Hepatoma-derived growth factor expression as a prognostic marker in cervical cancer

AIM: To examine the association of hepatoma-derived growth factor(HDGF) expression with the prognosis of patients with cervical cancer of the uterus(CC). METHODS: HDGF is a unique nuclear growth factor, and it may play an important role in the development and progression of carcinoma. HDGF expression in 88 CC patients aged 23 to 76 years(median, 54 years) was analyzed by immunohistochemistry. A rabbit polyclonal antibody against the C-terminal amino acids(aa 231-240) of the human HDGF sequence was used as primary antibody at a dilution of 1:5000. This specific anti-HDGF antibody was purified using C-terminal peptide-conjugated Sepharose columns. Staining of endothelial cells in the noncancerous areas of each specimen was used as an internal positive control. Samples with more than 80% of tumor cells showing positive immunoreactivity in both the nucleus and cytoplasm were regarded as HDGF index level 2, more than 80% positive immunoreactivity in either the nucleus or cytoplasm as level 1, and less than 80% in both the nucleus and cytoplasm as level 0. The chisquare test and Fisher's exact probability test were used to examine the relationship between HDGF expression and clinicopathologic parameters, and statistical significance was examined by the log-rank test. Multivariate analysis of factors related to survival was performed using Cox's proportional hazards regression model. Statistical significance was set at P 0.05. RESULTS: The five-year overall survival rate was 82.9%. Fourteen patients died due to tumors, nine of whom had tumor recurrence at 2-21 mo(median, 10 mo) after surgery. Tumor recurrence in five patients was determined at the time of the patients' deaths. Nineteen cases were regarded as HDGF index level 0, 11 as level 1, and 58 as level 2. Patients with level 2 expression showed higher rates of histological classification of keratinized squamous cell carcinomaand adenosquamous carcinoma(44.8% of level 2 patients and 13.3% in levels 0 and 1), deep invasion(p T2-4 in 65.5% of level 2 patients, and 30.0% in levels 0 and 1), the presence of lymphatic invasion(50.0% in level 2, and 20.0% in levels 0 and 1), and the presence of lymph node metastasis(37.9% in level 2, and 6.7% in levels 0 and 1). Patients with an HDGF index of level 2 CC showed poorer 5-year overall survival rates than those with level 0 or 1 CC(74.0% and 100%, respectively, P = 0.0036). Univariate analysis revealed that histological classification(P = 0.04), depth of tumor invasion(P = 0.0001), vascular invasion(P = 0.004), and lymph node metastasis(P = 0.0001) were significant factors affecting overall survival in addition to HDGF expression. Multivariate analysis revealed HDGF expression level and lymph node metastasis as independent prognostic factors for overall survival(P = 0.0148 and P = 0.0197, respectively). The prognostic significance of HDGF was further analyzed in p T1 and p T2-4 patient groups, respectively. Among patients with p T1 CC, one the 39 analyzed patients died during the study, and no difference was observed among patients with HDGF index level 0, 1, or 2 CC. However, prognostic significance of the HDGF index was observed in the p T2-4 patient group, in which the mortality rates of patients with HDGF index level 2 CC and those with level 0 or 1 CC significantly differed(P = 0.0463). CONCLUSION: The HDGF expression level is of prognostic significance in CC.     

Renal handling of phosphate can predict height velocity during growth hormone therapy for short children.

Renal tubular reabsorption of phosphate in response to GH administration was studied in 28 short Japanese children, aged 5-11 yr (height SD score, less than -2.0 SD). Three groups included a classical GH deficiency (group 1; n = 12), a partial GH deficiency (group 2; n = 7), and children with non-GH deficiency (group 3; n = 9), depending on the peak response of serum GH in four provocative tests. Serum phosphorus, alkaline phosphatase, insulin-like growth factor-I (IGF-I), osteocalcin, and ratio of the maximum tubular reabsorption rate for phosphorus to the glomerular filtration rate (Tmp/GFR) were all significantly lower in group 1 compared with findings in groups 2 and 3 (P less than 0.05, P less than 0.01, and P less than 0.001). After the administration of GH (0.1 U/kg.day) for 4 consecutive days, increments in serum phosphorus and Tmp/GFR were significantly higher in group 1 than in group 2 (P less than 0.01 and P less than 0.01) or group 3 (P less than 0.01 and P less than 0.01), whereas the increment in IGF-I was similar in all 3 groups, and the levels of serum alkaline phosphatase and osteocalcin remained unchanged in all 3 groups. The calculated ratio of the increment in Tmp/GFR to the increment in IGF-I (delta Tmp/GFR/delta IGF-I) was highest in group 1, intermediate in group 2, and lowest in group 3 (P less than 0.001). One year after the GH treatment (0.5 U/kg.week), height velocity was 7.9 +/- 2.2 cm/yr in group 1 and 5.9 +/- 1.2 cm/yr in group 2; no child in group 3 was treated. When the above calculated parameters, delta Tmp/GFR/delta IGF-I and increment in height velocity (difference between pre- and posttherapy values), were taken into account, there was a significant positive correlation (n = 19; r = 0.78; P less than 0.001). This parameter can be used for purposes of predicting the outcome after 1 yr of GH therapy.     

Open heart operation in a patient with hereditary spherocytosis: a case report.

A 9-year-old girl who had ostium secundum atrial septal defect (ASD) and hereditary spherocytosis (HS) is described. The patient had a history of splenectomy for HS and underwent repair of the ASD under cardiopulmonary bypass (CPB), however, no significant or persistent hemolysis was observed during and after CPB. Only 10 patients with HS who underwent cardiac operations using CPB have been reported. The case is presented due to its rarity.     

