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Biomedical subjects

M Kawamura

Publications and source records attributed to M Kawamura.

At least 361 records · Page 20Linked to original sources

[What are IgG antibodies to single-stranded DNA measured by enzyme immunoassay--re-evaluation of their clinical significance].

Enzyme immunoassay (EIA) to detect IgG antibodies to single-stranded DNA (ssDNA EIA) and EIA to detect anti double-stranded DNA antibodies (dsDNA EIA) have been developed and widely used in Japan. However, antigenecity of ssDNA and independence of anti ssDNA antibodies, and their clinical significance are still obscure. IgG anti dsDNA and ssDNA antibodies were simultaneously measured by dsDNA EIA and ssDNA EIA in sera of two hundred and eighty five patients from systemic lupus erythematosus (SLE) including other connective tissue diseases. Both EIAs were specific for SLE, although low levels of anti ssDNA antibodies were also detected in several other connective tissue diseases. Significant correlation was observed between two EIAs. All sera were divided into three group : 1 ) both EIAs were negative, 2 ) only ssDNA EIA was positive and 3 ) both EIAs were positive and in most sera ssDNA EIA levels were higher than dsDNA EIA levels. No sera were found which reacted only with dsDNA EIA or which reacted more strongly with dsDNA EIA than with ssDNA EIA. Both EIA titers were inhibited by dsDNA or ssDNA antigens by competitive inhipition study, but inhibition rate by ssDNA was higher than that by dsDNA. Previous reports by others that ssDNA EIA could be utilized to detect early stage of active SLE were not supported in this study. All these results suggested that most of what is called anti ssDNA antibedies detected by ssDNA EIA are not antibodies to purine and pyrimidine bases, but they might be anti dsDNA antibodies with low avidity which will react phosphate-ribose backbones or internal duplex structures in the ssDNA antigen. Only use of dsDNA-EIA is, thus, recommended for clinical purpose.

Connective Tissue Diseases↗

[A case of hemichorea presenting with inattention and denial of involuntary movement].

We report a case of hemichorea presenting inattention and denial of involuntary movement. A 64-year-old right-handed man was hospitalized with acute hemichorea on the right side of the body. The patient had hemichorea which was frequently followed by purposeful movement such as fumbling with his glasses or combing his hair. He claimed that the involuntary movements were habits showing both inattention and denial of the involuntary movements. These symptoms were very unique. On MRI of the brain, T2 elongated spots were detected at the bilateral pallidum, suggesting occulusive cerebrovascular disease. On 123I-IMP-SPECT hypoperfusion was observed at the right cerebral basal ganglia extending to the right medial frontal lobe. We supposed that this inattention and denial of involuntary movements were caused by dysfunction of the system connecting the medial frontal lobe with basal ganglia which was presented as hypoperfusion on SPECT.

Acute Disease↗

Seasonal differences in diurnal blood pressure of hypertensive patients living in a stable environmental temperature.

OBJECTIVE: To determine whether there is a seasonal variation in blood pressure in hypertensive patients whose daily lifestyle is similar in summer and in winter, and who live almost entirely indoors in a stable environmental temperature. SUBJECTS AND METHODS: During summer and winter, blood pressure was measured by ambulatory blood pressure monitoring in outpatients with essential hypertension, and environmental temperature was measured by electrothermometer while the patients were awake. The 24-h blood pressure data were analysed after being divided into four groups: morning, afternoon, night-time and sleeping periods. RESULTS: We studied 25 outpatients (mean +/- SD age 57 +/- 12 years) who spend virtually the entire day indoors in both summer and winter. Measurements of systolic and diastolic blood pressure in the morning and night-time periods were significantly higher in winter than in summer (differences of 7.5 +/- 14.7 and 4.1 +/- 8.8 mmHg and 8.2 +/- 14.8 and 4.5 +/- 8.1 mmHg, respectively). Blood pressure measured in the afternoon and during sleeping periods did not differ significantly. No correlation was observed between the seasonal change in blood pressure in the morning and that at night. Environmental temperatures were significantly higher in the morning, afternoon and night-time periods during summer than those during winter. The differences among these periods were not statistically significant. CONCLUSIONS: There is a seasonal variation in blood pressure in the morning and night-time periods during winter in hypertensive patients who live essentially indoors in a relatively stable environmental temperature. Pressor factor(s) may differ between morning and night-time periods during winter.

Activity Cycles↗

Regulation of low density lipoprotein receptor activity in Chinese hamster ovary cells transfected with the c-fms gene.

