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Biomedical subjects

K Hirano

Publications and source records attributed to K Hirano.

At least 289 records · Page 16Linked to original sources
PubMed1997

Genetic cholesteryl ester transfer protein deficiency is extremely frequent in the Omagari area of Japan. Marked hyperalphalipoproteinemia caused by CETP gene mutation is not associated with longevity.

Low levels of HDL cholesterol have been clearly demonstrated to be associated with an increased incidence of coronary heart disease, strongly suggesting that HDL particles have an antiatherogenic function. However, little information has been available concerning the atherogenicity of a marked hyperalphalipoproteinemia (HALP). There is no agreement about whether plasma cholesteryl ester transfer protein (CETP) deficiency is associated with an antiatherogenic state or not, although this disorder was reported to be one of the major causes of marked HALP. In the current study, we have found a unique area (Omagari City, Akita Prefecture, Japan) where CETP deficiency caused by a G-to-A mutation at the 5' splice donor site of intron 14 in the CETP gene is extremely frequent. In Omagari City, the mutation was detected more than 20 times more frequently and the prevalence of a marked HALP with plasma HDL cholesterol > or = 2.58 mmol/L (100 mg/dL) was 5 to 10 times higher than in other areas of Japan. This discovery has made it possible to perform a large population-based study concerning the atherogenicity of a marked elevation of HDL cholesterol in a genetically more homogeneous population. There was a statistically significant U-shaped relationship between HDL cholesterol levels and the incidence of ischemic changes in electrocardiograms. In cases of HDL cholesterol < 1.81 mmol/L (70 mg/dL), the incidence increased in proportion to the levels of HDL cholesterol. The frequency of the CETP gene mutation was higher in patients with coronary heart disease than in healthy control subjects. In subjects aged > 80 years, the prevalence of both marked HALP and the intron 14 splicing defect was significantly lower than in the younger generation. The current study indicated for the first time that a marked HALP caused by CETP gene mutation may not represent a longevity syndrome, suggesting the importance of reevaluation of the clinical significance and pathophysiology of a marked HALP.

Aged↗
PubMed1997

Purification and characterization of pranlukast hydrolase from rat liver microsomes: the hydrolase is identical to carboxylesterase pI 6.2.

Two carboxylesterases with pI 6.0 and 6.2 derived from rat liver microsomes were purified. The two isozymes were remarkably different in substrate specificity, but they had equal enzymatic activity for alpha-naphthyl acetate and were inhibited equally by phenylmethylsulfonyl fluoride (PMSF) and bis-(4-nitrophenyl) phosphate (BNPP). Carboxylesterases pI 6.0 and 6.2 are identical to the enzymes referred to as hydrolase A and B, respectively, from the results of amino acid sequence analyses. Pranlukast was effectively hydrolyzed by carboxylesterase pI 6.2 but not by the pI 6.0 enzyme, and the difference in the pranlukast metabolism between the human and the rat could be explained by the substrate specificity of carboxylesterase. Furthermore, prodrugs of angiotensin converting enzyme inhibitors were found to be converted to the active drugs after hydrolysis by the carboxylesterases pI 6.0 and 6.2. Carboxylesterases generally catalyze the hydrolysis of ester-type drugs preferentially rather than amide-type drugs.

Amino Acid Sequence↗
PubMed1997

Hydrolytic profile for ester- or amide-linkage by carboxylesterases pI 5.3 and 4.5 from human liver.

Carboxylesterases (EC 3.1.1.1) from human liver were purified using Q-Sepharose, Sephadex G-150, isoelectrofocusing and Con A-Sepharose. The calculated molecular mass of the pI 5.3 enzyme was 120 kDa and 61 kDa from the results of Sephadex G-150 gel filtration and SDS-polyacrylamide gel electrophoresis (PAGE), respectively, suggesting that this enzyme is a dimer. On the other hand, carboxylesterase pI 4.5, with a molecular mass of 64 kDa, was a monomer. The activities of both enzymes were inhibited by typical serine enzyme inhibitors. Amino acid sequence analysis of the purified enzymes pI 5.3 and 4.5 showed high homology with rabbit carboxylesterase form 1 and 2, respectively. The results also suggested that carboxylesterase pI 5.3 is identical to the deduced amino acid sequence from cDNA for HU1, and that carboxylesterase pI 4.5 is identical to the deduced amino acid sequence from the cDNA registered as human carboxylesterase (hCE-2) in GenBank. We first purified carboxylesterase pI 4.5 and investigated its hydrolytic activity upon various drugs. The two enzymes differed in substrate specificity. Prodrugs of angiotensin-converting enzyme inhibitors, such as delapril and imidapril, were converted to active metabolites by carboxylesterase pI 5.3, but not by carboxylesterase pI 4.5. The hydrolysis velocity of temocapril by carboxylesterase pI 5.3 was 12-fold faster than by carboxylesterase pI 4.5. In contrast, aspirin, oxybutynin and procaine were hydrolyzed by only carboxylesterase pI 4.5. We also found that an amide-linkage in drugs, except for that in aniracetam, was not a good substrate for the two enzymes. Consequently, carboxylesterases pI 5.3 and 4.5 may be involved in the metabolism of various drugs containing an ester-linkage.

