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Biomedical subjects

T K Watanabe

Publications and source records attributed to T K Watanabe.

At least 37 records · Page 2Linked to original sources

Genetic dissection of "OLETF", a rat model for non-insulin-dependent diabetes mellitus.

To elucidate the genetic factors underlying non-insulin-dependent diabetes mellitus (NIDDM), we performed genome-wide quantitative trait locus (QTL) analysis, using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF rat is an excellent animal model of NIDDM because the features of the disease closely resemble human NIDDM. Genetic dissection with two kinds of F2 intercross progeny, from matings between the OLETF rat and non-diabetic control rats F344 or BN, allowed us to identify on Chromosome (Chr) 1 a major QTL associated with features of NIDDM that was common to both crosses. We also mapped two additional significant loci, on Chrs 7 and 14, in the (OLETF x F344)F2 cross alone, and designated these three loci as Diabetes mellitus, OLETF type Dmo 1, Dmo2 and Dmo3 respectively. With regard to suggestive QTLs, we found loci on Chrs 10, 11, and 16 that were common to both crosses, as well as loci on Chrs 5 and 12 in the (OLETF x F344)F2 cross and on Chrs 4 and 13 in the (OLETF x BN)F2 cross. Our results showed that NIDDM in the OLETF rat is polygenic and demonstrated that different genetic backgrounds could affect "fitness" for QTLs and produce different phenotypic effects from the same locus.

Animals↗

Diagnosis and rehabilitation strategies for patients with hysterical hemiparesis: a report of four cases.

Conversion disorder is a psychological disturbance that produces subconscious alterations in sensorimotor function. Hysterical hemiparesis is a relatively rare, and difficult to diagnose, form of conversion disorder presenting as unilateral motor weakness with or without sensory deficits. We report four patients who required inpatient rehabilitation for hysterical hemiparesis, a diagnosis for which there is little information regarding rehabilitation management. In all cases, an extensive acute care evaluation including multiple imaging studies failed to identify a new neurologic lesion. All patients had rapid functional improvement using functional and behavioral therapies and extensive psychosocial support (mean length of stay of 11 days; mean Functional Independence Measure [FIM] gain of 22; mean discharge FIM of 112), consistent with other published reports of rehabilitation of conversion disorder. Evaluation of these cases reveals consistencies regarding presentation, psychosocial history, and rehabilitation course that can aid clinicians in making the diagnosis. Rehabilitation strategies for hysterical hemiparesis are reviewed.

Activities of Daily Living↗

Do calendars enhance posttraumatic temporal orientation?: a pilot study.

The purpose of this study was to determine the effectiveness of an in-room calendar to correct temporal disorientation in a brain-injured population. Thirty consecutive brain injured patients (16 traumatic, 14 non-traumatic) admitted to a brain injury rehabilitation unit were randomly assigned to either a group with in-room calendars (n = 14) or a group without calendars (n = 16). A baseline Temporal Orientation Test (TOT) score was obtained. Daily TOT scores were obtained for patients throughout their rehabilitation stay or until two consecutive normal scores were obtained. When orientation errors were made, they were corrected and the attention of the patient was drawn to the calendar. There were no statistically significant associations between group and age, gender or mean GCS (for patients with traumatic etiology). Only baseline length of post-traumatic amnesia (PTA) had a significant association with eventual emergence from PTA (as defined by a normal score on the TOT). Age and presence of calendar were not significant. In-room calendars have been espoused as orientation aides. The data from this pilot study suggest that calendars do not hasten re-orientation. This finding suggests that other widely held but not rigorously tested beliefs regarding cognitive rehabilitation may need to be examined.

Age Factors↗

cDNA cloning and functional analysis of p44.5 and p55, two regulatory subunits of the 26S proteasome.

We have employed cDNA cloning to deduce the complete primary structures of p44.5 and p55, two subunits of PA700, a 700-kDa multisubunit regulatory complex of the human 26S proteasome. These polypeptides consist of 422 and 456 amino acids with calculated molecular masses of 47463 and 52903, and isoelectric points of 6.06 and 7.56, respectively. Computer-assisted homology analysis revealed high sequence similarities of p44.5 and p55 with yeast proteins whose functions are yet unknown. Disruption of the yeast genes, termed NAS4 and NAS5 (non-ATPase subunits 4 and 5), resulted in lethality, indicating that each of the two subunits is essential for proliferation of yeast cells.

Amino Acid Sequence↗

Isolation and expression of a cDNA for human brain fatty acid-binding protein (B-FABP).

We have isolated and sequenced a novel 754-bp human fetal brain cDNA encoding a fatty acid-binding protein (FABP). The cDNA contains an open reading frame of 396 nucleotides (132 amino acids). Northern analysis revealed small amounts of a 1.2-kb transcript in adult human brain and a shorter transcript in skeletal muscle, but no message was detected in other tissues examined. On the other hand, it was abundantly expressed in fetal brain but not in fetal lung, liver or kidney tissues. The elevated level of transcript at immature stages and its subsequent decline In adult brain indicate that the encoded protein may be essential for development of the human brain.

