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Biomedical subjects

K Iguchi

Publications and source records attributed to K Iguchi.

At least 91 records · Page 5Linked to original sources

Effect of recombinant human granulocyte colony-stimulating factor administration in normal and experimentally infected newborn rats.

We investigated the effects of repetitive recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration at three different doses (every 12 h times six doses, starting at 12-24 h of age) on the kinetics of neutrophil production in Sprague-Dawley rats. We determined WBC counts, differentials, the number of total nucleated cells, the myeloid mitotic pool cells (promyelocytes and myelocytes), the storage pool cells (metamyelocytes, bands, and polymorphonuclear cells [PMNs]) and the granulocyte-macrophage (granulocyte-macrophage colony-forming units, CFU-GM) and macrophage (macrophage colony-forming units, CFU-M) progenitor cells of the bone marrow, spleen, and the liver before the first dose of rhG-CSF administration and 12 h after the second, fourth, and sixth dose. Control animals were given the diluent by the same schedule. Recombinant human G-CSF-treated rats showed a significant dose-dependent increase in the number of total WBC and neutrophil counts at all time points compared to control rats. The total number of CFU-GM and myeloid mitotic pool cells (marrow plus spleen plus liver) progressively increased with age in both control and G-CSF groups, but the G-CSF treated groups showed a significantly larger number of mitotic pool cells at hour 24, continuing up to hour 72, compared to the control group. However, there was no significant difference at any time point in the number of CFU-G/GM as detected by the granulocyte-macrophage colony-stimulating factor (GM-CSF)-supported culture system. Priming of newborn rats with injections every 12 h of rhG-CSF times two doses, or six doses followed by inoculation of group B streptococci (GBS) did not significantly change the sepsis death rate of animals, although the neutrophil counts in infected rhG-CSF-primed animals were significantly larger than the infected control animals. Injection of human i.v. gammaglobulin 3 h following inoculation with GBS significantly improved the survival of animals compared to G-CSF administration or administration of the diluent alone (control). Thus G-CSF alone may not be beneficial for the treatment of neonates with sepsis. Additional work is needed to determine whether combination of G-CSF with antibiotics or other cytokines, such as GM-CSF or interleukin 6 (IL-6) may be of benefit.

Animals↗

[Clinical investigation on acute respiratory failure in patients with severe hematologic malignancy].

Ten patients with severe hematologic malignancies (four with acute leukemia, three with multiple myeloma, one with prolymphocytic leukemia, one with malignant lymphoma and one with blastic crisis of chronic myelogenous leukemia) developed respiratory failure during the period between April 1986 and May 1990. Clinically, the patients manifested high-fever, dyspnea refractory to oxygen therapy, diffuse pulmonary rales and severe hypoxemia without evidence of cardiogenic pulmonary edema. Chest roentgenograms displayed diffuse alveolar infiltrates. Respiratory failure occurred as early as 48 hours and as late as 66 days after the administration of intensive anti-neoplastic chemotherapy. At that time leukocyte count was between 100/microliters and 54,900/microliters. Marked leukocytosis was observed in two patients with AML and PLL. Respiratory failure was preceded by sepsis in one patient with AML and by pneumonia in nine patients. DIC was diagnosed in four patients. All patients treated with high dose methyl prednisolone (mPSL) within 12 hours after the onset of respiratory failure. Only one patient required assisted ventilation. High dose mPSL had significant effect on seven of ten patients. But three patients died from progressive respiratory failure, sepsis, pneumonia and multi-organ failure.

Acute Disease↗

Is helodermin-like immunoreactivity in human thyroid C cells due to a salmon calcitonin-like substance?

