Mixed connective tissue disease with fatal pulmonary hypertension and a review of literature

Summary The paper presents an autopsy case of mixed connective tissue disease (MCTD) with pulmonary hypertension (PH) and a review of literature. A 33-year-old woman with Raynaud's phenomenon and dyspnea of one year duration was diagnosed as having MCTD on the basis of a higher titer (1:163,840) of serum antibodies to the ribonucleoprotein (RNP). Cardiac catheterization showed complicating PH, confirmed an autopsy by the findings of concentric intimal cellular proliferation and typical plexiform lesions in the small arteries and arterioles of the lung, suggesting primary PH. Fatal PH with MCTD has been reported only 6 cases in literature including our case. All were young females, with histopathological findings consistent with plexogenic pulmonary arteriopathy in 5 cases and with recurrent pulmonary thromboembolism in the other. The aetiology of PH is still unknown, but it may be due to vasoconstriction evoked by the hyper-reactivity of the vessels.     

Bradykinin Stimulates Type II Alveolar Cells to Release Neutrophil and Monocyte Chemotactic Activity and Inflammatory Cytokines

In the present study, we evaluated the potential of bradykinin (BK) to induce the release of neutrophil and monocyte chemotactic activity (NCA and MCA) and cytokines from an alveolar type II epithelial cell line, A549 cells. BK stimulated A549 cells to release NCA and MCA in a dose- and time-dependent manner (P < 0.001). Checkerboard analysis revealed that both NCA and MCA involved chemotactic and chemokinetic activity. Molecular sieve column chromatography showed three molecular weight masses (near 19 kd, 8 kd, and 400 d) for NCA and several molecular weight peaks (near 66 kd, 25 kd, 19 kd, 16 kd, and 400 d) for MCA. The release of NCA and MCA was inhibited by cycloheximide and lipoxygenase inhibitors (P < 0.01). The NCA and MCA were inhibited by leukotriene B4 (LTB4) receptor antagonist (P < 0.01), and the concentration of LTB4 was high enough for NCA and MCA. Antibodies to interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) attenuated NCA (P < 0.01), and antibodies to monocyte chemotactic protein-1 (MCP-1), G-CSF, and transforming growth factor (TGF)-β attenuated MCA (P < 0.01). The levels of IL-8, G-CSF, MCP-1, and TGF-β increased time dependently (P < 0.01). BK also stimulated the release of ILeukin-6 from A549 cells (P < 0.001). The receptors responsible for the release of NCA, MCA, and individual chemokines involved both BKB1 and BKB2 receptors. These data suggest that BK may stimulate alveolar type II pneumocytes to release inflammatory cytokines, which then may modulate the lung inflammation.     

Adhesion polypeptides are useful for the prevention of peritoneal dissemination of gastric cancer

We examined the effect of adhesion polypeptides on the adhesion and invasiveness of gastric cancer cell lines. We previously reported the establishment of an extensively peritoneal-seeding cell line, OCUM-2MD3, from a poorly seeding human scirrhous gastric carcinoma cell line, OCUM-2M. Both 21 and 31 integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM-2M cells, and the ability of OCUM-2MD3 cells to bind to the extracellular matrix (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion polypeptides, YIGSR and RGD, and two RGD derivatives significantly inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well differentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal dissemination given YIGSR sequenc e intraperitoneally was obviously longer than that of untreated mice. The survival of mice treated with RGD was also improved, and this effect was increased using the RGD derivatives, poly(CEMA-RGDS) and CM-chitin RGDS. These polypeptides appear to block the binding of integrins, which are expressed on OCUM-2MD3 cells, to the submesothelial ECM, and consequently inhibit peritoneal implantation. The peritoneal injection of adhe-sion polypeptides may be a new therapy against the dissemination of scirrhous gastric cancer, and may be useful for the prevention of dissemination in high-risk patients. © Rapid Science Ltd.     

Hemolytic pattern of erythrocytes in the newborn measured by the coil planet centrifuge system and its relationship to neonatal jaundice

Dynamic osmotic fragility of erythrocytes in cord blood and its changes during the neonatal period were studied by means of a coil planet centrifuge system. The starting-point for hemolysis in the newborn become similar to that of adult blood after approximately a week, while the shift of the end-point to the adult range required one month or more.The percentage of fragile cord blood cells with a hemolysis starting-point above 110 m osmol and the maximum bilirubin level during neonatal period were examined. A high percentage of fragile cells was associated with high bilirubin levels, and when fragile cells comprised more than 7.0% of the total cord blood erythrocytes, the bilirubin level tended to rise above 15 mg/dl.This study was aided by a grant from the Ministry of Health and Wellfare of Japan for research on handicapped children, 1976     

