Protection of hepatocytes from apoptosis by a novel substance from actinomycetes culture medium

A novel substance, #675, found from an Streptomyces sp. SM675 culture medium, dose-dependently stimulates the proliferation of human functional liver cell 4 (FLC4). When FLC4 cells were incubated under conditions without fetal bovine serum (FBS), typical features of apoptotic cell death such as shrinkage and nuclear condensation appeared; high molecular weight (HMW) DNA fragments were found; and caspase-3 and poly (ADP-ribose) polymerase (PARP) proteins were cleaved. When FLC4 cells were incubated with #675 and without FBS, the cells grew healthy, no HMW DNA fragments were found, and caspase-3 and PARP cleavage weakened, suggesting that #675 protects FLC4 cells from apoptosis induced by FBS-deprivation. The quantitative reverse-transcribed polymerase chain reaction did not show differences in PARP or Bcl-2 mRNA expression in FLC4 cells incubated with or without #675, indicating other genes may be involved in this anti-apoptosis effect. These results show that #675 enhances FLC4 proliferation via an apoptosis-inhibition pathway, implying potential pharmacological and clinical applications.     

Primary giant cell malignant fibrous histiocytoma of the kidney with staghorn calculi

Malignant fibrous histiocytomas (MFH) as primary renal tumours are rare, with less than 50 cases described in the literature. We report a case of primary renal MFH of giant cell type in a 56-year-old man, who presented with bilateral dull flank pain, intermittent gross haematuria and body weight loss (6 kg in 3 months). Intravenous urography, computerized tomography (CT) and magnetic resonance image (MRI) showed right ureteral stones with mild hydronephrosis, and a solid mass at the lower pole of the left kidney associated with staghorn calculi, as well as tumour thrombi in the left renal vein and inferior vena cava. Left radical nephrectomy and evacuation of tumour thrombi from the left renal vein and inferior vena cava were performed. Histopathologic examination revealed malignant fibrous histiocytoma (MFH) of giant cell type. To the best of our knowledge, this is the first report of primary renal MFH associated with staghorn calculi.     

Primary papillary carcinoma arising in a thyroglossal duct cyst

We report a case of papillary carcinoma arising in a thyroglossal duct cyst, presenting with an anterior neck mass of a 31-year-old woman. The tumor was judged to be a primary lesion on the basis of intraoperative examination of the thyroid and pathologic findings of the mass. One year later, a small nodular mass in the left thyroid gland and lymph node enlargement of the right cervical lymph node were noted by follow-up imaging studies. Total thyroidectomy, right modified radical neck dissection and central neck dissection were performed. The thyroid gland revealed nodular hyperplasia without evidence of malignancy. On the other hand, the dissected neck lymph nodes revealed metastatic papillary carcinoma. Taken together, these findings suggested the tumor was a primary papillary carcinoma arising in the thyroglossal duct cyst.     

Induction of apoptotic cell death in peripheral blood mononuclear and polymorphonuclear cells by an oral bacterium, Fusobacterium nucleatum

It is largely unknown why a variety of bacteria present in the oral cavity are capable of establishing themselves in the periodontal pockets of nonimmunocompromised individuals in the presence of competent immune effector cells. In this paper we present evidence for the immunosuppressive role of Fusobacterium nucleatum, a gram-negative oral bacterium which plays an important role in the generation of periodontal disease. Our studies indicate that the immunosuppressive role of F. nucleatum is largely due to the ability of this organism to induce apoptotic cell death in peripheral blood mononuclear cells (PBMCs) and in polymorphonuclear cells (PMNs). F. nucleatum treatment induced apoptosis of PBMCs and PMNs as assessed by an increase in subdiploid DNA content determined by DNA fragmentation and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling assays. The ability of F. nucleatum to induce apoptosis was abolished by either heat treatment or proteinase digestion but was retained after formaldehyde treatment, suggesting that a heat-labile surface protein component is responsible for bacterium-mediated cell apoptosis. The data also indicated that F. nucleatum-induced cell apoptosis requires activation of caspases and is protected by NF-kappaB. Possible mechanisms of F. nucleatum's role in the pathogenesis of periodontal disease are discussed.     

The relation between viable segments and left ventricular ejection fraction improvement

For patients with coronary artery disease and left ventricular dysfunction who undergo revascularization, it is important to estimate the left ventricular ejection fraction (LVEF) improvement after revascularization, as this is a strong indicator of the long-term outcome. Identification of viable segments from echocardiography has been considered a predictive sign of LVEF improvement. However, a quantitative relation between segmental function recovery and global ejection fraction improvement has not been established. There is a clinical need to determine parameters that are predictive to LVEF improvement. A cylindrical left ventricular model is proposed to establish the relation between segmental myocardial function and LVEF based on a 12-segment echocardiograph model. Model results show that LVEF improvement is directly related to the contraction ratio in normal segments and a weighted sum of the number of viable segments that recover to normal or hypokinetic, which is equal to a weighted sum of the change in wall motion scores. This new combined parameter is a better predictor of the amount of LVEF improvement than the total number of viable segments or preoperative ejection fraction. The predictive value of the model was illustrated in a group of four patients with coronary artery disease who underwent revascularization.     

