Effects of non-ablative vaginal erbium:YAG laser treatment for interstitial cystitis/bladder pain syndrome: a case series (UNICORN-2 study).

Purpose: There are no established treatments for treating interstitial cystitis/bladder pain syndrome (IC/BPS). We conducted a study to verify the effectiveness of non-ablative vaginal erbium:YAG laser (VEL) treatment for patients with IC/BPS who were resistant to conventional treatments.Methods: A total of 12 patients without improvement after several treatments before 2016 underwent VEL treatment once a month for 12 months as per their convenience. The numeric rating scale-11 (NRS-11), O'Leary-Sant interstitial cystitis symptom and problem indexes (ICSI and ICPI), functional bladder capacity, and daily urinary frequency were obtained.Results: In total, nine patients responded to the treatment and three did not. The NRS-11 scores and ICSI and ICPI improved in all responders. The bladder capacity and urinary frequency also normalized. The residual effect lasted for 18 months from the first treatment without long-term side-effects.Conclusions: VEL treatment is a safe and effective treatment in patients with IC/BPS.

Decrease in level of APG-2, a member of the heat shock protein 110 family, in murine brain following systemic administration of kainic acid.

APG-2 belongs to the heat shock protein 110 family. Although kainic acid (KA)-induced seizures are known to elicit expression of inducible heat shock protein 70 (HSP70) in the brain, no investigation has been carried out on the APG-2 level after excitatory amino acid-induced seizures. By means of an immunoblot assay, we determined the levels of HSP70 and APG-2 in discrete brain structures of mice after a single intraperitoneal injection of KA or N-methyl-D-aspartic acid (NMDA). APG-2 level was significantly decreased in frontal cortex, hippocampus, and striatum three days after the administration of KA, while HSP70 level was increased in these regions following the administration. In any of these regions, APG-2 levels were returned to the control levels 10 days after the administration. However, no significant changes were observed in levels of both HSP70 and APG-2 in hypothalamus, midbrain, medulla-pons, and cerebellum of the mice. By contrast, NMDA administration did not significantly affect both levels in any of the regions examined. These findings indicate that the transient decrease in APG-2 expression is one of the intracellular events elicited by signals peculiar to KA, but not by those peculiar to NMDA, in telencephalon of murine brain.

Helicobacter pylori infection increases mucosal permeability of the stomach and intestine.

It is important to study the effect of Helicobacter pylori infection on the permeability of the intestine. Permeability was evaluated by oral sucrose tolerance test using sucrose 25 g in 200 ml of water. Existence of H. pylori itself was associated with increased permeability of sucrose. Also, the permeability of sucrose increased as polymorphonuclear and lymphocyte infiltration increased. The increase of mucosal permeability suggests that antigens like protein penetrate into the body and result in systemic reactions. Thus, it is important to study the implication of increased permeability in relation not only to gastric diseases but also certain systemic diseases.

Experimental gastric carcinogenesis related to Helicobacter pylori.

In this paper, we present our research on the lipid A of Helicobacter pylori, an experimental study using the Mongolian gerbil model and experimental carcinogenesis using the mouse model to evaluate roles of host factors and bacterial factors which are related to the pathogenicity of Helicobacter pylori including gastric carcinogenesis. Future study on bacterial factors and host factors may give more insight into the role of Helicobacter pylori in gastric carcinogenesis.

Expression of APG-2 protein, a member of the heat shock protein 110 family, in developing rat brain.

APG-2 protein is a member of the heat shock protein 110 family, and it is thought to play an important role in the maintenance of neuronal functions under physiological and stress conditions. However, neither the tissue-distribution of APG-2 protein nor developmental change of its expression has been studied at the protein level. Therefore, we generated an antiserum against APG-2 protein and studied expression of this protein in rat brain and other tissues by use of the Western blot method. The results showed a high expression of APG-2 protein in various regions of the central nervous system (cerebral cortex, hippocampus, striatum, midbrain, hypothalamus, cerebellum, medulla pons, and spinal cord) throughout the entire postnatal stage. Similarly, a high level of APG-2 protein was detected in the whole brain of rat embryos and in adult rat tissues such as liver, lung, spleen, and kidney. In contrast, its expression in heart was high at postnatal days 1 and 3, but thereafter drastically decreased to a low level. Furthermore, APG-2 protein was detected in neuronal primary cultures prepared from rat cerebral cortex, and its level did not change notably during neuronal differentiation. These results show that APG-2 protein is constitutively expressed in various tissues and also in neuronal cells throughout the entire embryonic and postnatal period. suggesting that it might play an important role in these tissues under non-stress conditions.

