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Biomedical subjects

K Komatsu

Publications and source records attributed to K Komatsu.

At least 217 records · Page 12Linked to original sources

Production of R-(-)-Ketoprofen from an Amide Compound by Comamonas acidovorans KPO-2771-4.

R-(-)-2-(3(prm1)-Benzoylphenyl)propionic acid [R-(-)-ketoprofen] was produced from racemic 2-(3(prm1)-benzoylphenyl)propionamide (keto-amide) by the isolated bacterial strain Comamonas acidovorans KPO-2771-4. Sodium fumarate as the carbon source and 2-azacyclononanone or isobutyronitrile as the enhancer in the culture medium were effective for bacterial growth and the enhancement of R-(-)-ketoprofen-producing activity. R-(-)-Ketoprofen produced from the keto-amide by resting cells was present in 99% enantiomeric exess. C. acidovorans KPO-2771-4 has an R-enantioselective amidase for keto-amide because the purified amidase from the bacterium hydrolyzed keto-amide, producing optically pure R-ketoprofen and ammonia.

Journal Article↗

Melanotic neuroectodermal tumor of infancy in the epididymis. Case report and literature review.

We report a case of melanotic neuroectodermal tumor that originated in the right epididymis of a 4-month-old Japanese male and review reports of similar cases. Since we could not exclude malignant disease preoperatively, we performed a radical orchiectomy. Histopathological and immunohistochemical studies revealed features characteristic of a melanotic neuroectodermal tumor. Imaging studies showed no distant metastases.

Epididymis↗

Hydrochlorothiazide Increases Efferent Glomerular Arteriolar Resistance in Spontaneously Hypertensive Rats.

BACKGROUND: Micropuncture studies were performed to determine the intrarenal hemodynamic effects of two conventional antihypertensive agents, hydrochlorothiazide (HCTZ) and hydralazine (HYDR) alone and in combination. METHODS AND RESULTS: Male spontaneously hypertensive and normotensive Wistar Kyoto rats (19 weeks old) were treated for 3 weeks with vehicle (control), HCTZ (80 mg/kg/d), HYDR (5 mg/kg/d), or combined therapy (HCTZ 30 mg/kg/d and HYDR 2 mg/kg/d). Each treatment significantly reduced arterial pressure while effective renal plasma flow, glomerular filtration rate and single nephron glomerular filtration rate were unaffected by any treatment in either strain. In spontaneously hypertensive rats HCTZ decreased single nephron plasma flow (111 +/- 8 to 84 +/- 4 nL/min; P <.05) but, despite this reduction, glomerular pressure remained unchanged (51.4 +/- 0.7 to 52.1 +/- 0.8 mmHg) attributable to increased efferent glomerular resistance (1.58 +/- 0.14 to 2.11 +/- 0.12 10 U; P <.05). By contrast, HYDR increased single nephron plasma flow (to 147 +/- 8 nL/min; P <.01) and decreased efferent glomerular resistance (to 1.09 +/- 0.09 U; P <.05). Combined treatment produced responses similar to HCTZ when used alone, thereby nullifying the beneficial efferent glomerular resistance effects: single nephron plasma flow +/- fell (to 89 +/- 7 nL/min; P <.05) and efferent glomerular resistance increased (to 2.05 +/- 0.17 U; P <.05). In Wistar Kyoto rats, HCTZ and combined treatment had no effect. HCTZ alone induced glomerular ischemia that was associated with efferent glomerular arteriolar constriction in these spontaneously hypertensive rats. CONCLUSIONS: These findings provide a possible explanation for the lack of improved renal target-organ damage in controlled multicenter trials employing thiazide diuretics.

Journal Article↗

Pharmacological properties of traditional medicines. XXII. Pharmacokinetic study of mulberroside A and its metabolites in rat.

