Rapid evolution of a young L1 (LINE-1) clade in recently speciated Rattus taxa.

L1 elements are retrotransposons that have been replicating and evolving in mammalian genomes since before the mammalian radiation. Rattus norvegicus shares the young L1mlvi2 clade only with its sister taxon, Rattus cf moluccarius. Here we compared the L1mlvi2 clade in these recently diverged species and found that it evolved rapidly into closely related but distinct clades: the L1mlvi2-rm clade (or subfamily), characterized here from R. cf moluccarius, and the L1mlvi2-rn clade, originally described in R. norvegicus. In addition to other differences, these clades are distinguished by a cluster of amino acid replacement substitutions in ORF I. Both rat species contain the L1mlvi2-rm clade, but the L1mlvi2-rn clade is restricted to R. norvegicus. Therefore, the L1mlvi2-rm clade arose prior to the divergence of R. norvegicus and R. cf moluccarius, and the L1mlvi2-rn clade amplified after their divergence. The total number of L1mlvi2-rm elements in R. cf moluccarius is about the same as the sum of the L1mlvi2-rm and L1mlvi2-rn elements in R. norvegicus. The possibility that L1 amplification is in some way limited so that the two clades compete for replicative supremacy as well as the implications of the other distinguishing characteristic of the L1mlvi2-rn and L1mlvi2-rm clades are discussed.

Genetics of reproductive isolation in the Drosophila simulans clade: complex epistasis underlying hybrid male sterility.

We have analyzed the sterility associated with introgressions of the distal one-fourth of the X chromosome from either Drosophila mauritiana or Drosophila sechellia into the genome of Drosophila simulans using a series of visible and DNA markers. Because in Drosophila hybrids, male sterility is usually complete and is often tightly linked with each of several markers used in crosses, a simple genetic basis has generally been assumed. In our low resolution mapping experiment, we were not able to reject the null hypothesis that a single gene, introgressed from either D. mauritiana or D. sechellia, is the cause of male sterility. High resolution mapping, however, reveals a much more complex picture. At least three distinct factors from D. mauritiana, or two from D. sechellia, were identified that need to be jointly present to confer full sterility. Each individual factor by itself is relatively ineffective in causing sterility, or even a partial spermatogenic defect. Moreover, there appear to be more sterility factors on comparable introgressions from D. mauritiana than from D. sechellia. On the basis of these observations, we propose a model which suggests that multilocus weak allele interactions are a very common cause of reproductive incompatibility between closely related species. We also present theoretical argument and empirical evidence against extrapolating the results of within-species analysis to interpret the genetic basis of species differences. The implications of this model on the theories of evolution of species differences and the attempt to understand the mechanisms of hybrid sterility/inviability at the molecular level are discussed.

Population genetics of tandem repeats in centromeric heterochromatin: unequal crossing over and chromosomal divergence at the Responder locus of Drosophila melanogaster.

The Responder (Rsp) locus in Drosophila melanogaster is the target locus of segregation distortion and is known to be comprised of a tandem array of 120-bp repetitive sequences. In this study, we first determined the large scale molecular structure of the Rsp locus, which extends over a region of 600 kb on the standard sensitive (cn bw) chromosome. Within the region, small Rsp repeat arrays are interspersed with non-Rsp sequences and account for 10-20% of the total sequences. We isolated and sequenced 32 Rsp clones from three different chromosomes. The main results are: (1) Rsp repeats isolated from the same chromosome are not more similar than those from different chromosomes. This implies either that there are more homologous exchanges at the Rsp locus than expected or, alternatively, that the second chromosomes of D. melanogaster have diverged from one another more recently at the centromeric heterochromatin than at the nearby euchromatin. (2) The repeats usually have a dimeric structure with an average difference of 16% between the left and right halves. The differences allow us to easily identify the products of unequal exchanges. Despite the large differences between the two halves, exchanges have occurred frequently and the majority of them fall within a 29-bp interval of identity between the two halves. Our data thus support the suggestion that recombination depends on short stretches of complete identity rather than long stretches of general homology. (3) Frequent unequal crossover events obscure the phylogenetic relationships between repeats; therefore, different parts of any single repeat could often have different phylogenetic histories. The high rate of unequal crossing over may also help explain the evolutionary dynamics of the Rsp locus.

A test of reciprocal X-Y interactions as a cause of hybrid sterility in Drosophila.

Elucidation of the nature of the gene interactions that underly the sterility of interspecific hybrids is important in evolutionary biology. The interactions between the heterospecific X and Y (or Z and W) chromosomes are often used as an explanation for two reasons. First, the fertility of the hybrids of the heterogametic sex is much more often affected than that of the homogametic sex (Haldane's rule) and X-Y interactions are specific to the heterogametic sex. Second, sex chromosomes, especially the X chromosome, are often considered to be of special importance in determining the fertility of hybrids. X-Y interactions have been addressed in studies of males with a heterospecific Y chromosome in a mixed genetic background. A more stringent test of the X-Y interaction model requires each X chromosome sterility factor to be tested separately for its interaction with the Y chromosome in a homogeneous background of the pure species. Here we report such a test of the X-Y interaction model and conclude that X-Y interactions should not be assumed to be the only or even the most common cause of hybrid sterility.

Gastric nitrite processing in the surgically altered maximal and minimal bile reflux ferret model.

