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Biomedical subjects

K Yago

Publications and source records attributed to K Yago.

At least 37 records · Page 2Linked to original sources

Immunoglobulin variable region sequences of two human monoclonal antibodies directed to an onco-developmental carbohydrate antigen, lactotetraosylceramide (LcOse4Cer).

A human monoclonal antibody, 11-50, was generated and was shown to recognize an onco-developmental carbohydrate antigen, LcOse4Cer. The isotype of this antibody was IgM, lambda, similar to the previously known human anti-LcOse4 antibodies, such as IgMWOO and HMST-1. We raised a murine anti-idiotypic antibody G3 (IgG1, kappa) against 11-50, and tested its reactivity towards the affinity purified human polyclonal anti-LcOse4 antibodies prepared from pooled human sera using a Gal beta 1-->3GlcNAc beta-immobilized column. The results indicated that at least a part of the human polyclonal anti-LcOse4 antibodies shared the G3 idiotype with 11-50. We further analyzed the sequence of variable regions of the two anti-LcOse4 antibodies, 11-50 and HMST-1. Sequence analysis of the heavy chain variable regions indicated that the VH regions of these two antibodies were highly homologous to each other (93.5% at the nucleic acid level), and these antibodies utilized the germline genes VH1.9III and hv3005f3 as the VH segments, which are closely related germline genes of the VHIII family. It was noted that these germline VH genes are frequently utilized in fetal B cells. The JH region of both antibodies was encoded by the JH4 gene. For the light chain, the V lambda segments of the two antibodies were 96.3% homologous to each other at the nucleic acid level. The V lambda segments of both antibodies showed the highest homology to the rearranged V lambda gene called V lambda II.DS among reported V lambda genes, while the exact germline V lambda genes encoding the two antibodies were not yet registered in available sequence databanks. The amino acid sequences of the J lambda segments of both antibodies were identical. These results indicate that the two human antibodies recognizing the onco-developmental carbohydrate antigen Lc4 are encoded by the same or very homologous germline genes.

Amino Acid Sequence↗

[Synthesis and antibacterial properties of 3-O-alkyl-D-glucose derivatives].

A series of 3-O-alkyl-1,2-O-isopropylidene-alpha-D-glucofuranoses (3-7), 6-deoxy-3-O-dodecyl-6-halo-1,2-O-isopropylidene-alpha-D-glucofuranose s (9-11), and 6-deoxy-3-O-dodecyl-6-halo-D-glucopyranoses (12-14) were prepared from 1,2; 5,6-di-O-isopropyridene-alpha-D-glucofuranose and their antibacterial activities were evaluated. The compounds having C12 and C14 alkylchains at C-3 of 1,2-O-isopropylidene glucoses were the most effective in vitro antibacterial screening, of which the structure-activity relationships are also discussed.

Bacteria↗

[Synthesis and antimicrobial properties of methyl 3-O-alkyl-glucopyranosides].

A new type of nonionic surface-active agents containing sugars as the hydrophilic group were synthesized and evaluated for their antimicrobial activity. Methyl 6-deoxy-3-O-dodecyl-6-halo-D-glucopyranoside derivatives showed powerful antimicrobial activity, but no significant differences were observed on the activity with regard to the kinds of anomers as well as halogen atoms.

Bacteria↗

IgM-producing renal plasmacytoma.

A seventy-six-year-old woman with plasmacytoma presenting as a renal mass died three months after diagnosis. Bone surveys disclosed no lytic lesions. Gallium-67 scan showed an avid uptake of the radionuclide in the renal mass. Histologic and immunofluorescence studies of resected specimens demonstrated that the renal parenchyma was destroyed by sheets of immature plasma cells producing IgM-lambda and by massive deposits of amorphous, eosinophilic substance stained with anti-mu and anti-lambda antisera. The literature is reviewed. We believe this case is the first one of well-documented IgM-producing renal plasmacytoma.

Aged↗

[Synthesis and antimicrobial properties of 3-O-alkyl and 3-O-haloalkyl-D-glucoses].

A series of 3-O-alkyl and 3-O-haloalkyl-D-glucoses were prepared from 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose and their antibacterial activities were evaluated. The compounds with C12 and C14-alkyl chains were the most effective in vitro antibacterial screening, among 3-O-alkyl and 3-O-haloalkyl derivatives. The 3-O-alkyl derivatives were more effective than 3-O-haloalkyl derivatives.

Bacteria↗

Northern hybridization analysis of VH gene expression in murine monoclonal antibodies directed to cancer-associated ganglioside antigens having various sialic acid linkages.

