PubMed Health⌕ Search

Biomedical subjects

H Gotoh

Publications and source records attributed to H Gotoh.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect on prognosis of bone marrow infiltration detected by magnetic resonance imaging in small cell lung cancer.

The staging system of limited disease (LD) and extensive disease (ED) is widely used and has been shown to provide useful prognostic information in cases of small cell lung cancer (SCLC). However, accurate examinations are necessary for correct staging. In this report, we evaluated the clinical usefulness of magnetic resonance imaging (MRI) of bone marrow in SCLC. 37 patients with LD by standard staging and 41 with ED were examined with bone marrow MRI. Results of bone marrow MRI did not influence the choice of treatment in patients with LD. For subsequent analysis, patients with LD were divided into two groups: patients in whom bone marrow infiltration was detected with MRI (MRI-positive LD group) and those in whom it was not (MRI-negative LD group). Focal or diffuse metastases to bone marrow were detected with MRI in 46% (36/78) of all patients and 35% (13/37) of LD patients. The response rates to treatment in patients with MRI-positive LD were lower than those in patients with MRI-negative LD (P = 0.006). The survival of patients with MRI-positive LD was worse than that of MRI-negative LD (generalised Wilcoxon test: P = 0.0157), and closer to that of ED. Multivariate analyses using a Cox model that included the result of bone marrow MRI, performance status, chemotherapy regimen, radiotherapy and serum lactose dehydrogenase (LDH) level showed that the result of bone marrow MRI remained a prognostic factor in SCLC patients with limited disease. Bone marrow examination with MRI is useful for better staging of SCLC. According to our analysis of response rates and survival, MRI-positive LD should be considered a type of ED.

Bone Marrow Neoplasms↗
PubMed1997

Apoptosis-like cell death in experimentally-induced cryptorchidism in adult mice.

In order to elucidate the mechanism of germ cell degeneration in experimental cryptorchidism, we examined the testes of adult mice from a morphological standpoint. Adult ICR mice were made cryptorchid either unilaterally or bilaterally. In some mice, testes were surgically replaced back into the scrotum at 2 months after induction of cryptorchidism to observe the regenerative process. Morphological changes of cryptorchid and replaced testes have been studied by light and electron microscopy. Testes were also examined by the TUNEL (TdT-mediated dUTP-biotin nick end labelling) method to evaluate whether the degenerative cells, spermatocytes and spermatids, were dying by apoptosis or by any other process(es). At 8 weeks after the induction of cryptorchidism, the seminiferous epithelium consisted only of Sertoli cells, spermatogonia, and some spermatocytes of early meiotic stages. Soon after the replacement of testes to the scrotum, most of the seminiferous tubules resumed spermatogenic processes. Many degenerating cells, especially the spermatocytes, showed condensation of the nucleus and cytoplasm in cryptorchid testes. Although the cytoplasm was markedly eosinophilic under a light microscope to imply condensation of the cytoplasm, the extent of the condensation was not as pronounced under an electron microscope as reported in previous publications. The cytoplasm showed no expansion. By the TUNEL method, many of the degenerating cells, mainly the spermatocytes, have been shown as undergoing apoptosis. These data provide evidence that at least some of the cells die by apoptosis, or by a process similar to apoptosis.

Animals↗
PubMed1997

[Levels of matrix metalloproteinase-3 and urokinase-type plasminogen activator in knee synovial fluids from patients with rheumatoid arthritis and osteoarthritis].

