Interferon-γ-producing B cells induce the formation of gastric lymphoid follicles after Helicobacter suis infection.

Helicobacter (H.) suis is capable of infecting various animals including humans, and H. suis infections can lead to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Recently, we reported that interferon-γ (IFN-γ) was highly expressed in the stomachs of H. suis-infected mice, but the direct relationship between the upregulation of IFN-γ expression and the formation of gastric lymphoid follicles after H. suis infection remains unclear. Here, we demonstrated that the IFN-γ produced by B cells plays an important role in the formation of gastric lymphoid follicles after H. suis infection. In addition, IFN-γ-producing B cells evoked gastric lymphoid follicle formation independent of T-cell help, suggesting that they are crucial for the development of gastric MALT induced by Helicobacter infection.

Cot/Tpl2 regulates IL-23 p19 expression in LPS-stimulated macrophages through ERK activation.

We have previously reported that a serine/threonine protein kinase, Cot/Tpl2, is a negative regulator of Th1-type immunity through inhibiting IL-12 expression in antigen presenting cells (APCs) stimulated by Toll-like receptor (TLR) ligands. We here show that Cot/Tpl2(-/-) macrophages produce significantly less IL-23, an important regulator of Th17-type response, than the wild-type counterparts in response to lipopolysaccharide (LPS), which is a ligand for TLR4. The decreased IL-23 production in Cot/Tpl2(-/-) macrophages is, at least partly, regulated at the transcriptional level, as the LPS-mediated IL-23 p19 mRNA induction was significantly less in Cot/Tpl2(-/-) macrophages. Chemical inhibition of extracellular signal-regulated kinase (ERK) activity similarly inhibited IL-23 expression in LPS-stimulated wild-type macrophages. As Cot/Tpl2 is an essential upstream component of the ERK activation pathway of LPS, it is suggested that Cot/Tpl2 positively regulates IL-23 expression through ERK activation. These results indicate that Cot/Tpl2 may be involved in balancing Th1/Th17 differentiation by regulating the expression ratio of IL-12 and IL-23 in APCs.

Involvement of Cot/Tp12 in bone loss during periodontitis.

Periodontitis causes resorption of alveolar bone, in which RANKL induces osteoclastogenesis. The binding of lipopolysaccharide to Toll-like receptors causes phosphorylation of Cot/Tp12 to activate the MAPK cascade. Previous in vitro studies showed that Cot/Tp12 was essential for the induction of RANKL expression by lipopolysaccharide. In this study, we examined whether Cot/Tp12 deficiency reduced the progression of alveolar bone loss and osteoclastogenesis during experimental periodontitis. We found that the extent of alveolar bone loss and osteoclastogenesis induced by ligature-induced periodontitis was decreased in Cot/Tp12-deficient mice. In addition, reduction of RANKL expression was observed in periodontal tissues of Cot/Tp12-deficient mice with experimental periodontitis. Furthermore, we found that Cot/Tp12 was involved in the induction of TNF-alpha mRNA expression in gingiva of mice with experimental periodontitis. Our observations suggested that Cot/Tp12 is essential for the progression of alveolar bone loss and osteoclastogenesis in periodontal tissue during experimental periodontitis mediated through increased RANKL expression.

Oxidative stress causes alveolar bone loss in metabolic syndrome model mice with type 2 diabetes.

BACKGROUND AND OBJECTIVE: Alveolar bone loss is caused by a host response to periodontal pathogens, and its progression is often enhanced by systemic conditions such as insulin resistance. Alveolar bone dehiscence has been observed in KK-A(y) mice, which are metabolic syndrome model mice with type 2 diabetes. The aim of this study was to investigate inducements responsible for alveolar bone dehiscence in the KK-A(y) mice. MATERIAL AND METHODS: The expression of endothelial nitric oxide synthase in the mandibles of mice was detected using immunohistochemical staining and the reverse transcription-polymerase chain reaction. After administration of N-acetylcysteine, an antioxidant, to KK-A(y) mice, alveolar bone loss and the expression of endothelial nitric oxide synthase protein in gingival keratinocytes and of hydrogen peroxide concentrations in plasma, were analyzed. The effect of hydrogen peroxide on endothelial nitric oxide synthase expression in keratinocytes was examined using cultured keratinocytes. RESULTS: The expression of endothelial nitric oxide synthase was decreased in gingival keratinocytes from KK-A(y) mice compared with gingival keratinocytes from control mice. Administration of N-acetylcysteine to the mice restored endothelial nitric oxide synthase expression in the gingival keratinocytes, suppressed the alveolar bone loss and decreased the hydrogen peroxide concentrations in plasma without the improvement of obesity or diabetes. In vitro, stimulation with hydrogen peroxide decreased the expression level of endothelial nitric oxide synthase in cultured keratinocytes, which was restored by the addition of N-acetylcysteine. CONCLUSION: Reactive oxygen species, such as hydrogen peroxide, are responsible for the alveolar bone loss accompanied by decreased endothelial nitric oxide synthase expression in KK-A(y) mice. Therefore, we propose a working hypothesis that the generation of oxidative stress is an underlying systemic condition that enhances alveolar bone loss in periodontitis occurring as a complication of diabetes.

