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Biomedical subjects

M Kojima

Publications and source records attributed to M Kojima.

At least 343 records · Page 19Linked to original sources

Solution structure of bromelain inhibitor IV from pineapple stem: structural similarity with Bowman-Birk trypsin/chymotrypsin inhibitor from soybean.

Bromelain inhibitor VI from pineapple stem (BI-VI) is a unique double-chain inhibitor with an 11-residue light chain and a 41-residue heavy chain by disulfide bonds and inhibits the cysteine proteinase bromelain competitively. The structure of BI-VI in aqueous solution was determined using nuclear magnetic resonance spectroscopy and simulated annealing-based calculations. Its three-dimensional structure was shown to be composed of two distinct domains, each of which is formed by a three-stranded antiparallel beta-sheet. Unexpectedly, BI-VI was found to share a similar folding and disulfide bond connectivities not with cystatin superfamily inhibitors which inhibit the same cysteine proteinases but with the Bowman-Birk trypsin/chymotrypsin inhibitor from soybean (BBI-I). BBI-I is a 71-residue inhibitor which has two independent inhibitory sites toward the serine proteinases trypsin and chymotrypsin. These structural similarities with BBI-I suggest that they have evolved from a common ancestor and differentiated in function during a course of molecular evolution.

Amino Acid Sequence↗

Newly developed ST-T abnormalities on the electrocardiogram and chronologic changes in cardiovascular risk factors.

An ST-T abnormality on an electrocardiogram (ECG) is known to independently predict subsequent morbidity and mortality from cardiovascular diseases. But how ST-T abnormality develops in relation to chronologic changes in cardiovascular risk factors has not been fully discussed. Sixty-eight men whose ECG had been initially normal but who exhibited ST-T abnormality later (ST-T subjects) were identified among 21,579 apparently healthy adults who had undergone comprehensive health examinations for > 10 years. Echocardiography proved that 26 of 29 examinees among ST-T subjects had left ventricular hypertrophy. Antihypertensive drugs were given to 26 of the ST-T subjects. Their cardiovascular risk factors were chronologically reviewed from 10 years before the onset of definite ST-T abnormality, and were compared with those of 68 men whose ECG had remained consistently normal for 10 years (controls). Mean values of systolic and diastolic blood pressure gradually increased over 10 years (from 127/78 to 144/84 mm Hg) among ST-T subjects, but showed little change (from 122/76 to 124/77 mm Hg) during the same period in controls. The time course of blood pressure over 10 years was similar in ST-T subjects, irrespective of final blood pressure level. Mean serum cholesterol and glucose increased over 10 years in both ST-T and control subjects. Uric acid decreased over 10 years (from 6.1 to 5.6 mg/dl) only in ST-T subjects. Multivariate analysis revealed that blood pressure and uric acid before onset of ST-T abnormality were chronologically changed independent of other risk factors. The time course of risk factors may be of great importance in the development of cardiovascular disorders.

Blood Pressure↗

Expression of heat shock proteins in the developing rat retina.

Expression of three heat shock proteins (HSPs), HSP70, HSP90, and immunoglobulin heavy chain binding protein (Bip) was examined in the developing rat retina using Northern blot analysis. The expression of the inducible form of HSP70 remained uniformly low throughout the perinatal period until P5 and increased rapidly at P7. On the other hand, the constitutive form of HSP70, HSP90, and Bip were expressed constitutively in the rat retina throughout the developmental stage except P3-P5, at which a transient decrease of the expression was observed. The increase of inducible HSP70 mRNA at P7 may correspond to the functional maturation of photoreception in the visual nervous system and may be one of the stress responses to photostimulation. The potential roles of each HSP during development of the rat visual system are discussed.

Animals↗

Cloning and characterization of a cDNA encoding a precursor for human uroguanylin.

Uroguanylin, a member of the guanylin peptide family, is an endogenous activator of intestinal guanylate cyclase (GC-C). A cDNA encoding a precursor for human uroguanylin was cloned from a human colon cDNA library and sequenced. The precursor was 112 amino acids long and included a signal peptide at the N-terminus and the human uroguanylin sequence at the C-terminus. RNA blot analysis and the reverse transcription-polymerase chain reaction (RT-PCR) showed that human uroguanylin mRNA is expressed in the stomach and intestine. Uroguanylin, as well as guanylin, may be a potent physiological regulator of intestinal fluid and electrolyte transport.

