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Biomedical subjects

Y Kojima

Publications and source records attributed to Y Kojima.

At least 217 records · Page 12Linked to original sources
PubMed1996

Structure-activity relationships of dermorphin analogues containing chiral piperazin-2-one and piperazine derivatives.

The amide and ester carbonyl groups of four piperazin-2-one derivatives (N,N'-ethylene-bridged dipeptide ethyl esters) constructed from (R)- or (S)-phenylalanine and glycine were reduced with borane-tetrahydrofuran complex to produce the corresponding piperazine derivatives in 70-80% yields. These piperazin-2-one or piperazine derivatives were used as the carboxyl-terminal residues of eight dermorphin analogues (H-tyrosyl-D-alanyl-piperazine derivatives were used as the carboxyl-terminal residues of eight dermorphin analogues (H-tyrosyl-D-alanyl-piperazin-2-one or piperazine derivatives) whose opiate activities were examined in vitro by use of the guinea pig ileum and the mouse vas deferens assays. It was found in the guinea pig ileum assay that the configuration of pheylalanine and the replacement of the piperazin-2-one ring with a piperazine ring are important for enhancing or reducing the opiate activities of these analogues.

Analgesics, Opioid↗
PubMed1996

[Particle numbers in classified sizes of roadside dust caused by studded tires in the air at different heights from the pavement surface].

Increased use of motor vehicles has produced various risks to human health due to air pollution by noxious gases, heavy metals and roadside dust. Since the late 1970s, the wide spread use of studded tires for cars has caused pavement wear, resulting in not only economic losses, but also roadside air pollution in cold and snowy regions in Japan. The most serious environmental problem in Sapporo, a city with heavy snowfall, in the 1980s, was roadside dust derived from studded tires. The inhabitants suffered from this dust in the early winter and in the early spring when the streets were not covered with snow. To investigate the influence of such roadside dust upon human health, particle numbers in classified sizes of roadside dust were counted after the roadside dust in the air was collected with a device we constructed at 30, 60, 90, 120, 150, and 180 cm above the pavement surface. The results indicated that the concentration of roadside dust in the air did not greatly vary according to the height from the pavement surface. The results also suggested that xenogranuloma, reported in lungs of stray dogs, under roadside dust-pollution conditions such as those examined here, may occur in humans in the future.

Air Pollutants↗
PubMed1996

[A case of pulmonary dirofilariasis].

A 41-year-old man was admitted to the hospital for detailed evaluation of chronic hepatitis C. A nodular shadow (15 x 15 mm) was detected in the left middle lung field on a chest X-ray film. Roentgenologic, cytologic, and bronchial endoscopic examinations resulted in no definitive diagnosis. To rule out a malignant tumor the left lung was partially resected (S6). Histological examination of the resected specimen revealed Dirofilaria worms in a necrotic mass. In most cases of pulmonary dirofilariasis, thoracotomy is done to confirm the diagnosis. Recently, however, antibodies against Dirofilaria have been detected by immunologic methods and have been used to help make the diagnosis in some cases. A less invasive procedure, such as a reliable immunologic test or a technique for thoracoscopic resection, would be very useful in cases of this benign condition.

Adult↗
PubMed1996

Relative gold-binding capacity of metallothionein: studies in renal cytosols of gold-injected rats.

To determine the gold-binding capacity of metallothionein (MT) in cytosols of gold-injected rats, we examined the relationship between gold contents in cytosols and in MT fraction in rat kidneys. Each rat was injected intraperitoneally once with 0.9% NaCl or gold (5, 10 or 20 mg gold/kg b.w.). The gold contents in kidneys and in MT fraction increased following the injected amount of gold. The distribution profiles of the renal cytosols of gold-injected rats on a Sephadex G-75 column showed that the amount of the increased gold was attributable to the high molecular weight proteins (HP) and the MT fractions. There were close relationships between the gold contents in cytosol and in MT fractions, and between the gold contents in cytosol and in HP fractions. These results demonstrate that 14% of the increased gold in the renal cytosols of gold-injected rats was bound to MT and that 79% of the increased gold was bound to HP. Our results suggest that the role of metallothionein in gold accumulation in kidneys is different from that in zinc accumulation in kidneys.

