Biomedical subjects
Publications and source records attributed to T Ichikawa.
Thirty-five patients underwent CT examination 15 to 30 min after abdominal angiography with ioxaglate. The gallbladder was visualized in 12 patients in the absence of clinical evidence of renal impairment. Gallbladder opacification on CT examinations shortly after angiography shows that the hepatobiliary tract is important in the excretion of ioxaglate.
Tracheal agenesis is a rare congenital malformation that usually is fatal. This report describes our experience in two such cases. In both cases, the diagnosis was suspected at birth, because the patients had respiratory distress without an audible cry and were difficult to intubate. A gastrostomy and banding of the abdominal esophagus provided effective initial stabilization, in conjugation with respiratory management. The first patient also had complex cardiac malformations, and the infant died of cardiac failure 1 week after birth. The second infant, who had tracheal agenesis with a proximal tracheoesophageal fistula and a bronchoesophageal fistula, was managed successfully. At 9 months of age, a tracheotomy was performed, a long T tube was inserted to maintain the airway patency beyond the proximal tracheoesophageal fistula, and the patient was discharged. At 3 years of age, esophageal reconstruction was performed with a colonic interposition graft. The patient is thriving and developing normally at 4 years of age. Diagnosis at birth and maintenance of airway patency are essential for successful management of tracheal agenesis. Initial surgical interventions are palliative but lifesaving. Subsequent management focuses on improving the quality of life and allowing swallowing and speech.
A 60-year-old man who had a partial gastrectomy for gastric cancer 10 years ago was referred to our hospital for further examination for liver tumor. He was diagnosed as leiomyosarcoma of residual stomach associated with liver metastases. After preoperative transarterial embolization (TAE) with epirubicin of the anterior branch of right hepatic artery, residual stomach was resected, and the reservoir catheter and infusion arterial port were implanted. He was treated by intra-hepato-arterial chemotherapy of epirubicin. The patient has remained well for 2 years and 3 months without apparent complications.
Magnetic stimulation over the cervical spine using the 8-shaped coil was studied to determine the optimal site and intensity of stimulation. Twenty-one healthy volunteers and 9 patients with acute inflammatory demyelinating polyradiculoneuritis (AIDP) or chronic inflammatory demyelinating polyradiculoneuritis (CIDP) were examined. Each wing of the 8-shaped coil had a 5 cm outer diameter and the field (maximum 2.2 tesla) was produced with MAGSTIM200 (MAGSTIM company). The coil was placed along the line from the seventh cervical prominence to the acromion on the recorded side (C7 standard line) to give orthodromic stimulation to the motor nerve. The coil position was marked at the contact point of each wing. Motor evoked potential (MEP) was recorded from abductor digitorum minimi muscle by using surface electrodes. In normals, the latency of MEP did not change while the coil was moved vertically from 2 cm rostral to 2 cm caudal of C7 standard line and horizontally from the midline to 6 cm lateral. Increasing the stimulus intensity, MEP latency never got shorter when the intensity was over 180% of motor threshold. On the other hand, the MEP amplitude was highest when the stimulation was given at 4 cm lateral from the midline on the C7 standard line, but our equipment were unable to give the supramaximal stimulation. Our conclusion was therefore that the optimal stimulus point was 4 cm lateral from the midline on the C7 standard line, and the minimal latency of MEP was obtained by the stimulation with the intensity beyond 180% of motor threshold.(ABSTRACT TRUNCATED AT 250 WORDS)
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To clarify the effect of the change in motoneuronal excitability on the F wave, we studied the persistence, mean size, and minimum latency of the F wave in nine normal subjects while awake and asleep. Recordings were made from the abductor pollicis brevis muscle by stimulating the median nerve at the wrist. The persistence and size of the F wave markedly decreased during sleep, especially in stage REM. The mean size in stage REM was less than 5% of that in stage W in most subjects, and the F wave entirely disappeared in one subject. The minimum latency during sleep was longer than during wakefulness. Prolongation was within 2.0 ms when the persistence was more than 10%. A decrease in the number of motoneurons that elicit the F wave may be the major cause of prolongation. We conclude that the decreased motoneuronal excitability can cause the F wave to disappear without conduction block in the peripheral motor nerve and that the prolongation of the F wave for more than 2 ms provides a marker for proximal conduction delay in the clinical nerve conduction studies.