Amino Acid Sequence↗

HLA DRB1 and DQB1 alleles and haplotypes influencing the progression of hepatitis C.

Some HLA class II alleles and haplotypes were examined by restriction fragment length polymorphism of corresponding DNA fragments amplified by the polymerase chain reaction in 117 patients with chronic hepatitis C in Japan. The prevalence rates were compared between patients and 1216 controls and in 67 patients with liver cirrhosis, of whom 20 had hepatocellular carcinoma and 50 patients with chronic hepatitis who did not have cirrhosis or hepatocellular carcinoma. Notably, DRB1*0405 (49% [95% confidence range 38-60%] vs. 26% [16-40%]; P < 0.05, relative risk [rr] = 2.8) and DQB1*0401 (43% [33-54%] vs. 22% [13-34%]; P < 0.05, rr = 2.1) were detected more frequently in patients with cirrhosis than in those without cirrhosis. By contrast, DRB1*0901 (11% [6-19%] vs. 28% [18-40%]; P < 0.05; rr = 0.3) and DQB1*0303 (11% [6-19%] vs. 36% [25-49%]; P < 0.01; rr = 0.2) were detected less frequently in patients with cirrhosis than those without cirrhosis. Accordingly, the DRB1*0405-DQB1*0401 haplotype was more common (43% [33-54%] vs. 22% [13-34%]; P < 0.05; rr = 2.7), while the DRB1*0901-DQB1*0303 haplotype was less common (9% [4-17%] vs. 28% [18-40%]; P < 0.05; rr = 0.3) in patients with cirrhosis than in those without cirrhosis. These results suggest that there would be HLA class II alleles and haplotypes which may be associated with an accelerated or slower progression of chronic hepatitis C towards cirrhosis and eventually to hepatocellular carcinoma.

Alleles↗

Significance of free prostate-specific antigen and gamma-seminoprotein in the screening of prostate cancer.

BACKGROUND: Since free prostate-specific antigen (PSA) and gamma-seminoprotein (gamma-SM) recognize similar epitope(s) of PSA, the significance of serum-free PSA and gamma-SM in the early detection of prostate cancer was compared. METHODS: A prospective clinical trial was conducted on 701 male volunteers, age 50 years or older. Free PSA (Tandem-R free PSA, Hybritech) and gamma-SM (gamma-SM, Chugai) levels were determined, and biopsies were performed if the PSA (Tandem-R, Hybritech) level was > 4 ng/ml, or if digital rectal examination (DRE) was suspicious. RESULTS: One hundred and eighty-seven men (27%) had either a PSA level > 4 ng/ml or a suspicious DRE. Of 116 biopsies performed, cancer was detected in 13 (1.9%, 13/701). Receiver-operating characteristic analysis of free PSA to PSA ratio (free PSA ratio, %) and gamma-SM to PSA ratio (gamma-SM ratio), to differentiate normal biopsy findings from cancer, showed that the optimal values were 12% and 0.38, respectively. Positive predictive value for cancer was 24% (12 cancers/50 biopsies) for PSA alone, 42% (8/19) for the combination of PSA and DRE, 45.5% (10/22) for the combination of PSA and gamma-SM ratio, and 50% (10/20) for the combination of PSA and free PSA ratio. Regression analysis showed that gamma-SM highly correlated with free PSA, but that the analytical detection limit of gamma-SM was 1 ng/ml, significantly higher than that of free PSA. CONCLUSIONS: Free PSA determination might effectively eliminate unnecessary biopsies in subjects with PSA > 4 ng/ml, and gamma-SM might provide a complementary index to free PSA, but its validity should be further studied in other settings, such as after radical prostatectomy or during endocrine treatment.

Aged↗

Whole saliva dried on filter paper or diagnosis of HIV-1 infection by detection of antibody IgG to HIV-1 with ultrasensitive enzyme immunoassay using recombinant reverse transcriptase as antigen.

