Thermodynamic studies on poly(a) · poly(u) duplex-dye systems

The interaction between poly(A) · poly(U) duplex and dyes (proflavine (PF) and 9-aminoacridine (9-AA)) was studied by means of the heat of mixing. From the results, thermodynamic quantities of poly(A) · poly(U) duplex-dye systems for the intercalation process were estimated. The free energy change for the poly(A) · poly(U) duplex-(PF) system is smaller than that for the poly(A) · poly(U) duplex-(9-AA) system, indicating that PF intercalated into poly(A) · poly(U) duplex is more stable than the intercalated 9-AA. This conclusion is based on the absolute value of the heat of interaction between PF and poly(A) · poly(U) duplex being larger than that between 9-AA and the poly(A) · poly(U) duplex.     

Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig+ germinal center (GC) B cells which occupy GC at a high frequency during the primary antihapten response in mice

Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg^-) B cells (centroblasts), and most of their progeny are sIg⁺ B cells (centrocytes) in a resting state. It has been predicted that somatic hypermutation occurs in centroblasts, whereas antigen-driven selection takes place in centrocytes. The present analysis indicates that murine GC B cells bearing sIg with specificity for an immunizing antigen are in a rapidly cycling state and increase exponentially in number to occupy spleen GC at high frequency during the 1st week after primary immunization; however, the number of these cells is significantly reduced in the 2nd week of immunization. During that period, these proliferating sIg⁺ GC B cells accumulate somatic hypermutations with nucleotide exchanges indicative of affinity maturation. These sIg⁺ GC B cells co-express B7-2, ICAM-1, and LFA-1, and have potent antigen-presenting activity which results in T cell activation in vitro. These observations indicate that the sIg⁺ GC B cells accumulate somatic hypermutations and undergo antigen-driven selection through proliferation, probably upon activation by T cells. This sIg⁺ GC B cell population may represent cell cycling centrocytes; however, the possibility that these may represent centroblasts undergoing re-expression of sIg could not be excluded.     

Intrapulmonary lymph nodes: thin-section CT findings, pathological findings, and CT differential diagnosis from pulmonary metastatic nodules

We compared the thin-section CT findings of 11 intrapulmonary lymph nodes with pathological findings and evaluated the possibility of CT scan differential diagnosis from pulmonary metastatic nodules. First, we retrospectively reviewed CT scan and pathological findings of intrapulmonary lymph nodes. The median size of these nodules was 6.2 mm. The nodules appeared round (n=3) or angular (n=8) in shape with a sharp border, and they were found below the level of the carina. The median distance from the nearest pleural surface was 4.6 mm, and 3 of the 11 nodules were attached to the pleura. On thin-section CT scan, linear densities extending from the intrapulmonary lymph nodes were frequently visualized, and were pathologically proven to be ectatic lymphoid channels. We then compared the thin-section CT findings of 8 metastatic nodules less than 1 cm in diameter with those of the 11 intrapulmonary lymph nodes. The median size of these nodules was 6.8 mm, and the median distance from the nearest pleural surface was 16 mm. All nodules appeared round in shape. None of the nodules had linear densities extending from the nodules. The linear densities on thin-section CT scan may be the most useful characteristic of intrapulmonary lymph nodes, when differential diagnosis from metastatic nodules is necessary.     

Heats of dilution of poly[styrene-ran-(butyl methacrylate)] solutions measured with an automatic flow microcalorimeter

In order to obtain information about the thermodynamic behaviour of copolymers in solution, we built an automatic flow microcalorimeter equipped with a computer that satisfies the requirements of accuracy, reliability, and rapidity for the measurement of heats of dilution of copolymer solutions. By using this apparatus, the heats of dilution of the random copolymer, poly[styrene-ran-(butyl methacrylate)] in ethyl methyl ketone solutions were measured at 298 K. Furthermore, light scattering of the copolymer and its constituent homopolymer solutions was measured at 298 K. From the combination of the heat of dilution and the light scattering results, thermodynamic and intramolecular interaction parameters of the copolymer chain were determined.     

General Pathology Of Kawasaki Disease

Systemic pathological alterations were studied in thirty-seven autopsied patients with Kawasaki disease. Systemic vasculitis was the most characteristic pathological finding and was present in all the patients. In addition to the vasculitis, there was a high incidence of inflammatory lesions in various organs and tissues: in the heart, endocarditis, myocarditis, and pericarditis; in the digestive system, stomatitis, sialoduct-adenitis, catarrhal enteritis, hepatitis, cholangitis, pancreatitis, and pancreas ductitis; in the respiratory system, bronchitis and segmental interstitial pneumonia; in the urinary system, focal interstitial nephritis, cystitis, and prostatitis; in the nervous system, aseptic leptomeningitis, choriomeningitis, ganglionitis, and neuritis; in the hematopoietic system, lymphadenitis, splenitis, and thymitis. Dermatitis, panniculitis or myositis were also observed in some patients. Therefore, Kawasaki disease is a systemic inflammatory disease which mainly affects the cardiovascular system. These systemic inflammatory lesions are considered to correspond to the variegated clinical manifestaitions. The relationship between Kawasaki disease and infantile polyarteritis nodosa (IPN) were discussed, based on the clinicopathological characteristics.     