Specific Action of 4-Nitropyridine 1-Oxide on Escherichia coli K-12 Pro+ Strains Leading to the Isolation of Proline-Requiring Mutants: Mechanism of Action of 4-Nitropyridine 1-Oxide

Possible mechanisms involved in the action of 4-nitropyridine 1-oxide (4NPO) on Escherichia coli K-12 pro⁺ cells in Penassay broth leading to the selective isolation of proA⁻ and/or proB⁻ mutants but not proC⁻ mutant were studied. Reconstruction experiments between pro⁺ and pro⁻ cells, together with experiments on the bactericidal action of 4NPO on pro⁺ and pro⁻ cells, indicated that 4NPO is more toxic for pro⁺ and proC⁻ cells than for proA⁻ and proB⁻ cells. These results, coupled with data indicating little mutagenicity of 4NPO on E. coli cells, led us to conclude that the selection of proA⁻ and/or proB⁻ cells that arose spontaneously in the pro⁺ culture is a possible mechanism for the action of 4NPO. Examination of 4NPO sensitivity of pro⁺ transductants derived from proA⁻ and proB⁻ cells with P1 vir phage and pro⁺ cells as donor and of pro⁺ spontaneous revertants derived from those pro⁻ cells suggested that 4NPO-sensitive gene(s) should be on, or very close to, the proA and proB loci and that both products of proA and proB genes may be involved in the sensitivity of bacteria to 4NPO. The fact that the 4NPO-sensitive allele is dominant over the 4NPO-resistant allele further indicated the possible correlation between gene products of proA and proB and the 4NPO sensitivity of bacteria. Experiments on metabolic conversion of 4NPO with bacterial cells proved that the major metabolic pathway of the agent is reduction to (possibly via 4-nitroso-) 4-hydroxylamino- and 4-amino-pyridine 1-oxides, and then to 4-aminopyridine. Investigation of the effect of structural modification of 4NPO on the elective selection of Pro⁻ mutants in Pro⁺ culture further suggested that the structural feature indispensable for the action of the agent is the hydroxyl-amino or its more oxidized state at the 4 position and the N-oxide moiety at the 1 position on the pyridine skeleton. Action of 4NPO in minimal medium was found to be bacteriostatic on pro⁺ cells but not on pro⁻ cells, leading to the formation of long nonseptate multinucleate filament cells on pro⁺ cells. Possible biochemical mechanisms of the selective toxicity of 4NPO for pro⁺ and pro⁻ cells are discussed.     

Scirrhous colonic metastasis from lobular carcinoma of breast

A 68-year-old woman presented complaining of 2 months vague abdominal fullness and constipation. She had a history of surgery 5 years ago for invasive lobular carcinoma of the left breast. She had good appetite without any severe symptoms such as vomiting, diarrhea, or hematochezia. No abnormal subcutaneous lymph nodes were detected, and blood tests showed no abnormalities including serum tumor markers. Whole-body computed tomography and bone scintigraphy revealed no tumor recurrences. However, endoscopic findings demonstrated a smooth stenotic lesion with submucosal thickening in the transverse colon, but the colonic mucous membrane was grossly normal. The 3-cm-long stenotic lesion was confirmed by colon imaging using water-soluble contrast medium. A biopsy specimen revealed diffuse infiltration of noncohesive malignant cells with round, atypical nuclei from lamina propria to subserosa. Taken together with immunohistochemistry, a diagnosis of metastatic lobular carcinoma from the breast was made, and transverse segmentectomy was done. Colonic metastasis of breast cancer should be included as a differential diagnosis of any abdominal symptoms, even though mild, when patients have a present or previous history of breast cancer.     

Twelve-year experience with the Carpentier–Edwards pericardial aortic valve at a single Japanese center

Our aim was to evaluate the long-term results of implantation of the Carpentier–Edwards pericardial (CEP) valve in the aortic position. Between January 1996 and December 2007, 244 patients who underwent aortic valve replacement using the CEP valve were enrolled in this study. A 19-mm valve was used in 39 patients, a 21-mm valve in 94 patients, a 23-mm valve in 81 patients, and a 25-mm valve in 30 patients. The early and the late results were evaluated. Furthermore, echocardiographic examination was performed at follow-up. There were 5 early deaths, with an early mortality rate of 2.0%. Follow-up was performed in 95.4% of the survivors of the operation for a mean period of 4.1 years. Actuarial survival rates at 5, 10, and 12 years were 85.3 ± 2.8, 80.0 ± 3.7 and 70.0 ± 9.8%, respectively. Thromboembolism was observed in 6 patients, endocarditis in 2 patients, reoperation in 4 patients, and structural valve deterioration in 2 patients. Actuarial freedoms from thromboembolism, endocarditis, and reoperation at 10 years were 96.9 ± 0.14, 97.7 ± 0.16, and 97.0 ± 0.16%, respectively. Echocardiographic examination revealed that the pressure gradients across the valve prosthesis for valves of each size were acceptable. Left ventricular mass index decreased significantly in all valve sizes. The long-term results of implantation of the CEP bioprosthesis in the aortic position were satisfactory. The CEP bioprosthesis maintained its hemodynamic performance even as late as 10 years after implantation.     

Performance of Alzheimer's disease patients in judging word relatedness.

Sixty individuals with probable Alzheimer's disease (AD) and 48 normal elders were given a task in which they had to judge the relatedness of concepts as a means of evaluating semantic memory. Very mild AD patients performed similarly to normal elders. Mild AD patients were significantly inferior in performance to normals but the pattern of their performance did not suggest a loss of conceptual knowledge. Moderate AD patients were significantly inferior in performance to mild AD patients, and 8 moderate AD patients (compared to 1 mild AD patient) were unable to do the task. The pattern of performance of moderate patients suggests that conceptual knowledge may degrade and ultimately be lost.