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Biomedical subjects

K Kojima

Publications and source records attributed to K Kojima.

At least 397 records · Page 22Linked to original sources

[An improved method of preparation of autopsied human inflated-fixed whole lungs for radiologic-pathologic correlation].

Inflated-fixed lung specimens, prepared using polyethyleneglycol 400, the standard Heitzman method have the disadvantage of bad staining. The authors attempted to improve this short-coming using human autopsied lungs and evaluated both microscopical findings and the degree of specimen inflation. Fifty-five human autopsied whole lungs were examined. Forty-six lungs with cannulation through the main bronchus were distended with 20% formalin, after clamping the cannula for 15 minutes to six days, formalin in lungs was expelled by air at 10 cm H2O pressure, then fixed with fixative-fluid containing polyethyleneglycol 400, 95% ethyl-alcohol, 40% formalin and water mixed in a ratio of 10:5:2:3. In 9 lungs without cannulation, formalin was expelled manually. The degree of distension of 46 of the 55 cannulated specimens was satisfactory (score A: 42 specimens, score B: 4 specimens). In 9 specimens without cannulation, inflation was poor (Score C). Good or excellent staining was obtained in 29 specimens (Score A: 10 specimens, Score B: 19 specimens), but 3 specimens were not be improved (Score C). Both inflation and staining were good in 21 specimens. This new method, requiring cannulation in the main bronchus, inflated-fixation with 20% formalin and expulsion of formalin by air prior to the standard Heitzman method enables both high quality staining and radiographs of the inflated-fixed lung specimen.

Biopsy↗

[Clinical trial of IVC filter to temporary placement].

We developed a new inferior vena caval filter to prevent pulmonary embolism for a patient with IVC thrombus. This filter made by covering top half of Dotter Intravascular Retriever catheter with Dacron mesh sheet, was placed in IVC through a 10 F sheath from right jugular vein. In one case, after anticoagulant therapy and thrombectomy using balloon catheter, many free-floating thrombus were trapped in this filter and were taken out from the IVC. This filter was useful for preventing pulmonary embolism when removing thrombus in IVC, iliac and lower extremity veins. We propose to call this device "Hino's filter".

Adolescent↗

Distinct clonotypic Epstein-Barr virus-induced fatal lymphoproliferative disorder in a patient with Wiskott-Aldrich syndrome.

BACKGROUND: Recently, reports of Epstein-Barr virus (EBV)-induced lymphoproliferative disorders (LPD) have increased in number among immunosuppressed recipients of organ transplants. The importance of analyzing both the immunoglobulin gene and EBV termini is advocated for the investigation of pathogenetic mechanisms for clonal proliferation in EBV-induced LPD; however, the oncogenic mechanisms of EBV-induced LPD remain unclear. Furthermore, there are very few clonotypic studies of EBV-induced LPD in patients with primary immunodeficiency diseases. The authors studied the clonality of an EBV-induced fatal LPD in a 20-year-old patient with Wiskott-Aldrich syndrome (WAS), an X-linked recessive primary immunodeficiency disease. METHODS AND RESULTS: An autopsy showed non-Hodgkin lymphoma of B-cell origin with diffuse large cells in both systemic lymph nodes and extranodal organs. Immunohistochemical and Southern blot analyses showed polyclonal rearrangement of immunoglobulin genes in most of the lesions except for the pulmonary hilar lymph node. Furthermore, the analysis of restriction fragment length polymorphism with several fragments from EBV genome indicated that EBV genomes in all lesions were identical; however, a single but different-sized EBV termini was detected in every EBV-positive lesion when probed with the EcoRI-Dhet spanning terminal repeat region of EBV. CONCLUSIONS: The EBV-induced fatal LPD in a patient with WAS showed the characteristic clonotype, polyclonal immunoglobulin gene rearrangement, and monoclonal EBV terminal configuration. Furthermore, EBV termini in each lesion varied in size. This particular clonotype implicates several unique pathogenetic mechanisms for clonal proliferation of EBV-induced LPD.