Animals↗
PubMed1996

Copper replacement of cadmium-binding alpha-fragment of metallothionein expressed in Escherichia coli.

Titration studies of Cd-binding alpha-fragment, the carboxyl-terminal half of human metallothionein-2, which was independently expressed in Escherichia coli as a Cd-binding form, with Cu were performed. The Cu saturated alpha-fragment was not obtained when the alpha-fragment incubated with Cu (I), although completely saturated MT with Cu (I) was successfully obtained in the same conditions. The stoichiometry of the alpha-fragment replaced with Cu (I) was Cu 4 and Cd 1. It is considered that the Cu-binding alpha-fragment required the presence of Cd (II) to form a stable structure. Our results could suggest that each fragment was independent in the metal binding processes, e.g. alpha-fragment for Cd-binding.

Binding Sites↗
PubMed1996

Low molecular weight copper-binding protein in the liver of rats given a single and repeated injections of copper.

Whether Cu-metallothionein is the sole low molecular weight Cu-binding protein induced in Cu-loaded rat tissues or not is hotly debated, because several investigators reported that Cu-metallothionein did not exist and other Cu-binding proteins were induced in the Cu-loaded rat liver. Investigation by using rats given a single and repeated injections of Cu led us to settle the problem. Cu-metallothionein was identified in the liver of both groups of rats by the purification procedure established in this study. Moreover in the final purification step of Cu-metallothionein, an additional unknown protein which did not belong to the metallothionein group was found only in the rats given repeated Cu injections, and not in the rats given a single Cu injection. The confusion on Cu-metallothionein and other Cu-binding proteins was shown to be caused by inadequate purification of Cu-metallothionein.

Amino Acid Sequence↗
PubMed1996

Epidermoid cyst of the scrotum: a case report.

A 44-year-old male was admitted with the chief complaint of a huge mass in the right scrotum. Computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography demonstrated a homogeneous lesion in the right testis. Under the diagnosis of right testicular tumor, surgical resection was performed and the right testis itself was found to be essentially normal. The mass contained 500 ml of liquid. The pathologic diagnosis was an epidermoid cyst of the scrotum, a rare disease with only 11 cases reported in Japan.

Adult↗
PubMed1996

Effect of photic conditioning on blink reflex recovery function in blepharospasm.

Patients with blepharospasm may have selective sensitivity to photic stimuli, for their symptoms are often aggravated after exposure to brightness. To investigate the pathophysiology underlying this phenomenon, we compared the effects of electric and photic conditioning on electrically-evoked blink reflex in 21 patients with blepharospasm and 11 age-matched control subjects. With electric conditioning, R1 was facilitated at inter-stimulus intervals (ISIs) of up to 100 ms in both groups. R2 was inhibited at all ISIs longer than 20 ms in the normals, but to a much lesser extent in the patients, suggesting increased excitability of the multi-synaptic reflex pathway. Compared to electric conditioning, photic conditioning was less potent in inhibiting R2 in the normals. In contrast, photic conditioning in the patients produced R2 inhibition as powerful as electric conditioning. These findings indicate that, in patients with blepharospasm, photic input has a relatively more profound inhibitory effect on the test blink reflex than electric conditioning as compared with normal subjects. The greater susceptibility of the brainstem interneurons to photic conditioning in blepharospasm may be related to the clinically-observed light sensitivity.

Adult↗
PubMed1996

[An investigation of the factors influencing serum pepsinogen levels--sex, age, smoking, drinking].

