Role of macrophage and smooth muscle cell apoptosis in association with oxidized low-density lipoprotein in the atherosclerotic development.

To examine the role of the apoptosis of macrophages and smooth muscle cells in the development of atherosclerosis, human aortic tissues with intimal lesions were immunostained with antibodies against terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), single-stranded DNA (clone F7-26), and active caspase-3. Apoptotic cells were detected in the intima using both TUNEL and single-stranded DNA, however, the latter method was the more sensitive one for detecting apoptotic cells in the early stages of atherosclerosis. The number of apoptotic cells increased as the disease progressed. It implies that the apoptosis of intimal cells is involved in the formation of atherosclerotic lesions. In addition, quantitative analyses of the cell types undergoing apoptosis using double-immunostaining revealed that the susceptibility of macrophages and smooth muscle cells to apoptosis was greater specifically in atheroma than in the other atherosclerotic lesions, and macrophages were more susceptible to apoptosis than smooth muscle cells. The frequency and spatial distribution of oxidized low-density lipoprotein (oxLDL) (FOH1a/DLH3)-positive cells were examined by immunohistochemistry, and the results resembled those of apoptotic cells. The number of oxLDL-positive cells in the intima significantly correlated with the susceptibility of smooth muscle cells, but not with that of macrophages, to apoptosis. These results suggest that oxLDL affects the apoptosis of smooth muscle cells during the atherosclerotic development.     

Thrombopoietin in postoperative thrombocytopenia following living donor hepatectomy.

Thrombocytopenia is a frequent finding following living donor hepatectomy. It appears more pronounced in right graft donors than in left graft donors. This study analyzed postoperative thrombocytopenia in 20 living liver donors and examined the change of endogenous thrombopoietin (TPO) in its recovery. Platelet count, TPO level, fibrinogen degradation product (FDP), and D-Dimer were measured before surgery and on postoperative days (PODs) 1, 2, 3, 5, 7, and 14. Concurrently, liver and spleen volumes were calculated by computed tomography. Platelet count on POD 3 was significantly lower in right graft donors than in left graft donors (13.0 +/- 3.7 x 10(4)/microL vs. 16.8 +/- 4.0 x 10(4)/microL, P = 0.039) but recovered by POD 7 in all donors. Postoperative elevations of FDP and D-Dimer were significantly higher in right graft donors than in left graft donors. TPO level rose immediately after surgery, peaked on POD 5 in left graft donors and on POD 7 in right graft donors, and fell nearly to preoperative levels by POD 14. Postoperative TPO level per liver volume was significantly higher in right graft donors than in left graft donors. In conclusion, thrombocytopenia following living donor hepatectomy resolved within the first week regardless of graft type and was mainly associated with increasing consumption of circulating platelets, possibly due to intrahepatic and splenic congestion. With a reduced number of circulating platelets, TPO level rapidly increases. Also, with reduced consumption of platelets related to recovery from surgery, thrombocytopenia should resolve. As a consequence, TPO level would be expected to fall.     

Corticotropin response to combined administration of human corticotropin-releasing hormone and small-dose arginine vasopressin in normal subjects.

Arginine vasopressin (AVP) is known to potentiate corticotropin (ACTH) secretion by human corticotropin-releasing hormone (hCRH), and a combined administration of hCRH and AVP appears useful as a pituitary ACTH reserve test. This study was designed to evaluate the appropriate dose of AVP and its route of administration, for better estimation of pituitary ACTH reserve in humans, when used in combination with a conventional hCRH stimulation test. First, intravenous (IV) doses of hCRH (100 micrograms) and AVP (0, 0.1, and 0.3 U) were administered simultaneously in six normal subjects. Second, IV hCRH was administered with intramuscular (IM) AVP (0, 1.0, 3.0, and 5.0 U) in 10 normal subjects. Blood samples for measurement of plasma ACTH were obtained at 0, 15, 30, 45, 60, 90, and 120 minutes after the hCRH with and without AVP administration. The order of AVP doses was randomly chosen in each subject. The peak plasma ACTH level was 65.0 +/- 16.0 pg/mL (30 minutes) with hCRH alone and 139.5 +/- 35.6 pg/mL (15 minutes) with hCRH plus 0.3 U IV AVP in six normal subjects. Similarly, the peak plasma ACTH level was 43.5 +/- 5.6 pg/mL (30 minutes) with hCRH alone and 116.0 +/- 19.6 (15 minutes) and 96.6 +/- 24.0 pg/mL (15 minutes) with hCRH plus 3.0 and 5.0 U IM AVP in 10 normal subjects, respectively. The hCRH-induced ACTH responses (delta ACTH) with both IV and IM AVP were significantly (P less than .05) greater than the respective control values with hCRH alone. The responses (delta ACTH) were comparable between the two phases of 3.0 and 5.0 U IM AVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human T-Cell Leukemia Virus-1-positive Cell Line Established from a Patient with Small Cell Lung Cancer

