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Biomedical subjects

T Funato

Publications and source records attributed to T Funato.

At least 19 recordsLinked to original sources
PubMed1999

Complete androgen insensitivity in a 47,XXY patient with uniparental disomy for the X chromosome.

We describe a unique patient with complete androgen insensitivity syndrome and a 47,XXY karyotype. Androgen receptor assay using cultured pubic skin fibroblasts showed no androgen-binding capacity. Sequence analysis of the androgen receptor gene demonstrated two nonsense mutations, one in exon D and one in exon E. Microsatellite marker analysis showed that the patient is homozygous for all five Xq loci examined. The results suggest that the long-arms of the two X chromosomes are identical, i.e., uniparental isodisomy at least for Xq, and carry the same mutations in the androgen receptor gene. This explains how complete androgen insensitivity syndrome occurred in this 47,XXY individual.

Adult↗
PubMed1999

SRY mutation and tumor formation on the gonads of XP pure gonadal dysgenesis patients.

We report three patients with XY pure gonadal dysgenesis. Two of these patients developed gonadoblastoma and associated dysgerminoma. Molecular analyses were undertaken to investigate the relationship between the formation of these tumors and Y chromosome aberrations. Deletion analyses were performed by polymerase chain reaction (PCR) amplification of Y chromosome-specific DNA sequences (PABY, SRY, DYS250, DYS254, and DYZ1). A cryptic deletion of the short arm of the Y chromosome that included the PABY, SRY, DYS250, and DYS254 loci was observed in one of the patients (22-years-old) with an associated tumor. In the other two patients who did not demonstrate such a deletion, the sequence of the SRY open reading frame was determined by the dideoxynucleotide method. Two nucleotide substitutions followed by a seven nucleotide deletion were observed in the 3' end of HMG (high mobility group)-box in the other patient (15-years-old) with an associated tumor. The patient (22-years-old) without an associated tumor did not have the cryptic deletion or mutation of SRY. A Y chromosome specific sequence (DYZ1) was demonstrated by PCR amplification of microdissected tumor tissues from these two patients. These results suggest that SRY may play a role in the formation of gonadal tumors, especially dysgerminoma.

Adolescent↗
PubMed1999

Point mutations in the steroid-binding domain of the androgen receptor gene of five Japanese patients with androgen insensitivity syndrome.

We analyzed the androgen receptor (AR) gene in five Japanese patients diagnosed with androgen insensitivity syndrome (AIS). All AR genes from the five patients had single-nucleotide substitutions, which introduced a premature termination codon in three patients (Gln640, Arg752, and Gln640 and Trp751), and a single amino acid substitution in two patients (Arg831 to Gln, and Leu812 to Phe). All the mutations occurred in the steroid-binding domain, comprising exons D through G. The three patients with the premature termination codon(s) and the one patient with Arg831Gln were clinically diagnosed as having complete AIS, while the patient with Leu812Phe had a partial form of AIS. Pubic skin fibroblasts from four of the five patients did not show detectable androgen binding. These data on mutations that have not been reported previously, provide valuable information for the further characterization of structural and functional relationships in the steroid-binding domain of the AR protein.

Adult↗
PubMed1999

[In vitro activities of 23 antimicrobial agents against 4,993 gram-positive and gram-negative bacterial strains isolated from multicenter of Japan during 1994--in vitro susceptibility surveillance.Levofloxacin-Surveillance Group].

