Biomedical subjects

T Toda

Publications and source records attributed to T Toda.

At least 235 records · Page 13Linked to original sources

PubMed1993

Two novel protein kinase C-related genes of fission yeast are essential for cell viability and implicated in cell shape control.

Two novel protein kinase C (PKC)-like genes, pck1+ and pck2+ were isolated from fission yeast by PCR. Both contain common domains of PKC-related molecules, but lack a putative Ca(2+)-binding domain so that they may belong to the nPKC group. Gene disruption of pck1+ and pck2+ establishes that they share an overlapping essential function for cell viability. Cells of a single pck2 deletion display severe defects in cell shape; they are irregular and sometimes pear-like instead of cylindrical. In contrast, the induced overexpression of pck2+ is lethal, producing multiseptated and branched cells. These results suggest that fission yeast PKC-like genes are involved in the polarity of cell growth control. We show that pck2 is allelic to sts6, a locus we have previously identified by its supersensitivity to staurosporine, a potent protein kinase inhibitor [Toda et al. (1991) Genes Dev., 5, 60-73]. In addition, the lethal overexpression of pck2+ can be suppressed by staurosporine, indicating that fission yeast pck1 and pck2 are molecular targets of this inhibitor.

Alkaloids↗

PubMed1993

A linkage study with DNA markers (D4S95, D4S115, and D4S111) in Japanese Huntington disease families.

Attempts to isolate the Huntington disease (HD) gene based on its position have been frustrated by apparently contradictory recombination events in HD pedigrees that have predicted two non-overlapping candidate regions: 100 kb at the telomere of the short arm of chromosome 4, and a 2.2 Mb region located internally at 4p16.3. The proximal location is also supported by the detection of a linkage disequilibrium between HD and some restriction fragment length polymorphisms (RFLPs) at the D4S95, D4S98, and D4S127 loci. In the present study, a proximal marker D4S95 showed tight linkage to the disease locus in Japanese pedigrees (Zmax = 3.31, theta max = 0.00), while distal markers D4S115 and D4S111 did not. Particularly, a two point linkage analysis between D4S111 and HD yielded a lod score -2.01 for theta = 0.015. This result leads to the exclusion, as a possible region of localization of the HD gene, of more than 3 cM of the genome around D4S111 locus. At the same time our results favor aforementioned proximal location as a candidate location for the HD gene.

Adult↗

PubMed1993

Localization of a gene for Fukuyama type congenital muscular dystrophy to chromosome 9q31-33.

Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. Twenty-one FCMD families, 13 of them with consanguineous marriages, were analysed by genetic linkage analyses with polymorphic microsatellite markers to map the FCMD gene. Significant lod scores were obtained with the markers D9S58 (Zmax = 5.81 at theta = 0.06), D9S59 (Zmax = 4.33 at theta = 0.02), and HXB (Zmax = 3.28 at theta = 0.09) on chromosome 9q31-33. Multipoint analysis placed FCMD between D9S58 and D9S59, with a maximum lod score of 16.93. These markers will be useful for presymptomatic, prenatal and carrier diagnosis of family members carrying FCMD, and they represent important resources for the identification of a gene responsible for FCMD.

Chromosome Mapping↗

PubMed1993

Fission yeast genes nda1+ and nda4+, mutations of which lead to S-phase block, chromatin alteration and Ca2+ suppression, are members of the CDC46/MCM2 family.

Fission yeast cold-sensitive mutants nda1-376 and nda4-108 display a cell cycle block phenotype at the restrictive temperature (cell elongation with the single nucleus) accompanied by an alteration in the nuclear chromatin region. DNA content analysis shows that the onset of DNA synthesis is blocked or greatly delayed in both mutant cells, the block being reversible in nda4-108. Upon release to the permissive temperature, nda4-108 cells resumed replicating DNA, followed by mitosis and cytokinesis. The nda4 phenotype was partly rescued by the addition of Ca2+ to the medium; Ca2+ plays a positive role in the nda4+ function. The predicted protein sequences of nda1+ and nda4+ isolated by complementation are similar to each other and also, respectively, to those of the budding yeast, MCM2 and CDC46, both of which are members of the gene family required for the initiation of DNA replication. The central domains of these proteins are conserved, whereas the NH2- and COOH- domains are distinct. Results of the disruption of the nda1+ and nda4+ genes demonstrates that they are essential for viability.