Long-term follow up study of vertical HTLV-I infection in children breast-fed by seropositive mothers.

Infection of Human T-lymphotropic virus type-I (HTLV-I) was investigated by long-term follow up surveys of mother's milk-fed infants. HTLV-I infections of infants via seropositive mother's milk, that is, anti-HTLV-I antibody-positive infants, increased in number up to the age 2, but no infants became antibody-positive thereafter. Infants who had became antibody positive by age 2 remained so at age 11-12. HTLV-I infection via feeding with mother's milk was established by the age 2. While in epidemiologic surveys an increase of the anti-HTLV-I antibody-positive rate has been reported, this survey revealed that after acquisition of HTLV-I from breast feeding, there was no further horizontal transmission prior to puberty.

Long-term follow-up study of HTLV-I infection in bottle-fed children born to seropositive mothers.

Human T-lymphotropic virus Type-I (HTLV-I) infects children via mother's milk. Infection of Human T-lymphotropic virus Type-I (HTLV-I) was investigated by long-term follow-up surveys of modified milk-fed children. Our observations of modified milk-fed infants revealed that: 1 of 154 (0.6%) at year 1, 5 of 129 (3.9%) at 1.5 years, and 5 of 108 (4.6%) at year 2 were anti-HTLV-I antibody-positive. No infants or children became newly antibody-positive thereafter. Modified milk feeding could prevent the HTLV-I infection of infants from mothers in many cases, however the infants who had became anti-HTLV-I antibody-positive due to established infection by the age 2 remained positive at age 11-12 with persistent infections. Modified milk-fed infants who had been born from HTLV-I seropositive mothers did not show that they had complete protection from HTLV-I infection, but a low infection rate was seen, showing that modified milk feeding is useful to protect from HTLV-I infection.

Expression of prolactin gene in spontaneous mammary tumors in aging Fischer 344 rats.

Expression of extra pituitary prolactin (PRL) has been recently reported in the mammary gland. However, spontaneous mammary tumors occurring in aging rats have not been investigated for PRL production. The present study was undertaken to examine the expression of PRL gene in rat mammary tumors spontaneously arisen in rats with pituitary prolactinomas among 130 female Fischer-344 (F-344) rats. The tumors examined were fibroadenoma (adenomatous type) in the 18-month old rat and adenocarcinoma (alveolar/tubular type) in the 21-month old rat. PRL mRNA was examined by solution and in situ reverse transcription-polymerase chain reaction (RT-PCR) method. The predicted amplified products for PRL mRNA were identified in both tumors, and its expression was confirmed to be in the cytoplasm of epithelial cells. The results of the present study showed that PRL gene is expressed in spontaneously arising mammary tumors.

Laparoscopic diagnosis and treatment of nonpalpable testis.

OBJECTIVE: Laparoscopy has become one of the important diagnostic modalities of nonpalpable testis and has been developed and applied in the treatment of this disease. In the present study, we investigated the usefulness of laparoscopy in the diagnosis and treatment of nonpalpable testis. METHODS: Laparoscopy was carried out under general anesthesia on 21 patients (23 testes) from October 1991 to October 1999. If the internal spermatic vessels and vas deferens made their way into the internal inguinal ring, the inguinal canal was dissected with an incision in the inguinal region to look for the testis. Patients with intra-abdominal testis underwent laparoscopic orchiopexy or orchiectomy. If the internal spermatic vessels terminated with a blind end intraperitoneally, making it impossible to identify the testis, the case was judged to be vanishing testis and the operation was finalized without any further examination. RESULTS: In eight of 23 testes (35%), the internal spermatic vessels and vas deferens made their way into the internal inguinal ring. The inguinal region was examined in all the eight testes. Orchiopexy was carried out on two testes and orchiectomy was carried out on six testes. An intra-abdominal testis was detected in eight of 23 testes (35%). Laparoscopic orchiopexy was carried out on seven testes. One-stage orchiopexy was carried out on two of the seven testes and two-stage Fowler-Stephens orchiopexy was carried out on five of the seven testes. Orchiectomy was carried out on the remaining testis. Blocking or lack of the internal spermatic vessels and vas deferens was seen in seven of the 23 testes (30%) and this condition was diagnosed as vanishing testis. CONCLUSION: Laparoscopy for nonpalpable testis is considered to be the most effective technique for diagnosing the presence or absence of the testis and the location of the testis.