Soluble asialoglycoprotein receptors reflect the apoptosis of hepatocytes

Cell death is thought to take place through at least two distinct processes: apoptosis and necrosis. There is increasing evidence that dysregulation of the apoptotic program is involved in liver diseases. However, there is no method to simply evaluate apoptosis in the liver tissue at present. It has been reported that the expression of asialoglycoprotein receptors (AGPRs) increases with apoptosis, but there is no report until now that investigates the influence of soluble AGPRs on apoptosis of hepatocytes. Soluble AGPRs have been reported to be present in human serum under physiological conditions. In the present study, in order to investigate the correlation between apoptosis of hepatocytes and soluble AGPR, mouse soluble AGPRs were detected using SDS-PAGE and Western blot analysis was conducted using anti-extracellular mouse hepatic lectin-1 (Ex-MHL-1) antiserum (polyclonal rabbit serum). The mouse soluble AGPRs were present in culture medium and mouse serum when hepatocytes were damaged. The soluble AGPRs increased proportionately, as the number of dead hepatocytes increased. In addition, soluble AGPRs existed more when apoptotic cell death was observed in in vitro and in vivo than when necrotic cell death was observed. The extracellular moiety of MHL-1 exists in the culture medium and mouse serum as a soluble AGPR, but the detailed mechanism of releasing soluble AGPR from hepatocytes has not been revealed yet. We described the first evidence for the relation between quantity of soluble AGPRs with two kinds of cell death: necrosis and apoptosis. Based on the results of our study, soluble AGPRs might become a new marker of apoptosis in the liver tissue and be useful for clinical diagnosis and treatment for liver diseases.     

Relationship of third molar development and root angulation

Angled roots are seen in mandibular third molars, which have a high frequency of incomplete impaction. We examined the relationship between incomplete impaction and angled roots. We enrolled orthopantomographs to determine the prevalence of angled roots in 239 men and 222 women aged 21--35 years with bilateral mandibular third molars. Angled roots were more frequent in subjects in whom the third molars had a different status on each side than in those with the same status on both sides (men: P<0.05; women: P<0.01). The incidence of women with angled roots in those with bilateral incomplete impactions was higher than that in those with bilateral eruption (P<0.01). Angled roots among mandibular third molars are related to environmental factors. Angled roots occur more frequently in women with incomplete impaction than in those with full eruption.     

Different mechanisms involved in interhemispheric transfer of visuomotor information

Twenty-one subjects underwent event-related fMRI while carrying out a simple visuomotor task in which they responded to stimuli flashed either onto the right visual field, onto the left visual field, or onto both visual fields at once. The aim of this study was to clarify areas of brain activity associated with crossed-uncrossed differences (CUD) and to investigate differences of the brain activity between CUD and redundancy gain. An intriguing brain activation related to CUD was found in the genu of the corpus callosum (CC). The sites of activation related to redundancy gain were the extrastriate cortex and the cingulate cortex. Our results suggested that CUD depended on the interhemispheric transfer via the CC, and that CUD and redundancy gain involved different brain mechanisms.     

Twenty-five years followup of patients who had valgus osteotomy for arthritic hips

We reviewed the long-term outcomes of intertrochanteric valgus femoral osteotomies in patients with arthritic hips to clarify any influencing factors. One hundred six patients (127 hips) were followed up during an average of 25 years. The average age of the patients at surgery was 42 years. The preoperative extent of degenerative change was classified radiologically into one of four grades according to the criteria of T?nnis. Radiographic measurements of acetabular coverage were made using AP radiographs obtained immediately after surgery. Thirty-eight patients (41 hips) had total hip arthroplasties; the 25-year survival rate was 69%. Radiologic evaluations of patients with mild preoperative degenerative changes (T?nnis Grade 1) improved and good clinical outcomes were obtained. In addition, radiologic evaluations of patients whose hips had better acetabular coverage (center-edge angle > 0 degrees, sharp angle < 50 degrees, or acetabular head index > 60%) also improved. However, radiographic measurements did not influence clinical scores. The mean score of patients younger than 50 years at surgery was higher than patients older than 50 years. The mean score of patients with unilateral hip involvement was higher than patients with bilateral involvement. Therefore, valgus osteotomies seem appropriate for younger patients with unilateral involvement.     

Colon Cancer in a 14-Year-Old Female With Turner Syndrome

A 14-year-old female with Turner syndrome (karyotype 45,X) had a history of abdominal pain with distention, constipation, and fever. She was first operated on for the suspicion of appendicitis, failed to improve, and was later hospitalized for further investigation and treatment. Studies demonstrated an obstructing tumor of the transverse colon, and an emergency laparotomy was performed. The final diagnosis was a signet-ring cell carcinoma of the colon with diffuse peritoneal dissemination and metastasis to paracolic lymph nodes. On the basis of this case, we report the association of Turner syndrome with malignancies and also some aspects of colon cancer in childhood.