To detect anti-granulocyte antibodies (AGAs) in the sera of granulocytopenic patients is important to study the mechanism of the disease. In this report, we studied neutrophil associated immunoglobulin (NAIg) and neutrophil binding immunoglobulin (NBIg) in patients' sera using flow cytometry (FCM). We investigated the interference of circulating immune complexes (CIC) on measuring the NAIg and NBIg. No apparent effect of CIC was observed at concentrations up to 140 micrograms/ml. NAIg and NBIg were semiquantitated by determining the relative fluorescence intensity (RFI) on a flow cytometer and the normal ranges of NAIg and NBIg were less than 15 RFI and less than 10 RFI, respectively. Of 100 sera from patients with neutropenia, 5 were positive for NBIg and 3 of them were positive for granulocyte-specific antibodies. One serum of a patient with benign chronic neutropenia showed clear specificity for NA1 alloantigen but the other 4 AGAs were not specific for NA alloantigen system. Our NAIg, NBIg screening procedure, including NA specificity testing of NBIg and detection of reactivity with normal lymphocytes using FCM, is simple and useful for measuring and studying serological and immunological characteristics of AGAs.
Autoimmune uveoretinitis and pinealitis have been shown to develop spontaneously in BALB/c nude mice after their T cell function has been reconstituted by embryonic F344 rat thymus grafting (TG nude mice). Because anti-IRBP antibodies were detected in these mice, it was concluded that IRBP was the target antigen. In this study, we removed the eyes and/or the pineal body from TG nude mice, and examined anti-IRBP antibodies in their sera. It appeared that IRBP originating from the eyes and the pineal body were the immunogenic antigens in the TG nude mice, but the IRBP from the eyes was found to be more immunogenic and pathogenic than that from the pineal body. We also found that the incidence of uveoretinitis increases with pinealectomy in TG nude mice, even though the immune system is not affected.
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We examined the effects of the gastrin family of peptides on gastric mucus glycoprotein (mucin) biosynthesis in rat gastric mucosa using an organ culture technique. Radiolabeled mucin was obtained from the tissue and culture medium of the corpus and antrum of rat stomach incubated for 5 hr with [3H]glucosamine (GlcN), [14C]threonine (Thr), and [35S]sulfate in vitro. With the addition of 10(-8) and 10(-7) M tetragastrin to the culture medium, [3H]GlcN labeled mucin in the corpus tissue increased to 120-135% that of the control (P < 0.01). The biosynthetic responses to cholecystokinin (CCK)-8 and the 17-peptide gastrin were essentially the same as that to tetragastrin. Tetragastrin 10(-8) M also increased the incorporation of [35S]sulfate into the corpus mucin but failed to change [14C]Thr incorporation. In the antrum, biosynthetic activity showed no significant change with 10(-9) approximately 10(-5) M tetragastrin. Ranitidine, diphenhydramine and omeprazole at 10(-5) M did not suppress the tetragastrin-induced increase in [3H]GlcN incorporation into mucin, but L-365,260 at a concentration of 10(-6) M completely blocked this effect. These results suggest that gastrin stimulates mucin production via CCK-B/gastrin receptors in the oxyntic region of rat gastric mucosa.
Using polymerase chain reaction-single strand polymorphism(PCR-SSCP) and nucleotide analyses, p53 gene mutation was examined in 13 pontine gliomas many of which were of juvenile onset. A total of 15 mutations were detected in 8 cases, of which 5 revealed multiple or tandem mutations. The mutations included 6 G:C-A:T and 4 A:T-G:C transitions and 4 G:C-T:A and 1 A:T-T:A transversions. There was only 1 transition at the CpG site. Normal tissues of the same patients revealed no mutation, suggesting that these mutations were somatic, but not of germ line, in nature. The pattern of mutation characterized by frequent multiple or tandem occurrence, predominancy of transition at non-CpG sites and relatively frequent transversions suggested that pontine glioma might be related with some mutagenic or carcinogenic agents.
