Search PubMed⌕ Search

Biomedical subjects

H Ichikawa

Publications and source records attributed to H Ichikawa.

At least 145 records · Page 8Linked to original sources
PubMed1999

Biodistribution of gadolinium incorporated in lipid emulsions intraperitoneally administered for neutron-capture therapy with tumor-bearing hamsters.

Emulsions containing a distearylamide (Gd-DTPA-SA) or a distearylester (Gd-DTPA-SE) of Gd (gadolinium)-diethylenetriaminepentaacetic acid (Gd-DTPA) were intraperitoneally injected in Greene's melanoma-bearing hamsters at a dose of 2.0 ml (3.0 or 6.0 mg Gd) per hamster. In the standard-Gd and high-Gd formulations used, the weight ratios of soybean oil, water, Gd-DTPA derivative (Gd-DTPA-SA or Gd-DTPA-SE), hydrogenated L-alpha-phosphatidylcholine from egg yolk (HEPC) and co-surfactant (HCO-60, Myrj 53, Myrj 59 or Brij 700) were 7.36:92:1:2:3 and 7.36:92:2:1:3, respectively. When the effects of the co-surfactants on the biodistribution of Gd from Gd-DTPA-SA-containing emulsions in the standard-Gd formulation were compared, the HCO-60 emulsion exhibited the highest Gd accumulation in tumors, possibly resulting from its fast and complete absorption, its small particle size (78 nm) and the stable coat on the particle surfaces with polyoxyethylene. Brij 700 emulsion kept the highest blood Gd concentration for a prolonged period, possibly due to particle properties similar to those of HCO-60. However, it exhibited a slower Gd accumulation in tumors, only reaching an identical level, in comparison with the HCO-60 emulsion. This suggested the tumor to be saturated with lipid particles. When Gd-DTPA-SE was used instead of Gd-DTPA-SA, its HCO-60 emulsion exhibited only very poor Gd-accumulation due to its easy degradation. The HCO-60 emulsion particles containing Gd-DTPA-SA in the high-Gd formulation (6.0 mg Gd in 2 ml) exhibited in vivo behavior identical to those in the standard-Gd formulation; then the Gd level in tumors reached 107 micrograms Gd/g tumor (wet), and the tumor:blood (T/B) and tumor:skin (T/Sk) Gd concentration ratios were 13.2 and 5.6, respectively, at 48 h after intraperitoneal administration. These results suggest that when intraperitoneally administered, this HCO-60 emulsion, and possibly also the corresponding Brij 700 emulsion, may be an excellent delivery system for accumulating Gd in tumors in neutron-capture therapy (NCT).

Animals↗
PubMed1999

Preparation of lecithin microcapsules by a dilution method using the Wurster process for intraarterial administration in gadolinium neutron capture therapy.

Lecithin microcapsules containing gadolinium (Gd) were designed and prepared as a dosage form for intraarterial administration to accumulate Gd in tumors in neutron capture therapy. The microcapsules were composed of 1) a lactose core, 2) a layer of distearylamide of gadopentetic acid (Gd-DTPA-SAm) and polyvinylpyrrolidone (PVP) with or without soybean lecithin (SL) and 3) a membrane containing SL, cholesterol, stearic acid and PVP at three different compositions. A dilution method using the Wurster process was developed for small-scale preparation. In spite of using only 2 g of Gd-DTPA-SAm each, three types of microcapsules were obtained with a content of 24.9% as Gd-DTPA-SAm (3.66% as Gd) even at 150% coating level. The swelling type of microcapsules (MC-D1) did not release Gd at all for the entire 120 min of the experiment in a 0.9% saline solution. On the other hand, the rapid-erosion type (MC-D2) and the vesicle-dispersing type (MC-D3) released Gd with a lag time. The percent released depended on the coating level and the SL content in the Gd-fixing layer. A large number of droplet-like particles spouted out, and/or tubular vesicles formed with MC-D2 and MC-D3 in the saline solution. These phenomena implied that the water-insoluble Gd-DTPA-SAm would be entrapped in these particles/vesicles. When MC-D2 and MC-D3 were administered to normal rats via the hepatic artery, a Gd-accumulation as high as 70 and 71% of the injected dose was detected in the whole liver 2 h after administration. In addition, biochemical and histological evaluation of the liver after administration indicated that embolization of the microcapsules actually occurred in the blood vessels, and that necrosis induced by ischemia was not serious. These results suggested that administration of these microcapsules might be multiply repeated in order to accumulate the required amount of Gd in tumors.

Animals↗
PubMed1999

Preparation of gadopentetic acid-loaded chitosan microparticles for gadolinium neutron-capture therapy of cancer by a novel emulsion-droplet coalescence technique.