To identify the active components in Mori Cortex (Chinese medicine), Mori Cortex extracts were administered orally to rats, and then blood plasma, urine, and bile were analyzed. The results showed only a few remaining metabolites of mulberroside A. Consequently, to clarify the transitional properties of mulberroside A derivatives to tissues and the in vivo abundance ratio of mulberroside A compounds, the pharmacokinetics of mulberroside A derivatives were investigated in this study. When Mori Cortex extracts were administered orally, mulberroside A was only detected in small quantities in the plasma, and its bioavailability was about 1%. This is due to the first pass effect, by which most mulberroside A was converted into oxyresveratrol and transported into the circulating blood, and its absorption ratio was estimated at about 50%. Oxyresveratrol was found to be transported to tissues at high rates. As a result, when analyzing the pharmacological activity of the Mori Cortex in vitro, it is more useful to study oxyresveratrol than mulberroside A.

Animals↗

18S ribosomal RNA gene sequences of three Panax species and the corresponding ginseng drugs.

Total DNA was extracted from the fresh underground parts of three Panax separate species. The 18S rRNA regions of extracted DNA were amplified by the polymerase chain reaction (PCR) and their sequences were determined. In each species, the sequences were found to be of 1809 base pairs (bps) but with different gene sequences. Different base substitutions were observed at nucleotide positions 497, 499, 501 and 712. The same procedure was performed on commercial samples of Ginseng Radix, Panacis Japonici Rhizoma and American Ginseng. Each sequence completely corresponded with that of each original plant, namely P. ginseng, P. japonicus and P. quinquefolius, respectively. This is the first time that 18S rRNA gene sequencing on Panax species was carried out. Previously, Ginseng drugs have been identified mainly by their external and internal structure. Thus this method will be useful in identifying Ginseng drugs at the gene level.

Base Sequence↗

[Pharmacognostical studies on adiantum plants. V. Classification based on spore morphology and distributional patterns of silicon and calcium in the ultimate pinnules].

Crude drugs derived from Adiantum species are used as febrifuge, antidote, diuretic, tonic, etc. Some commercial samples of these drugs are composed of finely cut ultimate pinnules only, which have false indusia and spores. In this paper, in order to establish a classification method based on the characteristics of the ultimate pinnules and their attachments, the morphological study using stereoscope and scanning electron microscope, and X-ray microanalysis using an electron probe microanalyzer were carried out on the false indusia and spores, and the ultimate pinnules, respectively, of 19 Adiantum species. The results showed that examined all species could be distinguished from each other by the following characteristics: in the false indusium, the shape and the presence or absence of hairs; in the spore, the shape, the ornamentation, the ratio of the laesura, and the equatorial diameter; in the X-ray images of the ultimate pinnule, the distributional patterns of silicon and calcium. The distributional patterns of silicon were due to the presence of spicular cells, hairs and papillae, and calcium was present as crystals of calcium oxalate. The average content of silicon in the ultimate pinnules of Adiantum species was 1.99%.

Calcium↗

The scid mutation does not affect slowly repairing potentially lethal damage that is sensitive to 0.23 M NaCl.

The repair of slowly repairing potentially lethal damage (PLD) in radiosensitive cells from the severe combined immunodeficient (scid) mouse was compared with that in Balb/c 3T3 cells with "wild-type" radiosensitivity and that in RD13B2 cells derived from scid cells whose sensitivity is normal because of the presence of fragments of human chromosome 8. Treatment with 0.23 M NaCl was used for fixation of slowly repairing PLD. The scid cells repaired PLD sensitive to 0.23 M NaCl to a great extent whin 3-4 h, similarly to Balb/c 3T3 and RD13B2 cells. This indicates that the scid mutation hardly affects the repair of PLD sensitive to 0.23 M NaCl. On the other hand, as reported previously, the rapidly repairing PLD that is sensitive to 0.5 M NaCl was repaired only slowly (3-4 h) in scid cells, in contrast to the rapid repair (within 1 h) seen with Balb/c 3T3 and RD13B2. This suggests that scid mutation is responsible for this repair at reduced rate. To confirm the independence of repair of 0.23 M NaCl-sensitive PLD from that of 0.5 M NaCl-sensitive PLD, both treatments with 0.23 M NaCl and 0.5 M NaCl were combined in each line. It is found that the repair of either PLD was not affected by the other treatment. The scid mutation impaired only the repair of 0.5 M NaCl-sensitive PLD.

