Involution of lymph node histiocytes in AIDS

Lymph nodes of human immunodeficiency virus (HIV)-infected patients were studied histologically and immunohistochemically to elucidate the pattern of involution of various histiocytes in AIDS. Specimens consisted of one node with hyperplasia, five with atrophy, and three with severe atrophy. Antibodies such as L25, ID1, My4, 12, anti-Leu 3a, KiM4, OKT6 and anti-S100 protein were used for identification of the histocytes. Another antibody, VAK5, was used to demonstrate HIV antigen. T-zone histiocytes were mildly decreased in the hyperplastic node, but considerably decreased in the atrophic nodes. My4+ sinus histiocytes were unchanged in number and enlarged in the hyperplastic node, but not decreased in the atrophic nodes. Follicular dendritic cells (FDCs), defined by KiM4, were mostly depleted in the atrophic nodes. The T4 antigen was detected in some of the sinus histiocytes of the atrophic nodes. T6-positive cells were not found in any of the nodes. HIV antigen was detected only in FDCs. It is therefore suggested that various histiocytes respond differently to HIV, and that T-zone histiocytes and sinus histiocytes persist up to the late stage of AIDS.     

Genetic and phenotypic characteristics of enterovirus 71 isolates from patients with encephalitis and with hand,foot and mouth disease

Summary Biological and biochemical characters of seven enterovirus 71 (E71) isolates were compared. Four isolates (two from patients with hand, foot and mouth disease [HFMD] and two from patients with encephalitis) grew in cynomolgus monkey kidney cells both at 39.5 and 35° C. However, the remaining three strains (from patients with HFMD) grew at 35° C, but not at 39.5° C. Three temperature-resistant and two temperature-sensitive strains were tested for neurovirulence in monkeys. Temperature-resistant strains were shown to be neurovirulent, whereas temperature-sensitive strains were less neurovirulent. The results suggest correlation between temperature-sensitive growth and neurovirulence in monkeys of E71. Variation in the electrophoretic mobility of the viral polypeptides was detected in three out of seven strains. The fingerprinting of oligonucleotides generated from the viral genome showed similar patterns in two isolates from patients with HFMD and one from patient with encephalitis and variable patterns in each genomic map of remaining four strains. These variations of polypeptide patterns and of oligonucleotide maps could not be correlated with pathogenicity (encephalitis or HFMD), temperature-sensitive growth and neurovirulence in monkeys.With 4 Figures     

Sequence analysis of F, SH, and HN genes among mumps virus strains in Japan

Summary.  The fusion (F), small hydrophobic (SH), and hemagglutinin-neuram- inidase (HN) regions of 15 mumps virus (MuV) strains were sequenced to demon- strate the genetic variability since 1976 in Japan. The MuV strains were classified into 2 major genotypes, A and B, and genotype A was subdivided into three subtypes (A1, A2, and A3). A1 and A2 strains were mainly isolated in 1977 and 1980. A3 strains were isolated in 1985 and 1989 and genotype B strains in 1993 and 1994. Genotypes A1, A2, and A3 were closely related indigenous lineages in Japan but genotype B was in the similar cluster in Europe and North America. Received August 12, 1998 Accepted October 16, 1998     

Induction of HIV-specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV-capturing nanospheres in macaques

We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and that intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody response in mice. In this study, to evaluate the protective effect of immunization, each three macaques was intranasally immunized with Con A-NS or inactivated simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) and then intravaginally challenged with a pathogenic virus, SHIV KU-2. After a series of six immunizations, vaginal anti-HIV-1 gp120 IgA and IgG antibodies were detected in all SHIV-NS-immunized macaques. After intravaginal challenge, one of the three macaques in each of the Con A-NS- and SHIV-NS-immunized groups was infected. Plasma viral RNA load of infected macaque in SHIV-NS-immunized macaques was substantially less than that in unimmunized control macaque and reached below the detectable level. However, it could not be determined whether intranasal immunization with SHIV-NS is effective in giving complete protection against intravaginal challenge. To explore the effect of the SHIV-NS vaccine, the remaining non-infected macaques were rechallenged intravenously with SHIV KU-2. After intravenous challenge, all macaques became infected. However, SHIV-NS-immunized macaques had lower viral RNA loads and higher CD4(+) T cell counts than unimmunized control macaques. Plasma anti-HIV-1 gp120 IgA and IgG antibodies were induced more rapidly in the SHIV-NS-immunized macaques than in the controls. The rapid antibody responses having neutralizing activity might contribute to the clearance of the challenge virus. Thus, SHIV-NS-immunized macaques exhibited partial protection to vaginal and systemic challenges with SHIV KU-2.     