In a surveillance study conducted during 1994 at 24 medical institutes from different geographical areas of Japan, the susceptibility of clinical isolates to twenty three comparative agents, such as ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin, ampicillin, clavulanic acid/amoxicillin, oxacillin, piperacillin, cefaclor, cefotiam, cefdinir, cefclidin, ceftazidime, cefpirome, imipenem, aztreonam, vancomycin, minocycline, chloramphenicol, clarithromycin, sulfamethoxazole/trimethoprim, amikacin, and gentamicin, were tested by the standard broth micro-dilution method. A total of 4,993 isolates tested in this study included Streptococcus pneumoniae, methicillin susceptible Staphylococcus aureus (MSSA), methicillin resistant Staphylococcus aureus (MRSA), coagllase negative streptococci (CNS), Enterococcus faecalis, Enterococcus faecium, Enterobactericeae, Pseudomonas aeruginosa from patients with urinary tract infections or respiratory tract infections, and Haemophilus influenzae. For MSSA, S. pneumoniae, Enterobacteriaceae, and H. influenzae, more than 70% of the isolates was susceptible to fluoloquinolones. However, resistance occurred in more than 50% of MRSA and P. aeruginosa isolated from UTI. Fluoroquinolones were found to be effective against high level penicillin-resistant S. pneumoniae, the third generation cephem-resistant Enterobacteriaceae and ampicillin-resistant H. influenzae.

Anti-Bacterial Agents↗
PubMed1999

[Oncogenes and tumor suppressor genes as a tool for clinical diagnosis of solid tumors].

Over the past few years, numerous clinical studies have examined genetic technology to detect physical alterations of genes, such as mutations, translocations and amplification of oncogenes, deletion of tumor suppressor genes, the presence of oncogenic viruses, and the expression of genes specific to cancer tissues. The ability to identify individuals at high risk for cancer holds the promise of improved prevention and early diagnosis of cancers. The goal of genetic diagnosis in cancer is to provide information on abnormal oncogenes and tumor suppressor genes using recent molecular biology techniques. We introduced a highly sensitive method of detecting micrometastasis using PCR in prostate cancer, and strategies for guidelines in clinical diagnosis.

Genes, Suppressor↗
PubMed1999

[Detection of K-ras mutations in colon cancer by PHA-PHFA (preferential homoduplex formation assay)].

The mutations of K-ras gene have been demonstrated at frequencies of about 40% in human colorectal cancer. We applied a developed PCR-preferential homoduplex formation assay (PCR-PHFA) to detect a point mutation of K-ras gene in the surgical specimens from thirty patients with colorectal cancer. This method is based on the strand competition during hybridization between a double labeled amplicon, prepared from biotin and DNP labeled primers, and an unlabeled amplicon. The procedure of this method is simple and speedy, and suitable to detect mutations in a small number of samples. By using this method, the mutations were found in 37% (11/30) and confirmed by sequencing analysis. The results suggest that the PCR-PHFA system may be useful for detecting low frequent mutation of K-ras gene even in the case of an early cancer.

Colorectal Neoplasms↗
PubMed1998

A recurrent nonrandom translocation (3;7)(q27;p12) associated with BCL-6 gene rearrangement in B-cell diffuse large cell lymphoma.

Two cases of B-cell diffuse large cell lymphoma associated with the t(3;7)(q27;p12) and BCL-6 rearrangement are described. Cytogenetic studies revealed [case 1] 47,XY,t(3;7)(q27;p12),+12 and [case 2] 45,X,-Y,t(3;7)(q27;p12),del(6)(q21q25),+16,-21. The translocation of each case had a non-random chromosomal change involving a 3q27 locus associated with BCL-6 gene rearrangement identified by Southern blot analysis. Both cases involved multiple lymph nodes and extranodal regions, such as stomach and peritoneal cavity in case 1, extranodal retroperitoneal space, subcutis, probable liver, and colon in case 2. Chemotherapy provided only short survival after onset: 17 and 16 months, respectively. Altered expression of adhesion molecules CD44, CD54 (case 1) and CD11a and CD18 (case 2) may help to explain the poor outcome of these patients.

Aged↗
PubMed1998

Somatic mutation in autoantibody-associated VH genes of circulating IgM+IgD+ B cells.