Amino Acid Sequence↗
PubMed1997

A case report of salivary duct carcinoma.

We present a 65-year-old man with an enlarged mass in the right parotid gland. A fine-needle aspiration cytology suspected Warthin's tumor. The ill-defined margin of the tumor in diagnostic imaging and unexpected clinical course of the occurrence of facial nerve paralysis suggested malignant neoplasm. The patient was treated with surgical resection of the primary site and neck following radiation therapy. Pathologic diagnosis was a salivary duct carcinoma. Difficulty in early diagnosis of this tumor may result in local extension, early metastasis to regional lymph nodes and distant sites, and death.

Adenocarcinoma↗
PubMed1997

BE-32030 A, B, C, D and E, new antitumor substances produced by Nocardia sp. A32030.

New antitumor substances, designated BE-32030A, B, C, D and E, were isolated from the culture broth of Nocardia sp. A32030. The active principles were extracted from the mycelium by methanol and purified by Sephadex LH-20 and reversed-phase column chromatographies and finally by reversed-phase HPLC. BE-32030A, B, C, D and E inhibited the growth of P388 murine leukemia, DLD-1 human colon cancer, PC-13 human lung cancer and MKN-45 human stomach cancer cell lines.

Animals↗
PubMed1997

[A case of acquired immunodeficiency syndrome with disseminated Mycobacterium avium complex infection in which M. avium was isolated from bone marrow].

A 46-year old man was admitted to a hospital because of cough and dyspnea. He was diagnosed as interstitial pneumonia and was treated with prednisolone (PSL) and antibiotics. The symptoms improved temporarily but he soon developed acute respiratory failure and was transferred to our hospital. Chest X-ray and CT revealed ground-glass opacities in both lung fields. He was treated with methyl PSL, antibiotics, and antimycobacterial drugs but he died on the fourth hospital day. Retrospectively, hematologic laboratory examinations revealed that CD4+ cell count was 0/microliter and serological tests for HIV were positive by both EIA and Western blot methods. The culture of the bone marrow specimens was positive for mycobacteria other than M. tuberculosis, and the bacilli were identified as Mycobacterium avium. Thus, his disease was eventually diagnosed as disseminated Mycobacterium avium complex (MAC) infection. In the past reports, the diagnosis of disseminated MAC infection was most often made by blood cultures, however, the isolation of MAC from bone marrow is another sensitive and specific method for the diagnosis of this infection. In some cases, bone marrow examination would be useful to diagnose disseminated MAC infection.

AIDS-Related Opportunistic Infections↗
PubMed1997

Factors contributing to imaging of xenografts using anti-placental alkaline phosphatase monoclonal antibody.

PURPOSE: To investigate factors that influence the imaging of placental alkaline phosphatase (PLAP) producing xenografts using an anti-PLAP monoclonal antibody (MAb). MATERIALS AND METHODS: Three xenografts (human seminoma, HeLa Hep 2 cells, and KK-47 bladder cancer cells) each expressing PLAP to a different degree were used to immunolocalize an anti-PLAP MAb, HPMS-1. RESULTS: Although the highest PLAP level was found in seminoma xenografts, the MAb was not useful for the imaging of seminoma xenografts because of poor accumulation. Fragmentation of the MAb, such as F(ab)2, however, was shown to be efficient for imaging seminoma xenografts. A distribution study with T1-201 revealed the highest blood flow in HeLa cells and the lowest in seminoma. A difference in blood flow may partially explain the disparity between the amount of MAb accumulation and the level of antigen expression in these three xenografts. CONCLUSIONS: Blood flow in targeted tumors was shown to be more critical than their level of antigen expression for the imaging of xenografts with anti-tumor antibody. In addition, fragmentation of the MAb enabled tumor imaging because of a rapid clearance of the fragment from the circulation.

Alkaline Phosphatase↗
PubMed1997

[Indocyanine green angiography in Stargardt's disease].

We performed indocyanine green angiography (ICG angiography) and fluorescein angiography in order to investigate the choroidal circulation in patients with Stargardt's flavimaculatus. Eight eyes of 4 patients in Groups 2 approximately 3 (Noble classification) were included in this study. In the area with "dark choroid" in fluorescein angiography, ICG angiography revealed large choroidal vessels in all eyes, but some fluorescent choroidal vessels were dark around the atrophic macula and in the peripapillary area, which indicated a greater storage of lipofuscin within the retinal pigment epithelium in those areas. In the atrophic macula area, irregular hypofluorescence was observed in ICG angiography, which might be caused by filling defect and/or block. Many flecks revealed hyperfluorescence in fluorescein angiography and hypofluorescence in ICG angiography, suggesting that focal circulatory disturbances in the choriocapillaries exist beneath the flecks.