BACKGROUND: Until now, the influence of sex, age, smoking, drinking on serum pepsinogen levels has been assessed by single regression analysis. However, the influence of those factors on pepsinogen levels should be assessed exactly by multiple regression analyses. SUBJECTS AND METHODS: 891 subjects were collected from by questionnaire and serum tests. Analyses were done with serum pepsinogen I (PG I), pepsinogen II (PG II) and pepsinogen I/II ratio (PG I/II) as a criterion variable and as categorized explanatory variables, sex, age, current or past smoking habit, and current drinking habit. And analyses are done by Mann-Whitney U test, correlation coefficient, single regression method, multiple regression method. RESULTS: PG I level is significantly higher in men than in women by Mann-Whitney U test. But the effect of sex factor is not remarkable by multiple regression analyses. PG II level increased and PG I/II level decreased with progression of age by all analyses methods. Current or past smoking elevates PG I level by Mann-Whitney U test, but current smoking dose and past smoking amount showed no dose-dependent associations with PG I level. Current drinking elevates PG I level by Mann-Whitney U test, but current drinking dose showed no dose-dependent associations with PG I. However, the effects of current smoking and current drinking to serum PG levels is not so large by multiple regression analyses. CONCLUSION: The effects of sex, current smoking and current drinking to serum PG levels are not remarkable by multiple regression analyses. Significantly, PG II level increased and PG I/II level decreased with progression of age. Therefore it may not be necessary to consider the effects of sex, smoking habit and drinking habit when serum pepsinogen levels are used as markers for gastric cancer.

Adult↗
PubMed1995

Oxidative and nonoxidative mechanisms of site-specific DNA cleavage induced by copper-containing metallothioneins.

DNA cleavage induced by metallothionein (MT) containing copper was investigated by a DNA sequencing technique. Reconstituted Cd7-MT showed no ability to cause DNA cleavage. Commercially available rabbit MT I caused DNA cleavage, suggesting that DNA cleavage is due to the metal contained in commercial Mt. Cu2Cd5-MT and Cu12-MT were prepared by the treatment of commercial rabbit MT I with [Cu(CH3CN)4]CIO4. Cu12-MT frequently induced an alteration of thymine residues, especially in the 5'-GTC-3' sequence, and piperidine treatment led to chain cleavage at the thymine residues. The site specificity was similar to that obtained with Cu(I) plus H2O2. H2O2 enhanced DNA cleavage induced by Cu12-MT. Catalase and a Cu(I)-specific chelating agent, bathocuproine, inhibited DNA cleavage. These results suggest that Cu(I) and H2O2 have important roles in the production of active species causing DNA cleavage. Commercial MT and Cu2Cd5-MT induced DNA cleavage much less than Cu12-MT, but gave particularly specific DNA cleavage. Cu2Cd5-MT induced cleavage specifically at the central guanine residue of the 5'-GGT-3' sequence. A similar cleavage pattern was obtained with commercial MT. No effect of piperidine treatment suggests that the DNA cleavage might not be due to base damage and/or liberation. The DNA cleavage was inhibited efficiently by EDTA, but not by bathocuproine and catalase. Experiments with DNA ligands, albumin, and denatured DNA suggest that commercial MT and Cu2Cd5-MT induce nonoxidative cleavage of the deoxyribose phosphate backbone through its DNA recognition. These two types of cleavage mechanisms are discussed in relation to the possible role of Cu-MT in carcinogenesis.

Albumins↗
PubMed1995

Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V.

Gln506-factor V (FV) was purified from plasma of an individual homozygous for an Arg506Gln mutation in FV that is associated with activated protein C (APC) resistance. Purified Gln506-FV, as well as Gln506-FVa generated by either thrombin or FXa, conveyed APC resistance to FV-deficient plasma in coagulation assays. Clotting assay studies also suggested that APC resistance does not involve any abnormality in FV-APC-cofactor activity. In purified reaction mixtures, Gln506-FVa in comparison to normal FVa showed reduced susceptibility to APC, because it was inactivated approximately 10-fold slower than normal Arg506-FVa. It was previously reported that inactivation of normal FVa by APC involves an initial cleavage at Arg506 followed by phospholipid-dependent cleavage at Arg306. Immunoblot and amino acid sequence analyses showed that the 102-kD heavy chain of Gln506-FVa was cleaved at Arg306 during inactivation by APC in a phospholipid-dependent reaction. This reduced but measurable susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance is a mild risk factor for thrombosis because APC can inactivate both normal FVa and variant Gln506-FVa. In summary, this study shows that purified Gln506-FV can account for APC resistance of plasma because Gln506-FVa, whether generated by thrombin or FXa, is relatively resistant to APC.

