Supramolecular chemistry of pillar[n]arenes functionalised by a copper(i)-catalysed alkyne-azide cycloaddition "click" reaction.

Since we discovered pillar[n]arenes in 2008, many chemists have developed a strong interest in pillar[n]arene chemistry because of the many advantages associated with these materials, including their facile and high yielding synthesis, versatile functionality, planar chirality and unique host-guest properties. In this feature article, we discuss recent advances in the field of supramolecular chemistry based on the use of pillar[n]arenes as substrates for copper(i)-catalysed alkyne-azide cycloaddition (CuAAC) "click" chemistry. The CuAAC reaction provides facile access to 1,4-disubstituted triazoles by a reaction between alkyne and azido substrates in the presence of a Cu(i) catalyst. Pillar[n]arenes bearing alkyne or azido groups can therefore be used as substrates for this reaction. Herein, we discuss not only the synthesis of pillar[n]arenes bearing alkyne or azido groups but also the application of these functionalised systems to the CuAAC reaction to construct supramolecular assemblies. We also discuss the rational molecular design and synthesis of guest compounds using the CuAAC reaction because linear alkanes sandwiched between 1,2,3-triazole moieties are good guests for cyclic pentamer pillar[5]arenes.

Pillar[5]- and pillar[6]arene-based supramolecular assemblies built by using their cavity-size-dependent host-guest interactions.

Pillar[n]arenes, which we first synthesized and named in 2008, are new pillar-shaped macrocyclic hosts. Pillar[n]arene homologues with n = 5-10 have already been synthesized, but the cyclic pentamers, i.e., pillar[5]arenes, and cyclic hexamers, i.e., pillar[6]arenes, have been most widely used because these can be obtained in good yields. To date, nearly all pillar[n]arene-based supramolecular assemblies have been constructed using pillar[5]- and pillar[6]arene scaffolds. In this feature article, we describe supramolecular assemblies built using host-guest interactions depending on the cavity sizes of pillar[5]- and pillar[6]arenes. We first discuss the effects of the type of substituents on the rims of pillar[5]- and pillar[6]arenes on their solubilities, functionalities and host-guest properties. We then discuss supramolecular assemblies based on their host-guest properties and pillar-shaped architectures.

CD44H participates in the intrahepatic growth of murine colon 26 adenocarcinoma cells.

The purpose of this study was to determine if CD44, a metastasis-associated cell adhesion molecule, is involved in the hepatic colonization by murine colon 26 adenocarcinoma cells. Indirect membrane immunofluorescence and FACS analysis showed strong expressions of CD44 and integrin beta 1 on colon 26 cells. Injection of 1 x 10(5) colon 26 cells into the superior mesenteric vein of syngeneic BALB/c mice produced macroscopic hepatic nodules in 92% (22/24) of the mice 14 days after inoculation. When colon 26 cells were pretreated with an anti-CD44 monoclonal antibody (mAb), IM7, only 30% (3/10) of the mice produced minute nodules in the liver on day 14 (P < 0.001), though IM7 did not inhibit growth of the cells in vitro. Pretreatment of colon 26 cells with an anti-integrin beta 1 mAb did not significantly block the hepatic metastasis. Histologically, microcolonies of tumor cells were detected in all of the livers on day 14 including the IM7-pretreatment mice that were free of gross nodules. However, percentages of tumor-occupied areas in the liver were consistently lower in IM7-pretreatment mice than in control mice (0.82% vs. 5.0% on day 14; P < 0.005). Reverse transcription-polymerase chain reaction (RT-PCR) amplification of mRNA revealed that colon 26 cells and splenocytes only expressed the hematopoietic isoform of CD44 (CD44H), which had no insertion of variant exons, while normal colonocytes expressed possible variant isoforms. These data suggest that malignant transformation of murine colonic epithelium altered the expression pattern of CD44 isoforms and that CD44H participates in the intrahepatic growth of colon 26 cells.

Effect of dental cyst epithelium-conditioned medium on collagenase production by periodontal ligament fibroblasts.

Seven dental cyst epithelia were cultured in vitro and the conditioned media were analyzed for periodontal ligament fibroblast collagenase production. All the cyst epithelium-conditioned media stimulated fibroblast collagenase production, indicating that dental cyst epithelium, which is considered to be identical to the cell rests of Malassez, might play a role in periodontal pocket formation.

