Intra-bone marrow-bone marrow transplantation facilitates hemopoietic recovery including dendritic cells

In this report, we provide evidence using a serial bone marrow transplantation (BMT) protocol that intra-bone marrow (IBM)-BMT (IBM-BMT) can efficiently reconstitute the hemopoietic system with cells of donor origin, in contrast to conventional intravenous (IV)-BMT (IV-BMT). Furthermore, the hematolymphoid system of secondary recipients that had received bone marrow cells (BMCs) from primary recipients treated with IBM-BMT recovered earlier than that of the secondary recipients of BMCs from primary recipients treated with IV-BMT. This was the case when the Lin-/c-kit+ progenitor cells of the secondary and tertiary recipients were examined. These findings indicate that IBM-BMT can facilitate the development of not only cells of various lineages but also the effective generation and, more importantly, the maintenance of the progenitor cells. Furthermore, we show that IBM-BMT can reconstitute the dendritic cell (DC) subsets (myeloid and lymphoid DCs), which are critical for the initiation of both adaptive and innate immune responses. The frequency of both myeloid and lymphoid DC subsets was approximately equal to that of normal age-matched untreated controls and, after second and third BMT, this ratio was close to that observed in the normal controls. However, the lymphoid DCs were clearly reduced in the secondary and tertiary recipients of BMCs from mice that had received IV-BMT. Therefore, the development of DC subsets is also normally maintained in the IBM-BMT group.     

Chromium-induced pulmonary cancer. Report of a case and a review of the literature

A 57-year-old man, whose occupational history was that of a chromate worker for about 35 years, suffered nasal perforation during and died due to pulmonary cancer. In the autopsy materials, the concentration of chromium in the lung tissues was very high, being about 90 times the amount found in normal lungs. The chromium particles in the lung tissues could not be detected by analytical electron microscope, but they could be found in the anthoracotic lesions of the lungs by means of an X-ray microanalyser. The present case was judged to be a case of chromium-induced pulmonary cancer since all the pathologic data obtained were similar to those found in similar cases reported in the literature.     

Immunological functions in food-restricted rats: enhanced expression of high-affinity interleukin-2 receptors on splenic T cells

Several immunological functions of B and T cells including IL-2 receptor expression on T cells were measured in 12-month-old Fisher-344 male rats maintained from 6 weeks of age on an ad libitum (AL) or a 40% food-restricted (FR) diet. Direct anti-SRBC plaque-forming cell (PFC) assays revealed a higher response in FR rats than in AL rats when splenocytes were cultured with or without recombinant interleukin-2 (rIL-2). B cell functions were studied by using nylon wool-purified splenic B cells stimulated either with rIL-2, lipopolysaccharide (LPS), or Salmonella typhimurium mitogen (STM) as a thymus-independent antigen. Reserve plaque assay showed no difference between FR and AL rats in the secretion of anti-IgM and anti-IgG antibodies. In addition, no difference was found in proliferation of B cells stimulated by LPS, STM mitogens or rIL-2. Although purified splenic T cells demonstrated an equally proliferative response in FR and AL rats when cultured with concanavalin A (Con A) or phytohemagglutinin (PHA), T cells in FR rats developed higher responses when stimulated with an alloantigen and rIL-2. Time-course studies carried out to measure high-affinity (HA) IL-2 receptor (R) molecules by using purified T cells with rIL-2 and 125I-labeled IL-2 revealed a higher expression of IL-2R molecules on T cells of FR rats than on T cells of AL rats at 72 h after culturing with Con A.(ABSTRACT TRUNCATED AT 250 WORDS)     

The structure of human metaphase chromosomes: its histological perspective and new horizons by atomic force microscopy

