Nodular alteration of the paracortical area. An in situ immunohistochemical analysis of primary, secondary, and tertiary T-nodules.

With the use of in situ immunohistochemical techniques on freshly frozen and paraffin-embedded material from 63 reactive lymph nodes, the cellular composition of T-nodules observed in 30 cases with nodular alteration of the paracortical area was analyzed. T-nodules were composed of S-100 beta + interdigitating reticulum cells (IDRCs), variable numbers of OKT6+ dendritic cells (DCs), high endothelial venules, and a very high T helper/T suppressor ratio because of an enrichment of OKT4+, Leu3a+ helper/inducer T cells in these nodules. According to their localization in the paracortical area, and the arrangement of IDRCs and high endothelial venules, T-nodules could be divided into "primary" and "secondary" T nodules. In all cases of dermatopathic lymphadenitis, very large aggregates of S-100 beta + and OKT6+ DCs, admixed with few high endothelial venules and variable numbers of OKT4+, Leu3a+ helper/inducer T cells, were observed and were termed "tertiary T-nodules." It is suggested that T-nodules represent the paracortical counterparts of B-lymphoid follicles and are the in vivo equivalents of DC/T-cell clusters observed in vitro. According to their cellular composition and localization in the lymph node, "primary" and "secondary" T-nodules probably represent subsequent maturation stages of distinctive nodular paracortical structures, which play an important role in the presentation of antigens to helper/inducer T cells and in the proliferation of antigen-responsive T cells. Their close topographic relationship to B-lymphoid follicles may indicate their role in the extrafollicular generation of antibody-forming cells.     

Sensorless estimation of pressure head and flow of a continuous flow artificial heart based on input power and rotational speed

The present study has proposed a new method for estimating the pressure head (P(t)[mm Hg]) and flow (Q(t)[L/min]) of a centrifugal pump on the basis of voltage (V(t)[V]), current (I(t)[A]), and rotational speed (N(t)[k(rpm)]) of the DC motor for a pump without any additional sensors. In the proposed estimation method, two auto-regressive exogenous (ARX) models are employed. One ARX model has an output, P(t) or Q(t), and three inputs, VI(t) = V(t)I(t) and N(t) and the steady state gain (K) of the system from VI(t) to N(t). It can be assumed that K may include the information on viscosity of blood. The coefficient parameters of this ARX model are identified in an off-line fashion before implantation of the pump. After implantation, P(t) or Q(t) is estimated by the same ARX model with the already identified parameters. The other ARX model is used to identify Kon the basis of VI(t) and N(t) in an on-line fashion every time the viscosity of blood may change. In the experiment, a mock circulatory system consisting of a centrifugal pump and a reservoir with 37% glycerin or water was employed. The root mean square error between measured Q(t) and its estimate obtained from the proposed method was 1.66L/min. On the other hand, a different method based on a single ARX model with inputs of VI(t) and N(t), but without the additional input of K, yielded the corresponding estimation error of 2.22L/min. This means that the proposed method can reduce its estimation error by about 25% in comparison with a method that cannot cope with the change in blood viscosity.     

CC chemokine receptor 4 ligand production by bronchoalveolar lavage fluid cells in cigarette-smoke-associated acute eosinophilic pneumonia

We examined the production of macrophage-derived chemokine (MDC/CCL22) and thymus- and activation-regulated chemokine (TARC/CCL17) by bronchoalveolar lavage fluid (BALF) cells in cigarette-smoke-associated acute eosinophilic pneumonia (CS-AEP). The CC Chemokine Receptor 4 (CCR4) ligand levels in BALF from patients with CS-AEP were considerably higher than those in healthy volunteers and correlated well with Th2 cytokine levels. Interleukin-4 enhanced CCR4 ligand production. MDC expression was observed in CD68-positive cells from patients with CS-AEP and in healthy control smokers. In contrast, TARC expression in CD68- or CD1a-positive cells was detected only in CS-AEP. An in vivo cigarette smoke challenge test induced increases in CCR4 ligands in the BALF and in the cultured supernatant of BALF adherent cells. These results suggest that alveolar macrophages and dendritic cells contribute to the pathogenesis of CS-AEP by generating CCR4 ligands, probably in response to cigarette smoke.     

