Biomedical subjects
Publications and source records attributed to J Kudo.
A case of a solid and cystic tumor of the pancreas is presented. The immunohistochemical study of the resected tumor revealed alpha 1-antitrypsin and neuron specific enolase positive malignant cells proliferating pseudopapillary around fibrovascular stroma. Prominent calcification was characteristic in the present case.
We report fatal transfusion-associated graft-versus-host disease (GVHD) in a patient who was not severely immunosuppressed. A 58-year-old man received 800 ml of fresh whole blood from his son and an unrelated volunteer donor during open heart surgery. On the 10th day after the operation, he suddenly had a high fever, followed by generalized skin rash and liver dysfunction. Pancytopenia due to bone marrow aplasia developed a week later. A skin biopsy revealed a cutaneous lesion highly compatible with acute GVHD. The patient did not respond to high-dose methylprednisolone therapy, and died of multiple organ failure on the 18th day after the operation.
We show a northern transfer experiment revealed two mRNA of Ia-associated invariant chain (In) gene in chronic lymphocytic leukemia (CLL) cells which are approximately 1580 and 1440 nucleotides in length. Primer extension experiment shows that less prominent transcript was found to initiate 140 nucleotides upstream from the major cap site. The newly identified cap site was preceded by CG rich sequence but no typical promotor sequence. Southern hybridization analysis with In cDNA probe indicates no recombination or amplification of In gene in the CLL cells. This is the first documented example of such a mode of expression in malignant cells in vivo.
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We treated a 32-year-old man with hearing loss in the right ear followed by severe muscle weakness of the extremities. When admitted to hospital by ambulance, the serum potassium level was 1.5 mEq/L. The muscle weakness was improved following administration of potassium chloride but the hearing impairment continued. Hearing level of the right ear was extremely impaired at the level of 60-105 dB, while hearing in the left ear was fairly normal. Spontaneous nystagmus was also present. The triiodothyronine level was 290 ng/dl, thyroxine 14.4 micrograms/dl, thyroid stimulating hormone (TSH) 0.84 microU/ml, and the anti-TSH-receptor antibody was positive. Attaining an enthyroid state, the patient was discharged on 80th hospital day with the continuous medication of Methimazole. This is a very rare case of sudden deafness complicated by hypokalemic paralytic attacks. Circulatory insufficiency and electrolytes imbalance in the right inner ear was assumed to have caused the deafness.
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A cDNA clone encoding human thymosin-beta 4 was isolated from a cDNA library prepared from peripheral blood leukocytes of a patient with acute lymphocytic leukemia. This clone contained the entire coding sequence of 43 amino acid residues of thymosin-beta 4 and had an initiation codon and two termination codons. The amino acid and nucleotide sequences in the coding region were well conserved between rat and human. Nine of 132 nucleotides were different in the coding sequences (93% homology), but the deduced amino acid sequences were identical. No signal peptide was found in the deduced protein sequence. Human thymosin-beta 4 mRNA, approximately 830 nucleotides in length, was about 30 nucleotides larger than rat thymosin-beta 4 mRNA. Expression of the human thymosin-beta 4 gene in various primary myeloid and lymphoid malignant cells and in a few human hemopoietic cell lines was studied. Northern blot analyses of different neoplastic B lymphocytes revealed that steady state levels of thymosin-beta 4 mRNA varied as a function of differentiation stage. Thymosin-beta 4 mRNA levels were decreased in myeloma cells as are class II human leukocyte antigen, Fc receptor, and complement receptor, suggesting a relationship between thymosin-beta 4 and the immune response. Thymosin-beta 4 mRNA was more highly expressed in mature granulocytes than in immature blastic cells. Treatment of THP-1 cells, a human monocytic cell line, with recombinant human interferon-lambda reduced the levels of thymosin-beta 4 mRNA. Its level decreased after differentiation of THP-1 cells into Ia+ macrophages, but increased after differentiation of HL-60 cells into Ia- macrophages. The pattern of thymosin-beta 4 gene expression suggests that it may play a fundamental role in the host defense mechanism.