Amino Acid Sequence↗

PubMed1993

Isolation and characterization of the fission yeast protein phosphatase gene ppe1+ involved in cell shape control and mitosis.

We isolated a fission yeast putative protein serine/threonine phosphatase gene designated ppe1+ by hybridization. The predicted amino acid sequence is similar to those of the fission yeast ppa2 (53% identity) and dis2 (39%) phosphatases, and highly similar to those of the budding yeast SIT4 (72%), Drosophila PPV (68%) and rabbit PPX (61%) phosphatases. Antibodies against ppe1 protein identified a 37-kd polypeptide in fission yeast. A gene disruption (designated delta ppe1) caused cold-sensitive lethality and short, pear-shaped cells. These phenotypes were fully suppressed by a plasmid carrying ppe1+. Three classes of multicopy suppressor genes for delta ppe1 were identified as follows: 1) ppa1+ and ppa2+ encoding type 2A-like phosphatases, 2) mitotically essential dis3+ similar to the budding yeast SSD1/SRK1, a suppressor for sit4, and 3) pck1+ coding for a protein kinase C-like kinase. Consistently, the budding yeast SIT4 gene was also a multicopy suppressor for delta ppe1. Phosphatase ppe1 may play a role in cell morphogenesis and mitosis by either regulating or being regulated by these multicopy suppressor gene products. Consistent with this hypothesis, double mutants ppe1-ppa2 and ppe1-pck1 are lethal at the permissive temperature.

Amino Acid Sequence↗

PubMed1993

Gender-related differences in the inhibitory effect on liver regeneration in alcohol-treated rats: study of polyamine metabolism.

We studied gender-related differences in the effect of a single dose of ethanol (EtOH) on liver regeneration following partial hepatectomy in male and female rats by determining polyamines and their related enzymes. When rats were orally treated with EtOH at 3 g/kg 1 hr before partial hepatectomy, liver ornithine decarboxylase (ODC) activity at 4 hr post-hepatectomy was found to be lower in EtOH-treated female than male rats (51% vs. 42%, P < 0.01). Although no EtOH effect was observed on spermidine acetyltransferase (SAT) activity, female rats showed significantly higher values than male rats. Among intra-hepatic polyamines, putrescine was strongly affected by EtOH and significantly reduced in both male and female rats, but the effect was more marked in female than in male rats (88% vs. 51%, P < 0.01). With respect to spermidine and spermine, male rats were unaffected by EtOH, whereas EtOH-treated female rats had lower levels. The gender-related differences became more distinct in terms of total polyamine; the decrease in total polyamine due to EtOH was observed in female rats only. These results suggested that there was a gender-related difference in the effect of EtOH on liver regeneration after partial hepatectomy, with the variations in polyamines probably affecting the subsequent process of liver regeneration.

Acetyltransferases↗

PubMed1993

Effects of alanine and glutamine administration on the inhibition of liver regeneration by acute ethanol treatment.

We studied the effects of alanine and glutamine administration on the inhibition of liver regeneration by acute ethanol treatment after partial hepatectomy (PH) in rats. When rats were dosed i.p. with ethanol at 2 g/kg at the time of PH, DNA synthesis 48 hr after PH was significantly inhibited, but it was completely reversed by the combined use of alanine and glutamine. Although hepatic ornithine decarboxylase (ODC) activity in the alcohol-treated group 4 hr after PH was significantly inhibited, there was a tendency towards recovery of the ODC inhibition in the alanine and glutamine-treated group. The putrescine (PUT) level in liver which was decreased by ethanol was also increased by the administration of alanine and glutamine. However, the levels of spermidine (SPD) and spermine (SPM) in liver were unaffected either by ethanol or by alanine and glutamine. These results suggest that alanine and glutamine show a protective effect on the inhibition of liver regeneration caused by acute ethanol treatment by improving polyamine metabolism, particularly by increasing hepatic PUT levels.