The objective of this study is to determine the levels of matrix metalloproteinase-3 (MMP-3) and urokinase-type plasminogen activator (uPA) in knee synovial fluids from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Knee synovial fluids were collected from patients with RA and OA. Concentrations of MMP-3 were determined by enzyme immunoassay using a pair of monoclonal antibodies against human proMMP-3, and activities of uPA were measured by immunocapture assay using a polyclonal antiserum against human uPA. The median concentration of MMP-3 in synovial fluids was 97.5 +/- 82.6 micrograms/ml (range 1.06-336 micrograms/ml) for RA group and 20.5 +/- 11.3 micrograms/ml (range 6.19-42.8 micrograms/ml) for OA group. Levels of MMP-3 were significantly higher in RA group than in OA group. The median activity of uPA in synovial fluids was 0.053 +/- 0.052 i.u./ml (range 0.003-0.187 i.u./ml) for RA group and 0.072 +/- 0.059 i.u./ml (range 0.006-0.169 i.u./ml) for OA group. No significant difference of uPA activity was observed between RA and OA group. Significant correlation of the levels of MMP-3 with those of uPA was observed in RA group, however not in OA group. The increased levels of MMP-3 in synovial fluids in RA group may reflect an elevated matrix degrading activity due to joint inflammation. The significant correlation of MMP-3 with uPA in RA group suggests that MMP-3 could degrade cartilage matrix more actively in conjunction with PA-plasmin system than MMP-3 alone.

Aged↗
PubMed1997

[Evaluation of clinical utility of 111In-DTPA-IgG scintigraphy in the detection of inflammation/infection--a report of multicenter phase III clinical trials].

This is the report of phase III study to evaluate the safety and utility of 111In-DTPA-IgG in patients with strongly suspected inflammation/infection. One hundred and forty five patients with suspected sites of inflammation/infection were enrolled in the study. Only a few adverse experiences in one patient were reported, which were interpreted as having a possible relationship to the agent. A total of 171 suspected sites (12 in head and neck, 39 in thorax, 44 in abdomen and pelvis, 62 in musculoskeletal system, and 14 in other regions) were evaluated by investigators at each institute. Out of 171 sites, 18 were determined to be unevaluable, and 12 false negative and 5 false positive cases were observed. Overall sensitivity and specificity was 89.8% and 85.7%, respectively, and the agent proved to be effective in detecting lesions anywhere throughout the body. The analysis of data from this Phase III study indicates that 111In-DTPA-IgG is well-tolerated in patients and effective in determining focal sites of inflammation/infection although the physiological accumulation in some tissues such as the sinus or liver and possible excretion into the gastrointestinal tract may make it difficult to localize lesions.

Aged↗
PubMed1996

Developmentally regulated expression of Hsp70-2 and a Hsp70-2/lacZ transgene during spermatogenesis.

Germ cells synthesize large amounts of HSP70-2 protein during the meiotic phase of spermatogenesis. This developmentally regulated expression of HSP70-2 contrasts with the constitutive or inducible expression of other 70-kDa heat shock proteins (HSP70s). To better understand the genetic regulation of Hsp70-2, we used mRNA primer- extension, reverse transcriptase PCR (RT-PCR), and cDNA sequencing to determine that transcription began as far as 353 bp upstream of the start codon. We also identified a previously unrecognized 239-bp intron which is spliced out of the pre-mRNA transcript to leave a 114 nt 5'-untranslated region. Transgenic mice were then produced to delimit the upstream regulatory region required for developmental expression of Hsp70-2 during spermatogenesis. Results with multiple lines of transgenic mice containing promoter-reporter transgenes with varying lengths of Hsp7-2 sequence indicate that promoter sequences up to 640 bp upstream of the start codon and 287 bp upstream of the transcription start site are required for Hsp70-2/lacZ expression in spermatocytes. Histochemical detection of transgene beta- galactosidase activity was coincident with immunohistochemical detection of HSP70-2 protein, both in the first wave of spermatogenesis in juvenile mice and in ongoing spermatogenesis of adult mice. The distribution of Hsp7O-2 and Hsp7O-2/lacZ mRNAs was determined by Northern blot, in situ hybridization, and RT-PCR, and it was found that upregulation of expression of both Hsp7O-2 and Hsp7O-2/lacZ was specific to the meiotic phase of spermatogenesis.

Animals↗
PubMed1996

Ultrasonographic prediction of lethal pulmonary hypoplasia: comparison of eight different ultrasonographic parameters.

