Decreased Tongue Strength is Related to Skeletal Muscle Mass in COPD Patients.

Dysphagia is frequently observed in patients with chronic obstructive pulmonary disease (COPD). Decreased tongue strength is one of the causes of dysphagia, and it is often observed in patients with sarcopenia. Sarcopenia is also frequently observed in COPD patients. We hypothesized that tongue strength is lower in COPD patients compared to normal subjects. This was a single-center, observational, cross-sectional study. Maximum tongue pressure (MTP) was measured in 27 patients with COPD and 24 age-matched control subjects. We also evaluated handgrip strength, gait speed, and appendicular skeletal muscle mass to define subjects as having sarcopenia. We used bioelectrical impedance analysis to assess body composition. The eating assessment test-10 was used to diagnose dysphagia. MTP was significantly lower in COPD patients than in control subjects (33.8 ± 8.4 vs 38.0 ± 5.3; p = 0.032). All measures of muscle and fat free body mass, handgrip strength, and gait speed were also significantly lower in COPD patients compared to control subjects (p < 0.01). The prevalence of sarcopenia in COPD patients was higher than that in control subjects (6/27 versus 0/24; p = 0.007), but the prevalence of dysphagia was not different between groups (COPD: 5/27, versus control: 1/24; p = 0.112). MTP was moderately correlated with skeletal muscle mass index (r = 0.56, p = 0.003) and handgrip strength (r = 0.43, p = 0.027) in COPD patients. Tongue strength was lower in COPD patients compared to normal subjects, and decreased tongue strength may be correlated with sarcopenia in COPD patients.

Monoclonal and polyclonal immunoglobulin G deposits on tubular basement membranes of native and pretransplant kidneys: A retrospective study.

Monoclonal tubular basement membrane immune deposits (TBMID) are associated with progression of interstitial injury in renal allograft. However, the significance of monoclonal and polyclonal TBMID in the native kidney remains unclear. We retrospectively analyzed 1894 native kidney biopsies and 1724 zero-hour biopsies performed between 2008 and 2018 in our institution. The rate of immunoglobulin G (IgG) TBMID was found to be 8.4% among native kidney biopsies and 0.4% among zero-hour biopsies. Polyclonal TBMID is common in IgG4-related tubulointerstitial nephritis (37.5%), diabetic nephropathy (31.3%) and lupus nephritis (25.5%). Monoclonal IgG TBMID was identified in seven cases, including three zero-hour biopsies. The combination of IgG1κ was observed in two cases, IgG1λ in three, and IgG2κ in two. Electron microscopy revealed powdery electron-dense deposits in all cases. Monoclonal gammopathy of undetermined significance was diagnosed in one case. Although one patient with focal segmental glomerulosclerosis developed renal failure, all others exhibited stable renal function. Monoclonal IgG TBMID in the native kidney is not associated with renal prognosis. However, this may be an interesting immunopathological finding that would help clarify the pathogenesis of TBM immune deposits. Further study for both monoclonal and polyclonal TBMID is required in the future.

Serum Magnesium Levels and Mortality in Japanese Maintenance Hemodialysis Patients.

BACKGROUND/AIMS: Although hypomagnesemia was found to be a risk for cardiovascular diseases in the general population, the relationship between serum magnesium (Mg) levels and prognosis of patients on maintenance hemodialysis (MHD) has not been extensively studied. This study sought to determine the relationship of serum Mg levels with aortic arch calcification (AoAC) and mortality in Japanese MHD patients. METHODS: We measured serum Mg levels in a cohort of 392 patients on MHD, classified the patients into 3 groups according to these levels, and followed their course for 4 years. AoAC was assessed using chest-X-rays. RESULTS: During follow-up, there were 117 deaths. Kaplan-Meier analyses showed that the high serum Mg group tended to have better survival rates than the low and middle serum Mg groups but this did not reach statistical significance. We also found that patients in the high serum Mg group had better nutritional status associated with higher serum albumin, triglyceride, and phosphate levels and had a significantly lower serum C-reactive protein level. In total, 83 patients (59.3%) in the high serum Mg group had been prescribed Mg oxide (MgO). CONCLUSIONS: Hypermagnesemia tended to be associated with better survival and a higher prescription rate of MgO. Interventional studies are needed to clarify whether Mg supplementation is beneficial for improving patient prognosis.

A case of recurrent proliferative glomerulonephritis with monoclonal IgG deposits or de novo C3 glomerulonephritis after kidney transplantation.