Chinese hamster ovary (CHO) cells were transfected with the human c-fms gene, which encodes the receptor for macrophage colony-stimulating factor, to examine the effects on the low density lipoprotein (LDL) receptor activity. Degradation of [125I]LDL was significantly reduced in the transfected CHO cells as compared to non-transfected cells when incubated in lipoprotein-deficient serum. Quantitative analysis of LDL receptor mRNA using a competitive PCR method demonstrated that LDL receptor suppression occurred at transcription. These findings suggest that expression of the c-fms gene is involved in the regulation of LDL receptors on macrophages.

Animals↗

Expression of (Na, K) ATPase/Ca-ATPase chimeric proteins in Xenopus oocytes revealed that the COOH-terminal one-third of the (Na, K) ATPase alpha-subunit is involved in assembly with the beta-subunit.

Chimeric proteins consisting of parts from the alpha-subunit of Torpedo californica (Na, K) ATPase (N) and the rabbit sarcoplasmic reticulum Ca-ATPase (C) were expressed in Xenopus oocytes by injecting the respective chimeric cRNA in combination with cRNA for the beta-subunit of Torpedo (Na, K) ATPase. The chimeric protein (NCN) that consisted of the NH2-terminal and COOH-terminal one-thirds of the alpha-subunit of the (Na, K) ATPase and the central one-third of the Ca-ATPase was able to assemble with the beta-subunit in the same fashion as the wild-type alpha-subunit of the (Na, K) ATPase (NNN). On the other hand, chimeric proteins in which the COOH-terminal one-third was derived from the Ca-ATPase (NNC and NCC) were unable to form stable complexes with the beta-subunit. These results suggest that the COOH-terminal one-third of the (Na, K) ATPase alpha-subunit is required for the assembly with the beta-subunit.

Animals↗

Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID.

Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.

Animals↗

Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2.

Interleukin-2 is an autocrine growth factor for T cells which also activates other cells including B cells and natural killer cells. The subunits of the interleukin-2 receptor (IL-2R) lack intrinsic enzymatic activity, but protein tyrosine phosphorylation is a critical event following ligand binding and src family kinases, such as Lck, are known to be activated by IL-2 (refs 5-9). However, IL-2 signalling can occur in the absence of receptor interaction with Lck, suggesting that other protein tyrosine kinases might be important. Here we report that a new member of the Janus family of kinases (Jak-3) is coupled to the IL-2R in human peripheral blood T cells and natural killer cells.

Cell Line↗

Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes.

Protein-tyrosine kinases (PTKs) are critical enzymes for receptor-mediated signaling in lymphocytes. Because natural killer (NK) cells are large granular lymphocytes with specialized effector function, we set out to identify PTKs preferentially expressed in these cells. One such PTK was identified and molecularly cloned. The predicted amino acid sequence shows that this kinase lacks SH2 or SH3 domains typical of src family kinases but has tandem nonidentical catalytic domains, indicating that it is a member of the Janus family of PTKs. Immunoprecipitation using antiserum generated against a peptide corresponding to the deduced amino acid sequence of this gene revealed a kinase with a molecular weight of approximately 125,000. The pattern of expression of this kinase contrasted sharply with that of other Janus kinases, which are ubiquitously expressed. The kinase described in the present study was found to be more limited in its expression; expression was found in NK cells and an NK-like cell line but not in resting T cells or in other tissues. In contrast, stimulated and transformed T cells expressed the gene, suggesting a role in lymphoid activation. Because of its homology and tissue expression, we have tentatively termed this PTK gene L-JAK for leukocyte Janus kinase.

Amino Acid Sequence↗

The functional roles of disulfide bonds in the beta-subunit of (Na,K)ATPase as studied by site-directed mutagenesis.

The beta-subunit of Torpedo californica (Na,K)ATPase contains seven cysteine residues; one (Cys46) is in the single transmembrane segment and the other six (Cys127, Cys150, Cys160, Cys176, Cys215 and Cys278) are in the extracellular domain and form three highly conserved disulfide bonds. A beta-subunit mutant with replacement of Cys46 by Ser could assemble with the alpha-subunit, and the resulting alpha beta-complex was catalytically active. Mutants in which either the N-terminal side or both Cys residues of the Cys127-Cys150 bond were replaced by Ser could also tightly assemble with the alpha-subunit, but the resulting alpha beta-complex was catalytically inactive. On the other hand, disruption of either the Cys160-Cys176 or Cys215-Cys278 bond by substituting the N-terminal side only or both Cys residues with Ser led to a beta-subunit that could not assemble with the alpha-subunit. We conclude that the structure of the beta-subunit around the Cys160-Cys176 and Cys215-Cys278 loops is indispensable for assembly with the alpha-subunit, whereas the Cys127-Cys150 loop is not essential for assembly but is required for enzyme activity.

Amino Acid Sequence↗

Phenytoin, an antiepileptic drug, competitively blocked non-NMDA receptors produced by Xenopus oocytes.