The effect of Kupffer cells on natural killer (NK) cell-mediated cytotoxicity was examined. Kupffer cells prepared from rat liver suppressed NK activity against K562 cells and other tumor cell lines through a soluble factor secreted into the culture supernatant. When human peripheral blood mononuclear cells were incubated with the Kupffer cell-culture supernatant, a significant reduction of the cytotoxic activity was observed in the 6-hr chromium-release assay. This activity was dose dependent and was evident at various effector/target cell ratios. Lipopolysaccharide stimulated generation of the suppressive factor released from Kupffer cells in a dose-dependent manner. Suppression of the NK activity was observed when the Kupffer cell-culture supernatant was present in the assay system, whereas pretreatment of effector/target cells with the supernatant had minimal inhibitory effects. Autologous monocytes in human peripheral mononuclear cells were not related to this suppression. The suppressive factor in the fraction had a molecular weight below 10,000. Indomethacin, an inhibitor of prostaglandin synthesis, ameliorated the suppressive effects. These results suggest that Kupffer cells may modulate NK activity by producing PGs (E1, E2, and F2 alpha).
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Experiments were performed to study the projection of the group y of the vestibular nuclei and the dentate and fastigial nuclei of the cerebellum to the interstitial nucleus of Cajal (INC) in cats by using retrograde axonal transport of horseradish peroxidase (HRP) and electrophysiological methods; and to study the vestibular responses of such projection neurons. Following injections of HRP into the unilateral INC, with partial involvement of the surrounding reticular formation, including the nucleus of Darkschewitsch (ND), many retrogradely labeled neurons were found in the dorsal part of the group y nucleus contralateral to the injection site. Labeled cells were also seen in the contralateral dentate nucleus, frequently in its caudal-ventral part, and in the contralateral fastigial nucleus at all rostrocaudal levels, but most frequently in its caudal part. In electrophysiological experiments performed on cats anesthetized with alpha-chloralose or N2O and paralyzed with gallamine, group y, dentate and fastigial nuclei neurons were antidromically activated by weak stimuli that were confined to the contralateral INC. Depth-threshold curves for antidromic activation of such neurons revealed that the lowest threshold points were within the INC, but not in the ND. The INC-projecting neurons in the group y and dentate nuclei did not respond to electrical stimulation of the ipsilateral or contralateral vestibular nerve, indicating that they do not receive direct labyrinthine inputs. On the contrary, many fastigial neurons projecting to the INC responded to labyrinthine stimulation, suggesting that they may be involved in the vestibular reflexes. These results suggest a difference in properties of INC-projecting neurons in these nuclei.
A 38-year-old Japanese man had cholangiocarcinoma in association with typical features of Werner's syndrome. The replicative capacity of fibroblasts in culture was characteristically reduced, and the in vitro natural killer cell activity was deficient. He died of massive G-I tract bleeding 8 months after admission.
This is the first case report of fibrolamellar carcinoma of the liver (FCL) in Japan with reference to the relevant literature. A 56 year-old Korean male with positive HBsAg was complaining of generalized weakness. Alpha-fetoprotein level was elevated and a mass lesion in right lobe of the liver was detected. He underwent a wedge resection, of the liver and the follow-up study failed to show recurrence of the tumor in 15 months. The specimen showed a tumor consisting of a firm, grayish-white, circumscribed solitary mass measuring 4 cm in diameter. Microscopically the tumor was characterized by polygonal and eosinophilic tumor cells and abundant fibrous stroma around the tumor cells in lamellar fashion. FCL is a well-defined disease entirely with a distinct histologic pattern and a favorable prognosis.
Total RNA extracted from peripheral blood lymphocytes of a patient with B-cell chronic lymphocytic leukemia (CLL) and the poly (A+) RNA was purified. A cDNA library was constructed and approximately 4,000 clones were screened in order to identify genes preferentially expressed in CLL. A relatively low repetition frequency characterizes the majority of the abundant mRNA species present in CLL lymphocytes. One clone, corresponding to the mRNA encoding the HLA-DR-associated invariant chain, was selected and its expression was examined in different leukemic cell populations and in normal tissues. DNA-RNA hybridization studies showed that the invariant chain mRNA (In-mRNA) is detectable in RNA preparations from human blood cells and their precursors, whereas no In-mRNA is found in several other tissues examined. Among various normal and leukemic leukocyte populations, the highest levels of In-mRNA are found in CLL. Therefore, a role of In-chain mRNA as a marker of CLL is proposed. Our data support a relationship between high levels of invariant chain mRNA and the out of cycle condition of CLL peripheral blood lymphocytes.