Alanine↗

PubMed1993

Schizosaccharomyces pombe Spk1 is a tyrosine-phosphorylated protein functionally related to Xenopus mitogen-activated protein kinase.

Mitogen-activated protein kinase (MAPK) and its direct activator, MAPK kinase (MAPKK), have been suggested to play a pivotal role in a variety of signal transduction pathways in higher eukaryotes. The fission yeast Schizosaccharomyces pombe carries a gene, named spk1, whose product is structurally related to vertebrate MAPK. Here we show that Spk1 is functionally related to Xenopus MAPK. (i) Xenopus MAPK partially complemented a defect in the spk1- mutant. An spk1- diploid strain could not sporulate, but one carrying Xenopus MAPK could. (ii) Both Spk1 and Xenopus MAPK interfered with sporulation if overexpressed in S. pombe cells. (iii) Spk1 underwent tyrosine phosphorylation as does Xenopus MAPK. Tyrosine phosphorylation of Spk1 appeared to be dependent upon mating signals because it occurred in homothallic cells but not in heterothallic cells. Furthermore, this phosphorylation was diminished in a byr1 disruptant strain, suggesting that spk1 lies downstream of byr1, which encodes a MAPKK homolog in S. pombe. Taken together, the MAPKK-MAPK cascade may be evolutionarily conserved in signaling pathways in yeasts and vertebrates.

Amino Acid Sequence↗

PubMed1993

Aldose reductase inhibition and the phosphorus-31 profile of the intact diabetic rat lens.

Diabetic metabolic change and response to aldose reductase inhibition in the Wistar rat lens were examined with phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy. To avoid artifacts in sample preparation, we used freshly excised lenses and acquired NMR data for 20 min immediately after lens extraction. The results showed a diabetes-induced time-dependent loss of ATP and phosphorylcholine (PC), an increase in alpha-glycerophosphate (alpha-GP) and inorganic phosphate and the appearance of sorbitol-3-phosphate (S-3-P) and fructose-3-phosphate (F-3-P). Oral but not topical dosing of an aldose reductase inhibitor, 5-(3-ethoxy-4-pentyloxyphenyl)-2,4- thiazolidinedione, resulted in a positive dose-response correlation characterized by a restoration of PC, S-3-P and F-3-P to the prediabetic level; however, alpha-GP and ATP were only partially normalized. The significance of the 31P change was further discussed.

Adenosine Triphosphate↗

PubMed1993

Usefulness of serum CA125 measurement for monitoring pericardial effusion.

To investigate the clinical significance of carbohydrate antigen 125 (CA125), an antigen related to ovarian cancer, in patients with pericardial effusion, we examined the relationship between serum levels of CA125 and the presence or severity of pericardial effusion. Fifty-seven patients (25 with heart failure, 22 with pericardial metastasis, 4 with hypothyroidism, 4 with renal failure, and 2 with other diseases) in whom pericardial effusion was confirmed by echocardiography or autopsy, were used as subjects. Thirty-seven of these patients (65%) tested positive for CA125 in the serum. Of these, no significant differences in serum levels of CA125 were found between patients with benign and those with malignant underlying diseases or between those with, or without, pericarditis. However, CA125 values were higher in the patients with larger pericardial effusions and the serum level decreased when the pericardial effusion reduced. In some cases, the serum level normalized before the effusion resolved. Pericardial drainage was performed on 6 patients with cardiac tamponade. Four of these 6 patients had high serum CA125 levels and recurrent pericardial effusion. The other 2 patients had normal serum CA125 levels and no recurrence of effusion. An immunohistological study showed that a positive stain of pericardial tissues reacting to CA125 antibodies correlated to higher serum and pericardial fluid levels of CA125 than the levels of groups staining negative to the antibody. These results suggest that CA125 can be useful in assessing the status and clinical course of this disease.

Aged↗

PubMed1993

Intratumoral heterogeneity of DNA ploidy and regional differences in epidermal growth factor and epidermal growth factor receptor of esophageal carcinoma.