Fibronectin as a potent inhibitor of calcium oxalate urolithiasis.

PURPOSE: Fibronectin (230 kD.) is a multifunctional alpha2-glycoprotein distributed throughout the extracellular matrix and body fluids. Many investigators have demonstrated that fibronectin, because of its cell adhesive action, is related to biological processes such as morphogenesis, wound healing and metastasis. Recent studies have shown that a variety of molecules, including fibronectin, inhibit endocytosis of calcium oxalate crystals in vitro. We investigated other roles of fibronectin in calcium oxalate stone formation. MATERIALS AND METHODS: Immunoblotting of the crystal surface binding substance obtained from pooled healthy male urine samples was used to analyze whether fibronectin was adsorbed onto the surface of calcium oxalate crystals. To clarify the relationship between fibronectin and calcium oxalate crystals, we performed 6 experiments. Experiment 1 was immunohistochemical examination of fibronectin expression in stone forming rat model kidneys, and experiment 2 examined the fibronectin content of stone forming rat kidney models with the enzyme-linked immunosorbent assay. Experiment 3 was designed to determine fibronectin content of Madin-Darby canine kidney (MDCK) cells stimulated by addition of calcium oxalate crystals and experiment 4 identified the inhibitory effect of fibronectin on calcium oxalate crystal growth by the seed crystal method. For experiment 5 we used an aggregometer system to clarify the inhibitory effect of fibronectin on calcium oxalate crystal aggregation and experiment 6 examined the inhibitory effect of fibronectin on the adhesion of calcium oxalate crystals to MDCK cells. RESULTS: In the crystal surface binding substance immunoreactive bands at 230 kD., which correspond to the molecular weight of fibronectin, were detected by Western blot analysis. In stone forming rat kidneys strong expression of fibronectin was found on the renal tubules to which the crystals were attached. The fibronectin content of these kidneys was significantly greater than that of kidneys without calcium oxalate crystals. The fibronectin content of MDCK cells tended to increase in proportion to the concentration of calcium oxalate crystals added to the culture medium. The growth inhibition assay showed that the inhibitory effect of fibronectin on calcium oxalate crystal growth was small in relation to the quantity of fibronectin excreted. However, fibronectin had inhibitory effects on calcium oxalate crystal aggregation and adhesion of the crystals to MDCK cells. CONCLUSIONS: Fibronectin secretion can be stimulated by calcium oxalate crystals, and this protein, which is excreted from the tubular cells, may inhibit calcium oxalate crystal aggregation and attachment to cells.

Further study on the photochemistry of non-ortho substituted PCBs by UV irradiation in alkaline 2-propanol.

The photochemical behaviors of six non-ortho substituted PCB congeners, i.e., 3,4-DiCB, 3,5-DiCB, 3,3',5-TriCB, 3,4,5-TriCB, 3,3',4,5-TetraCB, and 3,4,4',5-TetraCB, irradiated at 254 nm in alkaline 2-propanol were investigated. Besides the determination of the photodechlorination pathways of these compounds, the presence of photorearrangement was observed in the case of 3, 4-DiCB with its products being identified. The results indicate that dechlorination is much more important than rearrangement during the process of PCB photolysis.

[A case of renal cell carcinoma associated with tuberous sclerosis].

Tuberous sclerosis is associated commonly with renal angiomyolipoma. On the other hand, the relation between tuberous sclerosis and renal cell carcinoma is not widely recognized. We report a case of renal cell carcinoma of the right kidney associated with tuberous sclerosis.

[Three cases of metastatic renal tumor].

Since solitary metastatic renal tumors are not commonly diagnosed before death, the conclusive treatment of the metastatic renal tumor has not been established. We report three cases of metastatic renal tumors and discuss the indication of surgical therapy for metastatic renal tumors. The first case was in a 64-year-old male who underwent esophagectomy for squamous cell carcinoma. Seven months after the operation, a right renal tumor was found. The second case was in a 63-year-old male who underwent right upper pneumonectomy for adenocarcinoma with a right renal tumor, which seemed to be a solitary metastasis. The third case was in a 69-year-old male who underwent right pneumonectomy for adenocarcinoma. One month after the initial operation, a left renal cystic tumor was found. Since, in all cases, the tumors seemed to be solitary metastatic renal tumors without any other metastatic lesions, nephrectomy was performed. Unfortunately, however, the nephrectomy did not improve prognosis and all three patients did within 10 months after the nephrectomy. Nephrectomy may not be recommended in cases of metastatic renal tumors even if no other metastatic lesions can be found by various image examinations.

