteosynthesis such as simple screw "osteosynthesis" with wire or thread are contraindicated.     

Habituation of the orienting response: a gating mechanism subserving selective attention

Possibilities of involution of changes in lesser circulation after closure of experimental aortopulmonary anastomosis were studied. 37 observations at various intervals after closure of anastomosis (several minutes to 13.5 months) in 25 dogs were analyzed. Before closure the anastomosis had functioned for 1-7 months. The results of histological examinations of lungs, pressure measurements in lesser circulation, heart weight, electrocardiographic and spirographic examinations were analyzed. It was found that complete involution of changes in lesser circulation was possible only in first month of existence of anastomosis, in this case with changes of both "early" and "late" types. "Late"-type changes after four months function of anastomosis had both reversible and irreversible character, whereas "early"-type changes became irreversible already after three-month duration of anastomosis. With the "late"-type changes, the operation itself (closure of anastomosis) was accompanied by symptoms of pulmonary vasomotor paresis and heart failure, whereas in the presence of "early"-type changes the operation elicited no morphological or functional changes.     

Systemic lupus erythematosus in children: the complex problems of diagnosis and treatment encountered in 101 such patients at the Mayo Clinic

Between 1945 and 1970, 101 children (86 girls and 15 boys) with systemic lupus erythematosus were evaluated at the Mayo Clinic. Only 9 children were less than 9 years old at the time of diagnosis. The most frequent presenting complaint was arthralgia; fever, fatigue, and a "butterfly" malar rash also were common. Renal involvement, found in more than 76 per cent of patients, was a prognostically poor sign. The overall survival of children with renal involvement is improved by the use of adequate steroid therapy.     

Atraumatic retrieval of the proximal end of a severed digital flexor tendon

A suction catheter technique is suggested as the next procedure of choice when proximal digital "milking" with wrist flexion fails to deliver the proximal end of the flexor tendon severed within the digital sheath.     

Bypass surgery for vascular disease of the carotid system

A series of 58 operations on 56 patients, in whom a branch of the superficial temporal artery was anastomosed to a branch of the middle cerebral artery (STA-MCA bypass or Yasargil procedure), is reviewed. These operations were performed chiefly for occlussions or for inaccessible stenotic lesions of the internal carotid or middle cerebral arteries. Patency in eight patients operated on from April 1971 through November 1973 was low (25%). Patency in patients operated on since July 1974 has been high (95%). There have been no deaths and no major ischemic strokes attributable to the surgery. The rationale for this procedure is considered in relationship to the anatomy and physiology of the cerebral circulation and the pathogenesis of syndromes of cerebral ischemia. The operation appears to have a low morbidity in good-risk patients. The role of this operation in managing common manifestations of cerebral vascular disease such as focal transient cerebral ischemic attacks (TIAs) and amaurosis fugax, although not fully established, appears encouraging. The procedure seems useful for orthostatic cerebral ischemia caused by multiple occlusions of major extracranial (and intracranial) vessels and, occasionally, for progressing strokes related to internal carotid artery occlusion, both of which are relatively uncommon manifestations of cerebral vascular occlusive disease. It may have application in the rare "slow stroke." The procedure is probably of limited value, if any, in the management of large completed infarcts but may be indicated in selected patients with small infarctions who have preserved most of their cerebral function and who have had evidence of subsequent focal ischemic events. The procedure is useful for bypassing giant aneurysms or basofrontal tumors invading major vessels. It may have a role in the management of fibromuscular disease of the internal carotid artery.     

Relationships of sexual activities in estrous cows to different frequencies of observation and pedometer measurements

Sexual activities were observed continuously for 120 h in Holstein dairy cows during moderate climate. Pedometer measurements of motor activity were correlated with total activities initiated, total activities received, mounts received, and time in estrus. Twelve of 14 individual sexual activities also were correlated on a within-cow basis with pedometer-measured increases in motor activity; disoriented mounts and licking front were not correlated to pedometer increases. Although observations of four 1-h and four or six 30-min observations accounted for greater variation, pedometer increases in activity accounted for as much variation in total sexual activities as periodic observations of 30 min or 1 h for 1 to 3 X /d. Combining periodic observations with pedometer measurements resulted in greater coefficients of determination for analyses of sexual activities than with each individual factor. Sexual activities and pedometer increases also were correlated positively with body condition score and day postpartum, and they were correlated negatively with milk production and body weight change since calving. Although mounting and total sexual activities were shifted significantly from expected on a quartile basis, shifts were probably not of practical significance and provided little evidence for more frequent occurrence of estrous activity during nocturnal periods. Rather, the most marked decrease in mounting and total sexual activities occurred at milking and feeding times, indicating that dairy farmers should be more concerned with disruptions of activities by management practices rather than nocturnal occurrence of estrus.     

Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers

Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in viral replication and their mutationally nonpermissive nature. On the basis of our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194-1197), we synthesized and evaluated variants of these dimers, including sets of 4,4'- and 3,3'-disubstituted diphenyl sulfones and their monomeric benzisothiazolone derivatives (BITA). BITAs generally exhibited diminished antiviral potency when compared to their disulfide precursors. Novel, monomeric structures were created by linking haloalkanoyl groups to the benzamide ring through -NH-C(=O)- (amide) or -S-C(=O)- (thiolester) bridges. Amide-linked compounds generally lacked antiviral activity, while haloalkanoyl thiolesters and non-halogen-bearing analogues frequently exhibited acceptable antiviral potency, thus establishing thiolester benzamides per se as a new anti-HIV chemotype. Pyridinioalkanoyl thiolesters (PATEs) exhibited superior anti-HIV-1 activity with minimal cellular toxicity and appreciable water solubility. PATEs were shown to preferentially target the NCp7 Zn finger when tested against other molecular targets, thus identifying thiolester benzamides, and PATEs in particular, as novel NCp7 Zn finger inhibitors for in vivo studies.     

15N NMR investigation of the reduction and binding of TNT in an aerobic bench scale reactor simulating windrow composting

T15NT was added to a soil of low organic carbon content and composted for 20 days in an aerobic bench scale reactor. The finished whole compost and fulvic acid, humic acid, humin, and lignocellulose fractions extracted from the compost were analyzed by solid-state CP/MAS and DP/MAS 15N NMR. 15N NMR spectra provided direct spectroscopic evidence for reduction of TNT followed by covalent binding of the reduced metabolites to organic matter of the composted soil, with the majority of metabolite found in the lignocellulose fraction, by mass also the major fraction of the compost. In general, the types of bonds formed between soil organic matter and reduced TNT amines in controlled laboratory reactions were observed in the spectra of the whole compost and fractions, confirming that during composting TNT is reduced to amines that form covalent bonds with organic matter through aminohydroquinone, aminoquinone, heterocyclic, and imine linkages, among others. Concentrations of imine nitrogens in the compost spectra suggest that covalent binding by the diamines 2,4DANT and 2,6DANT is a significant process in the transformation of TNT into bound residues. Liquid-phase 15N NMR spectra of the fulvic acid and humin fractions provided possible evidence for involvement of phenoloxidase enzymes in covalent bond formation.