Naive B cells expressing IgM and IgD on their surface have no or little somatic mutations in V genes. We have demonstrated that the human IgM+IgD+B cell clone (0-81), which expresses nephritogenic idiotypes, produces IgM anti-DNA antibodies which show monospecificity to DNA. Using a DNA probe which specifically links to the VH gene of antibody 0-81, we identified the counterpart germ-line V gene of 0-81, V3-7, which appears to be used by pathogenic autoantibodies in humans. Clone 0-81, which may belong to naive B cells in terms of cell phenotype, uses a somatically mutated V3-7 gene. We further studied DNA sequences of V3-7 genes in circulating IgM+IgD+B cells from normal subjects and patients with systemic lupus erythematosus (SLE). The results revealed that rearranged V3-7 genes in IgM+IgD+B cells from patients with SLE contained somatically mutated sequences at significantly increased frequencies. These data indicate an abnormal maturation of B cells in autoimmune states that may be associated with an escape of self-reactive B cells from the elimination process in the germinal center.

Amino Acid Sequence↗
PubMed1998

Failure in detection of Epstein-Barr virus and cytomegalovirus in specimen obtained by fine needle aspiration biopsy of thyroid in patients with subacute thyroiditis.

To study the possible role of viral infection in the etiology of subacute thyroiditis (SAT), we measured serum virus-specific antibodies to measles, rubella, mumps, type I herpes, chicken pox, human parvovirus B19 and cytomegalovirus (CMV) in 10 patients with SAT during the course of illness. In spite of the presence of IgG to each virus in more than 70% of patients, no significant changes in the IgG titers were observed except those to measles, rubella, chicken pox or CMV in only 10% of patients, respectively. Then we examined the presence of virus DNA in specimens of 9 patients with SAT obtained by fine-needle aspiration biopsy (FNAB) of the thyroid. DNA was amplified to detect that of Epstein-Barr virus and CMV by polymerase chain reaction. However, none of them were detected in all the specimens. Whereas previous studies suggest the involvement of viral infection in the pathogenesis of SAT, we failed to demonstrate significant changes in serum antiviral antibody titers or to detect viral DNA in the specimens obtained by FNAB of the thyroid. Thus further studies are clearly required to establish the definite role of viral infection in the pathogenesis of SAT.

Antibodies, Viral↗
PubMed1998

[Gene delivery using adeno-associated (AAV) vectors].

Gene transfer vectors based on the replication-defective adeno-associated virus (AAV) are emerging as promising vehicles for gene therapeutic approaches for the neurologic disease, cystic fibrosis and cancers. AAV vectors have been used to efficiently transduce genes into cells in vitro and in vivo. However, transduced recombinant AAV vectors are integrated into human chromosomes. Thus we have discussed that the review about the AAV vectors and transduction, and reported the results used AAV vectors for expression of ribozyme.

Animals↗
PubMed1998

[Quantitative PCR system].

We evaluated a real time quantitative PCR assay using dual-labeled fluorogenic probes for clinical application. Preliminary study using the house-keeping gene, beta-actin confirmed that this method was accurate and reproducible for the quantitative detection of the genes. The system also has merit with regard to the dynamic range of the starting target molecule determination. We then investigated DNA copies of cytomegalovirus (CMV) gene in vivo. The results demonstrated on association between the quantitation of CMV-DNA copies and clinical manifestation associated with CMV infection of immunodeficiency states or infantile hepatitis. It was also successful for quantitative estimation by RT-PCR. Namely, the assay made it possible to discriminate drug-sensitive leukemia cells from resistant cells based on the MDR1 gene and dCK gene. Real time quantitative PCR assay may be useful in a variety of clinical fields.

Cytomegalovirus↗
PubMed1998

[Terminal home care "Ikigai no Yoake--The real aim of our life"--case report].

It is difficult to provide home care especially for terminal cancer patients as their physical conditions deteriorate due to the cancer. It is important to enhance the will of home care providers to make this possible. Although a universal method has been worked out, personal and religious beliefs have made it difficult to create an effective method. We would like to introduce our experience in the paper entitled "Ikigai no Yoake" and subtitled "Influence of scientific study of reincarnation on view of life" by Fumihiko Ida of Fukushima University. It has encouraged home care providers and made it possible to provide home care to terminal patients along with benefits.