High-level expression of the Mnb/Dyrk1A gene in brain and heart during rat early development.

We previously isolated human MNB/DYRK1A cDNA from "the Down syndrome critical region" of human chromosome 21 (Shindoh et al., 1996, Biochem. Biophys. Res. Commun. 225: 92-99). As described herein, we prepared a polyclonal anti-MNB/DYRK1A antibody and used it in a Western blot assay to assess the expression of the MNB/DYRK1A protein during rat development. The MNB/DYRK1A protein was expressed strongly not only in the brain but also in other tissues from embryonic rats. At the early postnatal stage, expression of the protein was high in the central nervous system and heart, but low in liver, lung, spleen, and kidney. The level of MNB/DYRK1A protein in all tissues studied gradually decreased with postnatal growth. Similarly, Northern blot analysis revealed that a major 6.0-kb transcript of the Mnb/Dyrk1A gene was expressed at a high level in the brain during the early postnatal period but that its level was low in the adult. The finding that the MNB/DYRK1A protein is expressed strongly in the central nervous system and heart may indicate a significant role for this protein in the development of these organs.

Helicobacter pylori infection affects gastric ulcer healing in Japanese monkeys.

Although peptic ulcer frequently recurs in the presence of Helicobacter pylori infection, the effects of H. pylori on ulcer healing have yet to be studied in detail. Using an animal model, we examined the effects of H. pylori infection on the healing of peptic ulcer in Japanese macaques. Forty-four Japanese macaques, aged 5 years, were randomly divided into two groups, an H. pylori-infected group and a control group, with 22 animals in each. A total of 10(9) colony forming units per ml of an H. pylori strain clinically isolated from patients positive for the cagA gene, the vacA gene, and vacuolizing toxin production, was inoculated into the stomachs of the monkeys to induce H. pylori-associated gastritis. The monkeys were examined by endoscopy, and then 0.1 ml of 10% ammonia solution was injected into the angulus to produce an active ulcer. Endoscopic observations was performed every week for 8 weeks. Acid-reducing drugs and other cytoprotective agents were not administered during the 8-week observation period. No difference in the healing of the ulcers was seen between the two groups from the first to the third week. However, a significant delay in healing was noted in the H. pylori-infected group from the fourth week on wards (P < 0.05). At the sixth week, the proportion of ulcers in the S2 stage (presence of a complete scar) was 0% in the H. pylori-infected group and 38% in the control group, again indicating that healing was significantly delayed in the H. pylori-infected group (P = 0.0187). By the eighth week, the proportion of ulcers in S2 stage had increased to 18% in the H. pylori-infected group and 67% in the control group (P = 0.0719). In Japanese macaques with persistent H. pylori infection in the stomach, the speed of repair of the ulcer surface was reduced, leading to delayed ulcer healing, compared with the controls.

Exacerbated autoimmune hepatitis successfully treated with leukocytapheresis and bilirubin adsorption therapy.

A 58-year-old man with subacute fulminant onset of autoimmune hepatitis (AIH) was treated by leukocytapheresis (LCAP) and bilirubin adsorption therapy (BAT), rather than by administration of high-dose corticosteroids as he had mild glucose intolerance, and a definitive diagnosis of AIH was not obtained on admission; further, there was a risk of viral infection. After initiation of the therapies, serum transaminases and bilirubin, immunoglobulins, anti-nuclear antibodies, and rheumatoid factor decreased rapidly, as did the initially high levels of activated cells and several pro-inflammatory cytokines. Liver inflammation observed on liver biopsy settled during the course of the therapies, with no adverse side effects. A pause in the therapies was associated with deterioration; however, restoration of apheresis was followed by normalization. Remission was sustained throughout the period monitored, except for a recurrence 14 months after discharge, which was successfully resolved by two additional LCAP sessions. These results suggest that LCAP influences the causal mechanism(s) of exacerbation of AIH.

Efficacy of nutritional therapy for active Crohn's disease.