Helodermin-like and salmon calcitonin (sCT)-like immunoreactivities co-existed in a subset of human calcitonin (hCT)-containing cells in normal human thyroid tissue and medullary thyroid carcinomas. Helodermin/sCT-immunoreactive cells were mostly different from calcitonin gene-related peptide (CGRP)-positive cells. Helodermin and sCT immunoreactivities were not identified in pulmonary and pancreatic hCT-positive neuroendocrine tumors, except for a few lung tumor cells showing positive staining with one of two sCT antisera used. Helodermin immunoreactivity demonstrated by rabbit antiserum R0086 was completely abolished in the presence of synthetic sCT, while sCT immunoreactivity was not absorbed by synthetic helodermin. The carboxyl terminal Arg30-Thr31 sequence (and Pro35 amide structure) of helodermin would be the epitopic site recognized by this antiserum, since a similar amino acid sequence is present in sCT molecules but absent from hCT and CGRP.

Amino Acid Sequence↗

Content and distribution of vasoactive intestinal polypeptide (VIP) in cavernous tissue of human penis.

Penile erection is controlled by a valvular structure in the helicine artery in humans. The opening and closing of this valve are believed to be regulated by the autonomic nervous system, especially through the release of vasoactive intestinal polypeptide (VIP). We determined the content of VIP in cavernous tissue in 18 impotent patients and in 5 normal controls by radioimmunoassay, and we examined the distribution of VIP-ergic nerve fibers in cavernous tissue by an immunohistochemical method. As a result, it was found that the lower penile VIP content was more frequent among patients with organic impotence than among the controls. Furthermore, VIP-ergic nerve fibers were seen to be diffusely and loosely distributed in a large number of organic impotence patients. These findings suggest that organic impotence in some patients may be due to decreases in the VIP content and in VIP-ergic nerve fibers.

Adolescent↗

Metabolic activation of 2,4-dinitrobiphenyl derivatives for their mutagenicity in Salmonella typhimurium TA98.

In order to elucidate the mechanisms of mutagenic activation of nitroarenes, we tested the mutagenic potency of 18 kinds of nitroarenes including nitrated biphenyl, fluorene, phenanthrene and pyrene on Salmonella typhimurium TA98 in the absence and presence of S9 mix. The mutagenicities of 2,4-dinitrobiphenyl derivatives and 4-nitrobiphenyl were enhanced by the addition of S9. 2,4,6-Trinitrobiphenyl (3 net rev./10 micrograms without S9) was activated 60-fold by the mammalian metabolic system (181 net rev./10 micrograms with 10% S9). The mutagenic potency of 2,4,2',4'-tetranitrobiphenyl in TA98, TA98NR and TA98/1,8-DNP6 was also enhanced by the addition of 10% S9. But 1-nitropyrene and 1,3-dinitropyrene, which are well-known mutagens and carcinogens, were deactivated to 3% and 0.4%, respectively, by the addition of 10% S9. Separate addition of microsomal and cytosolic fractions slightly activated the mutagenicity of 2,4,6-trinitrobiphenyl, and 2,4,2',4'-tetranitrobiphenyl was activated not only by S9 but also by the cytosolic fraction.

Animals↗

Effect of haloperidol on immunoreactive neuropeptide Y in rat cerebral cortex and basal ganglia.

To clarify the dopaminergic regulation of neuropeptide Y (NPY) neurons, the effect of haloperidol on NPY in basal ganglia and the cerebral cortex of the rat brain was investigated by sensitive radioimmunoassay and immunocytochemistry using antiserum against rat NPY. After repeated intraperitoneal injections of haloperidol (5 mg/kg) for 6 days, the content of immunoreactive NPY was significantly decreased in the caudate-putamen, but significantly increased in the lateral prefrontal cortex. After treatment for 21 days, the content of immunoreactive NPY in the caudate-putamen remained significantly low, but the extent of change in the lateral prefrontal cortex diminished. In the medial prefrontal cortex, piriform cortex, parietal cortex and nucleus accumbens, no significant changes were found after treatment for either 6 or 21 days. These findings were compatible with those obtained by immunocytochemistry using the same antiserum: an increase of immunoreactive fibers and terminals in the lateral prefrontal cortex and their decrease in the caudate-putamen. However, in the nucleus accumbens the density of immunoreactive fibers and terminals was decreased in the rostral portion, but not in the caudal portion after haloperidol treatment for 6 and 21 days. These findings suggest that dopaminergic afferents region-specifically regulate dopamine-sensitive NPY neurons in the rat brain.

