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Biomedical subjects

M Nakajima

Publications and source records attributed to M Nakajima.

At least 199 records · Page 11Linked to original sources
PubMed2000

A bioassay for the activity of PSC 833 in human serum for modulation of P-glycoprotein-mediated multidrug resistance.

We established a rapid and sensitive ex vivo bioassay to detect the multidrug resistance (MDR)-inhibitory activity of SDZ PSC 833 ([3'-keto-Bmt1]-[Val2]-cyclosporin (PSC 833)) in two RPMI 8226 human myeloma sublines (parent 8226 and doxorubicin-resistant subline Dox6) in 75% human serum. In vitro sensitivity of the tumor to doxorubicin was determined by 3-h drug exposure growth inhibition assay (MTT assay). PSC 833 in serum restored the IC50 of doxorubicin in the P-glycoprotein (P-gp)-positive resistant subline to the same level as in the sensitive cells at 1 microg/ml, which has been shown to be an achievable concentration in clinical trials. In addition, the cytotoxic effect of doxorubicin was enhanced by PSC 833 in the sera of the patient in whom the blood level was 705.7 ng/ml. However, 10 microg/ml PSC 833 in serum does not cause a complete recovery in the IC90 of doxorubicin in the resistant sublines. This MDR-inhibitory activity was supported by the finding that PSC 833 in serum does not increase accumulation of rhodamine 123 in doxorubicin-resistant cells in an in vitro functional assay. The present study provides evidence that PSC 833 in human serum is effective to modulate P-gp-mediated MDR but insufficient for the reversal of MDR from the clinicopharmacological point of view.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Assessment of drug concentrations in tears in therapeutic drug monitoring: I. Determination of valproic acid in tears by gas chromatography/mass spectrometry with EC/NCI mode.

A rapid and sensitive method for the quantitation of valproic acid in tears has been developed using gas chromatography/electron capture negative chemical ionization/mass spectrometry. Valproic acid was converted directly into its pentafluorobenzyl ester derivative without the need to perform any extraction from the biologic fluid. The concentrations in tears [C]t correlated very well with those of the free form in the plasma [Cf]p and those of the total form in the plasma [Cb+f]p. The ratios between valproic acid concentrations in tears and plasma were as follows: [C]t/[Cb+f]p = 0.10 +/- 0.02; [C]t/[Cf]p = 0.57 +/- 0.11. Ratios of [C]t/[Cb+f]p were in good agreement with previously published data.

Anticonvulsants↗
PubMed2000

Characterization of monoclonal antibodies generated against Norwalk virus GII capsid protein expressed in Escherichia coli.

The Norwalk virus (NV) causes outbreaks of acute non-bacterial gastroenteritis in humans. The virus capsid is composed of a single 60 kDa protein. The capsid protein of NV36 (genogroup II, Mexico virus type) was expressed in an Escherichia coli system and ten monoclonal antibodies (MAbs) were generated against it. The reactivity of these MAbs was characterized using enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analysis towards 20 overlapping fragments of the NV36 capsid protein expressed in E. coli. All of the MAbs recognized sequential (continuous) epitopes on the three antigenic regions. Six of the 10 MAbs recognized fragment 2 (equivalent residues 31-70), three MAbs recognized fragment 13 (residues 361-403) and one MAb recognized fragment 7 (residues 181-220), suggesting that the N-terminal domain (residues 1-220) may contain more antigenic epitopes than the C-terminal domain (residues 210-548). Furthermore, two MAbs (1B4 and 1F6) reacted in WB with three purified NV strains (genogroup II) derived from patients' stool samples. It was also found that genogroup I recombinant NV96-908 (genogroup I, KY89 type) could be detected as sensitively as recombinant NV36 (genogroup II) by ELISA with a set of the MAbs produced here.

Amino Acid Sequence↗
PubMed2000

Relationships between colony morphotypes and oil tolerance in Rhodococcus rhodochrous.