We investigated the effect of nutritional therapy with an elemental diet (ED) for active Crohn's disease. One hundred and thirty-nine patients with Crohn's disease were enrolled in this study. Remission was judged to be present when the International Organization of Inflammatory Bowel Disease score was < or = 1 and the CRP and ESR values were within the respective normal ranges. An amount of 30kcal per 1kg of ideal body weight (IBW) per day was administered enterally, and the effect on the induction of remission in relation to various patient background factors, such as disease type, history of bowel resection, and the presence/absence of complications, was determined. An excellent remission rate was achieved in those patients to whom an adequate amount of ED could be administered. Remission rates were lower in the patient groups with any of the following complications: stenotic bowel lesions, abdominal masses, fistulas, and anal lesions. Even in those groups in which stenotic lesions or abdominal masses were present, when adequate amounts of ED could be administered, the remission rate did not differ from that in the groups without these complications. The remission rates in the groups with and without fistulas at any site, including fistulas in the anal region, were 40.0% and 82.5%, respectively, with remission being considerably easier to achieve in the patients without fistulas. Similarly, remission was difficult to achieve when anal lesions were present. These results suggest that, for active Crohn's disease, nutritional therapy with ED ( > or = 35kcal/kg IBW) should be enthusiastically administered, and in patients in whom the presence of complications necessitates therapy for 3 months or more, this point be considered to indicate a possible surgical approach.

Combination therapy with mucosal protective agent for the eradication of Helicobacter pylori.

OBJECTIVE: To investigate the effect of plaunotol in combination with proton-pump inhibitors on Helicobacter pylori eradication in patients with gastric ulcer. PATIENTS AND METHODS: We studied 65 H. pylori-positive gastric ulcer patients. They were randomly assigned to five treatment groups: omeprazole (group I, n = 8), lansoprazole (group II, n = 13), lansoprazole+plaunotol (group III, n = 12), lansoprazole+clarithromycin (group IV, n = 16) and lansoprazole+plaunotol+clarithromycin (group V, n = 16). Ulcer status was diagnosed by endoscopy and H. pylori status by culture, histology, a urease test and a urea breath test at baseline, and after 8 and 12 weeks. The clearance and eradication rates were compared in each group. RESULTS: The healing rates in groups I-V were 100, 92, 100, 100 and 100%, respectively; clearance rates were 0, 23, 42, 50 and 75%, respectively; and eradication rates were 0, 0, 8, 38 and 69%, respectively. CONCLUSION: Combination therapy with plaunotol is efficacious for the eradication of H. pylori in gastric ulcer patients.

Combination therapies with a proton pump inhibitor for Helicobacter pylori-infected gastric ulcer patients.

We investigated the eradication and recurrence rate of Helicobacter pylori-infected gastric ulcer patients by combination therapies. Eighty-six H. pylori-positive gastric ulcer patients were assigned randomly to one of seven groups: I, omeprazole 20 mg (n = 9); II, lansoprazole (LPZ) 30 mg (n = 16); III, LPZ 30 mg plus plaunotol 480 mg (n = 13); IV, LPZ 30 mg plus ecabet sodium 2 g (n = 11); V, LPZ 30 mg plus clarithromycin 600 mg (the first 2 weeks; n = 11); VI, LPZ 30 mg plus plaunotol 480 mg plus clarithromycin 600 mg (the first 2 weeks; n = 13); and VII, LPZ 30 mg plus ecabet sodium 2 g plus amoxicillin 1,500 mg (the first 2 weeks; n = 13). All therapy was for 8 weeks except where otherwise noted. H. pylori eradication rates as diagnosed by culture, histology, urease test, and [13C]urea breath test 4 weeks after stopping therapy were 0, 0, 8, 45, 6, 46, and 62%, respectively, in groups I-VII. No patient achieving H. pylori eradication suffered recurrence. The combination therapies with proton pump inhibitors in addition to antibiotics and antiulcer agents are safe and effective in H. pylori eradication.

Proton pump inhibitors for Helicobacter pylori eradication in patients with peptic ulcer.