Four human genomic DNA clones for 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) were isolated by screening a human genomic library with human CNP cDNA clones as probes. Restriction mapping and sequence analysis revealed that the human CNP gene is about 8.5 kb long and composed of four exons interrupted by three introns. There are two transcription start points and in human brain, two forms of CNP mRNA are produced from a single gene by alternative splicing, similar to mouse. A homology search of the 5'-flanking regions of exon 0 and exon 1 in the human CNP gene indicated the presence of oligodendroglia-specific elements and myelin basic protein transcription element (MBTE) motif, in addition to TATA-box-like sequences. Spot blot hybridization of flow-sorted human chromosomes with the 3'-noncoding region of the human CNP cDNA showed the localization of CNP to chromosome 17.
Androgen receptor is necessary for the proliferation of androgen-dependent tumors including human prostatic cancer and murine androgen-sensitive tumors. However, androgen-independent tumor containing functional androgen receptor was observed in CS 2 cells, which is a subline of androgen-dependent mouse tumor (SC 115). CS 2 showed a new expression of hst-1, the product of which is a family of FGF. CS 2 secreted a growth factor which promotes growth of CS 2 and original SC 115 in an autocrine and paracrine manner. The role of oncogene(s) and suppressor gene(s) on the progression of the tumor is discussed.
A cohort of 300 ACI rats was kept under standard laboratory conditions. After 30 months or upon natural death, complete autopsy was performed. In the genitourinary tract four kidney and five bladder tumors were found. Two of these bladder tumors, RBT323 and RBT157, are serially transplantable. In the fifth transplant generation the RBT323 tumor becomes metastatic to the lungs in more than 90% of animals. The metastatic ability of the RBT157 tumor changes from low to intermediate (50% of the rats have lung metastases) in the fourth passage. Histologically, the initial passages of the RBT323 and 157 tumors are grade II transitional cell carcinoma (TCC). The histological pattern of the RBT157 tumor remains essentially unchanged, whereas the RBT323 tumor progresses to a grade III tumor in the third passage. Electron microscopical studies reveal oblong elliptical and round vesicles lined by an asymmetrical unit membrane in the tumor cells, which stresses the urothelial origin of the tumors. Immunohistochemically both tumors show expression of cytokeratin 5, 7, 8 and 18. The progression of the tumors to a metastatic phenotype, however, is not associated with a specific change in the morphological characteristics. Cytogenetic analysis shows that both tumors are peridiploid with few marker chromosomes. Interestingly, both of these independently arising tumors exhibit a loss of chromosome 5. Rat chromosome 5 is syntenic to the major portion of human chromosome 9 (p23-qter). Loss of chromosome 9 is a cytogenetic trait of human superficial TCC, hence the RBT model is also in cytogenetic respect similar to human TCC.(ABSTRACT TRUNCATED AT 250 WORDS)
Interleukin 6 (IL-6) exerts well-established effects on cells of the immune system as well as on various other cell types. We have investigated the effects of IL-6 produced by human osteosarcoma cells on tumor cells from two clonal human osteosarcoma cell lines, KSU.C3 and NOS-1.C8. We were unable to identify any effects of IL-6 such as cell proliferation, alkaline phosphatase activity, osteocalcin production, or collagen synthesis on the bone-forming phenotypes. However, the KSU.C3 cell line, which showed a little osteoid and no bone formation and was accompanied by a few osteoclasts in the xenografted tumors, produced high levels of IL-6, the production of which was quickly and easily stimulated by various agents. On the other hand, the NOS-1.C8 cell line, which formed abundant osteoid or bone and was accompanied by no osteoclasts in the xenografted tumors, produced no detectable levels of IL-6 without stimulation, and the production of IL-6 in response to IL-1 beta was slower. Our data suggest that IL-6 produced by osteosarcoma cells does not play an important role in bone formation, but may mediate osteoclastic bone resorption.