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The primary structures of a cDNA and the genomic DNA of a gene selectively expressed in chronic lymphocytic leukemia were determined. A computer search of the nucleotide sequence data bank identified this gene as the invariant gamma-chain associated with class II histocompatibility antigens. The invariant gamma-chain genomic sequence spans about 11 kilobases, with eight exons and seven introns. Three of the introns contain members of the Alu repeat family. A putative cap site and promoter sequence were identified at the 5' end of the gene. One or two copies of the gene is present in each haploid genome, and no evidence for amplification or polymorphism was obtained.
Experiments were performed in cats to determine whether the head tilt following a unilateral lesion of the interstitial nucleus of Cajal (INC) can be attributed to removal of interstitiospinal fibers which have direct excitatory synaptic connections with ipsilateral neck extensor (biventer cervicis-complexus) and flexor (sternocleidomastoid, SCM) motoneurons. Unilateral INC lesions were made either electrolytically or reversibly by procaine infusion into the INC, and electromyographic activity was recorded bilaterally from biventer (BIV), splenius (SP) and SCM muscles. In both groups of lesions, activity of the ipsilateral SP and BIV was higher than that of the contralateral ones. When procaine was infused into the INC of awake cats, an increase of activity of the ipsilateral SP began before the cats presented the typical head tilt to the opposite side. Bilateral INC lesions caused dorsiflexion of the head. These results indicate that the head tilt resulting from unilateral INC lesions can not be explained by simple removal of the ipsilateral, direct excitatory interstitioneck impulses. When unilateral INC lesions were combined with hemilabyrinthectomies, cats that were given labyrinthectomies on the side opposite to the previous INC lesions showed very severe head tilt, whereas cats that received labyrinthectomies on the same side did not show obvious head tilt. Furthermore, it took a much longer time for the cats of the former group to compensate the head tilt than it took those that had single lesions of the INC or labyrinth.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of alpha 1-antitrypsin (alpha 1-AT), alpha 1-acid glycoprotein (alpha 1-AGP), and haptoglobin (Hp), the main constituents of alpha-globulin and which belong to acute-phase proteins, on NK activity were examined using K562 cells as the NK target cells. Among the three proteins, alpha 1-AT and alpha 1-AGP had inhibitory effects on NK activity for "fast target" K562 cells. The alpha 1-AT preparations having the same protein concentration and a different trypsin inhibitory capacity (TIC) had an equal effect. Although alpha 1-AT and alpha 1-AGP equally reduced the NK activity, the mechanism involved in the reduction differed, in that the effect of alpha 1-AT directed toward NK cells reduced their binding capacity with the target cells. alpha 1-AGP probably interacts with a cytotoxic factor secreted from NK cells following effector-target interaction. These studies suggest that each of the acute-phase proteins, which increase following inflammation, inhibits NK cell function by two distinct mechanisms.
Effects of procaine infusion into the interstitial nucleus of Cajal (INC) on vestibular nuclear neurons related to the horizontal canal were studied in cats anesthetized with nitrous oxide and paralyzed with gallamine. Neurons that responded to sinusoidal horizontal rotation (at 0.18 Hz) were recorded extracellularly in the medial and descending vestibular nuclei. Spontaneous activity of type I neurons increased, whereas that of type II neurons decreased following procaine infusion into the ipsilateral INC. Gain of the neuronal response to horizontal rotation decreased after the ipsilateral INC infusion, but there was no consistent effect on phase. Infusion into the contralateral INC seemed less effective. Similar effects were obtained with electrolytic lesions that were confined to the ipsilateral INC area. These results suggest that the INC influences type I neurons through inhibitory action of type II neurons and that it eventually controls the gain, but not the phase, of the horizontal vestibular reflexes.