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Biomedical subjects

K Yajima

Publications and source records attributed to K Yajima.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Leukemic B-cell colony formation in patients with B-cell prolymphocytic leukemia].

We performed in vitro B cell colony assay after coculture with phytohemagglutinin-P (PHA-P) and some cytokines (IL-2, IL-4, IL-6 and PHA-MTCM) in B leukemic cells from B-PLL and B-CLL patients. The number of colonies generated with PHA and PHA-MTCM was significantly smaller in patients with B-PLL than B-CLL. The surface markers of colony cells from a PLL patient were similar to those of circulating leukemic cells of the patient. IL-2, IL-4 and IL-6 did not enhance PHA-induced B cell colony formation in B-PLL. The expression of CD23 and CD25 antigens of the PLL cells was not enhanced after coculture with PHA for 72 hours in contrast to the enhancement of these antigens in B-CLL. B-PLL cells might be less responsive to PHA than B-CLL cells.

B-Lymphocytes↗
PubMed1992

Recombinant variants of tissue-type plasminogen activator containing amino acid substitutions in the finger domain.

Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7-9, 10-14, 15-19, 28-33, and 37-42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37-42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37-42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37-42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37-42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA.

Amino Acids↗
PubMed1992

Orthostatic intolerance in 6 degrees head-down tilt and lower body negative pressure loading.

6 degrees head-down tilt bed rest experiment for 6 days was conducted at Nihon University Itabashi Hospital for 10 male athletes. In order to observe the orthostatic intolerance due to six days head-down tilt bed rest, 70 degrees head up tilt tests were performed before and after the head-down tilt. Two types of orthostatic intolerance were distinguished by the time course of their cardiovascular responses. One was vagotonia type and the other was brain anemia type. The latter type was commonly seen among astronauts after space flight due to the lack of plasma volume. As this volume change is considered to be initiated by some fluid loss from the lower extremities, analysis was made to clarify the relation between the leg volume change and the types of orthostatic intolerance. Nakayama proposed a Heart Rate Controllability Index, which is calculated from the initiate leg volume change and heart rate increase in head up tilt, for an indicator of the orthostatic intolerability. The index was applied to the subjects of six days head-down tilt above mentioned. For the subjects who showed a sign of presyncopy, the index values were higher or lower than that of the rest subjects who showed no sign of presyncopy. In order to evaluate the validity of the index, another experiment was conducted to induce an orthostatic intolerance by a different way of loading. The same types of orthostatic intolerance were observed and the index value hit high in the brain anemia type of orthostatic intolerance, while the vagotonia type showed relatively lower values than the normal group.

Adolescent↗
PubMed1992

Characterization of human tissue-type plasminogen activator variants with amino acid mutations in the kringle 1 domain.

Recombinant variants of tissue-type plasminogen activator (t-PA) were constructed by site-directed mutagenesis and expressed in Chinese hamster ovary cells. Five variants were designed to improve the function of t-PA by mutagenesis in the kringle 1 (K1) domain. The amino acids were replaced with the corresponding residues present in the kringle 2 (K2) domain of native t-PA. The t-PA mutants expressed were as follows: variant E94V.D95G with point mutations in Glu94----Val and Asp95----Gly; variant N115P.S119M, Asn115----Pro and Ser119----Met; variant P125A.R129Q.R13OS, Pro125----Ala, Arg129----Gln and Arg130----Ser; variant G161R.K162R.-S165W, Gly161----Arg, Lys162----Arg and Ser165----Trp; and variant N115P, Asn115----Pro, respectively. The half-life following intravenous bolus injection in rabbits was prolonged in all variants except P125A.R130S. This was particularly true for N115P.S119M. The kinetic parameters for plasminogen activation were improved in t-PA G161R.K162R.S165W which showed a 0.6-fold decrease in Km, and a 1.8-fold increase in Vmax, thus promoting a 2.7-fold increase in kcat/Km compared to native t-PA. For a similar degree of thrombolysis in the rabbit jugular vein thrombosis model, the thrombolytic activity of G161R.K162R.S165W, at the dose tested, was four-fold greater than that of native t-PA. Thus, the substitution of the amino acids in the K1 domain with those corresponding in the K2 domain significantly enhanced the enzymatic activity of t-PA and improved the plasma survival.

Amino Acid Sequence↗
PubMed1992

In vitro proliferative and differentiated responses of lymphoma cells to PHA and IL-4 in a patient with intermediate lymphocytic lymphoma.