Whole saliva samples collected from HIV-1 seropositive subjects by simple spitting without using any devices were dried on filter paper strips, from which filter paper discs of 3-mm diameter were punched out. The eluates of the discs were subjected to the immune complex transfer enzyme immunoassay for antibody IgG to HIV-1 using recombinant reverse transcriptase of HIV-1 as antigen and a two-site enzyme immunoassay for whole IgG. The signals for antibody IgG to HIV-1 and the amounts of whole IgG obtained with one disc per assay tube were 126-290% of those obtained with 1 microliter of whole saliva samples, provided that filter paper strips were treated with nonspecific rabbit serum prior to drying whole saliva samples and that filter paper discs were tested within a few days after drying whole saliva samples. From these results, diagnosis of HIV-1 infection was indicated to be possible with whole saliva samples dried on filter papers, since the diagnosis was previously shown to be possible with 1 microliter of whole saliva samples. The test for HIV-1 infection with whole saliva samples dried on filter papers was suggested to be useful for various purposes.

Acquired Immunodeficiency Syndrome↗

Simple and more sensitive immune complex transfer enzyme immunoassay for antibody IgG to reverse transcriptase of HIV-1 using microplates, modified polystyrene solid phase and fluororeader.

In a previously reported ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for antibody IgG to HIV-1, polystyrene beads in test tubes were handled with tweezers, and bound beta-D-galactosidase activity was measured with a fluorometer. The use of tweezers was causative of false-positivity by carryover, and testing many samples was difficult. Recently, these drawbacks have been minimized using microplates, a fluororeader, and modified polystyrene beads with sticks for easy handling. The modified polystyrene beads were transferred from wells to wells more quickly and easily without tweezers, eliminating false-positivity due to carryover. The fluorescence intensity for bound beta-D-galactosidase activity was quickly measured with a fluororeader. As a result, it became easy to test many samples with high reliability. However, modified polystyrene beads used were handmade, and the sensitivity was lower than the previous assay with test tubes. In the present study, the condition of the immune complex transfer enzyme immunoassay for antibody IgG to reverse transcriptase of HIV-1 was optimized using microplates, a fluororeader, and polystyrene solid phase with stick, which is commercially available. Testing many samples became easy with higher sensitivity.

Adult↗

Possible use of ultrasonically-estimated bladder weight in patients with neurogenic bladder dysfunction.

In 25 patients with detrusor areflexia, ultrasonically-estimated bladder weight (UEBW) was compared with bladder capacity and compliance obtained by cystometry, and UEBW was also compared with grade of bladder deformity as evaluated by cystography. UEBW correlated significantly with compliance (P < 0.01) and degree of bladder deformity (P < 0.01). Taking a cutoff value of 40 g, UEBW revealed diagnostic accuracy as high as 96% and 80% for low-compliance (< 10 ml/cm H2O) and high-grade deformity (grade II/III), respectively. UEBW could be a new urodynamic parameter capable of evaluating functional as well as morphological changes of the bladder.

Adult↗

Combined effects of cabergoline and L-dopa on parkinsonism in MPTP-treated cynomolgus monkeys.

The behavioral effects of L-dopa or cabergoline alone were compared with those of the joint administration of the two drugs in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys with attention to the induction of hyperactivity and dyskinesia. Cabergoline alone at 0.2 mg/kg or less improved in a dose-dependent fashion the parkinsonism without inducing hyperactivity and dyskinesia following a single subcutaneous injection. L-dopa alone improved the parkinsonism, but induced hyperactivity and dyskinesia, depending on the dose applied. Doses required for 50% amelioration by L-dopa and cabergoline were 10 and 0.038 mg/kg, s.c., respectively. With low doses (50%-amelioration doses), cabergoline or L-dopa alone improved the parkinsonism without induction of hyperactivity and dyskinesia, but the duration of action was brief. Cabergoline in combination with L-dopa was highly effective in improving motor disability without induction of hyperactivity and dyskinesia. Moreover, the duration of action was more prolonged with the coadministration than with the single administration of each drug. These findings suggest that the combined therapy with low doses of L-dopa and cabergoline is beneficial for treating patients with advanced Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Inward and outward permeability of the blood-retinal barrier in experimental myopia.