Intratumoral regional differences in DNA ploidy patterns, and expression of epidermal growth factor (EGF) and EGF receptor (EGF-R) were studied to evaluate the biological and clinical significance of intratumoral DNA heterogeneity in 23 cases of esophageal carcinoma. Multiple specimens were subjected to histologic grading of carcinoma, DNA analysis and immunohistochemistry. DNA heterogeneity was found in 34.8% of the cases. Expression of EGF and EGF-R within a single tumor was observed in 69.6% and 73.9% of the lesions examined, respectively. A positive correlation was noted between the expression of EGF and that of the EGF-R. EGF expression showed positive correlation with the DNA index, but not with the proliferative index. There was no relationship between DNA heterogeneity and the degree of histopathological differentiation of carcinoma. Cases with DNA heterogeneity showed better prognosis than those with DNA homogeneity. The present study suggests that esophageal carcinoma consists of carcinoma cells with intratumoral regional polymorphism and variable types of clones. Furthermore, the autocrine mechanism of EGF and EGF-R could be one of the contributory factors on the development of DNA abnormalities during tumor proliferation.

Adult↗

PubMed1993

[A case of acetaminophen-induced pneumonitis].

A case of acetaminophen-induced pneumonitis is described. A 63-year-old woman took 2350 mg of acetaminophen for fever. She subsequently developed a non-productive cough and dyspnea. Chest X-ray revealed diffuse reticulonodular shadows in bilateral lung field and she was admitted to our hospital. PaO2 was 45.0 Torr and PaCO2 35.7 Torr while breathing room air. Bronchoalveolar lavage examination showed an increase in the percentage of lymphocytes and a decrease of CD4/CD8 ratio. Microscopic examination of a transbronchial lung biopsy specimen showed alveolar septal thickening. The lymphocyte stimulation test was positive for acetaminophen, with a stimulation index of 237%, while other drugs used were negative. Because drug-induced pneumonitis was suspected, all drugs were stopped and she was administered methylprednisolone. Consequently her symptoms, laboratory data and chest X-ray findings improved. Based on these findings, we diagnosed this case as acetaminophen-induced pneumonitis. To our knowledge, there has been only one previously reported case of acetaminophen-induced pneumonitis.

Acetaminophen↗

PubMed1993

Changes in cell proliferative activity in granulation tissue invading the root canal.

Root canal models were implanted in rats in order to investigate histologically the movement of granulation tissue invading apical canals and dead spaces and changes in cell proliferative activity as indicated by 3H-thymidine. The models were prepared to have 1, 2, and 3 mm apical canals, with and without dead spaces, to simulate preparations short of the apex and obturation to several levels. After 12 wks implantation of the models without dead spaces, granulation tissue invading 1 mm apical canals did not degenerate and cell proliferative activity remained high. However, tissue invading the 2 and 3 mm apical canals tended to be necrotic and cell proliferative activity was decreased. In the models with dead spaces, the tissue in the 1 and 2 mm apical canals developed and invaded the dead spaces, and still possessed proliferative activity 12 wks after implantation. In contrast, the tissue in the 3 mm apical canals did not invade the dead spaces, even after 12 wks, and no proliferative activity was observed.

Animals↗

PubMed1993

[A case involving coronary dissection caused after PTCA that was observed with intravascular echocardiography].

We encountered a case that was observed on coronary angiography (CAG) during coronary dissection after coronary angioplasty (PTCA) in which the dissected cavity disappeared on CAG but thrombolytic obstruction in the dissected cavity could be observed by intravascular echocardiography (IVUS). A 67-year-old woman was admitted with a diagnosis of acute myocardial infarction with ST elevation when experiencing chest pain. PTCR was performed for obstruction of the left circumflex artery (LCX) and the stenosis was improved to 90 percent. One month later PTCA was performed on an obstruction lesion in LCX and the feature of the dissected section at the same site was observed by CAG after PTCA. CAG showed that the dissected cavity had disappeared a year and a half later, but IVUS indicated thrombolytic obstruction in the dissected cavity.

Aged↗

PubMed1993

[A case of nonresectable esophageal cancer treated by the combination of cisplatin, 5-fluorouracil and THP-adriamycin].