Biodegradable gadopentetic acid (Gd-DTPA)-loaded chitosan microparticles (Gd-microCPs) were prepared as a device for gadolinium neutron-capture therapy (Gd-NCT) by a novel emulsion-droplet coalescence technique: a water-in-oil (w/o) emulsion A containing chitosan and Gd-DTPA in droplets and a w/o emulsion B containing NaOH in droplets were mixed and stirred to solidify chitosan as a result of collision and coalescence between droplets of each emulsion. Gd-microCPs prepared by using 100% deacetylated chitosan in 25% Gd-DTPA solution were 4.1 microns (non-lyophilized) and 3.3 microns (lyophilized) in mass median diameter, and were 3.4% in gadolinium content, corresponding to 11.7% as Gd-DTPA. The particle size and gadolinium content of Gd-microCPs were not affected by Gd-DTPA concentration in the chitosan medium. However, the deacetylation degree of chitosan influenced the particle size; as the deacetylation degree of chitosan decreased, the particle size increased. The incorporated Gd-DTPA was not released entirely from Gd-microCPs in an isotonic phosphate buffered saline solution despite the high water-solubility of Gd-DTPA (less than 0.8% with every type of Gd-microCPs). These results indicated that ion-complex formation might be contributable to incorporation of Gd-DTPA. As a preliminary study, it was confirmed that the loss of gamma-ray emission by gadolinium-loading in microparticle was negligible in the thermal neutron irradiation test in vitro. These results suggested that Gd-microCPs could be a useful device for intratumoral injection into solid tumor on Gd-NCT.

Carbohydrate Sequence↗
PubMed1999

[Surgery for mitral regurgitation in children].

In pediatric patients, mitral valve (MV) repair is preferable than MV replacement because of no need for anticoagulation and its feasibility in small children. However, long-term outcome of MV repair is still unclear. In the present study, fifty-two pediatric patients who underwent MV repair (n = 46) and MV replacement (n = 6) against mitral regurgitation (MR) between January 1970 and December 1996 were evaluated. 46 patients had associated diseases. Mitral annuloplasty was applied in 20 patients (by Kay method (n = 14) and Paneth-Burr method (n = 6) before and after 1991, respectively). Freedom from reoperation rate in patients with partial endocardial cushion defect (ECD) was significantly lower than that in other patients after MV repair, which was significantly higher than that in patients with MV replacement. Diameter of mitral annulus grew within normal range after MV repair. In conclusion, MV repair may provide better outcomes with respect to reoperation and growth of MV in pediatric patients except with partial ECD.

Cardiac Surgical Procedures↗
PubMed1999

Multiple organ harvesting from a single donor for transplantation. A comparison of simple cooling technique and bypass technique.

BACKGROUND: We compared a simple, cooling technique to a cardiopulmonary bypass (CPB) technique for multiple organ harvesting (MOH) from a single donor. METHODS: Adult mongrel dogs were divided into three groups. In the in situ cooling group, the aorta and IVC were first clamped and the hepatic and renal vascular beds were washed out with a cold lactated Ringer's solution. In the peritoneal cooling group, hypothermia was induced using an ice slush in the abdominal cavity, and in the CPB group using CPB. As the esophageal temperature reached 25 degrees C, the liver and kidneys were harvested using the same procedure in all three groups. After the splanchnic perfusion, the heart was harvested while it continued to beat. The heart was preserved for 12 hours, and the liver and kidneys for 24 hours in a cold UW solution. Myocardial high-energy phosphates were measured using 31P-MRS, and the hearts were transplanted. Hepatic vascular beds were flushed during preservation, and the effluent was analyzed. Following kidney transplantation, its function was measured. RESULTS: There's no significant difference in myocardial high-energy phosphate or in cardiac function after transplantation. During liver preservation, ALT and LDH levels of the effluent were significantly higher in the in situ group than those in other groups. There's no difference following kidney transplantation. CONCLUSION: The CPB method and peritoneal cooling technique demonstrated stronger early function of hepatic grafts compared with the in situ cooling method. The peritoneal cooling technique is a simpler, safer and more feasible alternative for MOH compared with CPB method, and it may have broad clinical application.

Animals↗
PubMed1999

Extended thymectomy for myasthenia gravis in an octogenarian. A case report.