Advance Directives↗
PubMed1998

[Benefits and problems of "home care score"--discussion of deviation from home care].

Care ability is the most important factor in providing home care. This ability to care can be classified into family care and community care. The "Home care score" is a system developed through the comprehensive scientific study on long life by the Ministry of Health and Welfare in order to evaluate such care ability. We have scored 71 patients since August 1997 until February 1998, and we found benefits and problems with the system. Here are the benefits: (1) General evaluation can be made on status of patients and home care providers. (2) Comparison of large numbers of patients can be easily made. (3) Helpful to work out practical support. On the other hand, the system has the following problems: (1) Scoring can differ by subjective evaluation. (2) Difficulty to reflect status of disease deterioration and so on. The factors of deviation from home care are: (1) of disease. (2) Loss of desire to provide care. We believe it is important for the home care nurse to intervene so that the will to provide care will not weaken until the end.

Aged↗
PubMed1997

A Turner syndrome woman with a ring X chromosome [45,X/46,X,r(X)(p22.3q27)] whose child also had a ring X chromosome.

OBJECTIVE: To describe a woman with Turner syndrome with ring X chromosome mosaicism who had a child who possessed the same ring X chromosome. DESIGN: Polymorphisms of genes located on the X chromosome from genomic DNA of the mother, father, and the child were evaluated. PATIENT(S): The mother's karyotype was 45,X [48]/46,X,r(X)(p22.3q27) [2], and the child's karyotype was 45,X[33]/46,X,r(X)(p22.3q27) [17]. INTERVENTION(S): Polymerase chain reaction was used to amplify short tandem repeats from the loci of the hypoxanthine phosphoribosyltransferase gene and the androgen receptor gene. RESULT(S): Alleles for both genes in the child originated from both parents in a heterozygous fashion. The alleles originating from the mother originated from the ring X chromosome. However, the amount of amplified DNA was less than that of a normal X chromosome. CONCLUSION(S): The ring X chromosome of the mother was most likely transmitted to the newborn. Thus, an ovum with the ring X chromosome can be fertile and can produce a viable zygote.

Adult↗
PubMed1997

Acute myelogenous leukaemia with t(8;21) translocation of normal cell origin in mosaic Down's syndrome with isochromosome 21q.

We report a 13-year-old girl with Down's syndrome (DS) having a mosaic karyotype of 46,XX/46,XX, -21,+i(21q), who developed acute myelogenous leukaemia (AML) (FAB M1). The t(8;21) translocation generating a AML1/MTG8 chimaeric gene of her blasts was demonstrated by cytogenetic analysis and reverse transcription-polymerase chain reaction. Interestingly, the leukaemic clone with t(8;21) did not have isochromosome 21q, indicating that the blasts were of normal cell origin. These findings suggest that, in older patients with DS, 21 trisomy cells have no greater predisposition to develop AML than normal karyotypic cells.

Adolescent↗
PubMed1997

[Reversal of drug resistance in human cancer cells by anti-oncogenes].

The demonstration that RNA can be cleaved by cis ribozyme (catalytic RNAs, RNA enzymes) has potentially important therapeutic implications. Ribozymes are effective for modulation of gene expression because of their simple structure, site-specific cleavage activity, and catalytic potential. The targets of ribozyme-mediated gene modulation have ranged from cancer cells to foreign genes that cause infectious diseases. Additional target sites for ribozymes are in initial phases of development and design. Ribozymes have been targeted against myriad genes, including oncogenes (ras, BCR-ABL) and drug resistance genes (MDR-1, c-fos). These ribozymes have cleaved the target RNAs in culture system and developed to the in vivo system. We reported that fos ribozyme has altered the expression of c-fos and DNA repair genes in drug resistance cancer cells, and reversed the sensitivity to cisplatin. Furthermore, we have developed high efficiency by the transfer system in vivo.

Animals↗