Crystal Growth in Poly(L‐lactide) Thin Film Revealed by in situ Atomic Force Microscopy

Direct visualization of crystal growth in poly(L ‐lactide) thin films was carried out by using a temperature‐controlled atomic force microscopy (AFM). At the initial stage of crystallization, edge‐on lamellar crystals have nucleated and elongated. Subsequently, the edge‐on lamellar crystals showed S‐shaped morphology and changed their orientation from edge‐on manner to flat‐on one. The curvature of edge‐on lamellar crystal has been discussed in terms of inclination and distortion of polymer chains in the crystal. In addition, mechanism on the formation of flat‐on crystal from edge‐on lamellae was proposed as derivative growth on the basis of in situ AFM observation of crystal growth and enzymatic degradation.

     

Long‐term observation of a Japanese mucolipidosis IV patient with a novel homozygous p.F313del variant of MCOLN1

Mucolipidosis type IV (MLIV) is an autosomal recessively inherited lysosomal storage disorder characterized by progressive psychomotor delay and retinal degeneration that is associated with biallelic variants in the MCOLN1 gene. The gene, which is expressed in late endosomes and lysosomes of various tissue cells, encodes the transient receptor potential channel mucolipin 1 consisting of six transmembrane domains. Here, we described 14‐year follow‐up observation of a 4‐year‐old Japanese male MLIV patient with a novel homozygous in‐frame deletion variant p.(F313del), which was identified by whole‐exome sequencing analysis. Neurological examination revealed progressive psychomotor delay, and atrophy of the corpus callosum and cerebellum was observed on brain magnetic resonance images. Ophthalmologically, corneal clouding has remained unchanged during the follow‐up period, whereas optic nerve pallor and retinal degenerative changes exhibited progressive disease courses. Light‐adapted electroretinography was non‐recordable. Transmission electron microscopy of granulocytes revealed characteristic concentric multiple lamellar structures and an electron‐dense inclusion in lysosomes. The in‐frame deletion variant was located within the second transmembrane domain, which is of putative functional importance for channel properties.     

Functional evaluation of lung by Xe-133 lung ventilation scintigraphy before and after lung volume reduction surgery (LVRS) in patients with pulmonary emphysema

We evaluated the respiratory functions of patients with pulmonary emphysema who underwent lung volume reduction surgery (LVRS) by the mean transit time (MTT) with Xe-133 lung ventilation scintigraphy, forced expiration volume in 1 sec (FEV1.0), residual volume (RV), distance walked in 6 min (6-min walk), and the Hugh-Jones classification (H-J classification) before and after LVRS. In 69 patients with pulmonary emphysema (62 men, 7 women; age range, 47-75 years; mean age, 65.4 years +/- 6.1, preoperative H-J classification, III (two were II)-V) who underwent LVRS, all preoperative and postoperative parameters (MTT 3 weeks after LVRS and the others 3 months after LVRS) were judged statistically by the Wilcoxon signed-ranks test and Odds ratio. Every postoperative parameter was improved with a significant difference (P < 0.05) compared to preoperative parameters. MTT at 3 weeks after LVRS was not associated with %FEV1.0 and the H-J classification at 3 months after LVRS, but was associated with RV and a 6-min walk at 3 months after LVRS. MTT was useful for the clinical evalution of aerobic capability after LVRS.     

Effects of dipyridamole on Plasmodium falciparum-infected erythrocytes

This study assessed the antimalarial activity of dipyridamole, a well-known vasodilator and inhibitor of platelet aggregation. Dipyridamole was effective against all of the erythrocytic stages such as rings, trophozoites and schizonts, and induced ultrastructural changes during the transition from trophozoite to schizont in vitro. Merozoites were also inhibited from invading dipyridamole-treated erythrocytes. It seems that dipyridamole binds to the erythrocyte membrane blocking the receptors for the merozoite. The 50% inhibitory concentration (IC(50)) of dipyridamole against Plasmodium falciparum infection was 30 nM. The IC(50) of chloroquine decreased from 97.0 nM to 13.7 nM when combined with dipyridamole (0.1 nM). Therefore, we suggest that dipyridamole has antiplasmodial activity due to its ability to arrest parasite development and by inhibiting merozoite invasion of the erythrocytes. Chloroquine activity against P. falciparum is also enhanced by the addition of dipyridamole. Treatment with a combination of chloroquine and dipyridamole may lead to a more effective treatment for chloroquine-resistant strains of P. falciparum.