Adult↗

Syntheses of nephritogenoside and related compounds.

Nephritogenoside has been prepared by coupling of the acyl azide derivative of a N-triglycosyl dipeptide, derived from the corresponding hydrazide derivative of O-(2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl)-(1-->6)-O-(2,3,4-tri-O -acetyl - beta-D-glucopyranosyl)-(1-->6)-2,3-di-O-benzyl-1-N-[N-(tert-butoxycarbon yl)- L-aspart-1-oyl-(L-proline methyl ester)-4-oyl]-alpha-D-glucopyranosylamine, with a nonadecapeptide, followed by deprotection of the desired protected nephritogenoside. The N-triglycosyl pentapeptide also has been prepared as a model compound.

Amino Acid Sequence↗

Poly(ADP-ribose) polymerase stimulates DNA polymerase alpha by physical association.

The direct effect of the eukaryotic nuclear DNA-binding protein poly(ADP-ribose) polymerase on the activity of DNA polymerase alpha was investigated. Homogenously purified poly(ADP-ribose) polymerase (5 to 10 micrograms/ml) stimulated the activity of immunoaffinity-purified calf or human DNA polymerase alpha by about 6 to 60-fold in a dose-dependent manner. It had no effect on the activities of DNA polymerase beta, DNA polymerase gamma, and primase, indicating that its effect is specific for DNA polymerase alpha. Apparently, poly(ADP-ribosyl)ation of DNA polymerase alpha was not necessary for the stimulation. The stimulatory activity is due to poly(ADP-ribose) polymerase itself since it was immunoprecipitated with a monoclonal antibody directed against poly(ADP-ribose) polymerase. Kinetic analysis showed that, in the presence of poly(ADP-ribose) polymerase, the saturation curve for DNA template primer became sigmoidal; at very low concentrations of DNA, it rather inhibited the reaction in competition with template DNA, while, at higher DNA doses, it greatly stimulated the reaction by increasing the Vmax of the reaction. By the automodification of poly(ADP-ribose) polymerase, however, both the inhibition at low DNA concentration and the stimulation at high DNA doses were largely lost. Furthermore, stimulation by poly(ADP-ribose) polymerase could not be attributed to its DNA-binding function alone since its fragment, containing only the DNA-binding domain, could not exert full stimulatory effect on DNA polymerase, as of the intact enzyme. Poly(ADP-ribose) polymerase is co-immunoprecipitated with DNA polymerase alpha, using anti-DNA polymerase alpha antibody, clearly showing that poly(ADP-ribose) polymerase may be physically associated with DNA polymerase alpha. In a crude extract of calf thymus, a part of poly(ADP-ribose) polymerase activity existed in a 400-kDa, as well as, a larger 700-kDa complex containing DNA polymerase alpha, suggesting the existence in vivo of a complex of these two enzymes.

Animals↗

A Japanese family of X-linked auto-immune enteropathy with haemolytic anaemia and polyendocrinopathy.

Three cases of X-linked auto-immune enteropathy with haemolytic anaemia and polyendocrinopathy are described from one related Japanese kindred. Two boys had died due to severe diarrhoea accompanied by total or subtotal intestinal villous atrophy. In contrast, although one patient showed the same symptoms and had circulating IgG antibodies against enterocytes, his condition improved dramatically and he developed well following the use of cyclosporin A (CSA). CSA may be beneficial in patients with this rare disorder. Auto-immune enteropathy should be considered as a cause of protracted diarrhoea with unknown aetiology.

Anemia, Hemolytic↗

Turner syndrome and occlusion of the internal carotid artery.