Adult↗

A demographic approach to selection.

The concepts of demography provide a means of combining the ecological approach to population growth with the genetical approach to natural selection. We have utilized the demographic theory of natural selection developed by Norton and Charlesworth to analyze life history schedules of births and deaths for populations of genotypes in Drosophila pseudoobscura. Our populations illustrate a stable genetic equilibrium, an unstable genetic equilibrium, and a case of no equilibrium. We have estimated population growth rates and Darwinian fitnesses of the genotypes and have explored the role of population growth in determining natural selection. The age-specific rates of births and deaths provide insights into components of selection. Both viability and fertility are important components in our populations.

Animals↗

Cloning and characterization of a novel member of the human Mad gene family (MADH6).

MAD (mothers against decapentaplegic)-related proteins (MADRs) are intracellular components that play critical roles in signal-transduction pathways involving the transforming growth factor beta (TGFbeta) superfamily. Some Mad genes are candidates for tumor-suppressor functions. From a human fetal brain cDNA library we have isolated a novel Mad-related gene. Two alternatively transcribed mRNAs encode deduced 430- and 467-amino-acid peptides that showed high levels of similarity to MADR1/Smad1/hMAD1 (about 80% identity at the amino acid level). This gene, which we designated MADH6, resides on 13q12-q14 between BRCA2 and RB, a region that frequently displays loss of heterozygosity in breast, liver, and prostate cancers.

Amino Acid Sequence↗

Isolation of a novel human cDNA (rhoHP1) homologous to rho genes.

A novel full-length cDNA showing homology with rho genes was isolated from a human placenta cDNA library. Sequencing of a total of 1086 nucleotides of this clone revealed an open reading frame of 630 nucleotides (210 amino acids). In view of its degree of homology to members of the Rho family of molecules (50-54% identical amino acids, 60-63% identical nucleotides within the coding region), the predicted product was designated RhoHP1(Rho-related protein HP1). Northern analysis indicated that a message about 1.2-kb long is expressed in human heart, placenta, liver, skeletal muscle, and pancreas and, with weaker intensity, in several other tissues.

Amino Acid Sequence↗

Randomized controlled trials in industrial low back pain. Part 3. Subacute/chronic pain interventions.

The most significant costs attributed to settlement of workplace back injury claims are related to chronic low back pain (LBP). Unfortunately, our knowledge of this fact has not led to a reduction of the considerable costs paid out annually by employers and insurers to deal with the chronic pain syndrome. This article is the third in a series of reviews on randomized controlled trials found in the English language medical literature between 1975 and 1993. Of more than 4,000 LBP citations, 35 studies met-the selection criteria of randomization, reasonable concurrent controls and work return comparisons. This review focuses on the 12 studies utilizing nonsurgical interventions for subacute and chronic LBP, including multidisciplinary pain clinics, exercise, cognitive-behavioral strategies, and others. A 26-point quality system was again used to compare the methodologic rigor of each study. The majority of prospective studies investigating return to work after chronic LBP have methodological limitations; additional research is clearly needed to more confidently answer the question of what interventions improve work capacity in patients with chronic LBP.

Behavior Therapy↗

Cloning and chromosome assignment to 1q32 of a human cDNA (RAB7L1) encoding a small GTP-binding protein, a member of the RAS superfamily.

A full-length cDNA homologous to RAB7, a member of the RAB-related GTP-binding protein subfamily, was isolated from a human placenta cDNA library. This cDNA, designated RAB7L1, has an open reading frame of 609 nucleotides encoding 203 amino acids. Northern analysis showed that the mRNA is ubiquitously expressed in human tissues, although signal intensities were different among the various organs examined. This gene was located on chromosome band 1q32 by fluorescence in situ hybridization.

Amino Acid Sequence↗

Cloning and characterization of two novel human cDNAs (NELL1 and NELL2) encoding proteins with six EGF-like repeats.

From a human fetal-brain cDNA library we isolated two novel genes encoding peptides containing six EGF-like repeats. Both showed significant homologies with nel, a gene strongly expressed in neural tissues of chicken. The cDNAs, designated NELL1 (nel-like, type 1) and NELL2 (nel-like, type 2), contained open reading frames encoding 810 and 816 amino acids, respectively. NELL2 is strongly expressed in brain of adult and fetus but only weakly in fetal kidney. NELL1 and NELL2 were mapped by FISH to chromosomal bands 11p15.1-p15.2 and 12q13.11-q13.12, respectively.

Adult↗

cDNA cloning of p42, a shared subunit of two proteasome regulatory proteins, reveals a novel member of the AAA protein family.

