Opsonic function and concentration of human serum ficolin/P35.

Collectins, C-type (Ca2+-dependent) animal lectins with both collagenous and carbohydrate recognition domains, function as opsonins against pathogens. We previously described an N-acetylglucosamine (GlcNAc)-binding lectin (ficolin/P35) with a collagen- and a fibrinogen-like sequence present in human serum. In this report we show that ficolin/P35 can serve as an opsonin and enhance the clearance of pathogens having surface GlcNAc. Ficolin/P35 bound to an Ra chemotype strain of Salmonella typhimurium (TV119) which has an exposed GlcNAc at the non-reducing termini of the polysaccharide. On the other hand, ficolin/P35 did not bind to LT2, a smooth type strain of S. typhimurium with additional O-polysaccharides covering GlcNAc. Ficolin/P35 enhanced the uptake of TV119 by monocytes or polymorphonuclear leukocytes but had no opsonic activity towards LT2. These results suggest that, like collectins, ficolin/P35 is a collagenous lectin which has a role in innate immunity against certain pathogenic organisms by acting as an opsonin. We prepared monoclonal antibodies against ficolin/P35 and developed an enzyme-linked immunosorbent assay (ELISA) for measuring ficolin/P35 concentrations in humans. The mean serum concentration of ficolin/P35 from 130 normal individuals was estimated to be 13.7 microg/ml.     

Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.     

Antitumor effects of oral administration of an interferon-inducing pyrimidinone,Bropirimine, on murine renal-cell carcinoma

Bropirimine [2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone] is a low-molecular-weight compound that acts as an inducer of interferon in several animal species. Experiments were designed to explore the possibility of using this drug for the treatment of renal-cell carcinoma (RCC). Euthymic BALB/c mice were inoculated with murine RCC (Renca) cells and given graded doses of Bropirimine p.o. for 5 consecutive days beginning on day 1 following tumor inoculation. These mice were killed and tumors were excised on day 21. Bropirimine significantly (P<0.01) inhibited the tumor growth at a daily dose of 1,000 or 2,000 mg/kg. No adverse effect or toxicity was noted at 1,000 mg/kg, and at 2,000 mg/kg there was only a marginal body-weight reduction without any other appreciable side effect. In addition to the inhibition of tumor growth, there was a small yet significant (P<0.05) increase in the duration of survival (in days) in the Bropirimine-treated animals. When the treatment was delayed to begin on day 6 following tumor inoculation, Bropirimine did not suppress tumor growth in euthymic mice, pointing to the importance of the timing of the treatment. In athymic nude BALB/c mice lacking T-cells or T-cell function, Bropirimine also inhibited tumor growth (P<0.01). The antitumor effect of this drug was abolished by pretreatment with anti-asialo GM1 serum, which eliminated natural killer (NK) activity in euthymic mice. In vivo treatment with Bropirimine augmented the cytotoxicity of lymphocytes isolated from the spleens or lungs of the tumor-bearing mice, which were active against Renca and YAC-1 cells in vitro. This activity was NK-cell-dependent as judged on the basis of the results of the in vitro complement-dependent cytotoxicity assay. Since Bropirimine induced interferon (IFN)-/ production, significantly (P<0.05) elevating its serum concentration, and since this drug mimics the effects of IFN-/, it seemed likely that the Bropirimine-induced NK cell augmentation we found was mediated by IFN-/. These results suggest that Bropirimine, a booster of NK activity, may have potential as an adjunct to other therapeutic modalities in the treatment of human RCC.     

Diaphragm reconstruction with autologous fascia lata: Report of a case

When the diaphragm is excised so wiely that the defect cannot be closed directly during an operation on either thoracic or epigastric tumors, a reconstruction of the defect is necessary. We used harvested autologous fascia lata to reconstruct the diaphragm in a patient undergoing a pleuropneumonectomy with a partial diaphragmatic resection for malignant mesothelioma.     