A mucoidal strain of Rhodococcus rhodochrous was resistant to 10% (vol/vol) n-hexadecane, while its rough derivatives were sensitive. When the extracellular polysaccharide (EPS) produced by the mucoidal strain was added to cultures of the rough strains, the rough strains gained resistance to n-hexadecane. Thus, EPS confer tolerance to n-hexadecane in members of the genus Rhodococcus.

Alkanes↗
PubMed2000

Two distinct antigenic types of the polysaccharide chains of Helicobacter pylori lipopolysaccharides characterized by reactivity with sera from humans with natural infection.

We have purified lipopolysaccharides (LPS) from 10 Helicobacter pylori clinical isolates which were selected on the basis of chemotype and antigenic variation. Data from immunoblotting of the purified LPS with sera from humans with H. pylori infection and from absorption of the sera with LPS indicated the presence of two distinct epitopes, termed the highly antigenic and the weakly antigenic epitopes, on the polysaccharide chains. Among 68 H. pylori clinical isolates, all smooth strains possessed either epitope; the epitopes were each carried by about 50% of the smooth strains. Thus, H. pylori strains can be classified into three types on the basis of their antigenicity in humans: those with smooth LPS carrying the highly antigenic epitope, those with smooth LPS carrying the weakly antigenic epitope, and those with rough LPS. Sera from humans with H. pylori infection could be grouped into three categories: those containing immunoglobulin G (IgG) antibodies against the highly antigenic epitope, those containing IgG against the weakly antigenic epitope, and those containing both specific IgGs; these groups made up about 50%, less than 10%, and about 40%, respectively, of all infected sera tested. In other words, IgG against the highly antigenic epitope were detected in more than 90% of H. pylori-infected individuals with high titers. IgG against the weakly antigenic epitope were detected in about 50% of the sera tested; however, the antibody titers were low. The two human epitopes existed independently from the mimic structures of Lewis antigens, which are known to be an important epitope of H. pylori LPS. No significant relationship between the reactivities toward purified LPS of human sera and a panel of anti-Lewis antigen antibodies was found. Moreover, the reactivities of the anti-Lewis antigen antibodies, but not human sera, were sensitive to particular alpha-L-fucosidases. The human epitopes appeared to be located on O-polysaccharide chains containing endo-beta-galactosidase-sensitive galactose residues as the backbone. Data from chemical analyses indicated that all LPS commonly contained galactose, glucosamine, glucose, and fucose (except one rough strain) as probable polysaccharide components, together with typical components of inner core and lipid A. We were not able to distinguish between the differences of antigenicity in humans by on the basis of the chemical composition of the LPS.

Adult↗
PubMed2000

Independent prognostic value of serum hepatocyte growth factor in bladder cancer.

PURPOSE: We retrospectively investigated whether the level of serum hepatocyte growth factor could predict the prognosis and extent of transitional-cell carcinoma of the urinary bladder. PATIENTS AND METHODS: Serum samples were collected from 113 patients with bladder cancer and from 200 healthy controls. Of the 113 patients, 59 had superficial bladder cancer and 54 had muscle-invasive cancer. Thirteen bladder cancer tissues (eight superficial and five muscle-invasive) were also collected. The levels of hepatocyte growth factor in the serum and tissues of these individuals were measured by enzyme-linked immunoadsorbent assay using hepatocyte growth factor antibodies. RESULTS: The levels of hepatocyte growth factor in the serum and tissues of patients with muscle-invasive cancer were significantly higher than those of patients with superficial bladder cancer (P <.0001 and P =.0054, respectively). The degree of elevation above the normal level of serum hepatocyte growth factor of the former (61.1%) was significantly higher than that of the latter (8.4%; P <.0001). The elevation was highest in patients with visceral metastasis (93.3%). Among patients with superficial bladder cancer, the overall survival rate of those with low levels of serum hepatocyte growth factor was significantly greater than that of those with high levels (P =.005). Among patients with minimally invasive bladder cancer, the disease-free and overall survival rates of those with high levels of serum hepatocyte growth factor were significantly lower than the same rates of those with low levels (P <.001 and P =.0028, respectively). CONCLUSION: Our study suggests that the level of hepatocyte growth factor in serum could be a predictor of patient survival and extent of bladder cancer.