HLA and hypocretin studies in Korean patients with narcolepsy

STUDY OBJECTIVES: Very few studies have evaluated narcolepsy in Asian countries, outside of Japan. Our goal was to study narcolepsy at the genetic, clinical and pathophysiological level in Korea. DESIGN: Prospective study of consecutive patients and age matched controls. Clinical data ascertained from the Stanford Sleep Inventory, Polysomnography and MSLT data, as well as clinical notes. High resolution DRB1 and DQB1 typing in all subjects and studies of CSF hypocretin-1 was also evaluated in a subset of patients. PARTICIPANTS AND SETTING: 20 patients diagnosed at St. Vincent and Korea University Hospitals (Seoul, Korea). 21 Korean control subjects. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: For narcoleptic subjects, mean age was 28.2 years old and 45% were female. Mean BMI was 23.9+/-3.4 kg/m2, a significantly higher value than that expected in an age- and sex-matched sample (p<0.01). All patients had sleepiness and cataplexy while the prevalence of other symptoms ranged from 60-75%. All but 2 subjects were HLA-DR15 (DR2), DQB1*0602 positive (90%). This high DQB1*0602 percentage compared with 24% DQB1*0602 positivity in 21 control Koreans. Protective effects were observed for the DQB1*0601 and DRB1*0406 alleles, Hypocretin (orexin) CSF studies were also performed in 6 cataplectic subjects, all of which had undetectable CSF hypocretin levels. Two of these subjects had started narcolepsy less than 1 year before analysis yet had undetectable hypocretin levels. CONCLUSION: These results illustrate the similarity of narcolepsy-cataplexy in Korea in comparisons with other more studied populations. We also identified a new potential HLA protective subtype, HLA-DRB1*0406.     

An explanation of renal hemodynamics in acute renal failure based on sequential CT in patients with Korean hemorrhagic fever

The pattern of renal enhancement and washout of contrast medium was observed on sequential follow-up CT in 12 patients with Korean hemorrhagic fever, in which acute renal failure is one of the most important clinical features. Renal contrast enhancement and contrast medium washout were delayed longer in patients with severe oliguric renal failure. The delayed washout peaked at 4-5 days and did not return to normal until 8-9 days in the patients with severe oliguria; in the patients without severe oliguria the times were 1-2 days and 3-4 days, respectively. A characteristic "cart-wheel" pattern was observed during the washout stage in patients without severe oliguria. This "cart-wheel" pattern of washout is thought to result from relief of vasoconstriction and repair of tubular function. Multifocal "wedge-shaped" nonenhanced areas of the kidney, seen on the 2 week follow-up postcontrast CT, are thought to be ischemic zones due to persistent vasoconstriction. On the 6 week follow-up postcontrast CT in one patient, scarring of the kidney was detected in the same area that did not enhance on the 2 week CT. This scarring is thought to be a result of permanent vasoconstriction.     

ANTIBODY MICROINJECTION A NEW APPROACH FOR STUDYING THE FUNCTIONS OF NEUROPEPTIDES

roiiowing the rapid progress iri molecular bio logy, we are moving from the period of "one peptide a year" to a period of "one peptide a day". To cope with the rapid emergence of novel biologically active peptides, new techniques are needed to clarify their physiological functions. Evidence is presented here to show that antibody microinjection is a rapid and reliable method to evaluate the functions of endogenously released peptides. It is especially useful when no specific receptor antagonist is yet avaiilable for pharmacological study.     

ASSESSMENT OF URINE SATURATION AND INHIBITORY INDEX IN PATIENTS WITH CALCIUM OXALATE KIDNEY STONE AND NORMALS

The formation of calcium oxalate nephrolithiasis can be estimated by measuring the concentration of calcium oxalate versus the inhibitory role of crystal formation in the urine. In recent studies, the calcium oxalate saturation index and the inhibitory activity (by modified Sarig's method) of the urine during fasting and after oral calcium loading in normal subjects and in patients with calcium nepliro- lithiasis were determined. It was shown that, in normal comrols after calcium loading the inhibitory activity of the urine increased in parallel with the increase in urinary excretion of calcium oxalate; in contrast, in patients with kidney stones, it remained unchanged or fell slightly. This abnormal response might result in a disturbance of the saturation-inhibi- tion balance and formation of kidney stone. In normal individuals, there may be a "protective re- sponse" to prevent the precipitation of calcium oxalate when the urrine is oversaturated with calcium oxalate while a defect of the "protective response" in patients may be an important factor in calcium oxalate stone formation.     

Cyclophosphamide, vincristine, adriamycin, and prednisone (CHOP) with and without intermediate dose methotrexate for the treatment of non-Hodgkin's lymphomas of diffuse histology

Seventy three patients with disseminated diffuse non-Hodgkin's lymphomas were treated with combinations of cyclophosphamide, vincristine sulfate, prednisone, and doxorubicin with and without 2 weekly doses of oral methotrexate in "intermediate" doses, followed by calcium leucovorin rescue. The addition of methotrexate did not increase the complete remission rate, the remission duration, or the survival (P value = 1.0, 0.74, and 0.78, respectively) in patients who did not have previous chemotherapy treatment. In previously treated patients, the complete remission rate was somewhat higher and the remission duration and survival were longer among those patients treated with the methotrexate containing program; however these differences were not statistically significant (P values = 0.88, 0.81, and 0.46, respectively). There was substantial morbidity and mortality during treatment with both treatment arms, among patients aged more than 60 years.