An 86-year-old woman with myasthenia gravis successfully underwent an extended thymectomy. The patient had a 2-year history of generalized myasthenia and had limited response to anticholinesterases and steroids. An extended thymectomy was successfully performed in the usual fashion. The postoperative course was uneventful except for an episode of psychosis probably due to postoperative steroid therapy. The steroid dosage was gradually reduced to 5 mg/day over seven months after the operation, during which she became fully asymptomatic. No symptoms due to myasthenia have surfaced for over 2 years after surgery. Although elderly patients are usually considered to be less responsive to an operation, thymectomy may sometimes be the treatment of choice for myasthenia gravis even in octogenarians.

Aged↗
PubMed1998

Postnatal changes in Bax-immunoreactivity and apoptosis of the rat trigeminal primary neurons.

The developmental changes of Bax protein-like immunoreactivity (Bax-ir) and naturally occurring cell death were investigated in the trigeminal primary neurons of rats, in the first 2 postnatal weeks. At 1 day postpartum, the trigeminal primary neurons exhibited intense cytoplasmic Bax-ir. A densitometric analysis indicated >95% of cells exhibited an ir-density (the staining intensity as compared to the background level) higher than 1.5. By 2 weeks the ir-density significantly decreased with >95% lower than 1.5, that was similar to the adult level. A nick-end labeling method revealed DNA fragmentation in apoptotic trigeminal primary neurons in newborn rats. During the first 11 days the percentage of apoptotic cells was highly correlated to the postnatal days with a regression line y = -0.083x + 0.877 (r = 0.976). A possible role of Bax in neonatal rat primary neurons is discussed.

Aging↗
PubMed1998

Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes.

We previously isolated RBP56 cDNA by PCR using mixed primers designed from the conserved sequences of the RNA binding domain of FUS/TLS and EWS proteins. RBP56 protein turned out to be hTAFII68 which was isolated as a TATA-binding protein associated factor (TAF) from a sub-population of TFIID complexes (Bertolotti A., Lutz, Y., Heard, D.J., Chambon, P., Tora, L., 1996. hTAFII68, a novel RNA/ssDNA-binding protein with homology to the proto-oncoproteins TLS/FUS and EWS is associated with both TFIID and RNA polymerase II. EMBO J. 15, 5022-5031). The RBP56/hTAFII68, FUS/TLS and EWS proteins comprise a sub-family of RNA binding proteins, which consist of an N-terminal Ser, Gly, Gln and Tyr-rich region, an RNA binding domain, a Cys2/Cys2 zinc finger motif and a C-terminal RGG-containing region. Rearrangement of the FUS/TLS gene and the EWS gene has been found in several types of malignant tumors, and the resultant fusion proteins play an important role in the pathogenesis of these tumors. In the present study, we determined the genomic structure of the RBP56/hTAFII68 gene. The RBP56/hTAFII68 gene spans about 37kb and consists of 16 exons from 33bp to 562bp. The longest exon, exon 15, encodes the C-terminal region containing 19 repeats of a degenerate DR(S)GG(G)YGG sequence. While the structure of the FUS/TLS gene has been reported previously, we determined the total DNA sequence of the FUS/TLS gene, consisting of 12kb. The RBP56/hTAFII68, FUS/TLS and EWS genes consist of similar numbers of exons. Comparison of the structures of these three genes showed that the organization of exons in the central part encoding a homologous RNA binding domain and a cysteine finger motif is highly conserved, and other exon boundaries are also located at similar sites, indicating that these three genes most likely originate from the same ancestor gene.

Base Sequence↗
PubMed1998

Neonatal primary neuronal death induced by capsaicin and axotomy involves an apoptotic mechanism.

To clarify the mechanism of capsaicin-induced primary neuronal cell death, newborn and adult rats were given a subcutaneous injection of capsaicin (50 mg/kg). Neonatal capsaicin injection induced neuronal apoptosis in the trigeminal ganglion. Apoptotic neurons had peripheral stacks of long parallel endoplasmic reticulum that are characteristic to primary neurons of the B-type, and exhibited nucleoplasmic condensation, nuclear shrinkage and cytoplasmic fragmentation. Light microscopically, apoptotic neurons exhibited a sign of DNA fragmentation as revealed by a nick end labelling method. The proportion of apoptotic cells was quite low during the first 12 h after capsaicin injection (<1%), rapidly increase to 10.44% by 24 h, and decreased to 0.29% by 48 h. Normal and vehicle control levels of apoptosis were <1%. Nerve growth factor (NGF, 0.5 mg/kg) simultaneously administered with capsaicin reduced the incidence of apoptosis by about 35% at 24 h post-injection. Neonatal transection of the infraorbital nerve induced neuronal apoptosis similar to that produced by the neonatal capsaicin in the maxillary division of the trigeminal ganglion. Unlike capsaicin, however, the neurotomy-induced apoptosis was seen in neurons of both the A- and B-types. Neither the capsaicin injection nor the neurotomy induced apoptosis in adult rats, though mitochondrial swelling similar to that seen at 0.5 h after neonatal capsaicin was observed after capsaicin injection in adults. The results indicate that the capsaicin-induced and nerve injury-induced primary neuronal damages in newborn rats share a common final pathway, apoptosis.

