The immunological and virological response in human immunodeficiency virus type-1 (HIV-1) infected Indian individuals on HAART therapy: a one-year follow up study

Currently, antiretroviral therapy has become more affordable even in developing countries and it is being used in India. Fifteen HIV-1 infected individuals, who were on highly active antiretroviral therapy (HAART), were followed up for an average period of one year. The plasma viral load and CD4+ T cell estimation done at mean intervals of 5 months and 11 months after initiation of therapy showed a good response to therapy in 14 (93%) individuals.     

Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations

Fundic gland polyps (FGPs) are the most common gastric polyps in patients with familial adenomatous polyposis (FAP). FGPs have traditionally been regarded as nonneoplastic, possibly hamartomatous lesions, but the pathogenesis of FGPs in both FAP and sporadic patients remains unclear. FGPs in FAP can show foveolar dysplasia, and rarely invasive gastric adenocarcinoma has been reported in patients with FAP and fundic gland polyposis. Using direct gene sequencing and allelic loss assays at 5q, we analyzed somatic adenomatous polyposis coli (APC) gene alterations in 41 FAP-associated FGPs (20 with foveolar dysplasia, six indefinite for dysplasia, and 15 nondysplastic) and 13 sporadic FGPs. The foveolar epithelium and dilated fundic glands of the polyps were separately microdissected and analyzed in 25 of 41 FAP-associated FGPs and 13 of 13 sporadic FGPs. Somatic APC gene alterations were identified frequently (21 of 41 cases, 51%) in FAP-associated FGPs. Both the foveolar epithelium and the dilated fundic gland epithelium comprising the FGPs were shown to carry the same somatic APC gene alteration in 24 (96%) of 25 cases. Furthermore, there was no difference in the frequency of somatic APC gene alterations between FGPs with foveolar dysplasia (10 of 20, 50%), indefinite for dysplasia (four of six, 67%), and nondysplastic (seven of 15, 47%) in FAP patients (P: = 0.697). In contrast, FGPs from non-FAP patients showed infrequent (one of 13, 8%) APC gene alterations (P: = 0.008). These results show that FGPs in FAP patients are pathogenetically distinct from sporadic FGPs. Somatic, second-hit APC gene alterations, which precede morphological dysplasia in many FAP-associated FGPs, indicate that FGPs arising in the setting of FAP are neoplastic lesions.     

Proposed criteria for mixed-dust pneumoconiosis: definition, descriptions, and guidelines for pathologic diagnosis and clinical correlation

We defined mixed-dust pneumoconiosis (MDP) pathologically as a pneumoconiosis showing dust macules or mixed-dust fibrotic nodules (MDF), with or without silicotic nodules (SN), in an individual with a history of exposure to mixed dust. We defined the latter arbitrarily as a mixture of crystalline silica and nonfibrous silicates. According to our definition of MDP, therefore, MDF should outnumber SN in the lung to make a pathologic diagnosis of MDP. In the absence of confirmation of exposure, mineralogic analyses can be used to support the pathologic diagnosis. The clinical diagnosis of MDP requires the exclusion of other well-defined pneumoconioses, including asbestosis, coal workers’ pneumoconiosis, silicosis, hematite miners’ pneumoconiosis, welders’ pneumoconiosis, berylliosis, hard metal disease, silicate pneumoconiosis, diatomaceous earth pneumoconiosis, carborundum pneumoconiosis, and corundum pneumoconiosis. Typical occupations associated with the diagnosis of MDP include metal miners, quarry workers, foundry workers, pottery and ceramics workers, and stonemasons. Irregular opacities are the major radiographic findings in MDP (ILO 1980), in contrast to silicosis, in which small rounded opacities predominate. Clinical symptoms of MDP are nonspecific. MDP must be distinguished from a variety of nonoccupational interstitial pulmonary disorders.     

Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway

Acinar cell carcinomas (ACCs) are rare malignant tumors of the exocrine pancreas. The specific molecular alterations that characterize ACCs have not yet been elucidated. ACCs are morphologically and genetically distinct from the more common pancreatic ductal adenocarcinomas. Instead, the morphological, immunohistochemical, and clinical features of ACCs overlap with those of another rare pancreatic neoplasm, pancreatoblastoma. We have recently demonstrated a high frequency of allelic loss on chromosome arm 11p and mutations in the APC/beta-catenin pathway in pancreatoblastomas, suggesting that similar alterations might also play a role in the pathogenesis of some ACCs. We analyzed a series of 21 ACCs for somatic alterations in the APC/beta-catenin pathway and for allelic loss on chromosome 11p. In addition, we evaluated the ACCs for alterations in p53 and Dpc4 expression using immunohistochemistry, and for microsatellite instability (MSI) using polymerase chain amplification of a panel of microsatellite markers. Allelic loss on chromosome 11p was the most common genetic alteration in ACCs, present in 50% (6 of 12 informative cases). Molecular alterations in the APC/beta-catenin pathway were detected in 23.5% (4 of 17) of the carcinomas, including one ACC with an activating mutation of the beta-catenin oncogene and three ACCs with truncating APC mutations. One ACC (1 of 13, 7.6%) showed allelic shifts in four of the five markers tested (MSI-high), two (15.4%) showed an allelic shift in only one of the five markers tested (MSI-low), and no shifts were detected in the remaining 10 cases. The MSI-high ACC showed medullary histological features. In contrast, no loss of Dpc4 protein expression or p53 accumulation was detected. These results indicate that ACCs are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to histologically similar pancreatoblastomas.     