Adult↗
PubMed1995

Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study.

To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, we performed a prospective study of Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with multiple insulin injection treatment. A total of 110 patients with NIDDM was randomly assigned to multiple insulin injection treatment group (MIT group) or to conventional insulin injection treatment group (CIT group). Fifty-five NIDDM patients who showed no retinopathy and urinary albumin excretions < 30 mg/24 h at the baseline were evaluated in the primary-prevention cohort, and the other 55 NIDDM patients who showed simple retinopathy and urinary albumin excretions < 300 mg/24 h were evaluated in the secondary-intervention cohort. The appearance and the progression of retinopathy, nephropathy and neuropathy were evaluated every 6 months over a 6-year period. The worsening of complications in this study was defined as an increase of 2 or more steps in the 19 stages of the modified ETDRS interim scale for retinopathy and an increase of one or more steps in 3 stages (normoalbuminuria, microalbuminuria and albuminuria) for nephropathy. The cumulative percentages of the development and the progression in retinopathy after 6 years were 7.7% for the MIT group and 32.0% for the CIT group in the primary-prevention cohort (P = 0.039), and 19.2% for MIT group and 44.0% for CIT group in the secondary-intervention cohort (P = 0.049). The cumulative percentages of the development and the progression in nephropathy after 6 years were 7.7% for the MIT group and 28.0% for the CIT group in the primary-prevention cohort (P = 0.032), and 11.5% and 32.0%, respectively, for the MIT and CIT groups in the secondary-intervention cohort (P = 0.044). In neurological tests after 6 years, MIT group showed significant improvement in the nerve conduction velocities, while the CIT group showed significant deterioration in the median nerve conduction velocities and vibration threshold. Although both postural hypotension and the coefficient of variation of R-R interval tended to improve in the MIT group, they deteriorated in the CIT group. In conclusion, intensive glycemic control by multiple insulin injection therapy can delay the onset and the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese patients with NIDDM. From this study, the glycemic threshold to prevent the onset and the progression of diabetic microangiopathy is indicated as follows; HbA1c < 6.5%, FBG < 110 mg/dl, and 2-h post-prandial blood glucose concentration < 180 mg/dl.

Albuminuria↗
PubMed1995

Expression of human metallothionein-2 in Escherichia coli: cadmium tolerance of transformed cells.

A genetic approach was undertaken to investigate the physiological roles of human metallothionein-2. A constructed expression plasmid, pEXPMTII, in which human metallothionein-IIA cDNA was inserted downstream of a tryptophan-lactose promoter, was used to transform Escherichia coli JM105 strain. Cadmium-binding metallothionein was successfully expressed in E. coli in the medium containing cadmium, while copper and zinc-metallothioneins were scarcely observed in copper- or zinc-containing medium. The amino acid composition and sequence of the biosynthesized cadmium-metallothionein were analyzed. The selectivity of metals bound to metallothionein and the stability of metal-binding forms of metallothionein in E. coli were discussed. In addition, cadmium, zinc, or copper resistance of the cells expressing metallothionein was examined. Cells transformed with the plasmid pEXPMTII and cultured in a medium containing cadmium exhibited tolerance only to cadmium. It was demonstrated that human metallothionein-2 functioned for cadmium detoxification in E. coli.

Base Sequence↗
PubMed1995

[A case of myelodysplastic syndrome who died of septic pulmonary embolism].

A case of myelodysplastic syndrome (MDS) complicated by septic pulmonary embolism is reported. A 61-year-old female who had been followed for refractory anemia with excess of blasts suddenly died of acute respiratory failure. An autopsy revealed massive pulmonary emboli with gram-positive cocci gathered in the emboli and alveolar spaces. Staphylococcus aureus was also detected through a blood culture from the right atrium. We speculate that pulmonary embolism was the result of septicemia induced by the immunosuppressive condition associated with MDS.

Fatal Outcome↗