3T3 Cells↗

Accumulation of cells at G2/M stage by low dose-rate irradiation renders the cell population more susceptible to the subsequent induction of 6-thioguanine-resistant mutations by 252Cf fission neutrons.

A previous study on mutagenesis by 252Cf radiation in mouse L5178Y cells showed that the frequency was higher when the dose was delivered chronically, which was in sharp contrast to the results by gamma-rays (Nakamura and Sawada, 1988). A subsequent study using synchronized cells revealed that the cells at G2/M stage were uniquely sensitive to mutation induction by 252Cf radiation but not so by gamma-rays (Tauchi et al, 1993). We carried out the present study to test the possibility that radiation-induced G2 block may be a major determinant of the inverse dose-rate effect following chronic 252Cf radiation. Growing cell population was first subjected to conditioning gamma or 252Cf radiation with different dose-rates, followed by cell cycle distribution analysis and 252Cf mutagenesis. We found that G2/M fraction increased by 3- to 4-fold when the conditioning doses (2 Gy of gamma or 1 Gy of 252Cf radiation) were delivered chronically over 10 hours but only slightly so when the same doses were delivered for 1 hour or less. Subsequent 252Cf irradiation gave higher mutation frequencies in the cells pre-irradiated with gamma-rays over a protracted period of time than in those with higher dose-rate gamma-rays. These results suggest that radiation-induced G2 block would be at least partly (but can not be totally) responsible for the inverse dose-rate effect.

Animals↗

Clinical manifestations of HBsAg and anti-HCV negative chronic liver disease in Nagasaki Prefecture, Japan.

The discovery of hepatitis C virus (HCV) has enabled the diagnosis of type C chronic liver disease, which had in the past been diagnosed as part of non-A, non-B chronic liver disease. Although most cases with chronic liver disease are caused by hepatitis B virus (HBV) or HCV infection, there are still cases of non-B, non-C chronic liver disease. Forty patients with chronic liver disease, who were seronegative for hepatitis B surface antigen and antibody to HCV, were followed for a mean period of 72 months. The clinical manifestations in these patients were compared with those reported for type B and type C chronic liver disease. Of the 40 patients, 22 were diagnosed with chronic hepatitis, 14 with liver cirrhosis and 4 with hepatocellular carcinoma (HCC). Twenty-seven (67.5%) patients showed mild alanine aminotransferase activity profiles, and the natural clinical course of most patients showed a slow progression compared with that reported for type B and type C patients. The yearly incidence of HCC was 9.7% in patients with liver cirrhosis and 3.9% in chronic hepatitis. These rates were similar to those in type B or type C patients. This suggests that our population sample contained a number of patients with type B, type C or other etiologic agent(s), because 66.7% of the patients who developed HCC had some evidence of exposure to HBV or HCV. Our results suggest that more detailed and accurate tests for detecting HBV and HCV should be considered before making the diagnosis of non-B, non-C chronic liver disease, and that there is the need to reveal unknown etiologic agent(s).

Adolescent↗

Keio multicenter trial in high-dose interferon-alpha 2b treatment for chronic hepatitis C. Keio Interferon-alpha 2b Study Group.

The efficacy of two different high-dose treatment of IFN-alpha 2b was evaluated in this study. Serum hepatitis C virus (HCV) RNA levels were semi-quantified by simplified reverse transcription-polymerase chain reaction. Seventy-one patients with chronic hepatitis C received 10 million units of IFN-alpha 2b daily for 2 weeks or twice a week for 24 weeks. Alanine aminotransferase (ALT) levels overall normalized in 78.1% and 51.6% of the cases at the end of the therapy and 6 months after that, respectively. HCV RNA disappeared in 71.9% and 35.7% of the patients at the end of the therapy and 6 months after that, respectively. There was no significant difference between the 2 different regimes. The efficacy of the treatment was fair in cases in which the pretreatment level of the viral amount was low. The results of this study indicate that daily administration of IFN in the first 2 weeks during 6-month course does not increase the efficacy of the therapy in such a high-dose treatment regime.