Animals↗

Necrotizing buccal and cervical fasciitis.

A bite wound led to necrotizing fasciitis in the temporal space, the lateral pharyngeal space and the carotid sheath, indicative of a Streptococcus and Bacteroides infection, and was successfully treated with repeated incisions, radical debridement and antibiotic therapy.

Aged↗

[Studies on the giardiasis as the zoonosis].

To obtain basic data on the route of Giardia infection as zoonosis, we examined feces from 80 dogs and 16 cats for Giardia cysts and evaluated the detection rates. In addition, familial infection was studied in 3 family members of the patient with giardiasis. Giardia cysts were detected in 10 of the 80 dogs (12.5%) but none of the cats. Of the 10 dogs from which Giardia cysts were isolated, 6 had been maintained by the breeders. Tow other dogs were for examination in the research institutions. None of the family members of the patient with giardiasis had this infection. Since the detection rates of Giardia cysts in the dogs and cats were low, the possibility that human infection is acquired from dogs or cats seemed to be low. However, some of patients with giardiasis we encountered had never been abroad. This fact together with the presence of Giardia cysts in the dogs despite the low detection rates suggest that attention should be paid to the possible association between human giardiasis and pets since the number of people keeping pets is increasing.

Animals↗

Gonadotropin-releasing hormone-associated peptide immunoreactivity in bovine colostrum.

Gonadotropin-releasing hormone(GnRH)-associated peptide (GAP) is a 56-amino acid peptide found on the C-terminal of the GnRH (also called luteinizing hormone-releasing hormone) precursor and is assumed to be co-produced with GnRH. The purpose of this report is to demonstrate the presence of GAP immunoreactivity in bovine colostrum. Radioimmunoassay of acidified methanolic extracts demonstrated a concentration of GAP immunoreactivity of approximately 1.5 +/- 0.1 pmol/g dry skim bovine colostrum. Gel filtration (Sephadex G-10) and high-performance liquid chromatography of extracts containing GAP immunoreactivity showed it to be of low molecular weight and a high hydrophobic character. The presence of GAP immunoreactivity in bovine colostrum suggests that the GnRH precursor is synthesized and processed in mammary tissue itself.

Animals↗

[A case of "neuralgic amyotrophy" with elevated serum antibody titer against Borrelia burgdorferi].

A 39-year-old man experienced an abrupt onset of right back pain. The pain improved spontaneously, but weakness of the right upper extremity developed. The weakness deteriorated during the next month, and he was admitted to our hospital. Neurological examination disclosed impairment of superficial sensation in his right upper extremity. Blood examination showed no abnormal data. The cerebrospinal fluid was normal. Neuroradiological findings were also negative. Electrophysiological examinations were normal except for needle electromyographic findings of the right upper extremity, which showed neurogenic patterns of moderate degree. Those findings suggest neuralgic amyotrophy. However, examining the serum sample significantly elevated levels of antibody titers against Borrelia burgdorferi were observed, and we suspected that his illness was Lyme disease. He recalled, however, no arthropod bite. Neuralgic amyotrophy is a syndrome which takes a characteristic clinical course. It includes some heterogeneous disorders. On the other hand, Lyme disease, a tick-transmitted spirochetal illness, occurs in stages, with remissions and exacerbations and different clinical manifestations at each stage. The neurological abnormalities include aseptic meningitis, encephalitis, cranial neuritis, motor and sensory radiculitis, and myelitis in various combinations. They can be diagnosed serologically. However, it is possible that elevation levels of the antibody titers mean nonspecific damages of peripheral nerves. Further study is necessary to decide whether cases like ours suffer from so-called Lyme disease or not.

