STUDIES ON PEPTIDES LXXXI. Application of a New Arginine Derivative,NG-Mesitylene-2-Sulfonylarginine,to the Synthesis of Substance P and Neurotensin

A new devised arginine derivative, N^G-mesitylene-2-sulfonylarginine, Arg(Mts), was employed for the synthesis of hypothalamic substance P and neurotensin. The former was obtained in 74% yield by treatment of the protected undecapeptide amide, Z - Arg(Mts) - Pro - Lys(Z) - Pro - Gln - Gln - Phe - Phe - Gly - Leu - Met(O)-NH₂, with methanesulfonic acid in the presence of anisole followed by reduction of the sulfoxide with 2-mercaptoethanol. The latter was obtained in 54% yield by the similar treatment of the protected tridecapeptide ester, Z-Pyr-Leu - Tyr - Glu(OBzl) - Asn - Lys(Z)-Pro-Arg(Mts) - Arg(Mts) - Pro - Tyr-Ile-Leu-OBzl, with methanesulfonic acid. As scavenger, a mixture of anisole-thioanisole-o-cresol (1:1:1, by vol.) was employed to suppress the side reaction, O-mesitylene-2-sulfonation of the Tyr residue.     

Psychometric properties of the Caregiving Burden Scale for Family Caregivers with Relatives in Nursing Homes: Scale development

Aim: Most family caregivers continue their caregiving for frail relatives after admitting them to long‐term care facilities. The characteristics of this caregiving differ from those related to caregiving in home‐care settings. Thus, a new tool to evaluate the burden of family caregivers in institutional settings is needed. The aim of this study was to develop a new scale, the Caregiving Burden Scale for Family Caregivers with Relatives in Nursing Homes, and to confirm its validity and reliability. Methods: We conducted two cross‐sectional questionnaire surveys. The participants were a convenience sample of family members of residents in seven nursing homes for the validation study and in three nursing homes for the test‐retest study in Japan. Statistical analyses examined exploratory/confirmatory factor analyses, internal consistency, concurrent/discriminate validity, and test‐retest reliability. Results: A four‐factor solution with 16 items was selected as the most interpretable questionnaire. In the confirmatory factor analysis, the indices of fitness highly supported these results. The Cronbach's alpha coefficient for the total score was 0.86 and varied between 0.77 and 0.87 in the four domains. The scale showed moderate correlation with the Nursing Home Hassles Scale, suggesting its concurrent validity. The four domains had only a medium correlation with each other, indicating discriminate validity. Conclusions: The developed scale has acceptable validity and reliability for measuring the caregiving burden of family members with relatives in Japanese nursing homes. Future studies using the scale might lead to the improvement of care for family members with relatives in a long‐term care setting.     

Two Different Types of Cancer Development in the Urothelium of the Human Urinary Bladder with Different Prognosis

Cancers of the urinary bladder which advanced in in situ lesionswere found to be quite different from common papillary cancerswith fibrovascular cores, with respect to the course of development,speed of advance and association with precancerous background.Even if both types of cancers eventually appeared in differentsites of the mucosa of the bladder in individual patients, bothwere independent of each other in distribution. After the initiationof subepithelial invasion, in situ cancer extended usually monthby month in gallops in the majority of cases, and many of themwere, therefore, already in an advanced state, when patientsfirst visited clinics for examination. Contrary to this, malignant progress of papillary cancers wasgenerally induced by a process in which there were repeatedrecurrences of papillary cancers of either less maturity ormore malignant property than the preceding one. Thus, malignancyof the papillary cancer grew step by step in grade and ultimatelyproliferated invasively downward over a period of four to fiveyears. Thus, it was concluded that the two types of bladder cancerscited above should be regarded as being quite different fromeach other in their pathologic entity, the identification ofwhich is presumably most important for the clinicopathologicdiagnosis of bladder cancers.     

Growth inhibition of leukaemic cells carrying the t(3;21) by the AML1/EVI-1 -specific antisense oligonucleotide

Summary. The t(3;21)(q26;q22) translocation is thought to play an important role in the acute phase transformation of CML. The formation of the AML1/EVI-1 fusion gene by the translocation leads to expression of the AML1/EVI-1 fusion protein. Here we demonstrate that the AML1/EVI-1 -specific antisense oligonucleotide markedly decreases the [H]thymidine incorporation and growth of leukaemic cells carrying the t(3;21) and the t(9;22), but not those of K562 cells. These results indicate that the AML1/EVI-1 fusion protein could contribute to proliferation of the t(3;21)-carrying leukaemic cells after entering the blastic crisis phase of CML.     

Loss of heterozygosity and analysis of mutation of p53 in hepatocellular carcinoma

Abstract Thirty-six hepatocellular carcinoma (HCC) tissues obtained from 34 patients were classified according to histological diagnosis into six well-differentiated HCC, 20 moderately differentiated HCC and 10 poorly differentiated HCC. High molecular weight DNA was prepared from each tumour and the corresponding non-tumour tissue. Loss of heterozygosity (LOH) on chromosomes 4q, 5q, 10q, 11p, 16q, 17p, mutation of the p53 gene and polymorphism of intron 25 of the retinoblastoma (RB) gene were simultaneously analysed. The patients were composed of three cases of small HCC (the diameter of which was < 3 cm) and 31 cases of advanced HCC. Twenty-nine of 34 (85.3%) patients analysed had been exposed to hepatitis B virus and/or hepatitis C virus. The frequencies of LOH on seven chromosomes were 57.9% in 17p13.3, 45.1% in 17p, 45.1% in 11p, 41.9% in 5q, 41.9% in 16q24, 29.0% in 4q, 25.8% in 10q in advanced HCC (four of well differentiated, 18 of moderately differentiated and nine of poorly differentiated carcinoma). In contrast, LOH was observed on 4q, 5q, 16q and 17p in 33% (1/3) of the small HCC (two of well differentiated and one of moderately differentiated carcinoma). The mutation of the p53 genes and polymorphism of the RB gene were present in 25.8% (8/31) and 12.9% (4/31) of the advanced tumours, respectively, but the mutation was not found in small HCC. LOH on every chromosome and the p53 mutation were observed more frequently in more advanced tumours, and the genetic changes accumulated with the increase of the histopathological grade. These findings suggest that the accumulation of genetic changes in multiple tumour suppressor genes is involved in the progression of HCC.