The expression of the VH genes in 46 murine hybridoma cells that secrete mAb directed to the cancer-associated carbohydrate Ag, especially acidic glycolipids such as gangliosides and sulfated glycoplipids, was analyzed by Northern hybridization of poly(A)+ RNA of hybridoma with cDNA probes for nine VH gene families. Different hybridomas tended to express VH genes of the same family when the cognate Ag had the same or similar carbohydrate structures; i.e., the VH genes of the J558 family (group 1) were preferentially expressed in the mAb directed to various gangliosides that have NeuAc alpha (or NeuGc alpha) 2-3 and/or 2-8 linkage (71%), the most common linkage of sialic acid residues in the gangliosides of higher animals, and the hybridomas directed to sulfated glycolipids also expressed mainly the VH genes of the J558 family (80%). In contrast, the five mAb directed to various gangliosides with NeuAc alpha 2-6 linkage were exclusively encoded by the VH genes of Q52 family (group 2, 100%), and three antibodies directed to gangliosides with a NeuAc alpha 2-9 linkage all expressed genes of J606 family (group 6, 100%). The VH family usage was largely correlated with the linkage of sialic acid residues in the cognate carbohydrate Ag, but was not correlated at all with the difference in the fine specificities toward the core neutral carbohydrate chain, to which the sialic acid residues were attached. These findings suggest that the VH gene family in these anticarbohydrate antibodies is selected, depending primarily on the linkage of the sialic acid residues in carbohydrate Ag; these residues form the immunodominant sugar residue in the respective antigenic determinant.

Animals↗

[Immunoglobulin genes encoding antibodies directed to oncodevelopmental carbohydrate antigens].

We investigated the immunoglobulin genes which encode the variable region of the monoclonal antibodies directed to the onco-developmental carbohydrate antigens such SSEA-1, fucosyl SSEA-1, SSEA-3 and SSEA-4. The VH region of these antibodies was preferentially encoded by the gene members of the X24, VH7183 and Q52 families, the families which are known to be located at the 3'-end region of the murine germ line VH gene. This result is interesting particularly when considering that the members of the 3'-end VH families are known to be preferentially expressed in embryonic B lymphocytes by an intrinsic genetic program. The comparative study of the nucleic acid sequences of mRNAs encoding these antibodies and the sequences of the corresponding germ line VH genes disclosed that the sequences encoding the antibodies contain no mutation from the germ line VH genes, or contain only a few somatic mutations, which are thought to be insignificant for the reactivity of the antibodies to the nominal antigens. These results imply that some of the embryonic B lymphocytes that express the unmutated germ line VH genes of the 3'-end families can be reactive with embryonic carbohydrate antigens, albeit rearranged with appropriate D-JH gene segments, and coupled with proper light chains. The VH region of the syngenic monoclonal anti-idiotypic antibodies directed to these anti-carbohydrate antibodies were also encoded preferentially by the members of the 3'-end VH families. We propose here that a part of the virgin embryonic B lymphocytes, which express the antibody encoded by the gene members of the 3'-end VH families at the cell surface, will be stimulated by the embryonic carbohydrate antigens which are abundantly present in the internal milieu of the embryo. The clonally expanded B lymphocytes, in turn, will facilitate the proliferation of other populations of embryonic B lymphocytes expressing the corresponding anti-idiotypic antibodies, which are also encoded by the gene members of the 3'-end VH families. This process will lead to the formation of the primitive immune idiotype network system directed to the embryonic carbohydrate auto-antigens in the embryo, which is rarely exposed to the external antigens.

Animals↗

Double Bence Jones proteinuria.

We have recently observed an unusual case of multiple myeloma with double Bence Jones proteinuria. Immunofixation clearly demonstrated monoclonal light chains of both kappa and lambda type in the urine. By double immunofluorescence staining, 11% of myeloma cells were found to be double producers. The marginal portion of cytoplasmic Russell bodies was stained with anti-lambda, while the core was diffusely stained with anti-kappa. Our results indicated that cells of common clonal origin produced Bence Jones proteins of both kappa and lambda type. No reference is found in the literature to such a finding in double Bence Jones proteinuria. In this article, in addition to the summary of nine cases of double Bence Jones proteinuria, possible explanations for this rare phenomenon are described to give a better understanding of this entity.

Aged↗

[A long-term observation of development from monoclonal gammopathy of undetermined significance (MGUS) into primary amyloidosis].

The term, "monoclonal gammopathy of undetermined significance (MGUS)" is used because it is not known at the time of recognition whether the M-component will remain stable or will develop into multiple myeloma (MM) or related disorders. Recently, we have encountered a case of MGUS in which a diagnosis of primary amyloidosis (PA) was made more than 10 years after the recognition of an M-component in the serum. A 64-year-old man presented in 1979 for evaluation of monoclonal gammopathy. The level of M-component (IgG-lambda) in the serum was 1.6 g/dl. The urinary Bence Jones proteins (BJP) were negative. Bone marrow aspirate contained 9.8% plasma cells. Skeletal surveys were normal. A diagnosis of MGUS was made. In 1982, a trace amount of BJP was detected in the urine. Since 1988, carpal tunnel syndrome, angina pectoris and congestive heart failure developed in succession. In November 1989, the patient was admitted to Kyoto University Hospital for examination. Serum electrophoretic pattern remained unchanged. The excreted amount of urinary BJP was less than 0.3 g/day. Bone marrow aspirate contained 5.4% plasma cells. Histologic studies of bone marrow biopsy specimens revealed amyloid deposition. An echocardiogram was thought to reveal amyloidosis. Significant uptake of Tc-99m (V) DMSA was found in carpal regions, kidneys and heart. A diagnosis of PA was made. It is noteworthy that the development of PA did not accompany an increase in the serum M-component. An early diagnosis of PA as well as MM should be kept in mind in the follow-up study of patients with MGUS.

Aged↗