An advanced esophageal cancer patient with multiple liver metastases was treated with a combination of CDDP, 5-FU and THP-ADM. Complete response was obtained against esophageal primary lesion endoscopically, and partial response was obtained against liver metastases observed by computed tomography. Bone marrow suppression of grade 3 was observed, but resolved within 2 weeks.

Antibiotics, Antineoplastic↗

PubMed1993

[A infant case of rhabdomyosarcoma arising from the left iliac region with complete remission for 2 years after combination therapy].

A case of rhabdomyosarcoma in a 14-year-female is reported herein. The patient developed left inguinal pain and tumor. She was initially seen by her local medical doctor, who biopsied her left inguinal tumor with a pathological report of malignancy. She was referred to the Ryukyu University Hospital in July, 1990. CT and MRI demonstrated a large tumor 10 cm in diameter arising from the left iliac region. The tumor was extirpated and the pathological report indicated rhabdomyosarcoma (alveolar type). The patient was treated with VAC chemotherapy and local irradiation. Her course has been uneventful for the past 2 years without any clinical manifestation of recurrence since surgery.

Adolescent↗

PubMed1992

Morphology of central terminations of intra-axonally stained, low-threshold mechanoreceptive primary afferent fibers from oral mucosa and periodontium in the rat.

Horseradish peroxidase (HRP) was injected intra-axonally into functionally identified primary afferent fibers within the rat spinal trigeminal tract in order to study the morphology of their central terminations. They were physiologically determined to be large, myelinated afferent fibers from periodontium or oral mucosa by means of electrical and mechanical stimulation of their receptive fields. Twenty-eight axons that innervated the periodontium of incisors and 21 axons that innervated the oral mucosa were stained for distances of 2-5 mm from the injection sites at the levels of the main sensory nucleus (Vms), spinal trigeminal nucleus and rostral cervical spinal cord. The collaterals of these primary afferent fibers formed terminal arbors in the medial or dorsomedial part of the Vms, and the oral and interpolar spinal trigeminal nuclei (Vo and Vi). In the caudal spinal trigeminal nucleus (Vc), the collaterals of one half of the periodontium afferent fibers terminated mainly in lamina V at the rostral and middle levels of Vc. On the other hand, the collaterals of the other half of the periodontium afferent fibers terminated mainly in lamina IV at the rostral level of Vc, and rostrally these terminal areas shifted to the most medial part of Vi. The collaterals of mucosa afferent fibers terminated in lamina V at the rostral level of Vc, and these terminal areas shifted gradually to laminae III and IV as the parent axons traveled more caudally. These shifts were staggered rostrocaudally according to the rostrocaudal locations of the receptive fields. The density of collaterals of periodontium afferent fibers in Vi was significantly larger than that of mucosa afferent fibers. The average size of the varicosities of periodontium afferent fibers was significantly larger than those of mucosa afferent fibers in Vo, Vi and Vc. The average number of varicosities belonging to single collaterals of slowly-adapting periodontium afferent fibers in Vi were significantly larger than those in Vo. In Vi, the average number of varicosities of single collaterals of slowly-adapting periodontium afferent fibers were significantly larger than those of rapidly-adapting periodontium afferent fibers.

Afferent Pathways↗

PubMed1992

Bulbar reticular neurons relaying somatosensory information to the mesencephalic parabrachial area of the cat.

Somatosensory neurons projecting to the mesencephalic parabrachial area (MPBA), which is located ventral to the inferior colliculus and dorsal to the brachium conjunctivum, were recorded from the bulbar reticular formation of adult cats anesthetized with alpha-chloralose. The majority (41 of 50 neurons) were nociceptive-specific neurons responding only to noxious mechanical and/or thermal stimuli to the skin, cornea and/or oral mucosa. The size of their receptive fields was smaller than that of the intrinsic MPBA-neurons, but larger than that of the trigeminal sensory nucleus neurons. Twenty-three neurons received input from the tooth pulp nerve and 10 of 32 neurons tested responded to electrical stimulation of the vagal nerve. These results indicate that these bulbar reticular neurons receive noxious inputs and transmit them to the MPBA, which also receives input from spinal or trigeminal sensory nucleus neurons projecting directly to the MPBA.

Animals↗