Adolescent↗
PubMed1997

Characterization of the human apobec-1 gene: expression in gastrointestinal tissues determined by alternative splicing with production of a novel truncated peptide.

In humans, both the expression of apobec-1 and the C to U deamination of apoB mRNA are confined to the small intestine. In order to understand the tissue-restricted pattern of apobec-1 expression, we have isolated the chromosomal gene spanning the human apobec-1 locus. The human apobec-1 gene spans 18 kb and contains five exons, all of which are translated. Transcription initiation, determined by RNase protection and primer extension analyses, is localized to a single start site 34 nt upstream of the open-reading frame in exon 1. A common, but functionally silent, gene polymorphism was detected than changes Ilc80 to MCl. RNase protection and reverse-transcription PCR analysis demonstrated the presence of an exon 2-skipped form of apobec-1 mRNA that arises through use of an alternative splice acceptor. This alternative splicing causes a frame-shift that produces a novel, 36 amino acid peptide. The exon 2-skipped form accounts for approximately 50% of apobec-1 mRNA in the adult small intestine and up to 90% of apobec-1 mRNA in the developing gut. An antipeptide antibody identified the truncated protein in villus cells of the adult small intestine. These data suggest that exon 2-skipping may represent an important control mechanism regulating apobec-1 gene expression in humans.

APOBEC-1 Deaminase↗
PubMed1997

[Conversion of chronic necrotizing pulmonary aspergillosis to invasive pulmonary aspergillosis, and successful treatment with fluconazole].

An 82-year-old man with rheumatoid arthritis was admitted to the hospital because of bloody sputum, appetite loss, and a chest-radiographic abnormality. He had previously been treated with oral steroid therapy. The chest X-ray film showed an infiltrative shadow with airlucency in the right upper lung field. Sputum culture for fungi was negative, but a test for aspergillus antigen in serum was positive. Other clinical findings were also compatible with conversion of chronic necrotizing pulmonary aspergillosis to invasive pulmonary aspergillosis. The patient was successfully treated with a drip infusion of fulconazole. The patients condition was stable for several months, after which he died due to uncontrollable atrial flutter. Mild immunosuppression due to oral steroid therapy probably caused chronic necrotizing pulmonary aspergillosis in this case. The patient's general condition worsened after admission and invasive pulmonary aspergillosis developed. This case taught us that therapy for chronic necrotizing pulmonary aspergillosis should include management of the patient's general condition as well as treatment of the pulmonary lesions.

Aged↗
PubMed1997

Cloning and characterization of the rat apobec-1 gene: a comparative analysis of gene structure and promoter usage in rat and mouse.

ApolipoproteinB (apoB) mRNA editing involves a C to U deamination of the nuclear apoB mRNA and occurs in mammalian small intestine and in the liver of certain species. This reaction is mediated by a multicomponent enzyme complex that includes a catalytic subunit, apobec-1. Apobec-1 mRNA is widely expressed in the rat and mouse and is subject to tissue-specific regulation. In order to understand the basis for the species- and tissue-specific pattern of apobec-1 gene expression we have cloned and characterized the rat chromosomal apobec-1 gene. We demonstrate its structural organization and regulation in comparison to that of the mouse apobec-1 gene. The rat apobec-1 gene spans 16 kb and includes one untranslated (exon A) and five translated exons (exons 1-5). The mouse apobec-1 gene contains eight exons, of which the first three (exons A, B, C) are untranslated. Independent approaches demonstrated three distinct clusters of transcription initiation sites in both species, including exon A, the distal region of exon 1, and a separate group in the proximal region of exon 1. These transcription start sites generate three distinct mRNA species whose proportions differ in a tissue-specific fashion. Promoter-luciferase reporter constructions using regions flanking exon A and exon 1 of the rat apobec-1 gene identified two functional regions upstream of exon 1 that independently promote luciferase expression in transfected hepatoma and colon cancer cells. These data serve as a basis for an understanding of the regulation of apobec-1 gene expression, in particular the mechanisms that serve to restrict its expression to the gastrointestinal tract in higher mammals.

APOBEC-1 Deaminase↗
PubMed1997

[Clinical evaluation on causes of death in patients with pulmonary tuberculosis who died within one year after diagnosing as TB].