An immunohistochemical study on a case of granulocyte-colony stimulating factor-producing gall-bladder carcinoma

Primary gall-bladder carcinoma producing granulocyte-colony stimulating factor (GCSF) is extremely rare. Only four cases, histologically investigated, have been reported to date in the English literature. We report a case of a 48-year-old female with primary gall-bladder carcinoma, associating with leukocytosis (15 700/mm3) and a high level of serum GCSF (54.0 pg/mL). The tumor was, histologically, a poorly differentiated adenocarcinoma with marked interspersed neutrophils invading into the primary tumor itself and the right lobe of the liver. Tumor cells distinctly showed positive immunoreaction in the cytoplasm with anti-GCSF antibody, and in the nucleus for anti-p53 antibody. After surgery, the leukocytosis and serum level of GCSF began to decrease. These findings confirmed the present case of GCSF-producing gall-bladder carcinoma, exhibiting leukocytosis. A total of five cases, including our case, reported as a GCSF-producing gall-bladder carcinoma were clinicopathologically reviewed.     

Developmental expression of carbonic anhydrase-related proteins VIII,X, and XI in the human brain

Three cDNA homologues of carbonic anhydrase with unknown biological functions have been reported: carbonic anhydrase-related proteins (CA-RP) VIII, X, and XI. In the present study, we produced monoclonal antibodies to these CA-RPs and studied their regional and cellular distributions in the human adult and fetal brains by immunohistochemical analysis. In the adult brain, CA-RP VIII was expressed in the neural cell body spreading to most parts of the brain. CA-RP X was expressed in the myelin sheath and its expression was shown in the cytoplasm of cultured tumor cells by immunocytochemical analysis. CA-RP XI was expressed in the neural cell body, neurites, and astrocytes in relatively limited regions of the brain. In the fetal brain, CA-RP VIII and XI were expressed in the neuroprogenitor cells in the subventricular zone as early as the 84th day of gestation and subsequently detected in the neural cells migrating to the cortex. CA-RP X first appeared in the neural cells in the cortex at the 141st day. In the choroid plexus, the epithelial cells gave CA-RP VIII and XI expressions in both adult and fetal brains.From the findings in the present study on the distribution and the developmental expression of CA-RP VIII, X, and XI in the human brain we suggest that these CA-RPs play roles in various biological process of the CNS.     

Immunoelectron microscopic study on the cross-reactivity of antibodies to adult T-cell leukemia-associated antigens in human and monkey sera

The cross-reactivity of antibodies to adult T-cell leukemia (ATL)-associated antigens (ATLA) in human and monkey sera was investigated by indirect immunoperoxidase and immunoferritin methods using a human cell line (MT-2) carrying a type C virus (HTLV), two monkey cell lines (Si-1 and Si-3) carrying HTLV, and a monkey cell line (Si-2) carrying a type C virus isolated from an anti-ATLA-positive monkey. Anti-ATLA-positive but not-negative human and monkey sera gave positive immunoperoxidase reaction with all four virus-positive cell lines when studied by light microscopy. Electron microscopic findings revealed ferritin or peroxidase labeling of virus particles and plasma membranes of these four cell lines with antibody-positive but not-negative human and monkey sera. These results clearly indicate the cross-reactivity of anti-ATLA antibodies in human and monkey sera at light and electron microscopic levels, and the presence of antigenic determinants common to the surface of type C virus particles of human and monkey origin.     

Periosteal osteosarcoma of the femur with bone marrow involvement: A case report

Periosteal osteosarcoma is an exceedingly rare type of chondroblastic osteosarcoma, showing rather better prognosis, and secondary bone marrow involvement is unusual. A case of a 22 year old male with periosteal osteosarcoma of the right femur with an associated bone marrow lesion is presented. The juxtacortical tumor, 16 ×11 × 9 cm, was located on the bone cortex of the upper diaphysis and extended into the surrounding soft tissues. A minimal bone marrow lesion was present, although the bone cortex was quite intact. Microscopically, the tumor consisted exclusively of atypical chondroblastic cells with a small osteoblastic area. The bone marrow lesion, interestingly, contained both multiple nodules of well-differentiated chondrosarcomatous components and a few demarcated foci of atypical spindle cells producing a fine osteoid matrix. It was reasonable to conclude, therefore, that this tumor was a periosteal osteosarcoma with an unusual secondary bone marrow lesion rather than a conventional (central) chondroblastic osteosarcoma with soft tissue invasion. The patients good prognosis with no tumor recurrence or metastasis during more than 7 years follow-up after surgery supports this conclusion.     