Animals↗
PubMed1998

Coexistence of s100beta and putative transmitter agents in vagal and glossopharyngeal sensory neurons of the rat.

The coexistence of S100beta with calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), nicotinamide adenosine dinucleotide phosphate-diaphorase (NADPH-d), and tyrosine hydroxylase (TH) was examined in the glossopharyngeal and vagal sensory ganglia. S100beta immunoreactive (-ir) neurons in the jugular and petrosal ganglia frequently colocalized CGRP- or SP-ir, whereas S100beta-ir neurons in the nodose ganglion infrequently contained CGRP- or SP-ir. No S100beta-ir neurons in the jugular and petrosal ganglia showed SOM-ir while the small number of SOM-ir neurons in the nodose ganglion colocalized S100beta-ir. Many neurons in the nodose ganglion colocalized S100beta-ir and NADPH-d activity, whereas S100beta-ir neurons in the jugular and nodose ganglia infrequently contained NADPH-d activity. S100beta- and TH-ir were frequently colocalized in nodose ganglion but not in petrosal or jugular ganglion neurons. These findings suggest relationships between S100beta and specific putative transmitters in functions of subpopulations of vagal and glossopharyngeal sensory neurons.

Animals↗
PubMed1998

Induction of immediate-early genes c-fos and zif268 in the subnucleus oralis by noxious tooth pulp stimulation.

c-fos and zif268 expression were assessed by immunocytochemistry for c-Fos and Zif268 proteins in the sensory trigeminal nuclear complex following noxious mechanical stimulation of the mandibular incisor pulp of rats. Marked up-regulation of both immediate early genes was observed in the subnucleus oralis ipsilateral to the stimulation. Cavity preparation of the dentine without reaching the pulp did not cause significant up-regulation detectable by immunocytochemistry. These results provide evidence that noxious dental signals reach the ipsilateral subnucleus oralis and up-regulate the transcription of immediate early genes c-fos and zif268.

Animals↗
PubMed1998

Design of and metrological results from a bent parabolic mirror.

This article describes the successful design and fabrication of, and metrological results from, an elastically bent parabolic mirror. The mirror is equipped with a bending structure that allows the mirror to be bent meridionally to a parabolic shape. This bent parabolic mirror is the key component of the extremely high-quality monochromators designed for the SPring-8 figure-8 soft X-ray undulator and the 2.0 GeV high-brilliance synchrotron radiation source (VSX).

Journal Article↗
PubMed1998

c-fos induction in the subnucleus oralis following trigeminal nerve stimulation.

Neurons with c-Fos protein-like immunoreactivity (fos-neurons) were examined in the rostral parts of the brainstem sensory trigeminal nuclear complex following intense electrical stimulation of the trigeminal nerves and noxious mechanical stimulation of the trigeminal receptive fields. Stimulation of all the examined nerves and receptive fields induced some fos-neurons at the medial edge of the subnucleus interpolaris but not in the principal sensory trigeminal nucleus. Stimulation of the primary neurons innervating the intraoral structures but not facial skin induced fos-neurons in the ipsilateral subnucleus oralis. These oralis fos-neurons were located in the dorsomedial nucleus that contained calcitonin gene-related peptide-like immunoreactivity. The oralis fos-neurons are considered to be involved in the processing of intraoral nociceptive signals.

Analysis of Variance↗
PubMed1998

Homozygous deletion and frequent allelic loss of the 21q11.1-q21.1 region including the ANA gene in human lung carcinoma.

The frequent occurrence of 21q deletions in human non-small cell lung carcinoma (NSCLC) indicates the presence of a tumor suppressor gene on this chromosome arm. Since the ANA (Abundant in Neuroepithelium Area) gene, a member of an antiproliferative gene family, was mapped to 21q11.2-q21.1, we searched for genetic alterations of the ANA gene in human lung cancers. The gene was homozygously deleted in a human NSCLC cell line, Ma17. The gene was mapped in the 0.33 Mb Not1 fragment at 21q21.1 of the Not1 restriction map for 21q. Loss of heterozygosity (LOH) at this locus was detected in 24/47 (51.1%) of NSCLC, and the frequency of LOH in brain metastases was significantly higher than that in stage I-II primary tumors (P = 0.018). These results suggested that the homozygously deleted region harbors a novel tumor suppressor gene involved in NSCLC progression. Since mutation of the ANA gene was not detected in other lung cancer cell lines and fresh lung tumors with LOH at this locus, it is unlikely that the ANA gene is a target gene inactivated by two mutational events in this chromosomal region. Physical mapping of the homozygously deleted region showed that the deletion had occurred interstitially at 21q11.1-q21.1 and the size of the deletion was estimated as being more than 3 Mb. Our mapping results will facilitate further efforts to identify a tumor suppressor gene on 21q.