Aged↗
PubMed2000

Antitumor 1,3-beta-glucan from cultured fruit body of Sparassis crispa.

Sparassis crispa is an edible mushroom recently cultivable in Japan. Polysaccharide fractions were prepared from the cultured S. crispa by repeated extraction with hot water (SCHWE), cold NaOH (SCCA), and then hot NaOH (SCHA). HWE was further separated by 1 volume (SCHWE1v) or 4 volumes (SCHWE4v) of ethanol-precipitable fractions. By chemical, enzymic, and NMR analyses, the primary structures of SCHWE1v, SCCA, and SCHA were 6-branched 1,3-beta-glucan, having one branch in approximately every third mainchain unit. All of these fractions showed antitumor activity to the solid form of Sarcoma 180 in ICR mice with strong vascular dilation and hemorrhage reaction. These fractions also showed enhanced hematopoietic response to cyclophosphamide induced leukopenic mice following intraperitoneal or peroral administration.

Animals↗
PubMed2000

Evidence for the degradation of maleate moiety in chlorpheniramine maleate solution using a stability-indicating HPLC method.

The degradation phenomenon of maleate moiety of chlorpheniramine maleate in solution has been demonstrated by means of a peculiar ion-pair HPLC method developed by the authors, which permits the simultaneous determination of chlorpheniramine and maleate. A commercial cough drug containing chlorpheniramine maleate was dissolved in water with m-hydroxybenzoic acid as an internal standard, and then kept for several days at room temperature. It was recognized that the maleate content in the drug solution had gradually decreased, whereas chlorpheniramine content had not decreased. A simple solution of maleic acid was also kept for several days at room temperature, and it was also recognized that the maleate content in the solution preserved at the same concentration as the solution of the commercial cough drug had gradually decreased, and the percent of remaining maleate reached zero. The degraded peaks on HPLC chromatogram were not detected at all by UV detector, and the disappearance of maleate was ascertained by GC-MS. No detectable example of maleate of chlorpheniramine maleate in a commercial cough syrup has suggested that maleate moiety of chlorpheniramine maleate decomposed to carbon dioxide.

Chlorpheniramine↗
PubMed2000

One-pot enantioselective synthesis of optically active homoallylic alcohols from allyl halides.

A one-pot, convenient method for the preparation of optically active homoallylic alcohols from allyl halides was developed. Allyltrichlorosilanes were generated in situ from allyl halides and trichlorosilane in the presence of cuprous chloride and tertiary amine. Without isolation of the allyltrichlorosilanes, benzaldehyde and chiral biquinoline N,N'-dioxide were introduced into the same flask, producing the corresponding homoallylic alcohols with good to high enantioselectivities.

Alcohols↗
PubMed2000

[Synthesis and application of novel biaryl compounds with axial chirality as catalysts in enantioselective reactions].

A highly efficient process of aerobic oxidative coupling of 2-naphthol derivatives catalyzed by Cu(OH)Cl.TMEDA has been developed. Enantioselective oxidative coupling of 2-naphthol derivatives was achieved by the use of a chiral catalyst prepared from proline-derived diamine and cuprous chloride, affording the corresponding BINOL derivatives in good enantioselectivities of up to 78% ee. A new catalytic, enantioselective allylation of aldehydes with allyltrichlorosilanes exploiting (S)-3,3'-dimethyl-2,2'-biquinoline N,N'-dioxide as a catalyst affords homoallylic alcohols in virtually complete diastereoselectivities and high enantioselectivities of up to 92% ee, wherein the use of diisopropylethylamine as an additive has proven to be crucial for the acceleration of the catalytic cycle. It is also noteworthy that the above finding represents the first successful example of asymmetric reactions utilizing amine N-oxide as a chiral catalyst.

Catalysis↗
PubMed2000

Serum KL-6 as a possible marker for amiodarone-induced pulmonary toxicity.

