A 140-megadalton plasmid (pWR110), which has previously been associated with virulence in Shigella flexneri, was transferred to Escherichia coli K-12. Segments of S. flexneri chromosomal material were then transferred to the plasmid-bearing K-12 strains. The virulence of these transconjugant hybrids was assessed in the HeLa cell model, in ligated rabbit ileal loops, or in the Sereny test. A K-12 strain which harbored only pWR110 invaded HeLa cells, produced minimal lesions in the rabbit ileal mucosa, and was negative in the Sereny test. Plasmid-containing K-12 hybrids which had incorporated various shigella chromosomal regions gave differential reactions in the rabbit ileal loops and in the Sereny test. Analysis of these transconjugants indicated that three regions were linked with virulent phenotypes. These included the his region (when the genes responsible for 0-antigen synthesis were cotransferred) and the kcp locus (linked to the lac-gal region). Either of these chromosomal regions was sufficient to allow invasion of the rabbit ileal mucosa. In addition to both of these regions, another shigella chromosomal segment linked to the arg and mtl loci was necessary for fluid production in the rabbit ileal loop and for a positive Sereny reaction. Thus, derivatives of an E. coli K-12 strain, constructed by the stepwise conjugal transfer of a large plasmid and three chromosomal segments from S. flexneri, appeared to contain the necessary determinants for full pathogenicity in a variety of laboratory models.

A B S T R A C T Strains of Salmonela typhimurium were studied in the ligated rabbit ileal loop model to gain insight into the mechanisms whereby bacteria which invade the gastrointestinal mucosa evoke fluid exsorption. The organisms employed differed in various biologic attributes including the ability to invade the ileal epithelium, multiply within the mucosa, elicit an acute inflammatory reaction, and disseminate across the intestinal wall. Some strains provoked small intestinal fluid exsorption although these did not elaborate enterotoxin. Only those strains which invaded the mucosa were accompanied by either mucosal inflammation or fluid exsorption. Noninvasive strains produced neither histologic abnormalities nor fluid secretion. While strains which invaded the mucosa caused an acute inflammatory reaction, not all such strains evoked flnid secretion. Furthermore, there was no correlation in ability of invasive organisms to evoke fluid secretion or in the intensity of mucosal inflammation, number of intramucosal salmonellae, or in ability to disseminate from the rabbit ileum.These observations suggest that, as is the case in shigellosis, mucosal invasion may be a necessary factor for the intestinal fluid loss in salmonellosis. A bacterial property or factor, in addition to invasion of the gastrointestinal mucosa, seems to be responsible for fluid exsorption. However, it is unlikely that a salmonella enterotoxin comparable to that elaborated by Vibrio cholerae, toxigenic Escherichia coli, or Shigella dysenteriae 1 is related to fluid secretion in salmonellosis.A preliminary report has been published in abstract form. 1972. Gastroenterology. 62: 752.

I n the studies by Hume el al.' on the functional survival of renal homotransplants in patients with chronic renal insufficiency, it was observed that the period of homotransplant function in 4 of 9 recipients ranged from 5 to 25weeks. The course of the renal homotransplant in the normal dog contrasts with this wide range and long duration of the period of functional survival of renal homotransplants in the uremic patient. Irrespective of the manner in which the donor and/or recipient have been modified, including procedures known to suppress antibody formation, functional survival of the renal homotransplant in the dog seldom exceeds 1 week. Since there has been no uniformly successful experimental counterpart of chronic renal insufficiency in the dog, no information is presently available on the renal homotransplant function in the dog under these circumstances. In man, when the recipient does not have a chronic renal insufficiency, as exemplified by the case of Michon et aE.,2 the renal homotransplant functions well for about 3 weeks and then ceases to function rather abruptly, with the homotransplant showing the same morphologic pattern of rejection seen in the dog. This pattern has been interpreted as a morphologic representation of an antigen-antibody reaction; the immune response of the recipient to the renal homotransplant is believed to be the basis for the rejection. A delayed rejection or prolonged acceptance, therefore, may well represent an impaired immune response. Homotransplantation studies by Dempster3 and Simonsen4 have established a close antigenic relationship between the kidney and the skin. Should this relationship apply in man, one would expect the uremic recipient, if the prolonged functional survival is a manifestation of an impaired immune response, likewise to show a prolonged survival of skin homografts. I t was on this basis that the study to be described was undertaken.The first group of patients studied had chronic renal insufficiency with uremia that ranged from 4 months to 6 years in duration (TABLE 1). It may be noted that a variety of chronic lesions is represented, with uremia a common denominator.Skin homografts were accompanied by skin autografts in each case. The grafts were approximately square with an area of 3 to 4 sq. cm. The bed of the recipient site was subcutaneous tissue, and the grafts were full thickness. Biopsies from the homograft and the autograft were obtained simultaneously. Tissues were fixed in buffered 10-per cent formalin and processed through a modified Bouin solution. Hematoxylin and eosin, periodic acid-Schiff, Verhoeff-van Gieson, reticulum, and Feulgen stains were used.TABLE 2 summarizes the data on the recipient, donor type of homograft, the time interval to biopsy, and the estimate of the degree of homograft survival. "Pure" refers to grafts obtained from normal donors, "cortisone" to grafts from 967The upper arm was used as the site for the skin grafts.

The seasonal host-seeking pattern of nymphal Ixodes dammini infected with Babesia microti or Borrelia burgdorferi was determined on Nantucket Island, Massachusetts, during 1985. The peak period of host-seeking by infected nymphal I. dammini occurred in May and June. On a per person-hour basis, the number of infected ticks collected reached a maximum in May (Babesia = 17.3; Borrelia = 16.2). The number of infected ticks remained high in June, but decreased notably in July, August, and September. Transmission risk of the tick-borne etiologic agents of Lyme disease and human babesiosis in Massachusetts is greatest during the late spring-early summer months of May and June.

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To evaluate the enteropathogenicity ofAeromonas hydrophila and Plesiomonas shigelloides, the rate of isolation of these organisms was compared among individuals with and without diarrhea in Thailand. In two groups of American travelers, A. hydrophila, but not P. shigelloides, was associated with episodes of travelers diarrhea more often than when individuals did not have diarrhea (P < 0.025). Among three populations of Thais, A. hydrophila and P. shigelloides were isolated with similar frequencies from individuals with and without diarrhea. The biochemical characteristics, production of cytotoxin, and ability to distend suckling mouse intestine were similar among A. hydrophila isolates from individuals with and without diarrhea. However, cytotoxic A. hydrophila strains distended rabbit and suckling mouse intestine and produced destructive lesions in intestinal mucosa of both species of animal. P. shigelloides strains produced neither cytotoxin nor distended intestine. Oral administration of whole cultures

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