Prevalence and classification of HIV-associated oral lesions

OBJECTIVES: An International Workshop addressed the prevalence and classification of HIV/AIDS associated oral lesions.
DESIGN: Five questions provided the framework for discussion and literature review. What is the prevalence of oral lesions in children and adults? Should the accepted classification of HIV-related oral lesions be modified in the light of recent findings? Why is there a gender difference in the prevalence of oral lesions in developed and developing countries? Are there unusual lesions present in developing countries? Is there any association between modes of transmission and the prevalence of oral lesions?
RESULTS: Workshop discussion emphasized the urgent need for assistance in the development of expertise to obtain accurate global prevalence data for HIV-associated oral lesions. Oral candidiasis has been consistently reported as the most prevalent HIV-associated oral lesion in all ages. Penicilliosis marneffei, a newly described fungal infection, has emerged in South-east Asia. Oral hairy leukoplakia and Kaposi's sarcoma appear to be associated with male gender and male-to-male HIV transmission risk behaviours. These lesions occur only rarely in children.
CONCLUSIONS: Additional prevalence data are needed from developing countries prior to substantially altering the 1993 ECC/WHO Classification of oral lesions associated with adult HIV infection. The workshop confirmed current oral disease diagnostic criteria.     

The quantitative analysis and stability of histochemical markers of altered hepatic foci in rat liver following initiation by diethylnitrosamine administration and promotion with phenobarbital

The stability and response of histochemical phenotypes of altered hepatic foci (AHF) were studied both in the presence and following the withdrawal of 0.05% phenobarbital (PB) treatment in rats previously given a single dose of diethylnitrosamine (DEN) 20-24 h following partial hepatectomy (PH). AHF were scored by their expression of three biochemical markers: gamma-glutamyl transpeptidase (GGT), adenosine triphosphatase and glucose-6-phosphatase (G6P). AHF demonstrated significant heterogeneity with respect to the marker alterations. The use of three markers in the present study confirmed the findings of our earlier study, which showed the maximal response of GGT+ AHF to PB administration following PH/DEN initiation and the stability of GGT+/AHF induced by the PH/DEN/PB regimen after the withdrawal of PB. In the regimen employed, the GGT marker alone scored the great majority of the AHF detected by all three markers. The frequency distribution of histochemical phenotypes remained relatively constant in AHF during continuous PB administration and in AHF promoted by PB followed by a 6-month period of feeding a diet containing no PB. These findings suggest that individual AHF remain phenotypically stable throughout the PB promotion phase, i.e., do not progress from one phenotype to another. In every marker class, the mean volume of AHF increased during continuous PB administration. These data illustrate the enhancing effect of PB on the growth of the AHF. The size of AHF continued to increase following the withdrawal of PB in the 3-month PB treatment group, but not in the animals treated for 4 months. A mechanism that may account for the differences in these two treatment groups is discussed.     

Cell Proliferation and regulation of negative growth factors in mouse liver foci

Foci of altered hepatocytes are preneoplastic lesions capableof progressing to hepatocellular carcinomas. To Characterizethe growth of preneoplastic hepatic lesions, size of hepaticfoci was analyzed with regard to growth factor regulation andhepatocyte proliferation in focal and non-focal hepatocytes.Twelve-day-old female B6C3F1 mice were initiated with a singledose of the potent mutagen N-nitrosodiethylamine (DEN) (5 mg/kgbody weight). Beginning at 6 weeks of age, mice were exposedfor 16 weeks to 2038 p.p.m. unleaded gasoline (UG) vapor or1 p.p.m. ethinyl estradiol (EE) in the diet. Analysis of hepaticfoci demonstrated that UG significantly increased, but EE significantlydecreased the size of DEN-initiated foci. Hepatic labeling index(LI), as measured by the incorporation of 5-bromo-2'-deoxyuridine,was similar in non-focal hepatocytes at 16 weeks in all groups(0.4–0.8%) and greatly increased in hepatic foci. HepatocyteLI was significantly increased in DEN/UG foci (29%, n = 41)and significantly decreased in DEN/EE foci (6% n=23) relativeto DEN/control focal hepatocytes(18% n=25). The mean LI of focicorrelated with the focal size differences observed in the treatmentgroups. Immunohistochemical analysis with antibodies directedto the negative growth regulator transforming growth factorbetal (TGF-ß1) demonstrated a consistent decreaseof TGF-ß1 in DEN/Ct and DEN/UG hepatic foci relativeto non-lesion hepatocytes. Similar results were seen with mannose6-phosphate/insulin-like growth factor-11 receptor (M6P/IGF-IIR), which facilitates activation of latent TGF-ß1.In contrast, only 50% of DEN/EE foci had decreased levels ofTGF-ß1 and M6P/IGF-II R relative to non-focal hepatocytes.These data suggest that proliferative responses observed inhepatic foci may be correlated with foci size. In contrast,chemically induced proliferative responses in non-focal hepatocytesafter subchronic exposure cannot necessarily be used to predictproliferative effects in preneoplastic cell populations. Furthermore,these studies suggest that hepatic foci may occur by M6P/IGF-IIR enhancing activation of latent TGF-ß1 in non-focalhepatocytes but not in the focal hepatocytes, thereby affordingfocal hepatocytes a selective growth advantage.     

Mitogenic stimulation of hepatocellular proliferation in rodents following 1,4-dichlorobenzene administration.

