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Biomedical subjects

H Kawaguchi

Publications and source records attributed to H Kawaguchi.

At least 361 records · Page 20Linked to original sources
PubMed1991

Synthesis and biological activity of 1-N-[4-(substituted)amidino and guanidino-2-hydroxybutyryl]kanamycins A and B.

The synthesis and biological properties of 1-N-[4-(substituted)amidino and guanidino-2-hydroxybutyryl]kanamycins A and B are described. Reaction of 3,3",6'-tri-N-tert-butoxycarbonyl-amikacin with an appropriate amidinating or guanidinating reagent and subsequent deblocking gave a series of amikacin derivatives having an amidino or guanidino group on the 4"'-position. The corresponding kanamycin B analogs were also prepared by a similar procedure. Among these derivatives, 1-N-(4-formamidino- and guanidino-2-hydroxybutyryl)kanamycins A (7a and 7k) and B (11 and 14) exhibited antibacterial activity similar to the corresponding 4-amino analogs. The nephrotoxic potential of selected compounds is also briefly discussed.

Animals↗
PubMed1991

Synthesis and activity of butirosin derivatives with 5''-amidino and 5''-guanidino substituents.

The preparation and antibacterial activity of the 5''-guanidino (6) and 5''-amidino (7) derivatives of 4'-deoxybutirosin A (1) as well as the 5''-guanidino derivative (8) of butirosin A are described. The key intermediates, tetra-N-benzyloxycarbonyl-5''-azido derivatives were selectively reduced with NiCl2-NaBH4 to give the corresponding 5'-amino derivatives. Subsequent guanidination or amidination followed by deblocking afforded the final compounds 6, 7 and 8. The 5''-guanidino derivatives (6 and 8) were more active against Gram-positive and Gram-negative bacteria than the corresponding 5''-hydroxy derivatives (1 and butirosin A). Compound 6 was also active against a variety of methicillin-resistant Staphylococcus aureus (MRSA).

Animals↗
PubMed1991

[A basic study on the plasma and serum levels of eosinophil cationic protein (ECP) in bronchial asthma].

A basic study on the blood eosinophil cationic protein (ECP) as an index for eosinophil activation in bronchial asthma was performed. 1) ECP concentration in the serum collected 2 hours after blood sampling and the peripheral eosinophil count were significantly higher in asthmatic patients than in normal individuals. A correlation between these two parameters was observed in normal controls but not in asthmatic patients. These findings suggest that the degree of eosinophil activation, which is reflected by the blood ECP concentration, varies with the clinical condition in asthmatic patients. 2) The plasma and serum ECP levels were compared. The serum ECP was higher than the plasma ECP in both normal controls and asthmatic patients. In asthmatic patients, however, plasma ECP levels poorly correlated with serum levels: the serum levels were markedly elevated in some cases, and only the plasma levels were significantly elevated during symptomatic periods compared with stable periods. Therefore, attention must be paid not only to the serum ECP concentration, but also to the plasma ECP concentration and the plasma-serum difference. 3) This plasma-serum difference in ECP concentration may be due to the in vitro release of ECP during coagulation after blood sampling rather than the effect of alpha 1-macroglobulin concentration, because supernatants from stimulated platelets elicited ECP release from eosinophils.

Asthma↗
PubMed1991

Immune mechanism facilitating clearance of Trypanosoma gambiense by IgG3 antibody from infected host.

The aggregation of trypansomes, immune adherence to macrophage and protection against infection of Trypanosoma gambiense are associated with IgG3 antibody. IgG3-mediated clumping trypanosomes are readily dissociated by the aid of complement to become free. Dissociation of the clumped trypanosomes in the equivalence area released approximately fifty percent of previous bound surface antigens. These antigens were capable of binding again to new IgG3 antibody. Experiments indicated that complement deposition altered functionally bivalent IgG3 antibody in the immune complex into a univalent one. Such event in the presence of complement is of great advantage to the infected host in killing pathogens in vivo, as it allows more antibodies to attach to surface antigens and subsequently initiate complement activity.

Animals↗
PubMed1991

[The efficacy and side effects of chemotherapy for primary lung cancer with cisplatin and etoposide].