Low grade amplification of MDM2 gene in a subset of human breast cancers without p53 alterations

MDM2 protein is thought to bind to p53 tumor suppressor protein leading to inhibition of p53-mediated transactivation. Amplification of the MDM2 gene has been frequently observed in human sarcoma, and relevant overexpression of the MDM2 protein is assumed to contribute to tumorigenesis through inactivation of the p53 function. In order to determine whether MDM2 amplification plays a role in the development of human breast cancer without genetic alteration of p53, we analyzed, MDM2 gene amplification by quantitative hybridization and genetic alteration of p53, in 32 primary tumors and 26 metastatic lymph nodes. Low grade amplification of the MDM2 gene (2-6 fold) was observed in four cases, none of which showed even subtle genetic alterations of p53 or loss of alleles on 17p. Moreover, in three of the four cases with MDM2 gene amplification, the level of gene amplification in the metastatic lymph nodes was slightly higher than that in the primary tumors. These results, taken together with previous findings, suggest that a subset of breast cancers without genetic alteration of p53 may also arise by inactivation of the p53 function through interaction with the overexpressed MDM2 protein induced by gene amplification.     

The increase in the intracellular Ca2+ concentration induced by mechanical stimulation is propagated via release of pyrophosphorylated nucleotides in mammary epithelial cells

Mechanical stimulation of one mammary tumor cell in culture induced an increase in its intracellular calcium concentration which spread to surrounding cells. The increase in calcium can also be induced by addition of a solution in which cultured mammary tumor cells were stimulated by repeated pipetting (solution after pipetting cells, SAPC). The activity of the SAPC was completely abolished by treatment with snake venom phosphodiesterase or pyrophosphatase. Uridine triphosphate (UTP), uridine diphosphate (UDP) and ATP (1 M each) were detected in the SAPC, whereas 5-UMP and 5-AMP were produced by phosphodiesterase digestion. A mixture of UTP, UDP and ATP (1 M each) elicited a calcium response which was comparable to that induced by SAPC, while UTP, UDP or ATP alone at 1 M elicited a small increase in calcium concentration in mammary tumor cells. Suramin, a competitive antagonist of P₂ purinoceptors, diminished the spreading of the calcium wave induced by mechanical stimulation. It also blocked the responses to SAPC, UTP, UDP and ATP. These findings suggest that the mechanical stimulation results in the release of UTP, UDP and ATP into the extracellular space which mediates induction of the spreading calcium response via P_2U-type purinoceptors.     

Percutaneous microwave hepatic tumor coagulation with segmental hepatic blood flow occlusion in seven patients

OBJECTIVE: We assess the usefulness of microwave hepatic tumor coagulation therapy with balloon occlusion of segmental hepatic blood flow for eight recurrent metastatic hepatic tumors in seven patients. CONCLUSION: Limited early experience with microwave hepatic tumor coagulation therapy and segmental hepatic blood flow occlusion has been positive, suggesting that further clinical evaluation is warranted.     

Indications for intentionally limited resection for non-small-cell lung cancer

Radiographically, there have been new advances in spiral computed tomography (CT) scanning are currently being studied as a screening tools. As a result, many cases of small-sized lung cancer have been discovered. Some are noninvasive or minimally invasive bronchioloalveolar carcinoma, which is characterized by a the unique sign of ground-glass opacity (GGO) on high-resolution CT (HRCT) scanning. In such cases, lymph node metastases are extremely rare. However, there is currently no definitive surgical modality for such lesions. To clarify the indications of limited resection (segmentectomy or wedge resection), preoperative tumor diameter, location, and, GGO area on HRCT were estimated in patients with clinical T1N0 disease. In patients whose tumor included > or = 50% GGO area and was 15 mm or less in diameter, or patients with pure GGO regardless of tumor size, wedge resection without lymph node dissection should be considered as an acceptable treatment. Video-assisted thoracic surgery is a useful approach for selected patients. On the other hand, in patients with tumors < 50% GGO area in the range of 10-15 mm in diameter, segmentectomy with systematic lymph node dissection or diligent lymph node sampling should be considered.     

Pharmacokinetics of 9alpha-fluoromedroxyprogesterone acetate in rats: comparison with medroxyprogesterone acetate

Medroxyprogesterone acetate (MPA) is widely used in endocrine therapy for breast cancer and other diseases. Recently, it has been demonstrated that 9alpha-fluoromedroxyprogesterone acetate (FMPA) also has anti-tumour activity in chemical-induced rat mammary tumour and its activity is greater than that of MPA. In the present study, the physico-chemical properties of FMPA and MPA and their pharmacokinetics in female rats were investigated. Partition coefficients (log P) of FMPA and MPA were 3.1 and 3.8, respectively, while the solubilities of FMPA and MPA in phosphate buffer saline were 3.8 and 1.1 microg/mL, respectively. When the two agents were intravenously or orally administered into female rats, there was no significant difference between their plasma concentrations. However, unmetabolized drug excreted into urine accounted for 4.7 and 0.7% of the intravenous dose of FMPA and MPA, respectively. The free fraction of FMPA in rat plasma was approximately four times that of MPA. Assuming the well-stirred model, hepatic intrinsic clearances of FMPA and MPA were estimated to be 64 and 293 L/h per kg, respectively. In addition, the free fraction of FMPA in blood is estimated to be higher than that of MPA, which may explain the higher anti-tumour activity.