OBJECTIVE: The aim of this study was to determine the usefulness of eight different ultrasonographic fetal parameters for predicting fetal pulmonary hypoplasia. STUDY DESIGN: Nomograms of eight different ultrasonographic fetal parameters were evaluated by studying uncomplicated single fetus pregnancies with well-established dates between 18 and 40 weeks of gestation. The eight parameters, which could reflect fetal lung mass, were as follows: thoracic circumference, thoracic area, thoracic area minus heart area, lung area, thoracic circumference/abdominal circumference ratio, thoracic area/heart area ratio, thoracic area minus heart area/thoracic area ratio and lung area/thoracic area ratio. The relative efficacy of the eight parameters was determined by studying 21 fetuses at high risk for development of lethal pulmonary hypoplasia and 30 fetuses with premature rupture of membranes within 1 week. RESULTS: The lung area (gestational age-dependent parameter) and the thoracic circumference/abdominal circumference (gestational age-independent parameter) ratio had the best diagnostic accuracy (sensitivity 81.3% and 90.5%, specificity 100% and 90.0%, positive predictive value 100% and 86.4%, negative predictive value 90.9% and 93.1%, respectively). There were significant linear relationships between lung weight and lung area and between the lung weight/body weight ratio and the thoracic circumference/abdominal circumference ratio. CONCLUSION: These data suggested that the application of lung area and the thoracic circumference/abdominal circumference ratio are clinically useful for the evaluation of fetal pulmonary hypoplasia.

Abdomen↗
PubMed1996

Rescue of Sendai virus cDNA templates with cDNA clones expressing parainfluenza virus type 3 N, P and L proteins.

Several years ago, we reported that a Sendai virus (SeV) defective genome (DIH4UV) could be rescued in vivo with human parainfluenza virus type 1 (hPIV1) and bovine PIV3 but not by measles virus or vesicular stomatitis virus. It was concluded that the cis-acting RNA sequences were conserved within the SeV/PIV1/PIV3 group but that interactions between the polymerase complex (P-L) and the template protein N were unique for each virus. We have re-examined these conclusions using proteins expressed from cloned N, P and L genes for SeV and PIV3. The results demonstrate the specificity of the protein-protein interactions between polymerase and template, and confirm the prediction of the earlier work that PIV3 N, P and L proteins are capable of assembling and replicating SeV mini-genomes also expressed from a cDNA clone.

Animals↗
PubMed1996

Measurement of beta 2-microglobulin in bovine serum and urine by radioimmunoassay.

A radioimmunoassay (RIA) system for quantification of bovine beta 2-microglobulin (beta 2-M) in serum and urine was developed. The protein isolated from bovine colostrum showed a single band in SDS-PAGE, and its molecular weight was approximately 11,600. Amino acid sequences for the first 24 residues and the amino acid composition of the protein were in agreement with those in the bovine beta 2-M of previous research works. In an Ouchterlony test, a single precipitation line was formed between the protein and the antiserum made by the protein. From these results, it was confirmed that the protein isolated from the colostrum was pure bovine beta 2-M. For creation of an RIA calibration curve for urine, a urine void of beta 2-M, as much as possible (beta 2-M-free urine), and a PBS were used as diluents. Intraassay (n = 10) and interassay (n = 3) variances were 1.7-4.6% and 7.1-11.5% in the PBS dilute method, and were 1.4-5.1% and 12.3-13.5% in the beta 2-M-free urine dilute method, respectively. Mean recoveries were 160 +/- 19% (mean +/- SD) and 98.4 +/- 7.9% in PBS and beta-M-free urine, respectively. It was found that the method using the beta 2-M-free urine as a diluent was more accurate than using PBS. The beta 2-M concentrations in serum and urine of healthy Holstein cows measured by this RIA system showed a logarithmic normal distribution for urine and a normal distribution for serum. The mean beta 2-M concentrations were 0.0305(+0.04443)(-0.0210) mg/l (Geometric mean +/- S.D., n = 43) in urine and 2.87 +/- 0.45 mg/l (Arithmetic mean +/- S.D., n = 26) in sera. Further, we could not observe the particular tendency of daily variation in urinary beta 2-M concentrations of healthy cows (Holstein, n = 3 x 2 days).

Amino Acid Sequence↗
PubMed1996

[Recanalization of dural sinus occlusion following the disappearance of dural arteriovenous fistula: report of a case].