Ingested nitrate and nitrite have been shown to contribute to endogenous, N-nitroso compound formation in man and experimental animals. N-nitroso compounds have long been suspected of contributing to higher levels of gastric cancer in various populations. Reconstructive gastric surgery to treat ulcers is accompanied by a change in bile reflux, gastritis and an increased incidence of gastric cancer in humans. To evaluate possible connections between gastric nitrite processing, reconstructive surgery and gastric cancer, the surgically altered domestic ferret, Mustela putorius furo, was used as an experimental model. The aim of the study was to determine if surgery would alter the stomach in a way which would increase gastric nitrite concentration, and thereby enhance the likelihood of gastric N-nitroso compound formation. Three groups of ferrets, one control group (n = 6) and two groups of surgically altered ferrets, one to simulate maximal bile reflux (MABR, n = 6), and the other to model minimal bile reflux (MIBR, n = 7), were studied. Each group's response to an exogenously administered dose of sodium nitrite did not differ significantly with respect to rate of gastric nitrite absorption, with half-lives in the 13-min range. Permeability of gastric mucosa to nitrite did not differ between controls and MIBR ferrets. Mean doubling time of gastric nitrate appeared slowed in surgically altered ferrets. Mean rate of gastric emptying was the same in the three groups, but appeared delayed initially in MIBR ferrets. Thiocyanate concentrations, pH and HCl secretion, all parameters which have been shown to affect gastric nitrite processing, did not differ significantly between groups. Gastric mucosal endoscopic biopsies obtained at 6-month intervals showed no clear difference in degree of mucosal inflammation and/or dysplasia in the three groups. These findings indicate that gastric mucosal neoplasia has not occurred in this model and that changes in parameters favoring gastric N-nitrosation, even if relevant to the disease process, are not apparent at this time.

Bile reflux and the gastric mucosa: an experimental ferret model.

To study the effects of chronic bile reflux on the mammalian gastric mucosa, the ferret model was chosen for its practical aptitude and for its similarity to human gastric anatomy and physiology. A technique was first perfected for endoscopically directed gastric mucosal biopsy in the ferret. Subsequently, a surgical model of maximal enterogastric reflux (MR) and a control model of minimal reflux or "nonreflux" (NR) were developed. A stable population of 9 MR and 9 NR ferrets surviving 1-3 years has been established. All 18 animals, plus 6 nonoperative control animals, have undergone multiple repeat endoscopy and gastric biopsy without complication. The surgical and endoscopic techniques, with preliminary findings, are described.

Gastric colonization by Campylobacter pylori subsp. mustelae in ferrets.

Campylobacter pylori subsp. mustelae was cultured from both normal and inflamed gastric mucosa of ferrets. Examination of neonatal, juvenile, and adult ferrets established that the gastric mucosa in the majority of preweanling (age, less than 6 weeks) ferrets sampled were not colonized with C. pylori subsp. mustelae, whereas the gastric mucosa of 100% of adult ferrets were colonized with this gastric organism. C. pylori subsp. mustelae was isolated from the gastric mucosa on a sequential basis from nine ferrets during a several-month period, inferring either persistent colonization or frequent reinfection with C. pylori subsp. mustelae.

Organizational resources for worksite health promotion: a selective national directory.

This article identifies 19 organizations (two federal government, nine not-for-profit and voluntary health agencies, and eight for profit) that offer resources on a national basis for employers and health professionals who desire to initiate worksite health promotion programs. These resources are divided into one of four categories: publications, consultive services, programmatic services, and audiovisuals. The variety represented by these organizational offerings suggests that it is unnecessary to "re-invent the wheel" in order to initiate a worksite health promotion program.

Campylobacter-like organisms isolated from gastric mucosa of ferrets.

Campylobacter-like organisms (CLO) were isolated from gastric lesions in 1 ferret and gastric mucosa of 2 healthy ferrets. The organism was not isolated from biopsies of gastric mucosa of 14 other healthy ferrets, 1 of which had small gastric lesions located at the pylorus. Lesions from which CLO were isolated were located in the antrum of 1 ferret and were classified as inflammation with repair. Affected gastric tissue was highly vascularized with fibrous connective tissue surrounding irregularly shaped glands. Necrosis and ulceration of adjacent mucosa also were observed. Using Warthin-Starry stain, Campylobacter-like organisms were seen on and in the glandular epithelium of the ferret with gastric lesions from which CLO were isolated.

Metastatic renal cell carcinoma to stomach.

Metastatic tumors to the stomach are distinctly unusual. Rarer still is renal cell carcinoma metastatic to the stomach following radical excision of the primary tumor several years previously. During evaluation for an upper gastrointestinal hemorrhage, a patient was found to have a large antral mass. Endoscopic biopsy revealed renal cell carcinoma. At celiotomy the tumor was found to have penetrated through to the liver capsule. An antrectomy and wedge resection of the left lobe of the liver was performed. There was no evidence of further metastatic disease. This is the first report of such a patient resected for cure, and emphasizes the unique biology of this tumor in its potential for late, solitary metastasis and surgical resectability.

Splenectomy in myeloid metaplasia.

A retrospective review of 19 patients with documented myeloid metaplasia undergoing, elective splenectomy during the past ten years at the Peter Bent Brigham Hospital is presented. The primary indications for splenectomy in 17 of these 19 were either hypersplenism or symptomatic splenomegaly. Eighteen of the 19 underwent both 59Fe-ferrokinetic studies and 51Cr-sequestration studies or, alternatively, 111In-marrow scintigraphy as a part of their routine preoperative evaluation. The death from sepsis of one patient six weeks post-operatively, whose marrow function was poor and whose level of splenic sequestration was minimal, confirms the efficacy of these studies in the preoperative prediction of hematologic response to splenectomy. Eighteen of the 19 patients benefited from the operation in terms of symptomatic relief and/or hematologic improvement, although surgery presumably did nothing to prolong survival in these patients. We conclude that splenectomy is indicated as a palliative maneuver for carefully selected patients with myeloid metaplasia without prohibitive operative risk, provided the criteria for selection of patients are adhered to and the surgeon and hematologist work together as a team.