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The CD4+ T cell count is an important determinant of disease stage and prognosis in human immunodeficiency virus (HIV)-infected individuals. This study evaluated the CD4+ T cell counts in individuals at the time of diagnosis of HIV infection at 4 community clinics in large urban settings with relatively high frequencies of HIV infection. Of 2223 individuals, 57% and 36% had CD4+ T cell counts < 350 and < 200 cells/mm(3), respectively, at the time of diagnosis. There were no clear differences by sex or race. Enhanced educational efforts regarding the importance of HIV testing for at-risk individuals across sex and race strata in community settings may be important for early identification of individuals with HIV infection. This in turn could impact efforts to reduce transmission, and it could impact the prognosis for patients who receive antiretroviral therapy. Copyright © 2002 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Pyrotheria is one of the most peculiar orders of South American native ungulates, whose members evolved from the early? Eocene to the late Oligocene period when they became extinct. Here, we described the most complete specimen of Propyrotherium saxeum ever found, one of the lesser-known representatives of pyrotheres that characterized the middle-late Eocene period of Patagonia (Argentina). It includes a nearly complete mandible and a tusk-like tooth of the same individual, as well as other isolated upper and lower teeth. Propyrotherium saxeum has a dental formula that includes at least P2-M3 and i2?-p3-m3 (lack of p2). It is characterized by some peculiar features of the mandible (e.g., ascending ramus longer than high, hiding the m3 and straight incisura mandibular) and dentition (e.g., cristid obliqua in p3-m3, cristid between posterior lophid and distal cingulid in m1-m3, P3-M3 and p3-m3 bilophodont, P2 and p3-m3 bi-rooted, P3-M3 three-rooted, paraconid in p3). The phylogenetic analysis reveals that Propyrotherium is more closely related to Pyrotherium and Baguatherium, differing from the previous hypothesis, and supports the monophyly of Pyrotheriidae including Carolozittelia, Griphodon, Pyrotherium, Baguatherium, and Propyrotherium. The absolute age obtained through U-Pb zircon dating of the Sarmiento Formation at Cañadón Pelado, the fossil's original locality, indicates that the fossil-bearing tuff would have been deposited between 39.65 and 40.41 Ma, with a weighted mean age of 40.03 ± 0.38 Ma (Bartonian). This implies a biochron much longer than previously thought for Propyrotherium and provides a chronological framework for the fauna of Cañadón Pelado., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Most human immunodeficiency virus (HIV)-infected individuals experience increases in peripheral CD4(+) T cell counts with suppressive antiretroviral therapy (ART) that achieves plasma HIV RNA levels that are less than the limit of detection. However, some individuals experience decreasing CD4(+) T cell counts despite suppression of plasma viremia. We evaluated 4 patients with a history of CD4(+) T cell decline despite successfully suppressive ART, from a median of 719 cells/mm(3) (range, 360-1141 cells/mm(3)) to 227 cells/mm(3) (range, 174-311 cells/mm(3)) over a period of 18-24 months; 3 of the patients were receiving tenofovir and didanosine, which may have contributed to this decrease. There was no evidence of HIV replication, nor of antiretroviral drug resistance in the blood or lymphoid tissue, or increased proliferation or decreased thymic production of naive CD4(+) T cells. All 4 patients had significant fibrosis of the T cell zone of lymphoid tissue, which appeared to be an important factor in the failure to reconstitute T cells.

The effects of different fiber types and processing on putative protective mechanisms for colorectal cancer were evaluated. Rats were fed diets of similar nutrient balance containing either no added fiber or 10% fiber from various sources. The rate of distal colonic epithelial proliferation, measured by the metaphase arrest method, was dependent on fiber type; ranking of fibers from highest to lowest yielded the following order: methylcellulose > coarse wheat bran > fine wheat bran approximately parboiled and extruded rice brans > no fiber (P = 0.012). Effect on stool output ranked identically. Ranking of effect on fecal pH, from most to least acidic was as follows: coarse wheat bran approximately the rice brans > fine wheat bran > no fiber approximately methylcellulose (P = 0.00001). Coarse wheat bran gave significantly higher fecal butyrate concentrations than did the rice brans, which in turn gave higher levels than fine wheat bran, methylcellulose and the no-fiber diet. Proximal colon epithelial proliferation was unaffected by diet although cecal short-chain fatty acid concentrations and pH were affected. Different fibers have different effects on events in the fecal environment and distal colonic epithelium. Putative protective events (increased output, low fecal pH, high butyrate, low proliferation) are not equally affected and are unlikely in themselves to allow prediction of the protective effect of a fiber.

