Temporal bone histopathological findings in campomelic dysplasia.

Both temporal bones of a newborn (35 gestational weeks old) with campomelic syndrome were studied histopathologically. This is to our knowledge the second temporal bone report (third case) of this syndrome. The findings included: abnormal cartilagenous and osseous tissues and abnormality in the globuli interossei in the otic capsule; deformities of the vestibule and semicircular canals, probably due to compression by the abnormal cartilaginous tissue; hypoplastic cochlea and semicircular canals; aberrant course of the facial nerve; wide dehiscence of the facial canal in the tympanic portion; slight hypoplasia of the malleus and anomalies in the incus and stapes; and large epitympanic space. These findings closely resembled those of the first report, and suggest that: 1) campomelic dysplasia is a definite disease entity with consistent pathogenesis, and 2) similar otologic manifestations may be expected in the majority of patients with this syndrome.     

Comparison of Incorporation and Extension of Nucleotides in vitro opposite 8-Hydroxyguanine (7,8-Dihydro-8-oxoguanine) in Hot Spots of the c-Ha-ras Gene

DNA templates with 8-hydroxyguanine (7,8-dihydro-8-oxoguanine, oh⁸Gua) at a site corresponding to the first or second position of codon 12 of the c-Ha-ras gene were prepared, and the nucleotides inserted opposite the modified base were compared. The Klenow fragment (KF) of Escherichia coli DNA polymerase I inserted C opposite oh⁸Gua at both positions. Taq DNA polymerase incorporated C and A opposite oh⁸Gua, and the ratio of C to A was higher at the first position than at the second position. DNA polymerase α (pol α) inserted A and C at the first position, and A at the second position of codon 12, indicating that the ratio of C to A was higher at the first position. Moreover, we studied the extensions of bases paired with oh⁸Gua by DNA polymerases with or without 3'-5'exonuclease activity. G and T opposite oh⁸Gua were removed, and subsequently C was inserted by KF. We found that an oh⁸Gua:A pair was recognized by the exonuclease activity of the enzyme and that A was partially subsituted by C. On the other hand, pol α extended only C and A opposite oh⁸Gua. No difference was observed with oh⁸Gua at the two positions. These results indicate that the ratio of nucleotides incorporated opposite oh⁸Gua depends on the sequence context, while there is no particular difference in the extension of base pairs involving oh⁸Gua by DNA polymerases.     

Presence in Pieris rapae of Cytotoxic Activity against Human Carcinoma Cells

Cytotoxic activity in extracts of pupae and adults of various kinds of butterflies and moths was tested in vitro against the human gastric carcinoma cell line, TMK-1, which was chosen as an example of human carcinoma cells. Among the species examined, cytotoxicity was limited to Pieris rapae, Pieris napi and Pieris brassicae . Activity was found down to a dilution of 1/10⁴, while with the other butterflies and moths no activity was observed, even at 1/10². When the cytotoxicity of the three developmental stages, larvae, pupae and adults, of Pieris rapae was compared, the pupae showed the strongest activity, the IC₅₀ against TMK-1 cells being at the 1/10⁶ dilution. For larvae and adults, the respective IC₅₀ values were at the 1/10⁵ and 5/10⁵ dilutions. The active principle in the pupae of Pieris rapae was found to be heat-labile and not extractable with organic solvents, but precipitated with ammonium sulfate and digested by proteases, suggesting that it is a protein. This cytotoxic factor was named pierisin.     

Clinicl Significance of Mesangial IgM Deposits in Minimal Change Nephrotic Syndrome

The clinicopathologic features and the response to corticosteroid therapy were compared in 9 patients with minimal change nephrotic syndrome (MCNS) and diffuse mesangial IgM deposits (Group I) and in 32 of those without IgM deposits (Group II). However, serum IgM levels in Group I in both relapse and remission were significantly higher than those of Group II and controls (p<0.001). In Group I mesangial IgM deposits were diffuse in 9 (100%), mesangial C_1q was present in 4, IgA and fibrinogen were each observed in 1, respectively. Electron dense deposits in the mesangium were also present in 2 to 5 patients in Group I. No significant differences were found between the two groups in age of onset, sex ratio, laboratory data except for serum IgM level, duration before biopsy, follow-up periods, outcome, and response to steroid therapy. Our data suggest that a more severe degree of either impairment of mesangial clearance of IgM or overproduction of IgM may be involved in patients with MCNS and mesangial IgM deposits but that these patients could not be considered a distinct group of patients.     

Hot spring bath and Legionella pneumonia: an association confirmed by genomic identification

A 59-year-old man developed pneumonia 9 days after bathing in a hot spring spa. Bilateral shadows on his chest radiograph rapidly progressed after admission. He was successfully treated with erythromycin and rifampicin. Legionella pneumophila serogroup 6 was recovered from an intratrachial specimen and a significant elevation was observed in a paired indirect fluorescent antibody to Legionella. Persistent slight fever and chest rentogenographic shadows resolved after administering low-dose prednisolone to treat organizing pneumonia shown by transbronchial lung biopsy. The same serotype of Legionella was recovered from the water of the hot spring spa where the man had bathed. When the extracted DNA of these two strains showed identical restriction fragments by pulsed-field gel electrophoresis, we had direct evidence that hot spring spas can be a source of Legionella pneumonia.     