A 2-year-old girl with Turner syndrome was admitted with left hemiplegia and left facial palsy. Serial cranial computed tomographic scan demonstrated multiple cerebral infarctions in the right putamen and right medial cortical areas. Single photon emission computed tomographic scan revealed hypoperfusion from the right frontal to the right temporal area. Right carotid angiography showed narrowing and occlusion of the right internal carotid artery at the sphenoidal portion. Collateral circulation was not detected between the external and internal carotid arteries. Left carotid angiography revealed that the left anterior artery was narrow, and that the left internal carotid artery provided blood to the right internal carotid artery through the anterior communicating artery. These findings suggested that the cerebrovascular abnormality might be due to congenital hypoplasia of arteries in this patient. The unusual combination of cerebral infarction and Turner syndrome was reported.

Arterial Occlusive Diseases↗

A novel fine granule system for masking bitter taste.

In order to prepare fine granules of sparfloxacin (SPFX), a new quinolone anti-bacterial drug that shows masking of the bitter taste of SPFX and dissolutes at a rapid rate, various film-coated fine granules containing 20% SPFX and 0-52% low-substituted hydroxypropylcellulose(L-HPC) in the cores, were prepared by a spray method. Mixtures of ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC), titanium dioxide and sucrose stearate in weight ratios of X:Y:2:1 (X + Y = 6) were used as film materials. The degree of masking of the bitter taste by water-insoluble film, mainly consisting of EC and HPMC, increased by increasing the content ratio of EC to HPMC and the amount of films, but was also slightly affected by the amount of L-HPC in the cores, which were coated with either EC or EC/HPMC (4/2). On the other hand, the dissolution rate increased with an increased amount of L-HPC in the cores and with a decreasing ratio of EC to HPMC in the films. Increasing the amount of L-HPC in the cores, which induced a considerable expansion of the fine granules owing to their taking up of water from the dissolution medium, resulted in bursting of the film after a short lag time. The bioavailability of the film-coated fine granules containing 20% SPFX and 52% L-HPC in the cores and 10% EC/HPMC (4/2) in the coating film, which masked the bitter taste of SPFX and showed the optimal release characteristics, was equivalent to that of conventional tablets containing 100 mg SPFX in beagle dogs.

Animals↗

Synthesis of 3-oxa-5-alkylideneisocarbacyclins.

3-Oxa-5-methyleneisocarbacyclin (14a) and 3-oxa-5-ethylideneisocarbacyclin (19a) were synthesized. Compound 14a showed a potent antiplatelet aggregating activity, whereas 19a was inactive.

Animals↗

SUT-8701, a cholecystokinin analog, prevents the cholinergic degeneration in the rat cerebral cortex following basal forebrain lesioning.

SUT-8701 is a cholecystokinin octapeptide (CCK8) analog and a more lipophilic peptide than CCK8. We previously demonstrated that intra-ventricularly administered CCK8 protected against the degeneration of the cholinergic neurons in the cortex of the nucleus basalis magnocellularis (nbm)-lesioned rat. We determined whether SUT-8701 and CCK8 have the ability to protect against cholinergic degeneration in the cerebral cortex of nbm-lesioned rats. Systemically administered SUT-8701 (0.1-1 micrograms/day/animal, s.c.) preserved choline acetyltransferase activity and K(+)-evoked acetylcholine release in nbm-lesioned rats. SUT-8701 was more potent than CCK8. However, SUT-8701 was much less potent than CCK8 in satiety action. The affinity of SUT-8701 to the cholecystokinin (CCK) receptors assessed by using [125I]-CCK8 was almost the same as that of CCK8 in the mouse cerebral cortex, but was 107 times less than that of CCK8 in guinea pig pancreas. These results suggest that SUT-8701 may be effective in slowing down the degenerative processes in Alzheimer's disease by preserving the integrity of cholinergic neurons in the nucleus basalis.

Acetylcholine↗

Intravenous methylprednisolone pulse therapy for Graves' ophthalmopathy.

