Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling

 In order to determine the dynamics of hematopoietic cell turnover, proliferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patients (20 in each group) included in addition to a control group, idiopathic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary polycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) thrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloid leukemia (AML). Apoptosis was demonstrated by the in situ end-labeling technique (ISEL) and proliferative activity by applying the monoclonal antibody PC10 raised against proliferating cell nuclear antigen (PCNA). To assess dynamic features of hematopoiesis, an index was calculated consisting of the ratio between PCNA-positive nuclei and the apoptotic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was significantly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH showed no relevant enhancement of this index in comparison to the control specimen. In vitro experiment results are in keeping with the finding that PG and PTH are not associated with a significant expansion of the erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryocyte proliferation (CFU-MEG) is the predominant feature of cell turnover. Differences between PTH and TH are in line with the reduced in vitro formation of CFU-MEG in the latter disorder. In conclusion, our in situ study on turnover rates of the bone marrow in various neoplastic and reactive lesions extends previous experimental data on hematopoietic cell kinetics. Received: 10 March 1997 / Accepted: 18 May 1997     

Assessment of deposition of inhaled aerosol in the respiratory tract of man using three-dimensional multimodality imaging and mathematical modeling.

Multimodality medical imaging enables measurement of the three-dimensional spatial distribution of a radiolabeled aerosol within the lung. Using a conceptual spatial morphological model these data may be transformed to provide information on deposition per airway generation. This methodology has been used to study the intrapulmonary deposition patterns of two formulations of a metered dose inhaler and two nebulizers in control subjects. The nebulizer study has also been stimulated using a computer model of deposition. The comparison between derived experimental results and those from computer modeling shows areas of agreement, although there are also areas of discrepancy. The new methodology has considerable potential value in the fields of inhalation therapy and deposition modeling, although more detailed validation is still required.     

Uveitis and immune responses in primates immunized with IRBP-derived synthetic peptides

Monkeys immunized with bovine IRBP-derived synthetic peptides R4 (sequence 1158-1180) or R14 (1169-1191) developed EAU which was detected by both clinical and histological examinations. The inflammation localized mainly in the choroid, with only minor changes being noticed in the adjacent retinal tissue. EAU developed in only one of the two monkeys immunized with each of the peptides and the animals with disease also showed higher levels of cellular immunity toward the immunizing peptide than did the monkeys with no disease. The cellular immune responses, measured by the lymphocyte proliferation assay, were specific toward the immunizing peptides, with no cross responsiveness to whole IRBP. This finding suggests that the two uveitogenic peptides were non-immunodominant in the tested monkeys. In contrast, peptide R14 is highly immunodominant in the Lewis rat. Also, the fine specificity of the monkey response to R14 differed from that of the Lewis rat. The possible genetic control of the monkey susceptibility to EAU induction by the peptides is discussed and the unique finding of an autoimmune disease induction by a non-immunodominant peptide is underscored.     

Evaluation of preoperative chemoembolization using ethiodized oil, cisplatin and gelatin sponge (sandwich therapy) for hepatocellular carcinoma

The significance of preoperative chemoembolization using ethiodized oil, cisplatin and gelatin sponge (Sandwich therapy) for resectable hepatocellular carcinoma (HCC) was evaluated. One hundred and thirteen patients with solitary and less than 10 cm sized HCC who underwent radical hepatic resection were chosen for this study. Fifty-three patients received Sandwich therapy before surgery (Group A), and the remaining 60 patients under-went surgery without any preoperative treatments (Group B). Any background factors between two groups were not significantly different. The anticancer effects of this therapy were evaluated by histologic examination in 31 patients who had preoperative Sandwich therapy. In 22 of 31 patients (71%), the main nodules were completely necrotic. The ratios of patients with complete necrosis in daughter nodules were 7/12 (58%), in portal vein tumor emboli, 7/10 (70%), in intracapsular invasions, 11/21 (52%), in extracapsular invasions, 4/11 (36%). The 4-year disease-free survival rates in Group A and Group B were 56% and 27% respectively, and the rate of the former was significantly higher than that of the latter (p less than 0.05). The 4-year survival rates in Group A and Group B were 83% and 53% respectively. The rate of Group A was also significantly higher than that of Group B (p less than 0.01). We concluded that preoperative Sandwich therapy was very significant to obtain successful long-term disease-free survival and survival in regard to relatively early stage HCC.     

The role of static-dynamic factors in genesis of femoral head and neck deformation in dysplastic hips. A physical-mathematical interpretation ]

The clinical material for a physical-mathematical analysis of femoral head and neck deformations in subluxated and luxated hips consisted of 1.574 case histories of children operated on in 1954-1988. In that material 21.9 per cent of the children had preoperative growth disorders of the head, and in the half of the cases also the femoral neck was involved. In 10.79 per cent of the children pre- and postoperative trophic disorders were also observed. On the basis of the physical-mathematical analysis of static-dynamic factors of the hip, it has been determined that the disordered shape of the femoral head and neck is most of all the result of defective formation of the roof. The oblique roof changes the static and dynamic forces acting on the femoral head and neck in such a way that large overloading of the growth zones of the medial side occurs and is followed by development of proximal femur deformation.     

Background-protein effects on fluorophotometric data.

Fluorescent tracers are commonly used in fluorophotometric studies of ocular fluids and tissues that contain background protein. Background-protein concentrations were found to decrease or increase significantly the measure of fluorescence emitted from solutions containing sodium fluorescein, fluorescein-labeled dextran, or fluorescein-labeled horseradish peroxidase. The effect of background protein on fluorescence was expressed as a function of the specific fluorescent tracer, tracer concentration, and background-protein concentration; it can be corrected in the analysis of fluorophotometric data. Fluorophotometric studies--particularly those in which the background-protein level is expected to be abnormally high, such as postoperative and pathologic studies--may need to include either a data correction based on measured effects of background protein on tracer fluorescence or, in the case of clinical investigations, recognize at least the potential for a range of possible interpretations.