A 73-year-old female was admitted to our hospital because of disturbed consciousness and left-sided motor weakness. Computed tomographic scans demonstrated a hemorrhagic infarction in the right parietal region. Right carotid angiograms showed both the posterior portion of the superior sagittal sinus (SSS) and the entire left transverse sinus simultaneously occluded. Left carotid angiograms revealed an enlarged occipital artery, which had direct communications to the left sigmoid sinus and the superior petrosal sinus. These findings were consistent with dural arteriovenous fistula (D-AVF). The laboratory examinations yieled normal results. The patient was managed conservatively with glyceol and anticonvulsants for four weeks and eventually recovered with complete resolution of hemiparesis. Follow-up angiography carried out 6 weeks later showed the SSS, partially stenotic, but recanalized with no evidence of venous congestion. The D-AVF still remained opacified, but there was a marked reduction in retrograde flow to the sigmoid sinus. Further repeated angiograms obtained at 10 months after the onset confirmed complete recanalization of the SSS and disappearance of the D-AVF. From the timing of the angiographies, we considered that the sinus occlusion was caused by the high arterial flow to the fistula and its disappearance made recanalization of SSS possible.

Aged↗
PubMed1996

[A case report of transaortic mitral valve replacement in Marfan's syndrome].

One-stage operation was successfully performed in 30-year-old male with annulo aortic ectasia and mitral valve regurgitation secondary to Marfan's syndrome. The replacement of the mitral valve was performed through aortic root. The transaortic mitral valve replacement employed here should prove useful for similar cases requiring reconstruction of aortic root and replacement of mitral valve simultaneously in Malfan's syndrome.

Adult↗
PubMed1996

[Assessment of clinical utility of 111In-DTPA-IgG scintigraphy in the detection of inflammation/infection--a report of multicenter phase II clinical trials].

A Phase II clinical study was performed in patients with strongly suspected focal sites of inflammation/infection to investigate clinical utility of 111In-DTPA-IgG. Neither adverse effects nor abnormal laboratory changes were noted in the all cases. Out of 59 patients, the clinical utility was evaluated in 56 patients with a total of 67 suspicious sites (19 in thorax, 13 in abdomen and pelvis, 30 in musculoskeletal system, and 5 in other regions). True positive results were obtained in 100% of lesions in the thorax (13/13) and the musculoskeletal system (26/26). There were three false negative and five false positive results. Overall sensitivity and specificity was 94.0% and 70.6%, respectively. Most of the true positive scintigram with the best image quality was acquired at Day 1 or Day 2 post-injection. A dose of 80 MBq was considered to be a practical dose for imaging. Our study indicates that 111In-DTPA-IgG is a safe and promising imaging agent for the detection of inflammation/infection, and that it is reasonable to proceed with Phase III studies to further evaluate clinical utility of the agent.

Adult↗
PubMed1995

Differential suppression of axoplasmic transport: effects of light irradiation to the growth cone of cultured dorsal root ganglion neurons.

1. Growth cones of cultured dorsal root ganglion neurons from mice were irradiated using a mercury lamp. 2. The flux of particles of fast retrograde axoplasmic transport decreased promptly after light irradiation without a change in velocity. 3. That of anterograde transport decreased as well, but with a significant latency. The decrease in anterograde flux was attributed to decreased velocity of particles. 4. Video-enhanced contrast microscopy of growth cones revealed transient swelling of growth cones and transient stagnation of particles in growth cones. 5. The longer the neurite, the larger the latency of the change of the anterograde transport; peripheral information was calculated to be conveyed to the cell body at a speed of 6 microns/min. 6. The mechanism of this information conveyance and the export of materials from the cell body are discussed.

Animals↗
PubMed1995

Phosphorylation and adrenergic chronotropism and inotropism in guinea pig cardiac muscles.