The blocking effect of phenytoin (PHT) and other antiepileptic agents on the glutamate receptors was investigated under voltage-clamp conditions using Xenopus oocytes that translated ddY-stock mouse brain mRNA. PHT shifted the concentration-response curve for kainate to right without significant block on the maximum response obtained, indicating that PHT competitively blocks the non-NMDA receptors. An apparent dissociation constant of PHT was 1.9 x 10(-4) M. The block was voltage-independent. Other antiepileptic agents examined hardly blocked the kainate responses except phenobarbital that blocked the responses. The possibility that the competitive block constitutes a part of the antiepileptic action of PHT was discussed.

Animals↗

Astasia without abasia due to peripheral neuropathy.

OBJECTIVE: To describe an unusual symptom characterized by an inability to stand still despite the ability to walk in eight patients with paraparesis due to peripheral neuropathy. DESIGN: Case series during the past 18 years. SETTING: Referral center. PATIENTS: Six patients with acute or subacute polyneuropathies recovering from flaccid paralysis of the lower limbs and two patients with chronic progressive polyneuropathy for more than 10 years were studied. Weakness around the ankle joints was profound, while muscle strength around the hip joints was well recovered or preserved. MAIN OUTCOME MEASURES: Standing and walking were recorded and reviewed on videotape or motion pictures. Spectral content of postural sway was analyzed in three recent cases. RESULTS: The symptom was transient in acute or subacute cases and was continual in chronic cases. The patients were compelled to take a series of steps forward and backward while standing until they initiated locomotion. They swayed rapidly around the hip joints before stepping. The anteroposterior component of postural sway in three patients had frequency peaks around 1 Hz. CONCLUSION: We have termed this symptom astasia without abasia, or stilts phenomenon, in which maintenance of the body mass depends on a moving base of support. Both an abnormal pattern of postural movements and defective somatosensory feedback for postural stabilization may be responsible for the symptom.

Adolescent↗

Correlation of asymmetry of visual field loss with optic disc topography in normal-tension glaucoma.

OBJECTIVE: To compare the differences in optic disc configuration with different stages of visual field loss in normal-tension glaucoma. DESIGN: Interocular pairwise comparisons. SETTING: Glaucoma clinic of a teaching hospital. PATIENTS: Thirteen patients with normal-tension glaucoma and asymmetric visual field loss of at least 2.5 dB in the mean defect of the visual field indexes. INTERVENTIONS: Areas under the optic disc profiles mapped from values for radial sections of the optic disc measured at intervals of 30 degrees and expressed as percentages of the area of a rectangle were obtained from stereophotographs with a computerized image analysis system. Visual fields were tested with automated perimetry (OCTOPUS), using program G1. MAIN OUTCOME MEASURE: Correlation analyses between the interocular differences in the areas under the optic disc profile and the interocular differences in the visual field indexes. RESULTS: The correlation coefficients between the interocular differences in mean defect and those of the area under the optic disc profile in the superior to temporal sections ranged from -.71 to -.61 (.007 < P < .028). The interocular differences in loss variance correlated with the differences in the area under the optic disc profile in the superior section (r = -.61, P = .0252). CONCLUSION: The differences in visual field loss between the two eyes in normal-tension glaucoma appear mainly to reflect morphometric changes in the superior half of the optic disc.

Aged↗

Modulation of the expression of CD5 antigen on the surface of human peripheral B lymphocytes.

In this study, we investigated the expression of CD5 molecules on the surface of mature human peripheral B lymphocytes. Human CD5+ B cells were isolated from tonsils and peripheral blood. Their terminal differentiation into plasma cells was induced with IL-2. In the presence of this lymphokine, a subset of CD5+ B cells ceased to express CD5 proteins on their surface. When CD5+ B cells and non-B cells were removed from the suspension. CD5 antigens were spontaneously reexpressed on the surface of CD5- B cells. This suggests that the CD5- phenotype of a subset of B cells in these suspensions resulted from pressure(s) exerted on them by the other cellular components of the suspensions. B cells which have reexpressed membrane CD5 in the absence of CD5+ B cells and non-B cells retained their ability to reprogress to CD5- phenotype and to undergo terminal differentiation into plasma cells when stimulated with IL-2. A short exposure (4 hr) of CD5- B cells to 5 nM IL-2 resulted in the loss of their capability to spontaneously reexpress surface CD5 in the absence of other lymphoid cells. Taken together, these data suggest that the expression of CD5 antigens on B cell membrane is governed by a network-type balance between all cellular compartments within the suspension. Fluctuations of this equilibrium results in the shuttling of B cells between CD5+ and CD5+ phenotypes until they become irreversibly engaged in the terminal differentiation pathway. The interconversion CD5+<==>CD5- on B cell membrane does not argue for CD5 molecule as the marker of a distinct B cell lineage.