BACKGROUND: To investigate the pathophysiology of the retina in myopia, vitreous fluorophotometry was used to evaluate the permeability of the blood-retinal barrier (BRB) in experimentally induced myopia in cynomolgus monkeys. METHODS: Five animals underwent unilateral eyelid suturing. The suture was removed temporarily at 3, 10, 16, 28 and 36 months, and the dioptric power and axial length were measured in both eyes. Vitreous fluorophotometry was performed before and 60 min after intravenous injection of fluorescein-Na. BRB inward permeability (P(in)) was determined by a computer simulation method. At 36 months, fluorescein-Na was injected into the vitreous cavity, and the intraocular fluorescence was measured. BRB outward permeability (P(out)) was determined by the computer simulation method. RESULTS: Significant myopia developed by 10 months after suturing and progressed thereafter. Starting at 10 months, the P(in) of sutured eyes increased significantly compared with control fellow eyes, and the increase continued throughout the observation period. At 36 months, the BRB P(out) was significantly lower (P < 0.05) in the myopic than in the emmetropic fellow eyes, suggesting decreased active transport mechanisms at the BRB in myopia. CONCLUSION: Our study demonstrated, for the first time, abnormal permeability of the BRB in myopic monkey eyes. Such abnormal permeability may play an important role in the development in human myopes of retinal and vitreous changes such as retinal detachment. Thus, simply correcting refractive errors surgically may not represent a cure for myopia. Patients who have had refractive surgery to correct myopia should also be closely followed up by vitreo-retinal specialists to manage vitreo-retinal disorders in originally myopic eyes.

Animals↗

Centroblastic and centroblastic-centrocytic lymphomas associated with prominent epithelioid granulomatous response without plasma cell differentiation: a clinicopathologic study of 12 cases.

To clarify the clinicopathologic features of B-cell lymphoma associated with prominent epithelioid granulomatous responses other than immunocytomas, 12 patients were studied. There were six men and six women. The lymphoma generally affected elderly patients (median age, 58.5 years) and was mostly nodal in origin. Seven of the 12 patients had a localized lesion (stage I or II), and five had an advanced lesion (stage III or IV). Histologically, four patients showed a follicular growth pattern and eight a diffuse growth pattern. Based on the updated Kiel classification, nine patients showed centroblastic lymphomas, and three showed centroblastic-centrocytic lymphomas. The epithelioid cells were accumulated in large, poorly demarcated masses. Trabecular fibrosis compartmentalized in the lymph nodes, producing a vague nodular pattern in low-power fields. Immunohistochemical studies of the tumor cells revealed positive membrane staining with L26 in all 12 patients and with LN-1 antibody in 9 of 10 patients. Expression of the bcl-2 protein was present in all seven patients tested. Genotypic investigation exhibited germline configuration of the immunoglobulin heavy chain gene, the T-cell receptor beta-chain gene and the bcl-2 gene in all three patients investigated. By in situ hybridization, Epstein-Barr virus genomes were detected in only a few tumor cells in three of the patients tested. This study indicated that most, if not all, of the B-cell lymphomas with prominent epithelioid granulomatous responses other than immunocytoma were of follicular center cell origin.

Adult↗

Ultrasonic estimation of bladder weight as a measure of bladder hypertrophy in men with infravesical obstruction: a preliminary report.

The aim of the present study was to evaluate the usefulness of ultrasonic estimation of bladder weight as a measure of bladder hypertrophy using transabdominal ultrasonography in men with infravesical obstruction. Ultrasonically estimated bladder weight (UEBW) was calculated from the thickness of the bladder wall measured ultrasonically and the intravesical volume at the ultrasonic measurement, assuming a spheric bladder. There was a statistically significant correlation (r = 0.970, P <0.001) between the actual bladder weight of cadaver bladders and the UEBW. The UEBW did not change with bladder filling. The UEBW in the obstructed group (group O, 49.7 +/- 19.5 g, mean +/- SD) was significantly greater than that in the normal control group (group NC, 25.6 +/- 5.7 g; P <0.001) or the nonobstructed group (group NO, 28.4 +/- 4.2 g; P <0.001). The greatest UEBW was 34.8 g in group NC and 35.2 g in group NO, whereas 94% (45 of 48) of group O had a UEBW greater than 35.0 g. In all 5 patients with benign prostatic hyperplasia (BPH), the increased UEBW decreased to a normal control level at 3 months after treatment of BPH. This new noninvasive method may be useful in investigation of bladder hypertrophy.