We investigated the effects of omeprazole or lansoprazole on peptic ulcer healing, eradication of Helicobacter pylori (Hp) and abdominal symptoms. A prospective, randomized study was performed for the administration of omeprazole or lansoprazole. Hp-positive peptic ulcer patients (n = 86) were randomly assigned to two groups. Gastric ulcer patients received omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 8 weeks. Duodenal ulcer patients were given omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 6 weeks. Endoscopy was performed at baseline, at the end of therapy, and 4 weeks after stopping therapy. The colony factor units (CFUs) of Hp in biopsy specimens were examined. The CFUs of Hp in gastric and duodenal ulcer were significantly decreased at 4 weeks after stopping lansoprazole therapy. We conclude that Hp eradication by combined use of lansoprazole with antibiotics appears to be a promising therapy.

[Induction of complete remission in a case of drug-resistant childhood acute megakaryoblastic leukemia by combination of G-CSF and chemotherapy].

In a 4-year-old girl having acute megakaryoblastic leukemia, recombinant human granulocyte colony-stimulating factor (G-CSF) was used in combination with chemotherapy for remission induction after the second relapse of her leukemia. G-CSF was given intravenously at a dose of 100 micrograms/m2/day 24 hours prior to chemotherapy until the peripheral neutrophil counts fully recovered. Cytosine arabinoside (Ara-c) [100mg/m2/day] and VP-16 [100mg/m2/day] were given from day 1 through day 10. Her leukemia was resistant to chemotherapy alone after the second relapse but complete remission and hematological recovery were achieved two months after the start of this therapy. Although in vitro clonal assay did not show significant stimulation of colony formation by G-CSF on leukemia cells of this patient, and the mechanism underlying remission induction by this combination therapy remains unclear, it may be of benefit to use G-CSF in combination with chemotherapy for patients with drug-resistant leukemia.

Differentiation induction of blast cells in two cases of childhood acute megakaryoblastic leukemia in vitro by interleukin-3 and interleukin-6: an ultrastructural cytochemical study.

Although hematopoietic growth factors influence renewal and differentiation of blast progenitors in acute myelogenous leukemia (AML), morphological maturation of leukemic blasts is thought a rare event, even when cultured in the presence of appropriate growth stimulants. However, light microscopic observation may not be sufficient to clarify precisely the effects of hematopoietic growth factors on the morphological differentiation of leukemic blasts. In this study, using cell culture techniques and electron microscopic cytochemistry for platelet peroxidase (PPO), we studied the effects of interleukin-3 (IL-3) and interleukin-6 (IL-6), both of which are considered to play an important role in normal megakaryocytopoiesis, on the growth and differentiation of blast cells from two patients with childhood acute megakaryoblastic leukemia (AMKL). In both of the two cases, IL-3 stimulated leukemic colony formation in methylcellulose culture, whereas IL-6 showed little such activity. However, in suspension culture, IL-6 was active in promoting megakaryocytic differentiation, although incomplete, as detected by increase in the number of PPO-positive cells, some having demarcation membrane-like structure. This effect was evident in culture with IL-6 alone in one patient, but it was detectable only when IL-6 was used in combination with IL-3 in the other patient. In contrast, IL-3 alone stimulated differentiation towards myeloid but not megakaryocytic lineage. These results indicate that IL-3 and IL-6 have a distinct role in leukemic megakaryocytopoiesis (IL-3 stimulates growth, whereas IL-6 promotes morphological differentiation) and that cooperation between these two cytokines functions most effectively for megakaryocytic differentiation of AMKL cells in a fashion similar to that for normal megakaryocytopoiesis.

Absence of albumin mRNA in the liver of analbuminemic rats.

Albumin synthesis in the liver of analbuminemic rats, established as a strain from a stock of Sprague-Dawley rats, was examined in vivo by labeling protein by intraperitoneal injection of L-[3H]leucine. Albumin was not synthesized in the liver of analbuminemic rats, whereas its synthesis amounted to about 14% of the total protein synthesis in the liver of normal rats. The RNA content and size distribution of the total polysomes in the liver of analbuminemic rats were not significantly different from those of normal rats. However, no functional mRNA coding for albumin was found in poly(A)-containing RNA from the liver of analbuminemic rats when tested with a cell-free translation system derived from rabbit reticulocytes. Moreover, the amount of the RNA sequence that could hybridize to purified albumin cDNA was more than 750 times greater in the liver of normal rats than in that of analbuminemic rats.