A stable cell line, KHM-3S, was established from a patient with small cell lung cancer (SCLC), who had a high serum level of soluble interleukin 2 receptors (sIL2-R) and was seropositive for human T cell leukemia virus (HTLV)-l. KHM-3S cells were positive for IL2-R (Tac) and NKH-1, but negative for other lymphocytic markers such as OKT 11, OKT 4, OKT 8, T cell receptor (WT 31), B 1, and B 4. Moreover, the KHM-3S cells were negative for leukocyte common antigen and strongly positive for neuron-specific enolase (NSE). Secretion of sIL2-R and NSE by the KHM-3S line was detected by an enzyme-linked immunosorbent assay. Rearrangement of the T cell receptor gene and monoclonal HTLV-1 integration were found by Southern blot analysis of KHM-3S DNA. However, Northern blot analysis showed no T cell receptor mRNA. KHM-3S may be useful for studies on the role of HTLV-1 in carcinogenesis and IL2-R expression in SCLC.     

Immunohistochemical analysis of inducible nitric oxide synthase (iNOS) and heat shock proteins (HSPs) in ameloblastomas

BACKGROUND: To clarify the possible role of nitric oxide (NO) and stress proteins in oncogenesis and cytodifferentiation of odontogenic epithelium. Inducible NO synthase (iNOS) and heat shock proteins (HSPs) were analyzed in ameloblastomas as well as in tooth germs. METHODS: Specimens of seven tooth germs, 36 benign ameloblastomas and five malignant ameloblastomas were examined by immunohistochemistry using antibodies against iNOS and 27-, 60- and 70-kDa HSPs (HSP27, HSP60 and HSP70). RESULTS: Immunoreactivity for iNOS was detected in normal and neoplastic odontogenic epithelial cells and was higher in malignant ameloblastomas than in tooth germs and benign ameloblastomas. HSP27 was expressed constitutively in all odontogenic epithelial cells in tooth germs and benign and malignant ameloblastomas. Expression of HSP60 and HSP70 was detected in normal and neoplastic odontogenic epithelial cells and was prominent in cells neighboring the basement membrane. HSP60 reactivity showed no apparent difference between normal and neoplastic odontogenic epithelium, whereas HSP70 expression was slightly higher in benign and malignant ameloblastomas than in tooth germs. CONCLUSIONS: Activation of iNOS might be associated with malignant potential of epithelial odontogenic tumors. Elevated expression of HSP70 is considered to be involved in neoplastic transformation of odontogenic epithelial cells.     

Two-level disc herniation in the cervical and thoracic spine presenting with spastic paresis in the lower extremities without clinical symptoms or signs in the upper extremities.

BACKGROUND CONTEXT: There is no report in the literature of two-level disc herniation in the cervical and thoracic spine presenting with spastic paresis/paralysis exclusively in the bilateral lower extremities. PURPOSE: To identify the clinical characteristics of specific myelopathy resulting from C6-C7 disc herniation through a case with spastic paresis in the lower extremities without upper extremities symptoms due to separate disc herniation in the cervical and thoracic spine, which was surgically removed in two stages. STUDY DESIGN/SETTING: A case report. METHODS: A 48-year-old man developed a gait disturbance as well as weakness and numbness in the lower extremities. Thoracic magnetic resonance imaging (MRI) showed a T11-T12 disc herniation, which was removed under the surgical microscope through a minimally invasive posterior approach. He improved, but 2 months after surgery developed recurrent numbness and spasticity. On this occasion, no evidence of recurrence of the thoracic disc herniation could be identified, but cervical MRI demonstrated a compressed spinal cord at the C6-C7 level. The patient had no neurological findings in the upper extremities. The herniated disc at C6-C7 was removed under the surgical microscope with laminoplasty. RESULTS: The symptoms gradually improved after surgery. At the present time, 2 years and 9 months after the initial operation, the patient had a stable gait and was able to work. CONCLUSIONS: Our experience suggests that in the diagnosis of patients with spastic paresis and sensory disturbances in the lower extremities, spinal cord compression should be explored by imaging studies not only in the thoracic spine but also in the cervical spine, especially at the C6-C7 level, even if the symptoms and abnormal neurological findings are absent in the upper extremities.     

Ectopic cervico-mediastinal thymoma confirmed by flow cytometric analysis of tumor-derived lymphocytes

Ectopic cervical or cervico-mediastinal thymomas are very rare and most of them are asymptomatic, except for the presence of a cervical mass. We present the case of a 71-year-old man with an ectopic cervico-mediastinal thymoma threatening superior vena cava syndrome. He had a slight headache and presented with venous dilatation on the chest wall. A computed tomographic scan and magnetic resonance, imaging of the chest demonstrated a mass extending from the right neck to the hilum, that indented the trachea and compressed and displaced the brachiocephalic veins anteriorly. Under a right hemicollar incision and median sternotomy, the mass was resected en bloc together with the thymus. The resected specimen was an encapsulated mass measuring 11×7×4 cm. The pathological diagnosis was type AB, non-invasive thymoma, confirmed by 3-color flow, cytometry of tumor-derived lymphocytes. Flow cytometry using biopsy material may contribute to the preoperative diagnosis of ectopic thymoma.