Interactions of the dynein-2 intermediate chain WDR34 with the light chains are required for ciliary retrograde protein trafficking

The dynein-2 complex drives retrograde ciliary protein trafficking by associating with the intraflagellar transport (IFT) machinery, containing IFT-A and IFT-B complexes. We recently showed that the dynein-2 complex, which comprises 11 subunits, can be divided into three subcomplexes: DYNC2H1–DYNC2LI1, WDR34–DYNLL1/DYNLL2–DYNLRB1/DYNLRB2, and WDR60–TCTEX1D2–DYNLT1/DYNLT3. In this study, we demonstrated that the WDR34 intermediate chain interacts with the two light chains, DYNLL1/DYNLL2 and DYNLRB1/DYNLRB2, via its distinct sites. Phenotypic analyses of WDR34-knockout cells exogenously expressing various WDR34 constructs showed that the interactions of the WDR34 intermediate chain with the light chains are crucial for ciliary retrograde protein trafficking. Furthermore, we found that expression of the WDR34 N-terminal construct encompassing the light chain–binding sites but lacking the WD40 repeat domain inhibits ciliary biogenesis and retrograde trafficking in a dominant-negative manner, probably by sequestering WDR60 or the light chains. Taken together with phenotypic differences of several WDR34-knockout cell lines, these results indicate that incorporation of DYNLL1/DYNLL2 and DYNLRB1/DYNLRB2 into the dynein-2 complex via interactions with the WDR34 intermediate chain is crucial for dynein-2 function in retrograde ciliary protein trafficking

Regulation of Iron Metabolism in NAFLD/NASH

The disturbance of iron metabolism is one of the characteristic features of NAFLD/NASH, and complicated Type2DM, however, as for the mechanisms of the iron deposition observed in the liver of NAFLD/NASH, as well as the correlation between iron metabolism and insulin resistance, the precise pathophysiology and dynamics are still uncertain. In addition, numerous factors might be involved in the pathogenesis of NAFLD/NASH and wide-ranged analysis, as well as multi-targeted treatment, should be considered and challenged for the improvement of the prognosis of NAFLD/NASH. In many NAFLD/NASH cases, a remarkable decline of serum ferritin, as well as the improvement of T2DM, were observed after treatment with Laennec (placenta-derived drug) in accordance with the improvement of the liver dysfunction and histopathological amelioration in the liver. In recent years, it was shown that hepcidin, the principal regulator of iron metabolism exists in human placenta in high concentrations. Then, we examined whether Laennec can restore the pathological background by regulating iron and glucose metabolism in NAFLD/NASH by the action of a “hepcidin inducer”

Leukemia autopsies in Japan

For the purpose to know whether the annual increase of leukemia incidence in Japan is due to some leukemogenic factors or due to the increased detection rate, the authors made some statistical survey of autopsy cases in which the diagnosis is reliable and not any type of leukemias escape the detection. The results showed that acute leukemias, which are found mostly in younger age, is actually increasing. In addition, it has been deduced that among the suspected factors the increase in ionizing radiation will be one of the most probable factors for the increase in leukemia incidence</p

AN AUTOPSY CASE OF PORTOPULMONARY HYPERTENSION ASSOCIATED WITH ALCOHOLIC LIVER CIRRHOSIS

We report an autopsy case of pulmonary pexogenic arteriopathy associated with portal hypertension due to alcoholic liver cirrhosis, termed portopulmonary hypertension (PPHT). A 49-year-old man who has had alcoholic liver cirrhosis for 10 years complained of severe dyspnea (Fletcher-Hugh-Jones V). Chest CT revealed marked enlargement of bilateral hilar pulmonary arteries and cardiomegaly associated with right ventricular hypertrophy. The patient died from hepatic. encephalopathy and respiratory failure. Autopsy c1early revealed the wall thickness of pulmonary small vessels diffusely in peripheral fields on cut surfaces and marked dilatation of the main pulmonary artery, together with liver cirrhosis. Microscopically, the pulmonary small arteries demonstrated grade 5 pulmonary plexogenic arteriopathy inc1uding plexiform lesions and a micronodule resembling an arachnoid granulation or meningioma throughout the lungs. This case suggested that a typical plexogenic arteriopathy morphologically and definitely contributed to confirm PPHT, although the patient was c1inically suspected of hepatopulmonary syndrome (HPS)

Clinical evaluation of suture materials for transtibial pullout repair of medial meniscus posterior root tear

Background: There are no recommendations for specific suture materials in transtibial pullout repair of medial meniscus posterior root tears. This study aimed to evaluate the clinical outcomes of transtibial pullout repair of medial meniscus posterior root tears using ultrahigh-molecular-weight polyethylene sutures and suture tape. Methods: We retrospectively reviewed the data of 36 patients (27 women and 9 men, mean age 64.1 years) who had undergone transtibial pullout repair of medial meniscus posterior root tears between November 2018 and December 2019. Two groups of 18 patients each received either two different cord-like sutures or suture tape. Clinical parameters were assessed preoperatively and on second-look arthroscopy (mean postoperative period 12 months). The meniscal healing status was assessed using a previously published scoring system (ranging from 0 to 10), and the incidence rate of suture cut-out was assessed on second-look arthroscopy. Results: All clinical scores significantly improved in both groups, with no significant between-group differences on second-look arthroscopy. The arthroscopic meniscal healing scores significantly differed between sutures (mean 6.7 points) and suture tape (mean 7.4 points; p = 0.044). No significant between-group difference in the suture cut-out rate was observed. Conclusions: This study found no significant differences in the clinical outcomes between ultrahigh-molecular-weight polyethylene sutures and suture tape. Favorable clinical outcomes were obtained using both types of suture; however, the usefulness of suture tape appears to be limited

Reactivity of IgE in fish-allergic patients to fish muscle collagen

ABSTRACTBackground: In addition to parvalbumin, the well- known major allergen in fish, collagen was recently identified as a new allergen in the muscle of bigeye tuna and in the skin of several species of fish. The aim of the present study was to evaluate fish muscle colla- gens for their reactivity with IgE in fish-allergic patients and antigenic cross-reactivity.Methods: Collagen was purified from the white muscle of five species of fish (Japanese eel, alfonsin, mackerel, skipjack and bigeye tuna) by acid extraction and salt precipitation, whereas parvalbumin was purified from bigeye tuna by gel filtration and reverse- phase HPLC. The IgE reactivities to collagen and parvalbumin were examined by ELISA, whereas antigenic cross-reactivity among fish muscle collagens was investigated by ELISA inhibition experiments.Results: When 15 sera from fish-allergic patients were subjected to ELISA using bigeye tuna collagen and parvalbumin, 10 sera reacted only to parvalbumin, two reacted only to collagen, two reacted to both collagen and parvalbumin and one reacted to neither collagen nor parvalbumin. The sera containing specific IgE to bigeye tuna collagen also reacted to collagens from the other four species of fish. In the ELISA inhibition experiments, bigeye tuna collagen inhibited the binding of IgE not only to bigeye tuna collagen, but also to that from the other four species of fish, suggesting cross-reactivity among the collagens from five species of fish.Conclusions: These results demonstrate that some Japanese fish-allergic patients have specific IgE to fish muscle collagen and that fish muscle collagen is a cross-reactive allergen among various species of fish