We treated 34 primary lung cancer patients with chemotherapy of cisplatin and etoposide. There were 2 cases of CR (15%) and 8 cases of PR (61%) out of 13 cases of small cell lung cancer. No case of CR and one case of PR (5%) were obtained out of 21 cases of non-small cell cancer. Side effects were leukopenia, increase of BUN and creatinine, angina pectoris, supraventricular premature contraction, and renal failure. WBC reached nadir on day 15 on average. When we repeated this regimen, we encountered 3 cases of acute myocardial infarction, and it was useful for small cell lung cancer.

Adenocarcinoma↗
PubMed1991

[Effect of UFT by oral administration using a murine hepatic metastasis model].

We examined the antitumor effect of UFT, a 5-FU derivative using a hepatic metastasis model in mice. BALB/c and CDF1 mice were given orally UFT (30 mg/kg, 50 mg/kg daily or 120 mg/kg every other day) for 20 days after inoculation of colon-26 tumor cells into the portal vein. The number of metastatic nodules and the weight of the liver decreased significantly in all groups of UFT treatment. The therapeutic effect with 50 mg/kg UFT was better than those with the other doses. NK and LAK activities of spleen cells obtained from UFT-treated tumor bearing mice were not significantly different from the untreated control. IL-1 and IL-2 production of the spleen cells were also not significantly changed by the treatment with UFT. These results suggested that the oral administration of UFT represents an antitumor effect against hepatic metastasis in mice without sever suppression of the host immune system.

Administration, Oral↗
PubMed1991

[Roentgenological manifestation of ossification of the posterior longitudinal ligament in the cervical spine causing severe spinal canal stenosis--a group comparison with and without marked spinal cord dysfunction].

Relationship between the degree of clinical symptoms and the lateral roentgenograms of the cervical OPLL causing severe spinal canal stenosis was studied among patients whose roentgenological minimum antero-posterior diameters of the available spinal canals were under 9mm. Lateral roentgenograms of 28 clinically mild patients were compared with those of 20 clinically severe patients. The type of ossification, the extent of OPLL, the narrowest level of the available spinal canal, and the minimum a-p diameter were not statistically significant parameters. The degree of canal stenosis at the 1cm cranial and 1cm caudal levels from the narrowest level, and the axial extent of canal stenosis around the narrowest level were less significantly in the group with mild symptoms than in the group with severe symptoms.

Adult↗
PubMed1991

[Fecal occult blood test and mass screening for colorectal cancer].

It has become promising to establish a method for mass screening of colorectal cancer through the development of immunological fecal occult blood test. It has been shown that such tests have higher specificity and sensitivity compared to conventional chemical tests not only in cancer subjects and normal controls but in population screening trials. Further study is required to decide the optimal system within the framework of the screening such as the number of specimens, target age, and screening interval, etc. The efficacy of fecal occult blood screening remains to be shown in spite of the several randomized controlled trials completed or on-going. However, a case control study has strongly suggested that such screening would reduce the mortality from colorectal cancer.

Colorectal Neoplasms↗
PubMed1991

[Tracheobronchoplasty for functional restoration].

We have experienced 10 cases of terminal mediastinal tracheostomy (TMT), 7 cases of laryngotracheal anastomosis with subtotal resection of cricoid cartilage (LTT), 5 cases of sleeve or wedge segmentectomy (SS, WS) for lung cancer with low pulmonary function, and 5 cases of carinal reconstructions (CR) with one stomal anastomosis between left lobar bronchus and trachea after partial resection of carina for tuberculous stenosis of left main bronchus. Modified TMT which stomaplasty was constructed with cervical and anterior chest skin flap different from primary procedure by Grillo was performed in 3 cases without innominate artery rupture nor cicatricial stomal stenosis. LTT by Pearson's procedure caused telescoped anastomosis. Pulmonary function was reserved in all 5 cases of SS and WS. Salvaged left lung by single stomal CR in the cases of tuberculous stenosis functioned well. Two different approaches for subaortic arch anastomosis, namely Pull-down and Pull-up, were proposed in single stomal CR. Pull-down provided excellent exposure of the carina without sacrifice of intercostal arteries. Indication of plasty was extended by TMT and LTT for upper limits of airway resection, SS and WS for limited operation against lung cancer, and single stomal CR for tuberculous stenosis of left main bronchus.

Bronchi↗
PubMed1990

Effect of streptokinase on prostacyclin synthesis and phospholipase activity in cultured pulmonary artery endothelial cells.