To investigate the efficacy of intravenous methylprednisolone pulse therapy on Graves' ophthalmopathy (GO), fifteen patients with severe GO were treated with large dose intravenous methylprednisolone (at a daily dosage of 1 g for 3 successive days). This treatment was repeated 3-5 times for 3-5 weeks. They were monitored before, 2 weeks after and 6 months after therapy by ophthalmological assessment, orbital magnetic resonance imaging (MRI), and by measuring serum antibodies to rat eye muscle (EMAB) in an enzyme linked immunosorbent assay and peripheral blood lymphocyte subsets by flow cytometry. Diplopia and periorbital edema markedly improved after treatment in 9 patients. Mean proptosis values and intraocular pressure measurements significantly decreased after pulse therapy. In 12 patients enlarged eye muscles significantly reduced in size after treatment, as determined by MRI. The overall ophthalmopathy index was improved from 4.8 +/- 2.4 to 2.5 +/- 1.6 at the end of pulse therapy (P < 0.01) and 2.4 +/- 1.5 six months after therapy (P < 0.01). Serum EMAB were detected in 8 out of 10 patients tested and their level significantly decreased after pulse therapy (from 3.3 +/- 1.4 to 2.5 +/- 1.2, P < 0.01). A significant increase in peripheral blood CD4+CD45RA+ cells was observed after pulse therapy. Increased numbers of CD11-CD8+ cells and decreased numbers of CD11+CD8++ cells were found prior to treatment and were normalized after pulse therapy. Our study indicates that methylprednisolone pulse therapy can be considered as a choice for the treatment of GO. The improvement in eye muscle involvement in these patients may be due to the effects of infused methylprednisolone on both humoral and cellular immune functions.

Adult↗

Acute obstructive hydrocephalus due to an unruptured basilar bifurcation aneurysm associated with bilateral internal carotid occlusion--a case report.

A patient with a higherly positioned and large basilar bifurcation aneurysm associated with bilateral internal carotid occlusion was described. A 63 year-old man was admitted to Yokokura Hospital with disturbed consciousness and mild left hemiparesis. On admission, an initial plain CT-scan showed an acute obstructive hydrocephalus with periventricular lucency caused by an abnormal lesion in the anterior part of the third ventricle. An emergency ventriculo-peritoneal shunt was inserted. The postoperative course was uneventful. The patient regained his consciousness with normal motor function by the following day. Postoperative cerebral angiography disclosed a large basilar bifurcation aneurysm at a higher position, 19 mm from the dorsum sellae. Bilateral internal carotid occlusion had occurred, but rich collateral blood supply from the vertebro-basilar artery via the bilaterally enlarged posterior communicating arteries to the anterior circulation was observed. This rich collateral blood supply to the vertebrobasilar artery might be responsible for the development of the aneurysmal formation due to the increased hemodynamic stress.

Acute Disease↗

Deoxypyrimidine cluster mediates the priming by calf thymus DNA primase subunit.

Homogeneously purified DNA polymerase alpha subunit-free primase was used to analyze primer RNA synthesis. On a chemically synthesized 36 mer DNA template, a part of upstream region of human c-myc gene, the primer synthesis started from a doublet of deoxythymidine (TT) in the deoxypyrimidine-rich sequence. The primase in DNA polymerase alpha-primase complex synthesized 21-mer reaction product, while DNA polymerase alpha-free primase gave the similar products, 21- and 22-mer, indicating that the site recognition was carried out by primase itself and DNA polymerase alpha subunit has an auxiliary role on it. Product analysis using DNA fragments carrying base substitutions further revealed that the existence of deoxypyrimidine residues around the starting sites was important for priming frequencies. Competition analysis showed that the priming was strongly competed by poly(dC), and to a much lesser extent by poly(dA). Gel-shift analysis showed that the primase could bind to the DNA template, and this complex formation was also competed by poly(dC), but not by poly(dA). These results indicate that primase subunit interacts with the starting site by binding directly with deoxypyrimidine residues.

Animals↗