We carried out in vitro B cell colony assays, with phytohemagglutinin-P (PHA-P) and IL-4, on B cells from one intermediate lymphocytic lymphoma (ILL) patient and four chronic lymphocytic leukemia (CLL) patients. Peripheral blood B cells from the ILL patient responded to PHA and IL-4, they proliferated, and differentiated into cells with plasmacytoid cell morphology. They lost the CD19 surface antigen after 10 day co-culture with PHA and IL-4. The bone marrow of this ILL patient contained atypical plasma cells with multiple nuclei. Peripheral blood B cells from the four CLL patients responded to PHA, but IL-4 did not increase PHA-induced B cell colony formation in these cells. The CLL cells did not differentiate into plasma cells, and they were clearly different from the ILL cells in morphology, as shown by scanning electron microscope examination. Since this study was performed on cells from only one ILL patient, further examination of cells from many patients might be necessary to confirm the difference between ILL and B cell-type CLL.

Antigens, Surface↗
PubMed1992

[Clinical study of intracranial pressure and auditory brain stem response in the cases of diffuse axonal injury].

The course of intracranial pressure (ICP) and the finding of auditory brain stem response (ABR) was discussed in the cases diagnosed as diffuse axonal injury (DAI) established by Gennarelli. ICP was measured in twenty-six cases which were divided into three groups according to the course of ICP: Group (1), in which ICP remained below 20 mmHg (group I, 9 cases). Group (2), in which ICP rose above 20 mmHg but was controlled by therapy (group II, 8 cases). Group (3), in which ICP rose above 20 mmHg and could not be controlled by any therapies (group III, 9 cases). Glasgow outcome scale 3 months after the injury in the cases of group I and II was severe disability (SD) and/or persistent vegetative state (PVS), but all of the cases in group III died. The findings of serial ABR were divided into 3 groups. These were group A (2 cases) which showed normal record, group B (5 cases) which showed elongation of latencies between the first and fifth waves, and group C (5 cases) in which there was no response in ABR. GOS in group A or B was SD and/or PVS, but all of the cases in group C were shown to be dead in GOS. Our studies suggest that the level of ICP in DAI is rather higher than that published in previous reports, and the continuous measurements of ICP and serial records of ABR are useful for evaluating the outcome of DAI.

Adolescent↗
PubMed1991

Constitutive high-level production of human lymphotoxin by CHO-K1 cells transformed with the human lymphotoxin gene controlled by a human beta-actin promoter.

To achieve high-level production of human lymphotoxin (hLT), a plasmid (p beta LT-ldhfr) containing the hLT genomic DNA, a mouse dihydrofolate reductase (DHFR) cDNA, and a bacterial Ecogpt gene was cotransfected with a plasmid (p beta LTML) encoding only the hLT genomic DNA into Chinese hamster ovary (CHO-K1) cells at a 1:7 molar ratio. Subsequently one of the Ecogpt-positive clones (clone A31) was grown in stepwise increasing concentrations of methotrexate (MTX). A large amount of the hLT was secreted by cells resistant to increased levels of MTX as a result of coamplification of the DHFR cDNA and the hLT gene. A cell clone (clone M-1) resistant to up to 500 nM MTX constitutively expressed the hLT at a concentration of 80 micrograms per ml at an elevated level for about 2 months. The hLT was produced in glycosylated form the molecular mass of which was 23,000 daltons and the mRNA was normally spliced, so the protein molecules were probably homogeneous.

Actins↗
PubMed1991

[CDDP-ip PMUE therapy in gastric cancer cases with liver metastasis].