Proliferative glomerulonephritis with monoclonal immunoglobulin (Ig)G deposits (PGNMID) is a rare disease with a treatment that is not well established. Several cases of recurrent PGNMID after kidney transplantation have been documented, but almost all cases reported symptoms such as elevated serum creatinine and/or urinary protein levels; subsequently, episode biopsies were performed and a diagnosis was made. This is the case of a 27-year-old man who underwent living-donor kidney transplantation. The aetiology of renal failure was membranoproliferative glomerulonephritis type III, which had been diagnosed at the age of 9 years. Protocol biopsy performed on postoperative day 62 revealed isolated granular C3 deposits in the glomerular capillaries and mesangium. We reviewed the native kidney biopsy and confirmed IgG3 deposition alone, with strong glomerular staining for lambda light chains and negative staining for kappa light chains. Accordingly, we re-diagnosed the aetiology of his renal failure as PGNMID and suspected recurrent PGNMID in the early stage; therefore, we administered plasma exchange therapy. Thereafter, protocol biopsies were performed twice, which revealed persistent isolated C3 deposition; therefore, we made a diagnosis of recurrent PGNMID or C3 glomerulonephritis. Currently, the patient has normal renal function, with negative urine findings for >1 year. Here, we present the histological findings of consecutive allograft biopsies performed in this patient.

Therapeutic potential of intracerebroventricular replacement of modified human ß-hexosaminidase B for GM2 gangliosidosis.

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of ß-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human ß-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB.

Low-density lipoprotein apheresis for PLA2R-related membranous glomerulonephritis accompanied by IgG4-related tubulointerstitial nephritis.

IgG4-related disease preferentially involves the kidney by tubulointerstitial nephritis with IgG4-positive plasma cell filtration and/or membranous glomerulonephritis. We reported the case of a 68-year-old man with IgG4-related tubulointerstitial nephritis combined with antiphospholipase A2 receptor (PLA2R)-related membranous glomerulonephritis, in which distinguishing between idiopathic PLA2R-related and IgG4-related secondary membranous glomerulonephritis was difficult. We diagnosed him as having IgG4-related disease, based on a serum IgG4 level of 170 mg/dL and the presence of IgG4-related parotiditis. On renal biopsy, there was tubulointerstitial nephritis with IgG4-positive plasma cell filtration, which was compatible with IgG4-related disease and membranous glomerulonephritis, with concomitant positive staining for PLA2R on immunofluorescence microscopy. The renal function immediately recovered after steroid treatment, probably because of the improvement in the tubulointerstitial lesions, but his nephrotic syndrome was steroid-resistant. Low-density lipoprotein (LDL) apheresis therapy was effective for membranous glomerulonephritis and increased his serum albumin from 1.4 to 2.8 g/dL. Although IgG4-related kidney disease usually accompanies secondary membranous glomerulonephritis, the positive PLA2R staining suggested a concomitant primary membranous glomerulonephritis. The recent treatment strategy, including LDL apheresis, for primary and secondary membranous glomerulonephritis was discussed briefly in this report.

Prognostic value of immunohistochemical analysis of tumor budding in colorectal carcinoma.

BACKGROUND: Tumor 'budding' of colorectal carcinoma along the invasive margin has been associated with increased malignant potential. This study investigated the possible prognostic significance of budding in invasive colorectal carcinoma. PATIENTS AND METHODS: Specimens resected from 149 patients who underwent potentially curative surgery for invasive colorectal carcinoma were studied. Budding was defined according to Ueno's criteria; budding intensity was assessed by examination of hematoxylin-eosin (HE)-stained specimens and immunohistochemical (IHC)-stained specimens using anti-cytokeratin antibody and anti-lymphatic vessel antibody. RESULTS: Immunohistochemical analysis identified many more budding foci that were not detectable by examination of HE-stained specimens. Multivariate analyses revealed that budding identified using immunohistochemical staining was a significant prognostic marker for disease-free survival and there was significant correlation between budding and microlymphatic vessel infiltration at the invasive tumor front. CONCLUSION: Budding, particularly as assessed with immunohistochemical staining, is a useful predictor of poor prognosis in patients with invasive colorectal carcinoma.

Proton Affinitive Derivatization for Highly Sensitive Determination of Testosterone and Dihydrotestosterone in Saliva Samples by LC-ESI-MS/MS.