Interaction of a 60-kilodalton D-mannose-containing salivary glycoprotein with type 1 fimbriae of Escherichia coli.

A 60-kilodalton glycoprotein previously isolated and purified from human saliva (J. B. Babu, E. H. Beachey, D. L. Hasty, and W. A. Simpson, Infect. Immun. 51: 405-413, 1986) was found to interact with type 1 fimbriae and prevent adhesion of type 1 fimbriated Escherichia coli to animal cells in a D-mannose-sensitive manner. Purified salivary glycoprotein agglutinated type 1 fimbriated E. coli and, at subagglutinating concentrations, blocked the ability of type 1 fimbriated E. coli to attach to human buccal epithelial cells or agglutinate guinea pig erythrocytes. Both interactions were inhibited by alpha-methyl-D-mannoside but not by alpha-methyl-D-glucoside. Complexing of the glycoprotein to type 1 fimbriae was demonstrated by molecular sieve chromatography and modified Western blots. When mixed with type 1 fimbriae, the radiolabeled salivary glycoprotein coeluted with type 1 fimbriae from a column of Sepharose 4B. When blotted from a sodium dodecyl sulfate gel to nitrocellulose sheets, the glycoprotein interacted directly with type 1 fimbriae applied to the blots. Both of the latter interactions also were blocked by alpha-methyl-D-mannoside but not by alpha-methyl-D-glucoside. Chemical modification of the glycoprotein with sodium metaperiodate abolished its ability to interact with isolated type 1 fimbriae or type 1 fimbriated E. coli. These results suggest that the carbohydrate moiety of the 60-kilodalton glycoprotein serves as a receptor for type 1 fimbriae in the oral cavity, and we postulate that the interaction may cause agglutination and early removal of E. coli, thereby preventing colonization by these organisms of oropharyngeal mucosae and dental tissues.     

Idiotypic relatedness of human monoclonal IgG cryoglobulins.

The serological relatedness of the idiotypic (ID) determinants of one type lambda light chain dimer and fifteen monoclonal IgG cryoglobulins were assayed. Rabbits were immunized with 9/15 IgG cryoglobulins, and twenty-three antisera were obtained and absorbed to render them specific for the ID determinant of the immunizing IgG cryoglobulin. By use of haemagglutination-inhibition, cross-reactivity was detected among five cryoglobulins. This was localized to the Fab region of the IgG, was not related to identity of the variable region subgroups of the heavy and light chains of the cross-reactive cryoglobulins, and was not detected in eighteen non-cryoprecipitable IgG myeloma proteins. The serological relatedness of the ID determinants suggests that a subset of IgG cryoglobulins may possibly have similar variable region structures and/or antigenic specificities.     

Reversible inhibition of spermatogenesis in rats and monkeys with a new class of indazol-carboxylic acids

The effect of oral administration of $\text{AF 1312}\text{TS}$ upon the testicular germinal epithelium was studied in the rat and monkey. A single oral dose of 100 or 200 mgm/kgm given to mature male rats was not effective, but five consecutive doses of 200 mgm/kgm produced marked decrease in testicular weight and complete inhibition of spermatogenesis, while the weight and histology of the prostate and seminal vesicles were not affected. Daily doses of 10 mgm/kgm for 37 weeks or five consecutive doses of 50 mgm/kgm for 1 week were ineffective in the monkey. However, when the five dose regimen was followed by single weekly doses of 50 mgm/kgm for 6 months, complete inhibition was achieved and maintained in the monkey after 8 weeks. Daily doses of 100 mgm/kgm for 6 months resulted in inhibition of spermatogenesis.Preliminary studies with AF 1890 (an analog of $\text{AF 1312}\text{TS}$) given at levels of 50 mgm/kgm for 5 days to rats resulted in complete inhibition of spermatogenesis. The activity of this analog was four times greater than $\text{AF 1312}\text{TS}$. In monkeys, a daily dose of 200 mgm/kgm for 2 weeks also resulted in suppression of spermatogenesis.