T-cadherin (CDH13, H-cadherin) expression downregulated surfactant protein D in bronchioloalveolar cells

T cadherin is a unique cadherin cell adhesion molecule that is anchored to the surface membrane through a glycosyl phosphatidyl inositol (GPI) moiety. In the present study, we postulated that T cadherin could regulate surfactant protein (SP)-D gene expression in human bronchioloalveolar type-II cells. We transfected A549 cells (human lung cancer cell line with alveolar type-II cell characteristics) with the T-cadherin expression vector. Both original and control plasmid-transfected A549 cells expressed SP-D; however, neither human nor murine T-cadherin-transfected A549 cells expressed SP-D mRNA. The downregulation of SP-D production in human T-cadherin-expressed A549 cells was also demonstrated using Western immunoblotting techniques. Control vector-transfected A549 cells showed a positive band of SP-D but not of T cadherin. In contrast, T-cadherin-transfected A549 cells, which expressed T-cadherin protein, did not produce SP-D. We further examined the relationship of T cadherin and SP-D expression in secondary pulmonary alveolar proteinosis associated with hematolymphoid malignancies. SP-D was detected in bronchioloalveolar type-II cells in alveolar proteinosis. However, little or no T-cadherin expression was detected in alveolar type-II cells in these patients. To our knowledge, this is the first report describing an effect of cadherin on SP production in bronchioloalveolar cells.     

Effects of succinylated concanavalin A on infectivity and syncytial formation of human immunodeficiency virus

The effects of various lectins on the infectivity of human immunodeficiency virus (HIV) type 1 was investigated. Among the 25 lectins investigated, 2 types of concanavalin A (Con A) and 3 types of phytohemagglutinin were found to inhibit HIV infection. Succinylated Con A (S-Con A) efficiently blocked HIV-induced formation of syncytia in a coculture of MOLT-4 cells and blocked cell-free infection by HIV of MT-4 cells. The HIV-binding study revealed that S-Con A only partially inhibited viral binding to cells, although the control Leu-3a monoclonal antibody strongly inhibited it. When S-Con A was added to cultures after the initiation of viral adsorption, the number of HIV antigen-positive cells that developed depended on the time interval before addition of the compound. S-Con A inhibited HIV infection even after viral binding to cells at 0 °C and further incubation at 37 °C for 1 day. These data suggest that S-Con A inhibited mainly the fusion process rather than viral binding to cells in exerting its anti-HIV activity.     

Determination of the prognostic significance of cyclin B1 overexpression in patients with esophageal squamous cell carcinoma

 Recent studies have identified a family of proteins referred to as cyclins, which control the cell cycle. Cyclin B1 activates cdc2, which regulates cell progression through the G2 and M phases. The main aim of this study was to examine the relationships between the cyclin B1 expression in human esophageal squamous cell carcinoma (SCC) and clinicopathological factors and prognosis of the patients. Eighty-seven cases of primary human SCC consecutively obtained at esophagectomy were immunohistochemically studied using an anti-human cyclin B1 protein antibody (2H1-H6). The relationship between cyclin B1 expression and clinicopathological factors, including prognosis, were also statistically assessed. Positive immunostaining of cancer cells, mainly in the cytoplasm, was detected in 72.4% (63/87): heterogeneous pattern in 37.9 % (33/87) and homogeneous pattern in 34.5% (30/87). The prevalence of cyclin B1 expression was significantly higher in cases with invasion deeper than the muscularis propria (P<0.005) and with venous invasion (P<0.01) than in other cases. Patients whose SCCs expressed high levels of cyclin B1 protein had a significantly poorer prognosis than did the other patients (P<0.05). Multivariate analysis demonstrated that cyclin B1 status was an important factor affecting survival (P<0.05). These findings demonstrated that overexpression of cyclin B1 protein is associated with tumor behavior and prognosis for patients with human esophageal SCC. Received: 25 June 1998 / Accepted: 21 October 1998