In this study, we examined the effects of streptokinase on arachidonic acid release and prostacyclin biosynthesis in cultured bovine pulmonary artery endothelial cells. When intact cells were incubated with streptokinase, a significant stimulatory effect on prostacyclin biosynthetic activity in cells was evident without any cellular damage at all concentrations used (1-10,000 units/ml). Streptokinase also caused a marked release of arachidonic acid. It induced rapid phospholipid hydrolysis, resulting in the release of up to 15% of incorporated [3H]arachidonic acid into the medium. After the addition of streptokinase, degradation of phosphatidylcholine and phosphatidylethanolamine was observed and lysophosphatidylcholine and lysophosphatidylethanolamine were produced. We also observed a transient rise in diacylglycerol after the addition of streptokinase. To test for phospholipase C activity, the release of incorporated [3H]choline, [3H]inositol and [3H]ethanolamine into the culture medium was determined. The level of radioactive inositol showed an increase, but the changes in choline and ethanolamine were comparatively small. An increase in inositol was detectable within 1 min after streptokinase addition and peaked after 15 min. Inositol phosphate and inositol trisphosphate were released, and these releases were suppressed by the addition of neomycin (50 microM). These results suggest that streptokinase stimulates phospholipase A2 and C activity, and that prostacyclin biosynthesis is subsequently increased in cultured endothelial cells.

Animals↗
PubMed1990

Mechanism of increased angiotensin-converting enzyme activity stimulated by platelet-activating factor.

We studied the effects of platelet activating factor (PAF) on angiotensin-converting enzyme (ACE). PAF (1 x 10(-10) to 1 x 10(-6) M) had a novel effect on angiotensin I conversion. Pulmonary artery endothelial cells converted 1 nmol/dish of 125I-angiotensin I to angiotensin II in the absence of PAF. ACE activity was increased to 2.5 nmol/dish by the addition of 1 x 10(-6) M of PAF. To clarify the mechanism of this stimulatory effect of PAF on ACE, Ca2+ influx and inositol 1,4,5-trisphosphate (IP3) release in pulmonary artery endothelial cells were determined. PAF stimulated Ca2+ influx in a dose-dependent manner. PAF also stimulated phospholipase C (PLC) activity and released IP3. To study the relationship between PLC activity and ACE activity, neomycin was added. The Ca2+ influx and IP3 release stimulated by 10(-6) M of PAF were suppressed by about 60-70%. ACE activity was also inhibited up to 70% in the presence of PAF (10(-10) - 10(-6) M) by 50 M of neomycin. These results suggest that ACE was stimulated by PAF, and that its activity in endothelial cells may be mediated by the PI-turnover pathway via changes in PLC activity and IP3-mediated Ca2+ release from intracellular stores.

Angiotensin I↗
PubMed1990

Organization of the chimpanzee C4-CYP21 region: implications for the evolution of human genes.

We prepared a cosmid library from chimpanzee DNA and screened it with a mouse probe specific for the complement component 4 (C4)-encoding gene. We isolated 29 clones and constructed restriction maps for 20 of these. The clones could be arranged into two overlapping clusters covering the entire C4 region of both chromosomes in this particular heterozygous chimpanzee. The region is about 100 kilobases (kb) long and contains two C4 and two CYP21 genes, the latter coding for the enzyme 21-hydroxylase. Using oligonucleotide probes we identified the genes as corresponding to human C4A, C4B, CYP21 and CYP21P genes. The last gene apparently contains an 8-base pair (bp) deletion (as does the corresponding human gene), which renders it a pseudogene. The genes are arranged in the order C4A...CYP21P...C4B...CYP21. Each of the two C4 genes is 16 kb long and thus corresponds to the short version of the human C4 genes. We suggest that the duplication of the basic C4-CYP21 unit that generated the standard arrangement of the human C4-CYP21 region occurred before the separation of the evolutionary lineages leading to humans and chimpanzees (i.e., more than five million years ago). We suggest further that the original form of the C4 gene was of the long variety and was generated by the insertion of a 6.8-kb element into one of the C4 introns. The element was subsequently excised in the ancestors of the chimpanzees and in at least one lineage of the human C4B gene. We speculate that the presence of the 6.8-kb insert in the human C4A and some C4B genes might largely be responsible for the great instability of this chromosomal region which leads to frequent duplications and deletions, some of which cause 21-hydroxylase deficiency.

Animals↗