Using in situ hybridization histochemistry, we analysed the localization of mRNAs for neuron-specific enolase (NSE) and non-neuronal enolase (NNE) in the rat cerebellum at various postnatal developmental stages. Synthetic 45 meric oligonucleotides corresponding to partial sequences of the non-coding region of rat NSE or NNE mRNA were 35S-labeled to approximately the same specific activity and used as hybridization probes. On examination of the adult rat cerebellum, both NSE and NNE signals were detected in all identified and presumed neurons which included Purkinje cells, internal granule cells and presumed stellate/basket cells in the cerebellar cortex and neurons of the dentate nucleus. Examination of the cerebellum during postnatal development also revealed coexistence of NSE and NNE signals in these neurons from early stages. During development, both signals coincidentally increased in Purkinje cells and neurons of the dentate nucleus, while only NSE signals showed a gradual increase in the internal granule cells in which NNE signals remained at the same level from early postnatal to adult stages. The external granule cells showed NNE signals until postnatal day 7 but thereafter the signals became less distinct, especially in cells if the inner zone of the external granule cell layer. Thus, it was shown that NSE and NNE were commonly coexpressed at the mRNA level in various neurons of the cerebellum except for very undifferentiated external granule cells which expressed only NNE mRNA.
We have previously reported that oxy radicals can contribute to the enhancing effect of glycerol on 4-nitroquinoline 1-oxide (4NQO)-induced lung tumorigenesis in ddY mice. In this study, we established that feeding high doses of vitamin E to male ddY mice treated with 4NQO plus glycerol could reduce glycerol-enhanced lung tumorigenesis, due to the inhibition of glycerol-induced oxidative stress on the pulmonary nuclei. At 4 weeks after 4NQO injection (10 mg/kg, s.c.), the levels of nuclear thiobarbituric acid reactive substances and oxidative damage to DNA in the lungs of mice treated with 4NQO plus glycerol (5% solution as drinking water) were significantly higher than those in mice treated with 4NQO. The glycerol-induced increase was completely inhibited when a high vitamin E diet was provided for 4 weeks after 4NQO injection. As previously reported, at 23 weeks after 4NQO administration (at the end of this experiment), the 4 week treatment with glycerol enhanced 4NQO-induced lung tumorigenesis in ddY mice. In contrast, the supply of high doses of vitamin E at 4 and 23 weeks after 4NQO injection suppressed glycerol's ability to enhance lung tumorigenesis. These results suggest that vitamin E is useful in protecting against oxy radical-enhanced lung tumorigenesis in mice.
Protein tyrosine phosphatases (PTPs), together with protein tyrosine kinases (PTKs), are involved in the regulation of cell activation, growth, and differentiation. To further elucidate the fine tuning of cell growth and differentiation through tyrosine phosphorylation, we tried to isolate mouse receptor-type PTP (RPTP) cDNA clones by screening mouse brain cDNA libraries with mouse CD45 PTP domain probes under reduced-stringency conditions. Characterization of isolated cDNA clones for RPTP showed that the cytoplasmic region contains two tandem repeats of PTP domain of about 230 amino acids with intrinsic phosphatase activity. The extracellular region was composed of immunoglobulin (Ig)-like domains and fibronectin type III (FN-III)-like domains. The gene was highly homologous to human PTP delta (HPTP delta) and thus was named MPTP delta (murine counterpart of HPTP delta). The MPTP delta gene appeared to generate at least three species of mRNA, which differ in the composition of the extracellular domain: type A, one Ig-like and four FN-III-like domains; type B, one Ig-like and eight FN-III-like domains; and type C, three Ig-like and eight FN-III-like domains. Interestingly, the 5' untranslated region and the leader peptide of types A and B were completely different from those of type C. Northern (RNA) blot analysis demonstrated that brain, kidney, and heart cells express three mRNA species of about 7 kb. Antibody directed against part of the extracellular domain of type A MPTP delta recognized a 210-kDa protein in brain and kidney lysates. In situ hybridization of brain samples revealed that MPTP delta mRNA is present in the hippocampus, thalamic reticular nucleus, and piriform cortex, where some Src family PTKs have been also demonstrated to exist. Although MPTP delta mRNA was not detected in lymphoid tissues, all of the pre-B-cell lines tested and one of three B-cell lines tested expressed MPTP delta mRNA, whereas antibody-producing B-cell hybridomas and T-cell and macrophage lines did not. Finally, the MPTP delta locus was tightly linked to the brown (b) locus on mouse chromosome 4.