Fatty acid binding protein 6 is overexpressed in colorectal cancer.

PURPOSE: Fatty acid binding protein 6 (FABP6) is a cancer-related protein that acts as an intracellular transporter of bile acid in the ileal epithelium. Because bile acids are implicated in the carcinogenesis of colorectal cancer, we evaluated FABP6 expression in colorectal cancer. EXPERIMENTAL DESIGN: The expression of FABP6 mRNA was evaluated in 78 paired samples of cancer/normal tissue representing colorectal cancer cases, plus 16 adenomas, and 16 metastatic lymph nodes. An immunohistochemical study was conducted with paraffin sections. In vitro transfection was done to determine FABP6's biological roles. RESULTS: The expression of FABP6 mRNA was significantly higher in cancer (75 of 78, 96.2%) than in normal tissue (P<0.001). The expression of mRNA was increased in cancer compared with adenoma, but was dramatically decreased in node metastases. Tumors with high FABP6 expression were smaller in size (P<0.01), more often in the left colon (P<0.05), and had shallower invasion into the bowel wall (P<0.05) compared with those with low expression. There was no significant difference between high- and low-expression tumors regarding clinicopathologic variables such as histologic type, lymph node, or liver metastasis, Dukes' classification, and prognosis. Immunohistochemical study revealed that FABP6 expression was primarily observed in cancer cells. In vitro transfection revealed that transfectants showed weaker invasiveness (P<0.05), more dominant proliferation (P<0.001), and less apoptosis than mock cells. CONCLUSIONS: The expression of FABP6 was higher in primary colorectal cancers and adenomas than in normal epithelium, but was dramatically decreased in lymph node metastases, suggesting that FABP6 may play an important role in early carcinogenesis.     

Association of systemic lupus erythematosus and hemolytic uremic syndrome in a child

We describe a 10-year-old girl with systemic lupus erythematosus (SLE) who first presented with hemolytic uremic syndrome (HUS). Diagnoses were based on the classic HUS triad, including the observation of fragmented red blood cells, and on the American College of Rheumatology criteria for SLE. Plasma exchange may have been effective against both HUS and SLE in this patient, as it was associated with improvement of platelet counts, renal function, and serological findings. Received: 24 September 1998 / Revised: 4 January 1999 / Accepted: 4 January 1999     

Optimal dose and duration of glucose administration during fasting period preceding surgery in rabbits

Purpose. We examined preoperative glucose administration to establish what dose and cutoff point were optimal for suppression of lipolysis and prevention of hypo- or hyperglycemia. Methods. Rabbits were preoperatively fasted and simultaneously received glucose at a constant rate of 0, 0.1, 0.2, 0.3, or 0.4 g·kg⁻¹·h⁻¹ in fluid infusion for 3 h. Plasma glucose, immunoreactive insulin activity, nonesterified fatty acids, and ketone bodies were measured 0, 1.5, 3 and 4 h after the start of infusion, and hepatic glycogen content was assessed 1 h after cessation of infusion. Results. Fluid infusion without glucose decreased plasma glucose. Glucose administration at more than 0.2 g·kg⁻¹·h⁻¹ caused hyperglycemia (>200 mg·dl⁻¹) in the infusion period; the differences were significant compared with the value at zero time or in the 0 g·kg⁻¹·h⁻¹ group (P < 0.01). The highest dose also raised plasma immunoreactive insulin activity, which was significantly higher than in the 0 g·kg⁻¹·h⁻¹ group (P < 0.01) at the midpoint of the infusion period. Plasma nonesterified fatty acids increased in all groups. The changes were, however, significantly reduced in both the 0.3 and 0.4 g·kg⁻¹·h⁻¹ groups (P < 0.05 and P < 0.01, respectively) by the end of infusion. All these effects of glucose supply, including suppression of lipolysis, disappeared regardless of dose within 1 h after the cessation of infusion. Conclusion. These results suggest that the optimal dose for preoperative glucose infusion, in order to preserve carbohydrate or fat metabolism, is 0.1–0.2 or 0.3 g·kg⁻¹·h⁻¹, respectively, and indicate that administration should not be discontinued until the start of surgery. Received for publication on July 16, 1998; accepted on August 23, 1999     