Non-synchronous double adenoma of the parathyroid gland.

A 46-year-old female underwent an excision of a parathyroid adenoma diagnosed as recurrent primary hyperparathyroidism 24 years after the initial excision of a parathyroid adenoma. We report a case of non-synchronous double adenomas of the parathyroid glands documented histopathologically.

[Renal cell carcinoma in acquired cystic disease of kidney (ACDK) manifested by spontaneous renal rupture: a case report].

We report a case of renal cell carcinoma in acquired cystic disease of the kidney (ACDK) presenting with a spontaneous renal rupture. A 41-year-old man on chronic hemodialysis for 16 years was referred to our hospital with sudden left back pain. On arrival, the patient was in a state of hemorrhagic shock but his general condition improved by conservative therapy. Computed tomography demonstrated a left renal rupture as well as bilateral ACDK. Although there was no definite evidence of a renal tumor, a left radical nephrectomy was performed one week later. The resected kidney contained a yellowish-brown tumor of 5.5 x 5.0 x 4.5 cm in size. Pathological examination revealed renal cell carcinoma, cystic type, clear cell subtype, pT2pN0M0. He has been free of recurrence for 3 months.

[Successful treatment of recurrent endometrial stromal sarcoma by radiotherapy and intra-arterial chemotherapy with CDDP and ADM].

Endometrial stromal sarcoma (ESS) is a rare uterine malignancy. We describe a case of an ESS recurrence arising near a stump after hysterectomy. The 47-year-old patient had the operation at another hospital because of myoma uteri as a preoperative diagnosis. Since the postoperative pathological diagnosis was ESS, CYVADIC was administered as adjuvant chemotherapy. But 3 years later, an isolated recurrent tumor was found locally near a stump in the pelvis. The patient underwent a combination of an intra-arterial chemotherapy and radiotherapy. Cisplatin and Adriamycin was administered in 20 mg/m2 everyday for 5 days and 60 mg for 1 day, respectively. On the other hand, the tumor irradiation dose was 50 Gy for 5 weeks. After this combination therapy, the recurrent tumor size grew smaller on CT. This result suggests that the combination of intra-arterial administration of cisplatin and Adriamycin, and radiation is an effective therapy for a localized recurrent tumor of ESS.

[A clinical study of renal pelvic and ureteral cancer associated with bladder cancer].

We reviewed 45 cases of transitional cell carcinoma of the renal pelvis and ureter with reference to the coexistence or subsequent development of bladder cancer. Bladder cancer was associated with an upper urinary tract neoplasm in 26 of the 45 cases. The 5-year survival rate for coexistence of bladder cancer was 56% and that for subsequent bladder cancer was 65.6%. The 5-year survival rate for 19 cases unrelated with bladder cancer was 46.7%. Therefore, there was no significant difference among the three groups. As to degree of the malignancy of the renal pelvis and ureter, the 5-year survival rate was 73.7% for G1 and G2 and 26.2% for G3. As to the depth of invasion, of the renal pelvis and ureter the 5-year survival rate was 71.8% and 31.1% in the patients with stage of T1, T2 and T3, T4. The prognosis of cancer of the upper urinary tract depended on the degree of the malignancy, and the depth of invasion. Ninety two percent of subsequent bladder cancer was detected within 2 years after resection of the primary cancer.

Autoimmunity induction by human T cell leukemia virus type 1 in transgenic mice that develop chronic inflammatory arthropathy resembling rheumatoid arthritis in humans.

We recently reported on an inflammatory arthropathy resembling rheumatoid arthritis that develops in high incidence among transgenic mice that carry the env-pX region of the human T cell leukemia virus type 1 genome. In an effort to elucidate the pathogenesis of this disease, we found that genes for inflammatory cytokines, including IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, transforming growth factor-beta 1, IFN-gamma, and IL-2, as well as MHC genes were activated in transgenic joints. Serum levels of IL-1 beta and IL-6 were also elevated. Interestingly, these mice produced Ab against IgG, type II collagen (IIC), and heat shock proteins accompanied by IgG hypergammaglobulinemia. The cellular immune response to IIC as well as that to heat shock proteins were activated. Moreover, these mice became immunologically responsive to exogenously administered IIC and developed arthritis, in contrast to their nontransgenic littermates, which showed little response to IIC. Taken together, the results suggest that human T cell leukemia virus type 1 can cause immune system hyperreactivity and induce autoimmunity. The possibility that elevated cytokine and/or MHC gene expression are involved in the development of autoimmunity and arthropathy are discussed.