Stimulation of human periodontal ligament fibroblast collagenase production by a gingival epithelial cell-derived factor.

To examine whether cell-to-cell interactions between human gingival epithelial cells (HGE) and periodontal ligament fibroblasts (PLF) or gingival fibroblasts (GF) take place in the periodontium, the effects on collagenase production by PLF and GF were analyzed after adding several concentrations of HGE-conditioned medium (HGE-CM) to PLF or GF culture. Collagenase production by both cell populations was stimulated by adding HGE-CM, which stimulated collagenase production by PLF to a greater extent than that by GF. The HGE-derived stimulatory factor had a molecular mass of approximately 20 kDa, and its stimulant effect was inhibited markedly in the presence of an anti-human interleukin-1 alpha (IL-1 alpha) neutralizing antibody, indicating that the factor was identical to, or antigenically cross-reactive with, IL-1 alpha. These results suggest that epithelial apical migration in the periodontium may occur after interstitial resident cells have released tissue-degrading enzymes, such as collagenase, and damaged the extracellular matrix, once a sufficient amount of IL-1 alpha-like factor for stimulating the production of proteolytic enzyme has been released by HGE in periodontal lesions.

[The "addiction trends" seen among the wives of alcoholics].

It has been noticed that wives of alcoholics tend to show an unhealthy relation to their husbands characterized by "addiction," which might hamper the recovery of their husbands from alcohol dependence. Generally speaking, the addiction differs from person to person in its strength and its behavioral expression. The present authors thought that it might be helpful for both wives and therapists if the approximate picture of addiction could be grasped by means of a standardized form of questionnaire. The questionnaire, ASTWA, which consists of 24 questions, was designed to make clear the wives' character trends and their addictions. As for the character traits, the obsessive-compulsive tendency and the tendency to low self-esteem were estimated by four questions each. The two types of addiction, "control" patterns and "caring" trends, were tested. The former was checked in two directions, namely "dominating" tendency and "involved" tendency, with four questions each. The caring trends were estimated by eight questions. A total of 162 wives were asked to rate their answers to the 24 questions as 1, 2, or 3, which stand for none, occasionally, or frequently. The test was carried out at various stages of sobriety. A total of 78 married employees of the Mie prefectural government were tested as control. Those whose added score exceeded 39 points were rated to have a tendency to "addiction." More detailed assessments were done in terms of the character traits and the addictions. The wives who scored more than 14 points in the character traits category were considered to have an affinity toward "addiction." The two types of addiction, i.e., "relation addiction," and "care addiction," were clearly demonstrated in this test. It was noticed that in many cases the scores decreased favorably in parallel with the prolonged term of abstinence of their husbands.

Characterization of mineral-binding 40-kDa glycoprotein extracted from young adult rabbit alveolar bone.

A forty-kilodalton (40-kDa) protein was extracted from alveolar bone of young adult rabbit with 0.5 M EDTA after extraction with 4 M GuHCl, and purified by gel-filtration, anion-exchange and hydroxyapatite columns using a high-pressure liquid chromatography system under denaturing conditions. The purified 40-kDa protein was not susceptible to bacterial collagenase and thrombin, but was cleaved by cyanogen bromide. The protein was stained blue with Stains-all. Among various lectins, concanavalin A and lentil lectin agglutinin bound to this protein, but peanut agglutinin, Ricinus communis agglutinin, phytohemagglutinin-E and wheatgerm lectin agglutinin did not. Lectin binding assays showed that the protein is a glycoprotein containing large amounts of mannose and/or glucose residues, but is not a fragment of proteoglycan. The amino acid composition of the protein shows a characteristically high content of acidic amino acids. Therefore, the mineral-binding 40-kDa glycoprotein is considered to be osteonectin/secreted protein acidic and rich in cysteine (SPARC), in terms of similarities to bovine and porcine osteonectins with regard to molecular weight and contents of glycoses and amino acids.

[Distribution of inhaled aerosol using nasal nebulizer].