To reduce liver metastasis and prevent carcinomatous peritonitis, we employed CDDP-ip PMUE therapy in gastric cancer cases with liver metastasis exceeding P0H2S2. Therapy consisted of cis-diammine-dichloroplatinum-ip (CDDP-ip), mitomycin C (MMC), uracil and futraful (UFT) and etoposide. From January 1990 to March 1991, primary lesions were resected in 6 gastric cancer cases with liver metastasis exceeding H2. On the basis of therapy, subjects were classified into 2 groups and the therapeutic effects were compared between them. One group was composed of 3 patients who were placed on CDDP-ip PMUE therapy beginning the 14th day after gastrectomy. The other group was composed of 3 patients who received only UFT oral administration (300 mg/body). As a rule, the following was the CDDP-ip PMUE therapy schedule: CDDP intraperitoneal administration (75 mg/m2) and MMC intravenous injection (10 mg/body) on day 1; etoposide intravenous injection (30 mg/body) on days 2 to 6; and consecutive UFT oral administration (300 mg/body). One case showed MR in a metastatic liver lesion, but treatment proved ineffective in the other cases. Although the 2 patients in the CDDP-ip PMUE therapy group, surviving 315 and 216 days, respectively, died of primary disease and hepatic insufficiency due to an increase in metastatic liver lesions, the third patient has been in good condition for 175 days. This therapy was thought to have prolonged survival. The post-operative survival period in the group of patients receiving only UFT oral administration ranged from 36 to 243 days, with all patients dying of primary disease. The main adverse effects of this therapy (i.e., digestive symptoms, leukopenia, and thrombocytopenia) were slight and transient in all cases. Because the subjects studied were gastric cancer cases exceeding H2, the present investigation resulted in the increase of metastatic liver lesions, a problem to be studied in future.

Administration, Oral↗
PubMed1990

Development of ophthalmoplegia in amyotrophic lateral sclerosis during long-term use of respirators.

Patients with amyotrophic lateral sclerosis (ALS), who survive longer on a life-support system, exceeding the natural course of this disease, show new features of ALS. We report here a clinico-pathologic study of a 51-year-old patient with sporadic ALS who developed progressive external ophthalmoplegia 3 years after he remained on a respirator and died 5 years later, 13 years after the onset of his illness. The external ophthalmoplegia was initially accompanied by preserved doll's eye phenomenon, which later became absent. Autopsy revealed not only degeneration of the upper and lower motor neuron systems typical of ALS, but also degeneration of the Clarke's dorsal nuclei, spinocerebellar tracts, substantia nigra and inferior olives in addition to intracytoplasmic neuronal inclusion bodies in various areas. The oculomotor and abducens nuclei were variably involved, accompanied by neurogenic atrophy of the extraocular muscles. Our case report is consistent with the idea that ALS comprises a heterogeneous group of disorders, and also indicates that long-term use of respirators may make some patients with this illness prone to developing atypical clinical and neuropathologic features which are not observed during the natural course of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1990

[A case of intracranial hypoglossal neurinoma with no preoperative hypoglossal nerve palsy].

A case of intracranial hypoglossal neurinoma without hypoglossal nerve palsy is reported. A 43-year-old housewife was admitted to our hospital with vertigo and left occipital headache. Neurologically, no cranial nerve deficits were present. CT scan and cerebral angiography showed a mass in the lower left posterior fossa. MRI also revealed a well circumscribed extra-axial mass compressing brain stem and cerebellum to the right. Left suboccipital craniotomy was performed and the tumor was removed subtotally. From the operative findings, the 8th to 11th cranial nerves were not related to the tumor, however, the origin of the tumor was not confirmed. The histology showed Antoni A type neurinoma mixed partially with Antoni B type. After the operation, the tongue deviation appeared to the left, but no other cranial nerve deficit was noticed. Post-operative neuroradiological reexaminations defined slight enlargement of the hypoglossal canal. Then, we concluded that the origin of the tumor must have been the hypoglossal nerve. Most intracranial hypoglossal neurinoma grow in the hypoglossal canal followed by enlargement or erosion of the hypoglossal canal. The author thought that this case suggests that this hypoglossal neurinoma originated from a few rootlets of hypoglossal nerve and grew mainly between the medulla and the hypoglossal canal.

Adult↗
PubMed1987

Cadmium-induced osteopathy: clinical and autopsy findings of four patients.

Clinical and autopsy findings of 4 patients with chronic cadmium toxication by peroral uptake of cadmium are reported. Cadmium toxication was liable to occur in multiparous postmenopausal women, and it began with proteinuria, glycosuria, lumbago and bone pain. Then, renal function gradually decreased being accompanied with renal tubulopathy. Autopsy disclosed renal tubulopathy, which consisted of the flattening of the epithelium of proximal convoluted tubules at the peripheral portion and the mild thickening of the tubular basement membrane. There was no primary change in the glomerulus and renal interstitium. Osteomalacia was observed in the vertebrae and several other bones. The degree of osteomalacia was in good agreement with chronic renal tubular dysfunction. A decrease of the estrogen content, in addition to renal tubulopathy due to biological saturation of cadmium, seems to play an important role in the pathogenesis of cadmium-induced osteomalacia.

Acidosis, Renal Tubular↗