1,4-Dichlorobenzene (DCB), a non-DNA-reactive compound, induced hepatocellular carcinomas at 600 mg/kg/day, but not 300 mg/kg/day in male and female B6C3F1 mice in a National Toxicology Program (NTP) bioassay. Cell proliferation studies were performed under conditions of the NTP bioassay to determine the mode of DCB-induced hepatocellular proliferation and whether this proliferative response may be related to the carcinogenic activity of DCB. The percentage of cells in S-phase (labeling index; LI) was measured using immunohistochemical detection of 5-bromo-2'-deoxyuridine. Time-course and dose-response studies revealed a sharp increase in LI 24 h after treatment in female mice and rats, and at 48 h in male mice with no increases in liver-associated plasma enzymes at up to twice the highest bioassay dose. During 13 weeks of DCB administration under bioassay conditions, a statistically significant transient peak of hepatocellular proliferation was observed during week 1 at 600 mg/kg/day, but not at 300 mg/kg/day, in male and female mice. Hepatocellular proliferation was also observed in female rats, which were reported as exhibiting no increased liver tumor incidence when compared to controls in the NTP bioassay. An increase in liver weight as a percentage of body weight compared to controls was observed in high dose male and female mice, and female rats at all time points. No significant elevations in liver-associated plasma enzymes were found at any time point, indicating a lack of overt hepatotoxicity. Histopathological evaluation revealed no evidence of hepatocellular necrosis in all groups. These data indicate an early mitogenic stimulation of cell proliferation, rather than regeneration secondary to cytolethality, in the livers of DCB-treated mice, which correlates with previously observed tumor formation in a dose-dependent manner. The mode by which a chemical induces cell proliferation is an important consideration in mechanistic studies and the risk assessment process. The demonstrated mitogenic activity of DCB raises the possibility that this early proliferative response may be sufficient for liver tumor formation in the B6C3F1 mouse, or that DCB may provide a selective growth advantage to preneoplastic cells in the mouse liver upon long-term treatment. The observed induction of cell proliferation by DCB in the rat in the absence of a tumorigenic response suggests important species differences and complexities in the relationship between cell proliferation and carcinogenesis, and indicates that caution be applied in equating cell proliferation to cancer.     

In vivo behavior of human radioiodinated antithrombin III: distribution among three physiologic pools

It has recently been shown that antithrombin III (AT) distributes between plasma, a noncirculating vascular-associated pool and an extravascular pool in rabbit. Study of the in vivo behavior of autologous human 131I-AT demonstrates that in humans AT also distributes among three pools that are analogous to those found in rabbit. From the in vivo kinetic behavior of the 131I-labeled AT, the fractions of total-body AT in the plasma, noncirculating vascular- associated, and extravascular pools were calculated to be 0.393 +/- 0.015, 0.109 +/- 0.016, and 0.496 +/- 0.014, respectively. From three- exponential plasma radioactivity disappearance curves, an average plasma fractional catabolic rate, j3, of 0.576 +/- 0.034 day-1 was obtained for five healthy young men. This is almost identical to the result obtained if plasma 131I-AT disappearance is assumed to fit a two- exponential curve (0.546 +/- 0.038), where the constant C2 from *Ap(t) = C1e-a1t + C2e-a2t is assumed to be equal to 1 - C1. The fraction of the total vascular AT catabolized daily, j3.5, was calculated to be 0.457 +/- 0.034, and the fractional catabolic rate of total-body AT, jT, averaged 0.2271 +/- 0.0176. The results give further support to a model of in vivo behavior in which the vascular AT distributes between plasma and an endothelial receptor. Thus, the latter may serve to mediate activation of AT for its reaction with coagulation proteases and to mediate its entrance into the endothelial cell, where it is either transported to the extravascular fluids or is catabolized.     

Digital and conventional chest images: observer performance with Film Digital Radiography System

The Film Digital Radiography System (FilmDRS) is a device with a laser optical film digitizer, 2,000 X 2,000 X 12-bit memory, and a 1,000-line video display. To evaluate the adequacy of this device for general radiography of the chest, four readers independently analyzed both radiographs and the corresponding video display of the digitized chest images of 150 patients, consisting of 100 images of abnormalities and 50 normal images. The overall results indicate equal sensitivity for the two systems. The FilmDRS, with interactive windowing, proved superior in the detection of hilar and mediastinal disease. X-ray film was superior in allowing detection of hyperlucent states. There was equivalent sensitivity for other disease categories. Superior specificity was achieved with conventional radiographs.     

Assessment of testicular metabolic integrity with P-31 MR spectroscopy

To evaluate the reliability of phosphorus-31 magnetic resonance (MR) spectroscopy in the assessment of acute testicular ischemia, vascular integrity, and spermatogenesis, the authors studied in vivo canine and primate testicles grouped as follows: group 1 testes (n = 8), in situ canine controls; group 2 (n = 11), canine testes subjected to warm ischemia; group 3, canine (n = 4) and primate (n = 4) testicles from hormone-treated animals. Group 1 control testicles showed high monophosphoester (MP) levels; low levels of inorganic phosphate (Pi), phosphodiester (PD), and phosphocreatine; and high levels of adenosine triphosphate (ATP). Group 2 testes revealed a time-dependent decay of MP/Pi ratios (from 2.1 to 0.70). Regeneration of ATP was noted in the acute reperfusion period. After 6 weeks of pituitary gonadotropin suppression, group 3 testes showed a significant decrease (P less than .05) in MP/PD ratios from a control level of 2.6 +/- 0.3 and a decrease in the MP/beta-ATP ratio from 2.4 +/- 0.1 to 1.8 +/- 0.3. P-31 MR spectroscopy appears to be a potential method for noninvasively assessing testicular ischemic injury and the metabolic integrity of spermatogenesis.