Studies on the structure of the human chromosome were reviewed from the histological perspective and discussed in connection with our recent findings obtained mainly by atomic force microscopy (AFM). In this paper, we introduce several hitherto known models of the high-order structure of the metaphase chromosome and discuss the actual structure of chromosomes in relation to such structures as spiral chromatids, chromosome bands, and chromosome scaffolds. In chromosomes treated with Ohnuki's hypotonic solution, the chromosome arms were elongated and showed a characteristic spiral pattern of chromatid fibers. On the other hand, alternating transverse ridges and grooves were clearly observed on the surface of chromosomes treated with 0.025% trypsin for G-banding, and these ridges and grooves corresponded to the dark and pale bands of G-banded chromosomes. Similar findings were also found in chromosomes treated with quinacrine mastards for Q-banding. Fibers bridging the gap between the sister chromatids were often observed in G/Q-banded chromosomes; these fibers tended to be restricted within the G/Q-positive portions, suggesting the presence of chromatin fibers bridging these regions. Based on these findings in conjunction with previous studies, we outlined the high-order structure of the human chromosome. Recent advances in nanotechnology have provided new AFM techniques for the imaging and handling of materials at nano-scale resolution. Application of these techniques to chromosome research is expected to provide valuable information on the chromosome structure in relation to its function.     

Laboratory interpretive reporting system. A prototypical approach for knowledge representation in acid-base and electrolyte disorders]

It is important to realize the problem-oriented diagnosis and the goal-oriented one to support general physicians as clinical decision makers under so many laboratory tests more than full with using practically. A prototypical model for computer-assisted interpretation of laboratory data was presented. To achieve both function of the problem-oriented inference and the goal-oriented one, knowledge base in this system was structured using the methods of semantic network and qualitative reasoning. Superficial knowledge level characterized by the intuitive reasoning from test results to diseases and deep knowledge level referring to the relations among the pathophysiologic states were stratified, and the heuristics based on the experiences at bed-side were incorporated in this knowledge representation. The pathophysiologic states were distilled from the textbooks and the articles, and were linked together by the relationships of cause and result, such as functional, constraint or conceptual relationship. Diagnostic knowledge on the computer was reconstructed by the causal network representing the pathological process as qualitative chaining between the pathophysiologic states, and was corrected and compiled by the clinical experiences and the experimental facts. Abnormal test data became a trigger of the start of inference, and presumptive pathophysiologic states and diagnoses were fired on the causal network. Consequently, the most important pathophysiologic states might become to be clear to understand the cause of changes of laboratory data.     

The expression of B7-H1 on keratinocytes in chronic inflammatory mucocutaneous disease and its regulatory role

PD-1 and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, have been identified recently as CD28-B7 family molecules that are implicated in immune regulation. Lichen planus (LP) is a T cell-mediated chronic inflammatory mucocutaneous disease. We investigated the expression and function of PD-1 and its two ligands in LP. Immunohistochemical examination revealed the abundant expression of PD-1 and B7-H1 in infiltrating T cells and macrophages, and lower-level expression of B7-DC on macrophages in the subepithelium. Interestingly, substantial expression of B7-H1 on keratinocytes (KCs) was found close to the numerous T cell infiltrates in the subepithelium. Unstimulated cultured KCs expressed both B7-H1 and B7-DC, and their expression was upregulated by proinflammatory cytokines, particularly IFN-gamma. The T-cell proliferative responses and IFN-gamma production that were induced by IFN-gamma-treated KCs were augmented preferentially by anti-B7-H1 mAb, but not by anti-B7-DC mAb. These results indicate the regulatory role of B7-H1 on KCs in the interactions with T cells. Our results suggest that the induction of B7-H1 on KCs may play an important role in tolerance induction in the inflamed oral mucosa and skin.     