Aged↗
PubMed1998

Overexpressed heat shock protein 70 attenuates hypoxic injury in coronary endothelial cells.

Previous studies indicate that heat shock protein 70 (hsp70) improves the myocardial tolerance to ischemia-reperfusion injury by a mechanism that is not well understood. To better define this protective function, it is important to distinguish a role of hsp70 on coronary endothelial cells (cEC) from that on cardiac myocytes. Thus, we transfected rat cEC with a human hsp70 cDNA by using hemagglutinating virus of Japan-liposome method (group H). Control cells (group C) were transfected with a vector containing no gene. Immunohistochemical staining demonstrated overexpression of hsp70 in the cytosol of the cells in group H. Western blotting also showed large amounts of hsp70 expression in these cells. After 18 h of hypoxia followed by 2 h of reoxygenation, the adenosine triphosphate content was higher in group H (H v C; 1.05 +/- 0.08 v 0.68 +/- 0.04 microgram/dish, P = 0.0007). In addition, lactate dehydrogenase leakage after hypoxic insult was lower in group H than that in group C (61.3 +/- 4.5 v 85.4 +/- 6.1 10(-3) IU/dish/37 degrees C, P = 0.004). Conversely, the leakage of FITC-albumin through a confluent monolayer of cEC after hypoxia-reoxygenation was less in group H than that in group C (11.1 +/- 1.8 v 27.4 +/- 3.1%, P = 0.0003). Thus, the high level expression of hsp70 caused by gene transfection enhanced the hypoxic tolerance of coronary endothelial cell. Therefore, coronary endothelial cell is an important targets of hsp70-mediated cardioprotection as well as cardiac myocytes.

Adenosine Triphosphate↗
PubMed1998

The immunosuppressive compound FK506 does not affect expulsion of Echinostoma trivolvis in C3H mice.

C3H/HeN mice were infected with Echinostoma trivolvis metacercariae on day 0, given intramuscular injections of the immunosuppressive agent FK506 daily for 5 or 7 days, and necropsied on days 5, 8, 12, 15, 20, and 30 postinfection (p.i.). Control mice were infected with the echinostomes but were not treated with FK506. A significant reduction in mastocytosis was seen from day 12 to day 15 p.i. in the treated group. No reduction was observed in numbers of goblet cells and eosinophils in the treated group. The number of white blood cells was lower in the treated mice than in the controls. No significant difference in the optical density values of immunoglobulins appeared in control versus treated mice. Treatment with FK506 did not delay worm expulsion markedly, probably because the drug did not suppress goblet-cell hyperplasia. Increased mucus production associated with goblet-cell hyperplasia is primarily involved in the expulsion of E. trivolvis in murine hosts.

Animals↗
PubMed1998

Churg-Strauss syndrome (allergic granulomatous angitis) presenting with ileus caused by ischemic ileal ulcer.

We report a rare case of Churg-Strauss syndrome (CSS) in a 41-year-old Japanese man with a history of middle-age onset of bronchial asthma who had severe abdominal pain. He presented with ileus caused by an annular ulcer of the ileum, attributable to mucosal ischemia resulting from necrotizing vasculitis of the mesenteric artery. He also had marked hypereosinophilia (51.5%), elevated serum IgE levels (34040 IU/ml), and generalized enlargement of the superficial cervical lymph nodes, containing eosinophilic granulomas. A stenotic lesion caused by an annular ulcer in the ileum was found and resected by laparotomy. Microscopic examination of the resected specimen revealed luminal narrowing or occlusion of small arteries in the ulcer base, subserosa, and mesenterium resulting from marked fibrotic intimal thickening with fragmentation or lack of the internal elastic lamina. These findings were diagnosed as vasculitis, scar stage. The postoperative course was uneventful, with the patient receiving a maintenance dose of prednisolone (10-15 mg/day) for 7 years subsequently. We must carefully diagnose and treat patients with middle-age onset asthma, because the symptom may be a lung manifestation of CSS, in which various organs including gastrointestinal tract are involved as a result of systemic necrotizing vasculitis.

Adult↗