A question whether phosphorylation is involved in adrenergic effects on cardiac tissues has long been a matter of dispute. We examined whether phosphorylation is involved in adrenergic chronotropism and inotropism in excised cardiac muscles from guinea pigs. KT5720, a specific inhibitor of A-kinase, abolished the late phase of adrenergic chronotropism. Okadaic acid, an inhibitor of phosphoprotein phosphatases, and IBMX (1-methyl, 3-isobutylxanthine), a phosphodiesterase inhibitor, potentiated the chronotropism. The adrenergic inotropism was influenced neither by KT5720, okadaic acid, nor by IBMX. The specific beta 1 -adrenergic agonist, denopamine, showed actions similar to adrenaline and susceptibility to the inhibitors. Adrenaline of 10 microM showed a chronotropic time course consisting of early and late components. We concluded that only the late component results from phosphorylation, and its early one and the inotropism is entirely independent of phosphorylation.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Localization and in vitro mutagenesis of the active site in the Saccharomyces cerevisiae mRNA capping enzyme.

The yeast mRNA capping enzyme is composed of 52 (alpha) and 80 kDa (beta) polypeptides, which are responsible for its mRNA guanylyltransferase and RNA 5'-triphosphatase activities, respectively. We isolated the gene encoding the alpha subunit (CEG1) and showed that CEG1 is essential for yeast cell growth [Shibagaki et al., (1992) J. Biol. Chem. 267, 9521-9528]. In this study, CEG1 was expressed in Escherichia coli and the alpha subunit protein was purified to near homogeneity. A [32P]GMP-bound tryptic peptide derived from the recombinant enzyme-[32P]GMP covalent reaction intermediate was converted to a [32P]phosphoryl-peptide through periodate oxidation followed by beta-elimination. Hydrolysis of the [32P]phosphoryl-peptide with alkali resulted in [32P]N epsilon-phospholysine as the only phosphoamino acid, indicating that GMP in the enzyme-GMP complex is bound to a lysine residue via a phosphoamide linkage. Microsequencing of the [32P]GMP-peptide showed that the GMP binding site was located in the region between amino acids 60 and 75, which contained an internal trypsin-resistant lysine at position 70. CEG1 was subjected to site-directed mutagenesis and the mutant proteins were expressed in E. coli. Substitution of His or Ile for Lys70 entirely abolished the enzyme-GMP formation activity, and this mutation was lethal to yeast in vivo, supporting the notion that the active site in the alpha subunit is located at Lys70. Replacement of Lys70 with Arg reduced the ability to form the enzyme-GMP complex; however, yeast cells bearing this allele were not viable. A series of mutations, including 8 amino acid replacements and 3 insertions, near the active site (Lys70-Thr-Asp-Gly motif) were also introduced and the mutant polypeptides were examined for catalytic activity in vitro as well as yeast cell viability in vivo. There was a good correlation between the in vitro and in vivo functions of the mutant proteins, except when Asp72 was replaced with Glu, which allowed formation of the enzyme-GMP complex but failed to support cell growth. The results with Lys70 to Arg and Asp72 to Glu substitutions indicated that guanylyltransfer to RNA and/or additional roles besides cap formation per se are impaired in these mutant proteins.

Acid Anhydride Hydrolases↗
PubMed1995

[The relationship between blood flow redistribution in umbilical artery and middle cerebral artery and fetal growth in intrauterine growth retardation].

The aim of this study was to evaluate the usefulness of umbilical artery and middle cerebral artery PI and the ratio of these values as predictors of fetal growth-retardation and adverse perinatal outcome. In 100 normal fetuses and 105 intrauterine growth-retarded fetuses Doppler velocity waveforms were recorded from the umbilical artery and middle cerebral artery, and we calculated the incidence of low birth weight, gestational age at delivery, fetal distress and umbilical artery blood gas. The results were as follows: 1. There were moderate correlations between umbilical PI and birth weight (r = -0.43, p < 0.0001) and between middle cerebral artery PI and birth weight (r = 0.37, p < 0.0001) and a close correlation between cerebral-umbilical PI ratio and birth weight (r = 0.71, p < 0.0001). 2. There was a significant association between the cerebral-umbilical PI ratio and the HC/AC ratio (r = -0.46, p < 0.0001). 3. The cerebral-umbilical PI ratio was the best predictor of birth weight, fetal distress and neonatal mortality compared with umbilical artery PI and middle cerebral artery PI. In growth retarded fetuses, high umbilical artery PI and low middle cerebral artery PI, the so called "brain sparing effect" was demonstrated. The cerebral-umbilical PI ratio provided a better predictor of IUGR and adverse perinatal outcome than umbilical artery PI and middle cerebral artery PI alone.