Adult↗

[Early and late results of surgical intervention for 32 active infective endocarditis patients in last 10 years].

Thirty-two active infectious endocarditis patients who underwent 36 surgical procedures (23 NVEs, 13 PVEs) in last 10 years were reviewed. Seven patients (19.4%) died early postoperatively, 3/23 (13%) in NVEs and 4/13 (31%) in PVEs, and the causes of death were LOS in 5, MOF in one and cerebral bleeding in one. NVE patients of double valve deterioration who developed cardiogenic shock had poor operative results, 3 death in 4 (75%) despite of circulatory assist. Aortic PVEs who underwent Danielson's translocation technique also showed 3 death in 4 (75%). Five in 25 survivors (20%) developed late death and 3 of them were related with reinfection of prosthetic valve. We concluded that surgical treatment for active IE provides reasonable results, although they are still challenging for double valve NVEs and aortic PVEs, for which aortic root replacement using homograft would be the procedure of choice.

Adolescent↗

[Maze operation for chronic atrial fibrillation with valvular heart diseases].

Between July 1994 and August 1995, 14 patients underwent combined modified maze procedure and valvular surgery including 5 patients having reoperation. Associated procedures were performed with mitral valve operation (n = 13), tricuspid annuloplasty or valve replacement (n = 9) and aortic valve replacement (n = 4). Duration of atrial fibrillation (AF) varied from 1 to 18 years (mean 8.0 +/- 5.8 year), the f-wave voltage ranged from 0.05 to 0.5 mV (0.21 +/- 0.13 mV), left atrial dimension (LAD) ranged from 35.6 to 66.3 mm (49.0 +/- 9.3). One patient died 2 months after undergoing combined maze procedure and MVR + TAP due to pulmonary infection and sepsis, but the other 13 patients survived. Nine patients (69%) regained atrial rhythm, two patients (15%) had junctional rhythm and another two (15%) remained in AF at follow-up periods between 1 to 11.5 months (6.3 +/- 3.1). The nine patients who recovered to normal sinus rhythm had preoperative f-wave for a significant higher voltage than the patients with AF and JR (0.27 +/- 0.12 vs 0.13 +/- 0.05 mV, p < 0.05) and a smaller left atrial dimension (44.5 +/- 0.7 vs 54.8 +/- 6.9 mm, p < 0.05). These data suggest that the maze operation is effective and should be considered for patients with chronic AF indicated for surgical valvular diseases.

Adult↗

[Expression of Bcl-2 and Bax in human gastric cancer tissue].

Deregulation of bcl-2 may function as a survival mechanism in cancer cells, predisposed to cell death. Aberrant Bcl-2 expression is a frequent occurrence in chronic atrophic gastritis, gastric epithelial dysplasia and gastric cancer. Inhibition of apoptosis through Bcl-2 expression appears to be specifically associated with promotion of gastric adenocarcinoma. In addition, loss of heterozygosity of the bcl-2 gene is a common event in well-differentiated adenocarcinoma, whereas overexpression of bcl-2 gene is observed in poorly differentiated adenocarcinoma. Bax, a homologue of Bcl-2, counters the death repressor activity of Bcl-2. In our study Bax immunostaining in gastric cancer tissue is not significantly correlated with tumor histology. Possible gene therapy using bax gene is discussed.

Adenocarcinoma↗

Addition of purified prostate specific antigen to serum from female subjects: studies on the relative inhibition by alpha 2-macroglobulin and alpha 1-antichymotrypsin.