Stimulatory effect of ipriflavone on formation of bone-like tissue in rat bone marrow stromal cell culture

The effects of ipriflavone (IP) (10^–5 M) on bone formation were studied in stromal cells from the femoral bone marrow of young adult rats cultured for 21 days in the presence of -glycerophosphate and dexamethasone. Stereoscopic microscopy showed nodule formation after 14 days of culturing, and both the number and the size of the nodules increased with time. The alizarin-red-stained calcified area in the nodules in the IP group was nearly 4 times as large as that in the control after 21 days. Light and electron microscopy revealed the presence of many osteoblast-like cells with developed rough endoplasmic reticulum and Golgi apparatus in the nodules in the control group after 14 days, and a collagenous fibril network was seen among the cells. After 21 days, calcification of the dense collagenous fibril network and bone matrix-like tissue were observed in many nodules, resulting in the formation of bone-like tissue containing osteocyte-like cells. In the IP group, the collagenous fibril network area in the nodules was greater than that in the control after 14 days, and a further increase in both the dense collagenous fibril network area and calcified bone-like tissue area was observed after 21 days. These findings indicate that IP stimulates bone-like tissue formation in the rat bone marrow stromal cell culture, suggesting that the promotion of collagen production by osteoblasts is involved in the stimulation of bone-like tissue formation by IP.     

Association analysis of the GABA(A) receptor subunit genes cluster on 5q33-34 and alcohol dependence in a Japanese population

Recent investigations suggest that genetic susceptibility to alcohol dependence may be conferred by GABA(A) receptor subunit genes. In this study, three RFLPs at the GABA(A)beta2, GABAAalpha6, GABA(A)alpha1 and two at the GABA(A)gamma2 receptor subunit genes, were examined for association with alcohol dependence in 189 subjects meeting DSM-III-R criteria for this disorder and 152 unrelated controls from a Japanese population. The results demonstrated no association between the AlwNI RFLP at the GABA(A)alpha6 receptor subunit gene and alcohol dependence (P = 0.059). However, the NciI RFLP at the GABA(A)gamma2 receptor subunit gene was associated with alcohol dependence comorbid with antisocial personality disorder (P = 0.021). This supports a recent finding reporting an association between the GABA(A)gamma2 receptor subunit gene and alcohol dependence with criminal record in a Finnish population. Taking into account the effects of multiple comparisons, this result should be interpreted with caution pending replication.     

Factors influencing joint-preserving operations in the treatment of the late stages of osteoarthritis of the hip

Between November 1983 and December 1992, 136 hips (119 patients) with coxarthritis were operated on using joint-preserving techniques based on the rationale of Pauwels' osteotomy. The criterion for selection was a patient in whom the height of the joint space in the weight-bearing area of the hip was less than 1 mm. The mean age at operation was 48 years and the mean follow-up 109 months (60 to 171). Hips were categorised using Bombelli's classification of osteoarthritis, into atrophic and non-atrophic types. The endpoint was defined as that at which the height of the joint space became less than 1 mm again. The Kaplan-Meier curve showed that the rate of survival of the non-atrophic group was significantly better than that of the atrophic group. Cox's proportional hazard model indicated that the factors influencing the results of joint-preserving operations included Bombelli's classification, postoperative incongruence of the joint and the height of the joint space.     

A clinical study of posttraumatic hydrocephalus

From 1989 to 1998, 721 patients with head injury were admitted to our department and 22 (3.1%) of them developed posttraumatic hydrocephalus. These patients included 16 males and 6 females, ranging in age from 17 to 86 years (mean age, 66 yrs) with peak incidence in the eighth decade. CT scan on admission immediately after head injury showed subarachnoid hemorrhage (SAH) in 18 cases. The other 4 cases without SAH had once suffered head injuries severe enough to give rise to consciousness disturbance. The typical clinical symptoms of hydrocephalus were observed in only 5 (23%) patients, and in the other 17 cases prolonged or deteriorated of consciousness disturbance were the main symptoms. Hydrocephalus was diagnosed between 1 and 3 months in 15 cases and in 7 cases after 4 months. Clinical improvement has been seen in 17 (77%) cases and marked recovery of consciousness was achieved in 12 cases after V-P shunt, but 5 cases with severe disturbance of consciousness revealed no improvement of clinical signs even after decrease of ventricular size. These results indicate that elderly patients with traumatic SAH should be followed up for at least 4 to 5 months, paying attention to development of hydrocephalus, and V-P shunt would be effective to improve consciousness disturbance in most of the cases.