We evaluated the combination therapy of angiotensin-converting-enzyme inhibitor (ACE-I) and angiotensin II type 1 receptor blocker (ARB) offered an additional effect in reduction of albuminuria in type 2 diabetic patients with angiotensinogen (AGT) M235T polymorphism. The study subjects were type 2 diabetic patients with nephropathy who were attending Hirosaki University Hospital. Fifteen patients with 235T allele (TT genotype 9, MT genotype 6) were evaluated who had diabetic nephropathy in stage 2 or 3 and already treated with ACE-I. Each patient administrated ARB (20-40 mg of termisartan) in addition to ACE-I for 16 weeks as the combination therapy. The addition of termisartan induced a significant reduction in systolic blood pressure (BP) of 14.0 mmHg and diastolic BP of 5.4 mmHg. The urinary albumin-creatinine ratio (ACR) was also reduced to 48.9 %. There was no significant correlation between the reduction rate of ACR and the antihypertensive response of systolic blood pressure (BP) (rs = 0.1277) and of diastolic BP (rs = 0.1420) by the addition of termisartan. These results indicated that the combination of ACE-I and ARB had an additional effect on urinary albumin excretion in type 2 diabetic patients with AGT 235T allele.
Total parathyroidectomy with autotransplantation (PTx · AT) is performed in dialysis patients with advanced secondary hyperparathyroidism (SHPT). The location of glands is not definite, some patients have more than 4, and so all parathyroid glands are not always removed during initial PTx. Occasionally, SHPT after PTx recurs because PTH over-secretion from remnant glands or autograft. We examined recurrence after PTx · AT. Subjects were 92 patients with SHPT, 101 PTx were performed. The patients were subdivided into 5 groups according to number of removed glands and serum PTH on the next day after surgery, mean number of removed glands and serum PTH (pg/ml) in each group, respectively, group A; 4.1, 15, group B; 4.2, 280, group C; 2.8, 29, group D; 2.8, 371 and group E (cases of re-operation); 1.4, 28. Criterion for recurrence was defined as PTH > 300 pg/ml. Recurrence rate was low in serum PTH < 60 pg/ml on the next day after PTx, in group A (11.9%), group C (20.0%) and group E (16.6%). On the other hand, recurrence rate was high in group B and group D almost 70% in these group of serum PTH ≧ 60 pg/ml on the next day after PTx. PTH almost secreted from autograft in group A, C and E, and from remnant glands in group B and D.
Toxic shock syndrome toxin 1 (TSST-1) produced by Staphylococcus aureus is one of superantigenic
exotoxins and is best known for its involvement in toxic shock syndrome. To investigate whether an intranasal
vaccination with a nontoxic mutant TSST-1 (mTSST-1) can protect against systemic infection and nasal colonization
of S. aureus, mice were immunized with mTSST-1 plus a nontoxic mutant heat labile toxin (mLT) of Escherichia
coli. After an intravenous challenge with S. aureus. bacterial growth in the organs of immunized mice reduced and
the survival rate was significantly higher, compared with the naive mice. To evaluate the effect of vaccination with
mTSST-1 against nasal S. aureus colonization, mice were challenged with S. aureus intranasally. The bacterial counts
in the nasal cavity of immunized mice were significantly reduced. Vaccination with mTSST-1 plus mLT efficiently
induced anti-TSST-1 antibodies in the sera and mucosal exudates, and increased anti-TSST-1 IgA-secreting cells in
nasal-associated lymphoid tissues. These results indicate that an intranasal vaccination with mTSST-1 plus mLT
could induce systemic and mucosal immune responses and provide protection against not only systemic infection but
also nasal colonization of S. aureus.
Introduction: Retinoic acid-inducible gene-I (RIG-I) is a putative RNA helicase. Upon viral infection, RIG-I
protein binds to the viral double-stranded RNA. Objectives: Tumor necrosis factor-α (TNF-α) and interferon-γ
(IFN-γ) stimulate the expression of RIG-I mRNA and protein in epidermal keratinocytes, and that mechanisms have
not been well elucidated. The purpose of this study was to investigate the cooperative efect of TNF-α and IFN-γ
to the expression of RIG-I. Results: The steady-state levels of RIG-I mRNA and protein amounts were analyzed by
semi-quantitative RT-PCR and Western blotting, respectively. RIG-I mRNA and protein levels were synergistically
increased through the administration of both the TNF-α and IFN-γ in HaCaT keratinocytes. Conclusion: These
findings imply that the induction of RIG-I expression by TNF-α and IFN-γ is utilized by the different signaling
pathway from each other.
AIM: Transforming .growth factor (TGF)-β related signaling may play an important role in the
pathogenesis of refractory ulcerative colitis (UC). We examined the expression levels of TGF-β receptor (R) I and
TGF-β R II, that is in the downstream pathway of TGF-β signaling. METHODS: Colonic tissue samples were obtained
from refractory cases and responsive cases with UC, and controls. RNA and protein were extracted from mucosal
samples, and real time-PCR and western blot analysis were performed. RESULTS: Both of TGF-β R I and TGF-β R II
transcripts were significantly suppressed in refractory cases with UC (0.106±0.0335, 0.185±0.0465) compared with
responsive cases (1.12±0.352, p<0.01, 1.82±0.877, p<0.05). Western blot analysis showed that TGF-β R I and R II
were significantly suppressed in refractory cases with UC (0.587±0.105, 1.02±0.318) compared with responsive cases
(1.89±0,670, p<0.05, 5.02±1.66, p<0.05). CONCLUSION: From these findings, we conclude that one of the mechanisms
of refractoriness of UC is due to the downregulation of TGF-β receptor at the transcriptional levels and the protein
levels that leads to the loss of TGF-β related signaling.