We have employed cDNA cloning to deduce the complete primary structure of p42, a protein previously identified as a common subunit of two proteasome regulatory proteins: PA700, a 700000-Da multisubunit complex that binds to the proteasome and promotes the ATP-dependent degradation of ubiquitinated proteins, and modulator, a 250000-Da PA700-dependent proteasome activator. Computer analysis reveals that p42 is a novel member of a large protein family characterized by a conserved 200 amino acid domain which contains a consensus sequence for ATP binding. Five other members of this family, termed AAA proteins (ATPases associated with a variety of cellular activities) are also subunits of PA700. Gel filtration chromatography was employed to determine the qualitative and quantitative distribution of p42 in crude soluble lysates of bovine red blood cells. These studies demonstrated that p42 was found in two multi-protein complexes: the 26S proteasome (formed from the 20S proteasome and PA700) and the modulator. These results establish the identity of a new protein involved in the regulation of proteasome function and indicate that this protein is found in at least two different protein complexes.

Adenosine Triphosphatases↗

Cloning, expression, and mapping of UBE2I, a novel gene encoding a human homologue of yeast ubiquitin-conjugating enzymes which are critical for regulating the cell cycle.

From a human fetal-brain cDNA library we isolated a novel gene sharing significant homology with two yeast genes, UBC9 and hus5, which encode ubiquitin-conjugating enzyme 9 (UBC9). In yeast this protein is critical for normal mitosis, and seems to be closely involved in progression of G2 to M phase of the cell cycle. The human UBC9 (h-UBC9) cDNA, (gene symbol UBE2I), contained an open reading frame of 474 nucleotides encoding 158 amino acids. Its predicted peptide showed respectively 56% and 66% identity (75% and 82% similarity) with the products of UBC9 and hus5. Northern-blot analysis revealed expression of three transcripts, 6.4 kb, 3.3 kb, and 1.35 kb, in all human tissues examined. This gene, UBE2I, was mapped to chromosome band 16p13.3 by FISH.

Amino Acid Sequence↗

Cloning, expression, and mapping of CKAPI, which encodes a putative cytoskeleton-associated protein containing a CAP-GLY domain.

From a human fetal-brain cDNA library we isolated a novel cDNA clone encoding a protein containing a CAP-GLY domain that is highly conserved among several cytoskeleton-associated proteins. The CAP-GLY domain is thought to be essential for their association with microtubules. The cDNA, designated CKAPI (for cytoskeleton-associated protein I, glycine motif) contained an open reading frame of 579 nucleotides encoding 193 amino acids. Northern-blot analysis revealed expression of three transcripts, 1.0, 3.4, and 4.6 kb in size, in all tissues examined. The 1.0-kb transcript was significantly higher in brain and heart than in other tissues. This gene was mapped by FISH to chromosome bands 19q13.11-->q13.12.

Amino Acid Sequence↗

Cloning, expression, and mapping of TCTEL1, a putative human homologue of murine Tcte1, to 6q.

From a human fetal-brain cDNA library we isolated a putative human homologue of the murine Tcte1 gene. The cDNA, designated TCTEL1, contained an open reading frame of 339 nucleotides encoding 113 amino acids. The predicted peptides of TCTEL1 showed 94% and 55% identity (100% and 94% similarity) with those of murine Tcte1 and human RP3. Northern-blot analysis revealed a 0.9-kb transcript in all tissues examined. This gene was mapped by FISH to chromosome bands 6q25.2 --> q25.3, the syntenic region of the murine t-complex locus of chromosome 17.

Animals↗

Cloning, expression pattern and mapping to 12p 13.2 --> p13.1 of CLAPS3, a gene encoding a novel clathrin-adaptor small chain.

From a human fetal-brain cDNA library we isolated a novel gene encoding a peptide homologous to clathrin-adaptor small chains in rat, mouse, and yeast. The cDNA, designated CLAPS3 (clathrin-associated/assembly/adaptor protein, small 3, 22 kDa), contained an open reading frame of 579 nucleotides encoding 193 amino acids. Northern-blot analysis revealed expression of a 1.35-kb transcript in all human tissues examined. This gene was mapped to chromosome bands 12p13.2 --> p13.1 by FISH.

Adaptor Protein Complex 3↗

Isolation and mapping of the human glycoprotein M6 gene (GPM6A) to 4q33-->q34.

We have isolated a human cDNA that is highly homologous to the murine gene (Gpm6) encoding a membrane glycoprotein, M6. The human gene (GPM6A) contains an open reading frame of 834 nucleotides encoding a peptide of 278 amino acids. Northern-blot analysis revealed specific expression in human brain. We assigned the GPM6A locus to chromosome bands 4q33-->q34 by radiation hybrid mapping.

Amino Acid Sequence↗

Molecular cloning of UBE2G, encoding a human skeletal muscle-specific ubiquitin-conjugating enzyme homologous to UBC7 of C. elegans.

From a human fetal-brain cDNA library we isolated a novel ubiquitin-conjugating enzyme. The cDNA, designated UBE2G, contained an open reading frame of 510 nucleotides encoding 170 amino acids. The predicted peptide product showed 74% identity at the amino acid level with UBC7 of C. elegans, a high degree of homology with UBC7s of other species, and significant homologies with other subgroups of UBCs. Northern-blot analysis revealed strong expression of 4.4-kb, 2.4-kb, and 1.6-kb transcripts in skeletal muscle. Weak expression was observed in 15 other tissues examined. Radiation-hybrid mapping localized this cDNA to chromosome band lq42.

Animals↗