Amiodarone is a useful drug for the treatment of life-threatening cardiac arrhythmias. However, amiodarone can induced pulmonary toxicity (APT) and may cause life-threatening lung damage. APT can be difficult to diagnose, but early diagnosis is important. Here, in a 51-year-old man with APT, the high serum KL-6 level was correlated with the severity of symptoms and chest X-ray findings, and it was inversely correlated with PaO2 and diffusion capacity for carbon monoxide levels. The findings suggest that the serum KL-6 level may be increased in APT and that therefore it's the determination of serum KL-6 may provide a useful indicator and/or monitoring marker of APT. KL-6 is believed to be produced and secreted by type II pneumocytes. Typical pathological findings of APT include proliferation of type II pneumocytes which may produce KL-6, and result in increased serum KL-6 levels.

Amiodarone↗
PubMed2000

Parkinsonian symptoms as an initial manifestation in a Japanese patient with acquired immunodeficiency syndrome and Toxoplasma infection.

We studied a Japanese patient who developed parkinsonian symptoms over 3 months before the diagnosis of acquired immunodeficiency syndrome. Brain MRI showed multiple lesions with mass effect and ring enhancement in the basal ganglia and subcortical white matter suggesting Toxoplasma infection. Anti-Toxoplasma therapy and highly active antiretroviral therapy for 6 months allowed improvement of parkinsonism, brain MRI findings, and immune system.

AIDS-Related Opportunistic Infections↗
PubMed2000

Trigeminal neuralgia associated with tentorial agenesis and temporal lobe herniation--case report.

A 22-year-old female presented with an extremely rare case of trigeminal neuralgia associated with tentorial agenesis. The pulsating pain in her left maxillary region persisted for an abnormally long time and had no trigger zone. The pain later spread to the periorbital region. Coronal magnetic resonance imaging revealed left medial temporal lobe herniation caused by tentorial agenesis. The herniated temporal lobe, which had distorted the superior cerebellar artery, was causing compression of the trigeminal nerve. Her condition improved following microvascular decompression surgery. Tentorial agenesis should be considered as a cause of atypical pulsating facial pain, especially in younger patients.

Adult↗
PubMed2000

Idiopathic hypertrophic cranial pachymeningitis with perifocal brain edema--case report.

A 51-year-old female presented with an extremely rare case of idiopathic hypertrophic cranial pachymeningitis manifesting as markedly thickened frontotemporal meninges with expanding perifocal edema. Magnetic resonance imaging with gadolinium revealed enhancement of the thickened dura mater protruding into the brain parenchyma accompanied by focal edema causing a mass effect. Histological examination of a biopsy specimen revealed thickened dura with infiltrating lymphocytes. Serological and immunological tests were normal. No inflammatory response or evidence of malignant tumors was observed. The patient was treated with predonisolone, resulting in marked improvement of the mass effect. High-dose steroid therapy appears to be effective for intracranial pachymeningitis associated with expanding perifocal brain edema.

Anti-Inflammatory Agents↗
PubMed2000

[Analysis of glomerular anionic charge status in renal biopsy specimens of childhood minimal change nephrotic syndrome using confocal laser scanning microscopy].

Analysis of glomerular anionic charge in human renal biopsy specimens has been restricted previously to staining of sites at the electron microscopic level, which is a product that needs skills and precludes a wide observable area. The introduction of a new tool, confocal laser scanning microscopy together with FITC conjugated poly-L-lysine as a cationic tracer, which demonstrates fixed anionic sites in thin sections from routinely formalin-fixed and paraffin-embedded renal biopsy tissue, has now enabled glomerular charge at light microscopic level. In this method, the patterns of staining in tissue showing minimal change nephrotic syndrome (MCNS) indicate that the intensity of anionic charge in 4 children with heavy proteinuria was significantly less than that in 7 children without proteinuria at remission, supporting previous observations using electron microscopy. Furthermore, staining the serial sections after methylation or saponification revealed that carboxyl components such as sialic acid may be responsible for proteinuria. We anticipate that this method may facilitate the investigation of the participation of charged components in the pathogenesis of MCNS and their role in relation to glomerular proteinuria.

Adolescent↗