Proteoglycans are one of the most important components of the extracellular matrix in the cartilage
and the levels of proteoglycans, such as versican and aggrecan, increase during chondrogenesis. The purpose of
this study was to investigate the effect of exogenous proteoglycans from salmon nasal cartilage on chondrogenesis
of mesenchymal stem cells. Mesenchymal stem cells derived from bone marrow aspiration of rabbit femurs were
induced to chondrogenic lineage using a pellet culture technique. Pellets were cultured in the medium with or
without cell growth factors, with or without proteoglycans, or a combination of these agents. Pellets treated with cell
growth factors became hypertrophic and showed lacuna formation, and synthesis of cartilage matrix was recognized
histologically. The expression of type II collagen and aggrecan mRNA were decreased in pellets incubated with a
combination of cell growth factors and proteoglycans, compared to those incubated with only cell growth factors.
Exogenous proteoglycans may down-regulate the expression of cartilage-specific mRNA directly, or may interact
with growth factors in the culture medium. As the increase of glycoprotein during chondrogenesis is important for
determining the direction and degree of differentiation, exogenous proteoglycans may have a similar effect.
The purpose of this study was to determine predictive factors for pleural dissemination of lung cancer based on preoperative CT findings. Among 138 patients with primary lung cancer who underwent thoracotomy since Jan. 2003 until December 2005, 31 patients had abnormal pleural CT findings, and six of them were found to have pleural dissemination. In 5 of 6 patients, pleural nodules or thickening were detected on preoperative CT.
All patients with pleural dissemination were confirmed to have pleural invasion by surgical specimens. Review of
thin-Slice CT revealed that all these patients had pleural thickening and 4 patients had invasion of primary tumor.
From these results, we conclude that meticulous survey of primary tumor on CT is essential for detecting pleural
dissemination of primary lung cancer.
Patients with chronic pancreatitis are not only suffered from pancreatic exocrine but also endocrine
deficiency. Also, in diabetic patients with long duration, there are some patients with impaired amylase secretion
and pancreatic atrophy or fibrosis. Recently, advanced glycation endproducts (AGE) and receptor for AGE (RAGE)
are reported as one of causes of diabetic vascular complications such as neuropathy, retinopathy, nephropathy and
macroangiopathy. Relationship of diabetes with pancreatic exocrine deficiency and AGE-RAGE is unknown. So we
investigated whether there exist “diabetic pancreatopathy” and effects of RAGE on the diabetic pancreas using an animal model. Spontaneously Diabetic Torii (SDT) rat reveals insulin deficiency and fibrosis of islets of Langerhans.
We induced recurrent acute pancreatitis in the SDT rat with repeated caerulein injection and investigated the
severity of diabetes and pancreatic fibrosis. Also we examined RAGE-mRNA expression before and after diabetes
onset and pancreatitis by RT-PCR. As results, the onset of diabetes and its severity as well as, pancreatic fibrosis
were not altered with or without pancreatitis. Expression of RAGE-mRNA was low ln the pancreas, and was not
altered after the onset of diabetes and pancreatitis. In conclusion, different mechanisms for fibrosis may operate in the
islets of Langerhans and in pancreatic lobules.
Hyaluronan (HA) is a major component of the pericellular matrix, and is implicated in cell adhesion,
invasion, and tumor metastasis. We have reported that 4-methylumbelliferone (MU) inhibits HA synthesis
by cultured skin fibroblasts, melanoma cells, and pancreatic cancer cells. We focused in the present study, on
mesothelioma which has an extremely poor prognosis, and in which no effective therapy has yet been established.
We investigated dealing with this neoplasm whether MU and 4-methylesculetin (ME), a MU derivative, are able to
inhibit HA synthesis by the mesothelioma cell line NCI-H2052. MU inhibited HA synthesis by about 20%, and ME
by about 40%, in comparison with the control group. MU inhibited the adhesion of NCI-H2052 cells by about 30%,
and ME by about 50%, compared with the untreated control. MU inhibited cell locomotion by about 30%, and ME
by about 40%. It is suggested through these results suggest that MU and ME inhibit HA synthesis, adhesion, and
locomotion by human mesothelioma cells and weaken their pericellular matrix, and that the inhibitory effect of ME
on HA synthesis is stronger than that of MU. It is presumed that both MU and ME may have potential as new
therapeutic or prophylactic medicines against mesothelioma.
The changes in proteoglycan (PG) expression and glycosaminoglycan (GAG) constituents in the
intervillous space of the pregnancy-induced hypertension (PIH) placenta were investigated. PGs and GAGs were
purified from the extract of the placental intervillous space by the DEAE-Sephacel column and salt-concentration
gradient method, and the GAG sugar chains were released by the actinase and cellulase treatments. The
sugar chains from the placentas of normal pregnancy and PIH were compared by cellulose-acetate membrane
electrophoresis. No difference was observed in the expressions of hyaluronic acid, heparan sulfate, and chondroitin
sulfate, but a clear increase in the expression of dermatan sulfate (DS) in the placenta of the PIH was confirmed.
An increase of the DS that specifically activates anticoagulants can be a body reaction to counteract the hemostatic
condition observed in PIH.