Blood Flow Velocity↗
PubMed1994

Bradykinin-responsive cells of dorsal root ganglia in culture: cell size, firing, cytosolic calcium, and substance P.

1. We analyze bradykinin-sensitive cells of the mouse dorsal root ganglion in culture from the viewpoints of cell size, electrical responses, and Ca2+ concentration change due to bradykinin and immunocytochemistry of substance P. 2. Sixteen percent of cells in the cell group 26-30 microns in diameter fired in response to 10 microM bradykinin. None of other cell groups showed a firing response to bradykinin. 3. We measured a cytosolic Ca2+ change due to bradykinin using a Ca(2+)-sensitive fluorescent dye, Fura 2. The rapid rise (peak time, 20 sec) in the Ca2+ concentration was ascribed to Ca2+ release from intracellular Ca2+ stores. The profound change in the Ca2+ concentration was observed again in the cell group 26-30 microns in diameter. Seventeen percent of cells in this group increased the Ca2+ concentration by approximately seven times that at resting level. 4. Among cells which increase Ca2+ concentration responding to bradykinin, 83% of them contain substance P (an immunocytochemical study). 5. We conclude that 16-17% of the cell group 26-30 microns in diameter of the dorsal root ganglia in culture are polymodal nociceptors and respond to bradykinin.

Animals↗
PubMed1994

Survival of steroid 21-hydroxylase-deficient mice without endogenous corticosteroids after neonatal treatment and genetic rescue by transgenesis as a model system for treatment of congenital adrenal hyperplasia in humans.

The genome of mice with the H-2aw18 haplotype has a deletion of approximately 80 kilobases in the H-2 class III region of chromosome 17. Mice that are homozygous for the mutation die soon after birth. A functional form of steroid 21-hydroxylase (21-OHase) is encoded by the deleted DNA fragment, and H-2aw18 homozygotes are deficient in this enzyme. 21-OHase catalyzes the conversion of progesterone to deoxycorticosterone during adrenal steroidogenesis in mice; therefore, H-2aw18 homozygous mice are unable to synthesize corticosteroids. The deleted region also includes the gene for complement component C4, which has a role in the classical pathway of the complement activation cascade. To clarify the cause of the lethality of the mutation, we first administered either an adrenal homogenate or synthetic steroids to newborn mice; as a result, several H-2aw18 homozygotes were rescued. The results demonstrated that the mutant mice die as the result of a defect in adrenal steroidogenesis. The low efficiency of the rescue by treatment of newborns (16.0% by the adrenal homogenate and 14.8% by the synthetic steroids) suggested that mutant mice should be treated prenatally. Moreover, because the 21-OHase gene is expressed before birth, introduction of a gene for 21-OHase should improve the efficiency of rescue. The results of the murine mutation are similar to those of the inherited human disease known as congenital adrenal hyperplasia, which is caused by steroid 21-hydroxylase deficiency. As a model system for treatment of the human disease by genetic therapy, we used transgenic approaches to introduce a recombinant DNA fragment containing the murine genomic gene for 21-OHase into the mutant mice. We produced four lines of transgenic mice, and in all four transgenic lines, the transgene rescued the lethal mutation. The apparent efficiencies of rescue were 80.2%, 80.0%, 68.7%, and 16.7% for the respective lines of transgenic mice. During the course of our experiments, we also found an unexpected property associated with the role of corticosteroids. The H-2aw18 homozygous mice rescued by neonatal treatment survived for a long period without further treatment. This observation indicates that corticosteroids down-stream of 21-OHase in the pathway for adrenal steroidogenesis are not essential for the survival of mice, except during the period immediately after birth.

Adrenal Cortex Hormones↗