PURPOSE: Two forms of prostate specific antigen (PSA), 1 complexed to alpha 1-antichymotrypsin and the other a free PSA, are recognized by current commercially available immunoassays. A third form of PSA complexed to alpha 2-macroglobulin also is present in the serum. To study these 3 different molecular forms of PSA in vivo, we simulated leakage of PSA from the prostate into the serum in vitro. MATERIALS AND METHODS: Purified seminal fluid PSA was incubated with fresh sera from female subjects at different concentrations. Following gel filtration chromatography, the 3 forms of PSA were studied by immunoassays and Western blot analysis. RESULTS: Using a commercial immunoassay, 60% of immunoreactivity of seminal fluid PSA was lost after incubation with sera from female subjects. Western blot analysis showed that most of this loss in PSA signal was caused by complexation to alpha 2-macroglobulin. Minimal, if any, complexation to alpha 1-antichymotrypsin occurred even when excess alpha 1-antichymotrypsin was added to the serum. CONCLUSIONS: Our studies demonstrated that alpha 2-macroglobulin is a much stronger inhibitor to PSA than alpha 1-antichymotrypsin. Further studies of these complexes may be important. They clearly explain why spiking PSA into sera from female subjects to be used as quality controls for PSA assays leads only to the free form of enzymatically inactive PSA in the serum, and not to the dominant form of complexed PSA and alpha 1-antichymotrypsin present in human serum.

Female↗

Prolonged survival of hamster-to-rat pulmonary xenografts by tacrolimus (FK506) and cyclophosphamide.

BACKGROUND: Severe shortage of donor organs in clinical lung transplantation prompted us to investigate the potential use of pulmonary xenografts. The purpose of this study was to determine whether an immunosuppressive regimen of tacrolimus (FK506) and cyclophosphamide would prolong the survival of hamster-to-rat pulmonary xenografts. METHOD: Left lung transplantation was done with male Golden Syrian hamsters used as donors and inbred male Lewis rats as recipients. Control animals (n = 10) received no immunosuppressive drugs whereas experimental animals (n = 6) were treated with tacrolimus and cyclophosphamide. Tacrolimus was administered intramuscularly at a dosage of 2 mg/kg per day on postoperative days 0 to 4, followed by 1 mg/kg per day on days 5 to 29 and 0.5 mg/kg per day on days 30 to 99. Cyclophosphamide (8 mg/kg per day) was administered orally from the day before transplantation to day 8. After transplantation the animals were monitored by chest radiography. Recipient animals were killed at timed intervals (days 60 and 100) and when the chest radiograph showed complete opacification of the transplanted lung. At necropsy, pulmonary xenografts were examined histologically for evidence of rejection, which was graded on a scale of 0 (no rejection) to 4 (severe rejection). Antihamster lymphocytotoxic antibody titer was also measured in recipient animals after transplantation. RESULTS: Pulmonary xenografts in the control animals had a median [correction of medium] survival time of 3 days, whereas the median survival in treated animals was more than 74 days. All pulmonary xenografts in control animals had severe rejection on day 3 after transplantation, whereas those in the treated animals had no rejection on days 60 and 100. The lymphocytotoxic antibody titers in control animals increased from 1:16 before operation to 1:4096 on day 3 (p < 0.01). In the treated animals, the lymphocytotoxic antibody titer on day 21 was 1: 8, which was not different from the preoperative value (1:16). CONCLUSION: These results indicate that a combination of tacrolimus and a short course of cyclophosphamide prolongs the survival of pulmonary xenografts in a hamster-to-rat model.

Animals↗

[Botanical origin of commercial samples of traditional Chinese drug xixin (Herba Aasari)].

It has been found out that amony the 158 samples of commercial drug. Xixin (Herba Asari) collected from 28 provinces/cities of China, only three guarters are derived from the species specified in the Chinese Pharmacopoeia and the rest are not. One hundred and eleven samples are derived from Asarum heterotropoides var. mandshuricum and are presently used in 26 provinces/cities, 25 samples are derived from A. himalaicum and used in 10 provinces, the other 22 samples are derived from 9 species such as A. sieboldii, A. forbesii, etc.

China↗