The amount and type of dietary fibre ingested influences colonic luminal characteristics, especially the concentration of carbohydrate fermentation products such as butyrate. This study aimed to assess whether diets supplemented with fibres of differing fermentability (delivering different amounts of butyrate to the colon) influence mucosal activities of urokinase and brush border hydrolases, and epithelial turnover. Groups of five rats were fed one of four diets containing low (2%), highly fermented (guar 10% or oat bran 10%) or slowly fermented fibre (wheat bran 10%) for 4 weeks. Activities of urokinase, alkaline phosphatase, dipeptidyl peptidase IV and maltase were measured in mucosal homogenates of proximal and distal colon and from rectum. Proliferative kinetics were assessed in distal and proximal colon by the metaphase arrest technique. Hydrolase activities were similar across all four dietary groups but a significant difference was found for urokinase (P = 0.014). This was due to a reduction in urokinase activities of > 30% at the three sites in the wheat bran group compared with the other groups. Of proliferative indices, only crypt column height differed across the groups (P = 0.038) and was highest in rats fed wheat bran and lowest in those fed the low fibre diet (P = 0.047). The proportion of mitoses in the top one-fifth of the crypt also differed across groups (P = 0.038) due to the high values in the distal colon of the low fibre group. Thus, addition of a slowly fermented (but not highly fermented) fibre to the diet of rats reduces net urokinase activity in large bowel mucosa and increases the life span of colonic epithelial cells without changing activities of brush border hydrolases.

Expression of brush border hydrolases can reflect the state of differentiation of an epithelium. To determine if expression of these enzymes is disordered in patients with neoplastic or hyperplastic lesions, the activities of alkaline phosphatase, maltase, and dipeptidyl peptidase IV were measured spectrophotometrically in colonoscopic biopsies from the proximal and distal colon and rectum in 50 controls, 17 patients with large bowel adenomas, 29 with carcinoma, and 9 with hyperplastic polyps. In normal controls, a descending cecorectal gradient of alkaline phosphatase activities and an ascending gradient of maltase activities were seen (P < 0.001). Though regional patterns of expression were generally preserved in disease groups, there were significant differences of activities across patient groups for alkaline phosphatase (greater in cancer, adenoma, and hyperplastic groups than in normals; P < 0.05) and for dipeptidyl peptidase IV (greater in hyperplastic polyp group than normals, greater in adenoma than cancer group; P < 0.05). Compared with normal controls, abnormalities of site-specific activities were confined to the rectum in patients with adenoma (maltase decreased, P = 0.02; dipeptidyl peptidase IV increased, P < 0.01) or with carcinoma (alkaline phosphatase increased, P = 0.03) but dipeptidyl peptidase IV activities were increased in all regions in bowels bearing hyperplastic polyps (P < 0.01). These data suggest that neoplastic and hyperplastic lesions, while focal in nature, occur in large bowel epithelium, which is diffusely abnormal in terms of its expression of these enzymes.

The in vitro effect of butyrate on expression of differentiation markers in colonic epithelial cells was assessed in the colon cancer cell line, LIM1215 and in epithelial cells isolated from a surgically resected histologically normal colon. Markers used to assess cell differentiation were: net glycoprotein synthesis ([3H]-glucosamine uptake) expressed relative to net protein synthesis ([14C]-leucine uptake), and the expression of the brush border glycoproteins (alkaline phosphatase and carcino-embryonic antigen) in cell homogenates calculated relative to cellular protein content. In response to 24 h exposure to 1 mmol/L butyrate, all markers significantly increased in LIM1215 cells whereas they all significantly decreased in isolated colonic epithelial cells under identical culture conditions. Similar effects were seen at butyrate concentrations of up to 4 mmol/L. Butyrate suppressed proliferation of LIM1215 cells but had no consistent effect on [3H]-thymidine uptake by, or DNA content of, normal epithelial cells. Additional experiments found no evidence of a toxic effect of butyrate at those concentrations nor of an alteration of cell responsiveness to butyrate due to the isolation process itself. In contrast to its differentiative effect on neoplastic cells, butyrate reduces the expression of phenotypic markers of differentiation in vitro in colonic epithelial cells from non-neoplastic mucosa.