A comparative, well-controlled study of ceftizoxime suppository against ceftizoxime intravenous injection in infantile acute pneumonia

We have attempted to clinically define the therapeutic usefulness of ceftizoxime suppository (CZX-S) in children with bacterial pneumonia, in a randomized trial. Intravenous injection of ceftizoxime (CZX) was used as the control. The results are summarized below. Subjects were inpatients with bacterial pneumonia, ranging in age from 9 months to 7 years and 10 months. As a rule, the daily dose was either four 250 mg (in potency) suppositories given at 6-hour intervals or 60 mg/kg body weight intravenous CZX (control) given in 4 injections at 6-hour intervals over a period of 7 days. The number of children in the study was 67. These children were divided into 2 dosage groups (suppository, 35; injection, 32) with matching pretreatment background factors. The severity of the target disease in the majority of the children was "moderate". The rate of therapeutic effectiveness was 97.1% for the suppository and 93.8% for the injection, and did not differ significantly between the 2 groups. Rates of efficacy by severity, presence or absence of underlying diseases, daily dose and/or complications were high without exception, and did not differ significantly between the 2 groups. Eradication rates for causative microorganisms, as studied in 16 children of each group, were both 93.8%. The 2 most frequently isolated causative organisms were Haemophilus influenzae and Streptococcus pneumoniae. Side effects were examined for 36 children of each group. The frequency of side effects did not differ significantly between the suppository group (2 with diarrhea and 1 with abdominal pain) and the injection group (1 with urticaria), and 8.3% and 2.8%, respectively. The frequency of abnormal laboratory test findings differed significantly (P less than 0.01) with respect to eosinophilia which occurred in 7 (20.6%) of the injected subjects but was not encountered in the subjects treated with suppositories. Other abnormal laboratory findings included thrombocytosis in 3 (14.3%) of the injection group and increased GOT in 1 (3.2%) of the suppository group. The suppository formulation of CZX appears to be a highly useful substitute for the injectable form, and should find a special use in children whose treatment with injections experiences some difficulty.     

Expression of membrane-bound and soluble receptor activator of NF-kappaB ligand (RANKL) in human T cells

The receptor activator of NF-kappaB ligand (RANKL) and its receptor RANK are critical regulators for immune responses as well as bone remodeling. RANKL is a type II transmembrane protein that has two forms-a membrane-anchored protein and a secreted protein. In this report, we demonstrate for the first time the kinetical expression of two forms of RANKL in human T cells using two monoclonal antibodies (mAbs) against human RANKL, which we newly derived. Freshly isolated T cells rarely expressed mRANKL, while the activation of T cells induced a substantial but minimal level of mRANKL as well as the accumulation of considerable amounts of sRANKL. The addition of the metalloprotease inhibitor KB-R8301 efficiently suppressed the release of sRANKL from activated T cells or RANKL-transfectants, and reciprocally enhanced the mRANKL expression. The membrane form of RANKL was also expressed on the infiltrating T cells in the rheumatoid synovial fluid and in the gingival tissues of patients with periodontitis. Our results demonstrate that the expression of mRANKL on T cells is strictly limited, and the majority of RANKL protein produced by T cells may be active in the soluble form after shedding. The mAbs that were derived in this study may be useful for investigating the regulation and function of RANKL in immune responses and bone remodeling.     

Experimental and clinical evaluation of the splenic capping method in the treatment of injured spleens

Polyglycolic acid elastic mesh was tailored and wrapped around the entire surface of experimentally injured spleens in 11 dogs, while carefully avoiding the splenic hilum, like a "hair-net", to achieve complete hemostasis by compression. All 11 dogs survived the experiment with no postoperative bleeding observed. Histological examination, performed 6 weeks postoperatively, revealed histiocytes, fibroblastic proliferation with collagen and cellular collagenized fibrous tissue forming a neocapsule covering the spleen. Hematologically, the platelet count was increased at 2 weeks postoperatively, but subsequently decreased to within the normal levels by 4 weeks. We employed this splenic capping method clinically in four cases to avoid splenectomy and sufficient hemostasis with ultimate splenic recovery was achieved in each case without any abscess formation, postoperative bleeding, or complications related to the use of the mesh. These experimental and clinical results thus indicate the efficacy and safety of the splenic capping method for preserving the injured spleen.