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Kazuo Murakami

Publications and source records attributed to Kazuo Murakami.

24 records · Page 2Linked to original sources

[Rifampicin-induced severe thrombocytopenia in a patient with miliary tuberculosis].

A 74-year-old female visited a local clinic complaining of fever on January 21, 2002. A chest X-ray and a chest computed tomography (CT) showed diffuse micronodules in all lung fields, which strongly suggested miliary tuberculosis. On January 23, she was referred to our hospital for further examinations. Though sputum was negative on smear, culture, and polymerase chain reaction (PCR) for M. tuberculosis, bone marrow aspirate examined on admission revealed epithelioid granuloma. Therefore we diagnosed her as a miliary tuberculosis, and she was treated with 300 mg of Isoniazid (INH), 450 mg of Rifampicin, and 750 mg of Streptomycin (SM) daily. Five days later, severe thrombocytopenia (platelet count 0.3 x 10(4)/microliter) was observed. We immediately discontinued all antituberculous drugs and administered concentrated platelets and immune globulin. Platelet-associated IgG was detected, and megakaryocytes were slightly increased in moderately hypocellular marrow on the bone marrow aspirate examined again after the appearance of thrombocytopenia. Eleven days after discontinuing all antituberculous drugs, platelet count recovered to 10.2 x 10(4)/microliter. INH, SM, Levofloxacin (LV) were administered afterward, and these drugs did not induce thrombocytopenia. Though challenge administration of RFP was not performed, we concluded that the thrombocytopenia was immunologically induced by RFP. We should keep in mind that RFP-induced thromobocytopenia could appear in the first week after the initiation of therapy.

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Expression, purification, and characterization of two N,N-dimethyltransferases, tylM1 and desVI, involved in the biosynthesis of mycaminose and desosamine.

Methylation catalyzed by an S-adenosylmethionine- (AdoMet-) dependent methyltransferase is an effective means to alter the hydrophilicity and/or nucleophilicity of a molecule. While a large number of enzymes capable of catalyzing methylation at carbon, oxygen, sulfur, and nitrogen atoms are known, only a few are able to catalyze N,N-dimethylation. Mycaminose and desosamine are aminohexoses found in several macrolide antibiotics, such as tylosin and methymycin, respectively. Both sugars contain a C-3 N,N-dimethylamino group which has been shown to confer the biological activity of these unusual sugars. Recently, sequence analysis as well as genetic studies has led to the assignment of tylM1 in the tylosin biosynthetic gene cluster and desVI in the methymycin biosynthetic gene cluster as genes encoding the corresponding N,N-dimethyltransferases. To verify the proposed roles of the tylM1 and desVI genes, we have overexpressed and purified their encoded products, synthesized the predicted substrates, and characterized the catalytic function of these proteins. Our studies showed that TylM1 and DesVI are homodimeric proteins and have nearly identical biochemical properties. These enzymes do not have strong preference for binding either the unmethylated substrate or the monomethylated intermediate. It is the chemical reactivity of the nitrogen functional group that determines the relative rate of a particular methylation step. Thus, our results not only establish TylM1 and DesVI as new members of a small family of enzymes that are capable of catalyzing N,N-dimethylation of an amino group but also provide evidence indicating that the methylation catalyzed by AdoMet-dependent methyltransferases proceeds in a stepwise manner and is nucleophilic in nature.

Amino Sugars↗

Renal interstitial fibrosis is reduced in angiotensin II type 1a receptor-deficient mice.

Unilateral ureteral obstruction (UUO) results in tubulointerstitial fibrosis of the affected kidney by stimulating the renin-angiotensin system. This study established a UUO model in angiotensin type 1a receptor (AT1a) deficient (mutant) mice to elucidate the role of angiotensin II through AT1a on the fibrosis of the obstructed kidney (OBK). The relative volume of the tubulointerstitium was measured by an image analyzer; deposition of collagen types III and IV and monocyte/macrophage infiltration were histologically examined using specific antibodies. Also determined were the mRNA levels of transforming growth factor-beta by Northern blot analysis. Nuclear factor-kappaB activity was assessed by gel shift assay. UUO in wild mice resulted in a marked expansion of relative volume of the tubulointerstitium, together with increased deposition of collagen types III and IV and number of infiltrated monocytes/macrophages in the interstitium, relative to sham-operated mice. In comparison, these changes were significantly lower in mutant mice with UUO. The mRNA level of transforming growth factor-beta was significantly higher in the OBK of wild mice with UUO compared with sham-operated mice. In contrast, the increase in mRNA level in the OBK of mutant mice was significantly less than in wild mice. Finally, UUO resulted in activation of nuclear factor-kappaB in wild mice but was inhibited in the OBK of mutant mice. The results provide direct evidence that angiotensin II acting via the AT1a plays a pivotal role in the development of tubulointerstitial fibrosis in UUO.

Animals↗

Malignant fibrous histiocytoma of the lung.

Primary malignant fibrous histiocytoma (MFH) of the lung is very rare. To date, only 32 reports of 63 cases of primary MFH of the lung have appeared in English, excluding tumors arising from the pulmonary arteries and pleura. We describe a patient with primary MFH of the lung who developed brain metastasis and involvement of pulmonary great vessels. In addition, we reviewed previously reported cases to establish the clinical characteristics and most appropriate management of primary pulmonary MFH. When disease is sufficiently limited, complete resection remains the mainstay of treatment.

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