Adult↗

[Encephalomyelitis with elevated serum antibody against Borrelia burgdorferi].

A 60-year-old female was admitted because of intermittent fever, arthralgia, itching of whole body, pretibial edema, urinary incontinence, pain of both legs and gait disturbance, after an insect bite. On admission, she had fever of 38 degrees C, and nuchal pain and stiffness. Neurological examination revealed spasticity of lower legs and increased deep tendon reflexes of all extremities. Hyperesthesia and hyperalgesia were noted on C2-4 and L5-S5 areas. Leukocyte count was 10,100/mm3 and CRP was 2+. CSF showed no pleocytosis (3/mm3, lymphocyte), but total protein (50 mg/dl) and IgG (10.5 mg/dl) were increased. On T2-weighted images of brain MRI, multiple small high signal areas were shown. The symptom improved markedly by prednisolone, but 3 months later left lateral gaze palsy appeared abruptly. A demyelinating lesion of the pons to the medulla oblongata including the left paramedian pontine reticular formation was suspected, and a corticosteroid pulse therapy was very effective. Serum titer of anti-Borrelia burgdorferi-IgG antibody by indirect immunoperoxidase method was 400 x at first and 1600 x after 3 months. Neuroborreliosis was diagnosed, but high doses of intravenous penicillin were not effective, and an immune-mediated demyelinating mechanism was probably thought to play a role in the pathogenesis of neuroborreliosis.

Antibodies, Bacterial↗

Demonstration of two distinct insulin-binding components in solubilized human placental membranes by radioimmunoassay using synthetic peptide and anti-synthetic peptide antibody.

A peptide corresponding to the 957-980 sequence of human placental insulin receptor precursor (HIRP) was synthesized and antisera were produced against the synthetic peptide. Anti-synthetic HIRP(957-980) serum HIR-27 was proved to cross-react with HIRP-related proteins in solubilized human placental membranes. A radioimmunoassay developed with the antiserum and synthetic peptide HIRP(957-980) enabled us to separate, in combination with gel filtration, two insulin-binding components in solubilized human placental membranes which conceivably correspond to the alpha 2 beta 2 and alpha beta structures of the placental insulin receptor. The two components were shown to be distinct in insulin-binding behavior depending on conditions of pH and ionic strength in the binding assay.

Antibodies↗

Recent advances in brain-gut hormones.

Although recent advances in gene technology have made it possible to produce peptides and proteins by the recombinant technique, chemical synthesis either by the solution or by the solid-phase technique is still only a method of choice for the syntheses of a brain-gut hormone and its superagonist and/or antagonist. In addition, synthetic replicates of brain-gut hormones, their analogus and fragments or their precursor-related peptides are important haptenic immunogens to produce region-specific antisera to the respective peptides. In the present study, antisera against proglucagon and pro-LH-RH related peptides were proved to be useful not only for identifying hormone-producing cells, but also for demonstrating the post-translational biosynthetic processing in the cells. For galanin, a novel brain-gut hormone, have structural similarity in its C-terminal region to tachykinins, a monoclonal antibody against synthetic porcine galanin (1-15) was prepared for immunohistochemical study. This monoclonal antibody was found to recognize specifically galanin-producing cells and not to cross-react with any of tachykinins examined. These observations indicate that monoclonal antibodies are highly useful for identifying cells possessing a brain-gut hormone containing structures common to those of different known peptides.

Animals↗

[Experience with clarithromycin in pediatric patients].

Clarithromycin (TE-031, A-56268), a newly synthesized macrolide antibiotic, was administered to children and its efficacy was examined. The clinical efficacy rate of TE-031 was 88.5% in 26 patients with pediatric infections. This rate was regarded as quite high. A side effect, transaminase elevation, was observed in 1 out of the 26 patients but it was subsided after a cessation of the antibiotic treatment. TE-031 was considered to be effective antibiotic for the infectious disease in the pediatric fields because of highly efficacy rate.