Adult↗

Three-dimensional imaging of ENT diseases with helical computed tomography.

We have employed helical computed tomography (CT) to evaluate ear, nose and throat diseases, and present herein seven typical cases: middle ear surgery, osteoma of the external ear canal, maxillary fracture, tripod fracture, submandibular gland calculus, epiglottic abscess and vocal fold palsy. Helical (CT) facilitates the assessment of these diseases and its high diagnostic value is described.

Adult↗

2-Deoxy-2-fluoro-D-glucose as a functional probe for NMR: the unique metabolism beyond its 6-phosphate.

Epimeric conversion of 2-deoxy-2-fluoro-D-glucose (FDG) to its 2-epimer 2-deoxy-2-fluoro-D-mannose (FDM) proved by 19F NMR has been shown to reflect the brain activity. To examine the feasibility of FDG as a new NMR probe for in vivo functional monitoring, we studied here the fundamental NMR properties of metabolites, spectral assignments, and reliability of NMR quantification. Metabolites confirmed in brain besides FDM-6-phosphate were as follows: FDG-1-phosphate, FDG-1,6-bisphosphate, FDM-1-phosphate, FDM-1,6-bisphosphate, and FDG and FDM derivatives of nucleotide diphosphate. NMR quantification of these metabolites was evaluated in comparison with the method of 18F-labeled FDG. In the NMR functional study using FDG, where a high dose is inevitable, the dose dependence of uptake was investigated. FDG uptake in mouse brain was shown to be in the range of interpretation using the biochemical parameters of enzymes for glucose uptake as long as a dose of < 200 mg/kg was used.

Animals↗

Clinicopathologic study of PRAD1/cyclin D1 overexpressing lymphoma with special reference to mantle cell lymphoma. A distinct molecular pathologic entity.

Mantle cell lymphomas (MCLs) are frequently associated with the overexpression of PRAD1/cyclin D1, activated by 11q13 translocation and its molecular counterpart BCL-1 gene rearrangement. We recently described the correlation of positive nuclear staining using monoclonal antibody against a PRAD1/cyclin D1 product with mRNA overexpression in MCLs. In the present study, we immunohistochemically investigated the PRAD1/cyclin D1 protein in a large series of 334 lymphoproliferative disorders, including 39 cases of MCLs on paraffin sections. Based on the cyclin D1 positivity, CD5 expression, and the morphologic features of the tumor tissue, four groups of MCL-related lesions were identified among the B-cell lymphomas examined: 36 cases with cyclin D1 overexpression, 35 (95%) of which exhibited CD5-positivity and MCL-morphology (Group 1); four cases of lymphomas with MCL morphology and CD5 expression but lacking cyclin D1 overexpression (Group II); four cases of lymphomas without cyclin D1 overexpression and surface CD5 but that fall within the morphologic boundaries of MCLs (Group III); and 11 cases of CD5-positive diffuse large cell lymphomas without cyclin D1 overexpression (Group IV). The Group I cases demonstrated quite homogeneous clinicopathologic features identical to those of MCLs. This group showed a poor prognosis (11% had 5-year survival), which is highly contrasted with that of Group II (100%). Although the four groups of MCL-related lesions sometimes overlapped in their histologic or phenotypic spectrums, each appeared to show distinct clinicopathologic and prognostic profiles. Our study provides a basis for further clarification of the nature of the neoplasms of Groups II, III, and IV. Moreover, this comprehensive study may indicate that the overexpression of PRAD1/cyclin D1 is biologically essential to defining MCLs.

Aged↗

Traumatic rupture of hepatic hemangioma.

Although hepatic hemangioma is common, its rupture after trauma is rare. We report a 47-year-old woman with a traumatic hepatic hemangioma rupture following a traffic accident who successfully underwent operation. Only four cases of hepatic hemangioma rupture caused by blunt trauma have been reported including this one. Each patient (two men and two women) had a giant right lobe hemangioma. The causal injury included a traffic accident in two, a fall in one, and minor trauma in another. Three patients underwent surgery, and one was conservatively managed. All the patients survived.

Female↗