In this paper, we examined distribution and deposition of inhaled 99mTc aerosols in human respiratory tract, nebulization equipment and expired aerosols. Jet nebulizers were used and aerosols were inhaled through the nose. Results were as follows: 1. On normal breathing, deposition rate of human respiratory tracts in normal subjects were 22% of total dosage and there was no difference from sinusitis group. But, deposition rate of nasal cavity was higher than in sinusitis group normal in group. 2. In normal subjects, there was no influence of breathing pattern to deposition rate of nasal cavity. 3. Distribution of the lung was significantly increased on deep breathing in both groups. 4. Residual volume of nebulizer bottle were about 50% of total dosage.

[Short-term and long-term prognosis of alcohol dependence: a follow-up study of Danshu-Kai (Alcohol Abstinence Club) members].

595 alcohol dependent cases had been enrolled in the Mie Danshu-Shinsei-Kai (The Alcohol Abstinence Club in Mie) since its establishment in Jan. 1972 by Oct. 1984 when this study started. 163 cases of them, who had been practising abstinence at least for 6 months when the first observation was made in Oct. 1984, were selected for the follow-up study. Relapses in these cases were checked twice, 2.5 years later in 1987 and 5 years later in 1989. The results obtained were summarized as follows: It was observed that 64% of those who had practised abstinence for 2 years sustained abstinence successfully at least for the next 5 years, and 74% of those who had kept non-drinking for 3 years continued abstinence for the next 5 years. Those who had practised abstinence for shorter than 2 years just before the first observation showed that the closer the term of abstinence approached to 2 years, the more sharply the following 5 year abstinence rate increased. It was noticed among those who had kept abstinence for longer than 3 years that the longer the abstinence period became, the more slowly the next 5 year abstinence rate increased, eventually reaching to as high as 81%. A turning point from sharp increase to slow increase was found in between 2 and 3 years of abstinence. From the observation mentioned above, the period of abstinence can be classified into three categories in view of prognosis: shorter than 2 years, 2 to 3 years, and longer than 3 years, which stand for "unstable," "intermediate," and "stable" period respectively. The intermediate period is considered to be critically important in terms of prognosis and treatment of alcohol dependence. It would be reasonable therefore to prospect prognosis in the short term or in the long term basis according to the period of abstinence. The object and contents of treatment might become different before and after the intermediate period. The major factors which affect the prognosis can be classified into 5 categories; 1) the degree of insight into his or her drinking, 2) biological condition, 3) financial problems like "debt," 4) tendency toward multiple addiction, and 5) problems of "co-dependency." It was noticed that although all of these factors remained unresolved in most cases of unstable period, factors 1), 2) and 3) were mostly successfully resolved in a stable period. Factors 4) and 5) are found in not rarely even in a stable period.(ABSTRACT TRUNCATED AT 400 WORDS)

[Clinical studies on the reaction of the skin to various doses of Su-polysaccharide in cancer patients].

The reaction of skin to 10-micrograms and 20-micrograms quantities of Su-polysaccharide (Su-Ps) were examined in 117 patients with cancer, and the results obtained were as follows. Reaction was a little greater to the 20-micrograms dose than to the 10-micrograms dose, but the two parameters were much correlated with each other. The rates of patients showing positive reactions to each dose were 30.8% for 10-micrograms and 34.2% for 20-micrograms. The reactions were augmented by administration of OK-432. The augmentation of skin reaction by OK-432 was more prominent at 20-micrograms doses than at 10-micrograms doses, therefore appearing to be Su-polysaccharide dose-dependent. The ideal Su-polysaccharide dose for Su-Ps skin reaction thus seemed to be 20-micrograms.

[Case of rectal cancer with high level of serum alpha-fetoprotein].

A 61 year old male with a high serum alpha-fetoprotein level (2750 ng/ml) is reported. He had undergone curative surgery for early gastric cancer in June 1979, and palliative resection of a primary rectal lesion in December 1981. The postoperative alpha-fetoprotein level decreased to 1300 ng/ml but gradually increased despite the intraarterial infusion of 5-FU (9.25g) and Mitomycin-C (30 mg). He died of cachexia in February 1982. Histological examination revealed moderately differentiated adenocarcinoma; alpha-fetoprotein positive substances were found in the cytoplasm of rectal cancer cells by the enzyme labeled antibody method(peroxidase-antiperoxidase immune complex method). This rectal cancer patient had multiple primary cancers and gastric cancer.