Adolescent↗

[Experience of fluconazole in pediatric patients].

Fluconazole is a triazole agent and possesses a potent antifungal activity against fungi such as Candida, Cryptococcus and Aspergillus. Fluconazole is well absorbed following oral administration and shows bioavailability almost comparable to that attained in intravenous administration. The serum half-life is as long as about 30 hours and distributed widely into organs and tissues. Because of these it is expected to exhibit good clinical efficacy in the deep-seated mycosis. We evaluated the efficacy of fluconazole given orally to 3 pediatric patients with deep mycosis and also with aim of evaluating its prophylactic effect, gave fluconazole to 4 patients who had high risks of mycotic infections. Pathogenic fungi isolated from the 3 patients with mycosis were all Candida albicans and diagnoses made were Candida pneumonia, oral candidiasis and gastrointestinal candidiasis. Clinical efficacies were judged to be good in all of the 3 patients and C. albicans were found eradicated following the treatment. In the 4 patients to whom fluconazole was given prophylactically, no mycosis developed. Fluconazole was well tolerated and no incidence of side effects or clinical laboratory parameter abnormalities were seen any of the patients involved in the study.

Administration, Oral↗

[Using specific radioimmunoassay for guinea pig VIP (GP VIP), immunoreactive GP VIP levels in respiratory tract tissue of normal and airway-allergic guinea pigs].

Vasoactive intestinal polypeptide (VIP) has recently received widespread attention with respect to its control of airway constriction, and is now regarded as the most promising candidate as a neurotransmitter for nonadrenergic noncholinergic inhibitory nerves in the airway. A specific system of radioimmunoassay (RIA) was devised to measure guinea pig VIP (gp VIP) concentration in airway tissue. An antiserum, R 550, was obtained by immunizing rabbits with newly synthesized gp VIP. The detectable VIP concentration was assessed to be 10 fmol/tube with the RIA system. The concentration of gp VIP in the respiratory tract tissue of normal guinea pigs was 0.04-0.22 pmol/g wet weight of tissue. The VIP level was highest in the trachea, in contrast to lower levels in both the major bronchus and lower lung. After being passively sensitized with ovalbumin, the experimental guinea pigs were exposed to the same antigen. After three minutes, as the expiration time was prolonged and the respiratory resistance increased, the immunoreactivity in the trachea and the major bronchus was significantly higher than the pre-exposure levels. After six hours, however, they returned to the original levels except in the lower lung where the level was constant throughout the respiratory change. As described above, the possibility of controlling airway constriction by VIPergic nerve in immediate-type allergic reactions is suggested by our findings.

Amino Acid Sequence↗

Structure requirements for antiproliferative and cytotoxic activities of marine coral prostanoids from the Japanese stolonifer Clavularia viridis against human myeloid leukemia cells in culture.

The structural requirements for antiproliferative and cytotoxic activities of marine coral prostanoids from Japanese stolonifer Clavularia viridis and related compounds were examined in HL-60 cells in culture. From our data on the structure-activity relationship of these compounds, we elucidated that 1) the alkylidenecyclopentenone structure in these prostanoids was required for the antiproliferative and cytotoxic activities against HL-60 cells, but the epoxy prostanoids without cross-conjugated cyclopentenone system had the activities; 2) the presence of hydroxyl group at C-12 position in the prostanoids enhanced the activities, but the stereospecificity of the 12-hydroxyl group was not required for the activities; 3) the introduction of halogen atom at C-10 position of the prostanoids potentiated the activities (Cl greater than Br = I greater than H); 4) the introduction of blocking groups for blocking beta-oxidation to the alpha-side chain of the prostanoids did not cause the marked increase of the activities; 5) the presence of dienone (C5-6 and C7-8) in the structure potentiated the activities. These results provide the basis for drug-design of a new class of antitumor agent from marine coral prostanoids.

Animals↗