Endoscopic surgery for lateral cervical cysts

The infection of an intervertebral disk is a serious condition. The diagnosis often is elusive and difficult to make. It is imperative to have appropriate microbiologic specimens before the initiation of treatment. We report the case of a 51-year-old woman with lumbar spondylodiscitis caused by infection after the placement of an epidural catheter for postoperative analgesia. A spinal magnetic resonance imaging (MRI) scan confirmed the diagnosis, but computed tomography (CT)-guided fine-needle biopsy did not yield adequate material for a microbiologic diagnosis. Laparoscopic biopsies of the involved disk provided good specimens and a diagnosis of Propionibacterium acnes infection. We believe that this minimally invasive procedure should be performed when CT-guided fine-needle biopsy fails to yield a microbiologic diagnosis in spondylodiscitis.     

Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation

Brain natriuretic peptide (BNP) is a cardiac hormone produced by the ventricle, and its secretion is markedly increased in heart failure, hypertension, and renal failure. Transgenic mice that overexpress BNP in the liver (BNP-Tg) were recently generated, resulting in low BP. To elucidate the role of BNP in renal pathophysiology, the effect of chronic excess of BNP in transgenic mice on glomerular injury after subtotal nephrectomy induced by resection of the renal poles was examined. After nephrectomy, glomerular cross-sectional areas in control nontransgenic mice markedly increased as compared with those in sham-operated mice (+81 +/- 7%), whereas there was only a modest increase in BNP-Tg (+10 +/- 6%). Expansion of the mesangial area and increase in the intraglomerular cell number were also inhibited in BNP-Tg. Glomerular expressions of transforming growth factor-beta and fibronectin were increased with hypertrophy and were significantly suppressed in BNP-Tg. Furthermore, increases in the urinary albumin excretion and BP were significantly ameliorated in BNP-Tg. Chronic hydralazine treatment in nephrectomized nontransgenic mice failed to inhibit glomerular hypertrophy. These findings indicate that the chronic excess of BNP in mice ameliorates glomerular hypertrophy and mesangial expansion after renal ablation. The results also suggest that the observed effects of natriuretic peptides under reduced renal mass are not due merely to systemic BP reduction and may be therapeutically applicable in various renal diseases.     

Longitudinal evaluation of anthracycline cardiotoxicity by signal-averaged electrocardiography in children with cancer

BACKGROUND: The aim of the present study was to investigate the detection of anthracycline cardiotoxicity by signal-averaged electrocardiography (SAE) in children with cancer. METHODS: There were 29 patients with a cumulative anthracycline (ATC) dose of 75-600 mg/m2. None of them had congestive heart failure. Patients underwent SAE just before (detection of chronic cardiotoxicity) and just after (detection of acute cardiotoxicity) ATC therapy. Echocardiography and Holter electrocardiography were performed at the same time. The rates of abnormal SAE, echocardiography, and electrocardiogram findings were calculated and compared for every 100 mg/m2 of ATC. RESULTS: The SAE showed a significantly higher detection rate for acute cardiotoxicity was at a cumulative ATC dose of less than 400 mg/m2 when compared with other methods (P < 0.05). The lowest dose at which acute cardiotoxicity was detected by SAE was 117.3 mg/m2. The detection of chronic cardiotoxicity by SAE was significantly higher at a cumulative ATC dose of 100-400 mg/m2 when compared with other methods (P < 0.05), and the lowest value showing toxicity was 373.3 mg/m2. The lowest ATC dose causing chronic cardiotoxicity was significantly lower in patients less than 2-years-old (120.0 +/- 28.3 mg/m2) than in the other age groups (P < 0.05). CONCLUSIONS: Acute and chronic ATC cardiotoxicity were detected by SAE at lower cumulative doses compared with other methods. The technique of SAE was a potentially useful method for detection of cardiotoxicity among those investigated and it provides useful information on subclinical cardiac dysfunction in patients receiving ATC therapy.     