In this study, proton affinitive derivatization using picolinic acid and its analogs (3- and 6-methylpicolinic acid and 5-butylpicolinic acid) with proton affinitive moieties was performed for the highly sensitive determination of testosterone (T) and 5α-dihydrotestosterone (DHT) in saliva by LC-ESI-MS/MS. T and DHT were converted to their corresponding picolinate esters and their chromatographic behavior was investigated with a reversed phase column. The picolinate ester of each steroid exhibited a clear single peak and elution occurred in the following order: picolinate, 3/6-methylpicolinate, and 5-butylpicolinate. Estimation and understanding of the separation and retention time of each picolinate ester was made simple using the develop method. Although the peaks of picolinate and 3/6-methylpicolinate esters were suppressed by interference from the saliva background (matrix effect), the 5-butylpicolinate esters were only marginally affected.

Treatment of Posttransplantation Anemia.

Kidney transplantation represents a renal replacement therapy for end-stage renal failure, with outcomes improving from year to year. With the improved survival prognosis, treatment of complications of chronic kidney disease after transplantation is becoming increasingly important. In particular, posttransplantation anemia (PTA) is often protracted, which could be related to a variety of factors, including the renal function status, graft rejection episodes, and infectious causes. PTA occurs in about 30-40% of transplant recipients, and is known to affect the function of the transplanted kidney as well as patient survival. Early PTA is associated with a risk of death and cardiovascular disorders, however, during this phase, priority is given to the appropriate maintenance of immunosuppression rather than to the treatment of anemia. Maintenance-phase PTA exerts a strong influence on the survival, prognosis of the transplanted kidney, quality of life, etc. Unlike the disease state and treatment of usual renal anemia, it has been suggested that PTA may possibly reflect the functional state of the transplanted kidney. Therefore, it has been suggested that proper renal function may be maintained by ensuring a normal hemoglobin level in kidney transplant recipients. Proper management of PTA could be expected to be associated with an improved prognosis of the transplanted kidney and improved patient survival in kidney transplant recipients. It is advisable to provide appropriate treatment by setting target levels in accordance with the dialysis vintage, primary disease, cardiovascular complications, and kidney transplant function and delineation of the transplant recipient characteristics.

In vitro bone formation induced by immunosuppressive agent tacrolimus hydrate (FK506).

When rat bone marrow cells were cultured with an immunosuppressive agent, tacrolimus hydrate (FK506), as well as with beta-glycerophosphate and vitamin C, numerous cell clusters became positive for alkaline phosphatase activity. Scanning electron microscopy revealed mineralized bone matrix in the cell clusters, which was identical to that of living bone. High levels of alkaline phosphatase (ALP), indicating osteoblastic activity, and high levels of osteocalcin (Oc) and calcium were found in the mature bone matrix of the cultures. There was significantly increased expression of mRNAs for ALP and Oc. These results indicate that the cultures contained both bone matrix and high osteoblastic activity, suggesting that FK506 induces ossification.

Clinical and pathological features of non-alcoholic steatohepatitis.

Clinical and pathological features were reviewed in 76 Japanese patients with non-alcoholic steatohepatitis (NASH). Forty-one were male and 35 were female with the mean age of 49.7 years old (range 15-75 years old, males; 46.3, females; 53.7 years old). Fifty-four percent of patients were preobese with a body mass index (BMI) between 25 and 30, while 16% of the patients were non-obese, and only 30% of the cases were morbidly obese, indicating that Japanese have a greater tendency to develop insulin-resistance and fatty liver disease than Western people. Hyperlipidemia was found in 51%, diabetes mellitus in 38%, and hypertension in 33% of the patients. Abnormally elevated liver function tests were found in one-third to two-thirds of the patients and were characteristically mild with 2- to 3-fold elevation from the normal range in the majority of the cases. Histological features of the liver were similar or identical to those reported in English literature and were characterized by fatty change, perivenular and pericellular fibrosis in zone 3, hepatocyte ballooning and necrosis with occasional Mallory's body formation and polymorphonuclear leukocyte infiltration. Mallory's bodies were found in 39% of patients and were characteristically small and poorly formed compared with those in alcoholic hepatitis. Eosinophilic granular or dirty foggy aggregated, not sufficient to be identified as Mallory's bodies, were a rather characteristic cytoplasmic expression in NASH patients. Portal inflammation and fibrosis were not found in the early stage of NASH, but were found as the disease progresses with formation of C-C and/or P-C bridging fibrosis, and eventually resulting in liver cirrhosis.