Superimposition of post-streptococcal acute glomerulonephritis on the course of IgA nephropathy: predominance of Th1 type immune response

A 23-year-old man was admitted with macrohematuria and systemic edema appearing after an acute upper respiratory tract infection. He had been diagnosed 6 years earlier with IgA nephropathy (IgA-N). On admission, hypertension, nephrotic syndrome and hypocomplementemia were evident together with a high titer of anti-streptokinase (ASK). Renal biopsy showed severe glomerular mesangial proliferation, segmental endocapillary proliferation and crescent formation. Immunofluorescence microscopy (IF) showed strong deposition of C3 and reduced deposition of IgA. Electron microscopy showed a so-called "hump" on the epithelial side of the glomerular basement membrane.These features were consistent with post-streptococcal acute glomerulonephritis (PSAGN) superimposed on IgA-N. Following 2 weeks of observation, blood pressure, C3 level and ASK titer returned to normal ranges, although nephrotic syndrome was still evident, which necessitated oral prednisolone (30 mg/day) therapy. Another biopsy taken 2 months later demonstrated regression of endocapillary proliferation and IF showed decreased deposition of C3. Immunohistochemical staining of the specimen taken on admission revealed the presence of numerous T cells and macrophages in the interstitium. Macrophages were also seen in the glomerular tuft. Many interstitial infiltrating cells were positive for interferon-gamma, but their number diminished after treatment. Our findings suggest that PSAGN complicating pre-existing IgA-N activates cellular immunity and augments renal tissue injury.     

Inhibition of tumor-promoting effects by poricoic acids G and H and other lanostane-type triterpenes and cytotoxic activity of poricoic acids A and G from Poria cocos

The structures of two novel 3,4-seco-lanostane-type triterpenes isolated from the sclerotium of Poria cocos were established to be 16alpha-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid (1; poricoic acid G) and 16alpha-hydroxy-3,4-seco-24-methyllanosta-4(28),8,24(24(1))-triene-3,21-dioic acid (2; poricoic acid H) on the basis of spectroscopic methods. These two, and eight other known compounds isolated from the sclerotium, poricoic acid B (3), poricoic acid A (4), tumulosic acid (5), dehydrotumulosic acid (6), 3-epidehydrotumulosic acid (7), polyporenic acid C (8), 25-hydroxy-3-epidehydrotumulosic acid (9), and dehydroabietic acid methyl ester (10), showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Evaluation of the cytotoxicity of compounds 1 and 4 against human cancer cell lines revealed that 1 was significantly cytotoxic to leukemia HL-60 cells [GI(50) (concentration that yields 50% growth) value 39.3 nM], although it showed only moderate cytotoxicity to the other cells. Compound 4 exhibited moderate cytotoxicity to all of the cancer cell lines tested.     

Poor prognosis associated with thrombocytosis in patients with gastric cancer

Background Thrombocytosis is commonly associated with malignant disease and has recently been suggested to be a poor prognostic indicator in patients with lung cancer and gynecological cancers. The prevalence of thrombocytosis in patients with gastric cancer was reviewed, and its association with poor prognosis was investigated. Methods Platelet count (PLT) and hemoglobin concentrations (Hb) were reviewed in 369 consecutive patients with histologically verified gastric cancer from 1994 to 2000. Differences between categories were analyzed with analysis of variance, and survival was compared by using the log-rank test on the Kaplan-Meier life table. Multivariate Cox regression analysis was used to evaluate whether thrombocytosis is an independent prognostic marker. Results Thrombocytosis was found in 42 patients, and anemia was found in 200 patients. PLT was negatively correlated with Hb. Mean PLT was significantly increased in patients with noncurative operations. There was a positive correlation between the depth of tumor invasion and PLT. One- and 3-year survival expectancies in patients with or without thrombocytosis were 52.4% and 23.4% and 85.7% and 72.9%, respectively. PLT was identified as an independent prognostic factor after lymph node metastasis and depth of tumor invasion. Conclusions Thrombocytosis is an independent prognostic indicator of survival in patients with gastric cancer. Presented at the 4th International Gastric Cancer Congress, New York, New York, April 29–May 2, 2001.     

Assessment of cardiovascular dynamics by pressure-area relations in pediatric patients with congenital heart disease

OBJECTIVES: It is particularly useful to separately quantify the ventricular contractility and loading conditions for a better understanding of the cardiovascular dynamics in congenital heart disease, where abnormalities in chamber and loading properties may coexist. Furthermore, ventricular contractility and loading conditions may alter independently or simultaneously with disease progression and therapeutic intervention. The objectives of the present study were (1) to test whether ventricular pressure-area analysis can provide such quantitation among patients with various forms of congenital heart disease, (2) to reveal basal cardiovascular interaction in congenital heart disease by means of pressure-area analysis, and (3) to test the feasibility of this method in a simplified and less invasive form to further enhance its clinical value. METHODS: We constructed pressure-area loops during caval occlusion by using transthoracic echocardiographic automated border detection combined with ventricular pressure recordings in 59 pediatric patients with congenital heart disease and in 7 normal control subjects. RESULTS: Area measurements obtained by automated border detection were highly reproducible, and area changes reflected volume changes. The pressure-area data provided load-independent measures of contractility, which were consistently increased by use of dobutamine (P <.05). End-systolic and arterial elastance individually quantified simultaneous changes in ventricular contractility and loading with milrinone infusion and predicted net cardiac performance. The pressure-area analysis better characterized the ventricular contractile states under a variety of loading conditions in congenital heart disease, whereas predominant load dependence of conventional indices confounded them. Furthermore, pressure-area relations were reasonably estimated from a single beat and from aortic pressure data during abdominal compression. CONCLUSIONS: Pressure-area analysis should provide a useful modality with which to assess cardiovascular dynamics in pediatric patients with congenital heart disease in more detail and should thus help improve the management of patients with this disease.