Biallelic inactivation by somatic mutations of the MEN1 gene in sporadic parathyroid tumors.

We report three sporadic parathyroid tumors with biallelic inactivation of the multiple endocrine neoplasia type 1 (MEN1) gene. Three parathyroid tumors had two somatic mutations (K119del and 864del8, 363insT and 1767delT, and 508del33 and W341X, respectively). The mutations in both alleles detected by long-range polymerase chain reaction and subcloning in three tumors would likely result in a nonfunctional menin protein in parathyroid glands. These results show that the MEN1 gene is inactivated not only by a combination of somatic mutations and loss of heterozygosity, but also by somatic double mutations located on different alleles. The results directly confirmed the participation of MEN1 in the tumorigenesis of sporadic parathyroid tumors.     

Efficacy of carboplatin with an MEP (mitoxantrone, etoposide and prednisone) regimen for relapsed and CHOP-resistant diffuse large B-cell lymphomas.

Mitoxantrone, etoposide and prednisone (MEP)-based regimens using granulocyte colony-stimulating factor (G-CSF) were designed for relapsed and CHOP-resistant diffuse large B-cell lymphomas in a single institution, and the therapeutic effects and adverse reactions were studied. In a total of 49 patients, the MEP regimen had a 41% (9/22) overall response rate compared with 48% (13/27) for the MEP plus carboplatin (C-MEP) regimen (Chi-squared test, P=0.602). Among 38 CHOP-resistant patients, however, the overall response rate to C-MEP [42% (10/24)] was significantly superior compared with MEP [7% (1/14)] (P=0.023), and the overall survival to C-MEP was superior compared with MEP (P=0.088). Taken together, our results, although non-randomized, suggest that a combination of MEP with carboplatin is better than MEP alone in CHOP-resistant diffuse large B-cell lymphomas.     

Suppression of Lung Metastasis by Aspirin but Not Indomethacin in an in vivo Model of Chemically Induced Hepatocellular Carcinoma

To examine the effect of non-steroidal anti-inflammatory drugs on metastasis formation, aspirin (ASP, 0.5% in diet) and indomethacin (IM, 0.005% in drinking water) were applied to an in vivo highly metastatic rat hepatocellular carcinoma (HCC) model in F344 male rats. Administration for 8 weeks after induction of highly metastatic HCC by sequential treatment with diethylnitrosamine and N-nitrosomorpholine did not cause any significant change in survival rate or body weight. Multiplicity of HCC in the liver increased during ASP or IM treatment without any significant histological alteration. Although absent in the rats killed at the end of the period of carcinogen exposure, lung metastasis at the end of the experiment was found in 100%, 89% and 100% of rats in the control, ASP and IM groups, respectively. Degree of metastasis was classified into three groups according to the number of metastatic nodules, i.e., slight (1–5 nodules), moderate (6–50) and severe (more than 51), which amounted to 0%, 43% and 57% in the control group. ASP significantly reduced the degree of metastasis, the incidences being 33%, 44%, and 11%, respectively, whereas IM was without significant influence. Both agents suppressed cell proliferation in HCCs, without any alteration of pan-cadherin expression. However, expression in HCC of mRNAs for intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, both of which are considered to play key roles in attachment of cancer cells to the endothelium, was significantly suppressed by ASP. Thus, the present study demonstrated that ASP, but not IM, has the potential to inhibit lung metastasis of rat HCC in vivo , possibly via reduced attachment of tumor cells to the vascular endothelium. Moreover, these data indicate this in vivo model for induction of rat highly metastatic HCC to be a useful tool for the assessment of the efficacy of therapeutic treatments to block metastasis formation.