Antigens, CD↗

Interocular asymmetry of optic disc size and its relevance to visual field loss in normal-tension glaucoma.

We evaluated the relevance of interocular asymmetry of optic disc size to the level of intraocular pressure and the extent of optic disc and visual field changes in normal-tension glaucoma (NTG). Fifty-two eyes of 26 patients with NTG were measured for optic disc topography using a computerized image analysis system (IMAGEnet, Topcon), diurnal intraocular pressure (IOP), and Octopus automated visual field. Of the 26 patients, 22 had interocular asymmetry of the optic disc area of at least 0.01 mm2 and of mean IOP of at least 0.3 mmHg. Of these 22 patients, 8 had the higher mean IOP in the eye with the larger optic disc. In these 8 patients, the visual field defect was significantly more advanced in the eye with the larger optic disc (Wilcoxon signed ranks test, P < 0.05). These findings appear to support the hypothesis that an eye with a large optic disc may be more vulnerable to a rise in IOP.

Adult↗

The effects of calcium antagonists and prostaglandin E1 on isolated canine coronary arterial tension.

The effects of calcium antagonists (nifedipine, nicardipine, diltiazem, and verapamil) and prostaglandin E1 (PGE1) on the tension of isolated canine coronary arterial strips were studied. In a solution containing 20 mEq/L of K+, 127 mEq/L of Na+, the tension was increased by 500-1,000 mg with 4 mEq/L of Ca2+. This increase in tension was suppressed by Ca-antagonists and PGE1 dose-dependently. Nifedipine 10(-5) M, nicardipine 3 x 10(-7) M, diltiazem 3 x 10(-6) M, and verapamil 3 x 10(-6) M completely suppressed the increased tension. The maximal suppression of the tension produced by PGE1 was about 40% at 10(-10) M. In 20 mEq/L K+ solution (0 mEq/L Ca2+, 37 degrees C), the reduction of the Na+ concentrations from 127 mEq/L to 12 mEq/L increased the tension by 50 to 100 mg. This increase in tension was not suppressed by Ca-antagonists or PGE1. In conclusion, this study demonstrated that Ca-antagonists and PGE1 suppressed an increase in the tension caused by Ca2+ but did not suppress an increase in the tension caused by Na+ reduction.

Alprostadil↗

Effects of fluoride intake on the mineral content, acid solubility and resorption caused by experimental periodontitis of rat alveolar bone.

Adult rats were given either distilled water or drinking water containing 100 parts/10(6) of fluoride. The alveolar bone of rats given fluoride for 90 days showed an increased mineral content and decreased acid solubility compared to the bone of rats given distilled water. Experimental periodontitis was initiated in both groups after 110 days of treatment to cause alveolar bone resorption. Fourteen days later, the rats were killed and it was found that the alveolar bone resorption caused by experimental periodontitis was significantly smaller in the rats given fluoride in their drinking water than in those given distilled water. The findings suggest that fluoride intake might have a protective effect on rapidly progressing alveolar bone resorption.

Alveolar Bone Loss↗

Inhibition of low density lipoprotein oxidation in vitro by the 6- and 7-hydroxy-metabolites of doxazosin, an alpha 1-adrenergic antihypertensive agent.

Antioxidants may be of use in the prevention of coronary artery disease by inhibiting low density lipoprotein (LDL) oxidation, a process that is believed to play an important role in atherogenesis. Because the structures of the 6- and 7-hydroxy-metabolites of doxazosin, an alpha 1-adrenergic-blocking antihypertensive agent, suggest that they might have antioxidant properties, studies were performed to determine whether these metabolites inhibit LDL oxidation. Micromolar concentrations of 6- and 7-hydroxydoxazosin, but not doxazosin itself, inhibited Cu(2+)-mediated oxidative modification of LDL in a dose-dependent fashion, similar to that observed with the lipophilic antioxidant, probucol. LDL modified in the presence of these metabolites was not taken up and degraded by macrophages to the same extent as LDL oxidized in their absence. In contrast to probucol, the antioxidant effect was lost after reisolation of LDL incubated with the metabolites. Whereas probucol, like vitamin E, sequesters with LDL, 3H-labeled 6- and 7-hydroxydoxazosin did not comigrate with lipoproteins on FPLC, but were associated with albumin and occurred free in solution. Thus, these metabolites of doxazosin may exert their antioxidant effect in the aqueous milieu of the lipoprotein, similar to vitamin C, and may be useful for the prevention of atherosclerosis in hypertensive individuals.

Adrenergic alpha-1 Receptor Antagonists↗