We evaluated the cause of death in patients with pulmonary tuberculosis who died within one year after diagnosing as tuberculosis. Of 325 bacillary patients during the past seven years, 43 (13.2%) died within one year. Twenty-three patients (53.5%) died directly of tuberculosis. In this group, 13 patients died in emaciation state. Most of them were aged and under a poor nutritional condition. Some patients died in spite of improvement of tuberculosis. The fact indicates the need to detect tuberculosis as early as possible in elderly persons, and treatment should be initiated immediately. Eight patients died of respiratory failure and their chest X-ray film showed wade-spread tuberculosis. Seven of the patients died in spite of initiating treatment within one month after the onset of symptoms. This fact suggests the importance of regular check up by chest X-ray to detect tuberculosis early. Two patients died of massive hemoptysis. They had an episode of bloody sputum and the laboratory examination showed anemia. On the other hand, 20 patients died due to coexisting diseases unrelated to tuberculosis. Ten patients died of malignant diseases and most of them were lung cancer. Two patients died of hepatic failure possibly caused by the adverse reaction of TB chemotherapy. The interval between the onset of the treatment and death was less than a month, and the fact suggests the need to observe carefully for adverse reactions especially in the early stage of treatment.

Aged↗
PubMed1997

[Eosinophils in stool smear in normal and milk-allergic infants].

Stool smears of newborn infants were investigated sequentially from birth through 6 months of life in order to study relation between appearance of eosinophils in stool and feeding of babies. In babies born to non-atopic parents, eosinophils appeared in stool smear soon after start of feeding, but disappeared in a short time. Eosinophils were found irrespective of types of feeding, i.e., breast feeding, powdered milk or amino acid formula. There was tendency of sustained presence of eosinophils in stool smears in babies born to severe atopic parents. These results suggest that appearance in stool of eosinophils does not necessarily mean allergic reaction to ingested foods and need attention in diagnosing milk allergy. Mechanisms of appearance and function of eosinophils in stool in normal babies may differ from those in pathological situations and need further detailed investigation.

Breast Feeding↗
PubMed1997

Histopathologic alterations of retinacular vessels and osteonecrosis.

To probe into the pathogenesis of osteonecrosis of the femoral head, the authors obtained 37 asymptomatic human femoral heads at autopsy; of these, 13 were cases of high dosage corticosteroid therapy (steroid group) and 24 were cases without steroid therapy (nonsteroid group). The steroid group included two asymptomatic cases of osteonecrosis incidentally recognized. These femoral heads then were studied histologically and morphometrically using 2-mm stepwise tissue sections of the whole femoral head and serial sections to examine the histopathologic alterations of superior retinacular arteries and veins in detail. There was no significant difference in the luminal stenotic rate of the superior retinacular arteries between the steroid and nonsteroid groups. However, the draining veins morphometrically were more stenotic or obliterated in the steroid group than were those in the nonsteroid group. In fact, the number of stenotic veins was significantly greater in the steroid group. These findings indicate that the stenotic changes of the draining veins may participate in the development and progression of steroid induced osteonecrosis of the femoral head.

Adult↗
PubMed1997

[Home infusion therapy for cancer patients at a near-terminal stage--analysis of cases who died at home].

To improve the quality of life in cancer patients at a near-terminal stage, we assisted patients to stay home using a system for home infusion therapy (HIT) established at Osaka Prefectural Habikino Hospital in 1994. From April in 1995 to April in 1996, 25 patients were treated at home using the HIT system for longer than 7 days. Thirteen out of 25 patients still stayed at home even at a terminal stage and died in their residences. There was no difference either in the mean age or in the HIT duration between 13 patients who died at home and the remaining 12 patients who were readmitted to their hospitals before death. However, 47% of the patients who died at home had been told their diagnoses by doctors and realized their own prognoses, while only 17% of the patients who died in the hospital knew their diagnoses and prognoses. Seventy-seven percent of the patients who died at home were given home oxygen therapy (HOT), against 33% of the patients who died in the hospital. Furthermore, the patients who died at home were given more intensive care than the patients who died in the hospital, because the former had a larger family than the latter. In conclusion, HIT at a near-terminal stage and death at home may be more readily accepted by patients who know their diagnoses and prognoses and have a large family.

Adult↗
PubMed1997

[Binocular functions in amblyopia and strabismus].

Regarding the changing trends in the concept, definition, etiological classification, and criteria for diagnosis of amblyopia, we reviewed a total of 4,693 cases of amblyopia seen during the past 37 years. The amblyopia was divided into four types: strabismic, anisometropic, ametropic, and form vision deprivative. There was a definite trend for the incidence to decrease and for the diagnosis to be made during earlier age in recent years. Although favorable recovery of visual acuity is obtained after treatment of amblyopia and strabismus, there are difficulties in obtaining good binocular functions in early-onset amblyopia and strabismus. This feature was evaluated in regard to motion perception asymmetry (MPA) and binocular depth from motion (DFM). Many cases of early-onset amblyopia and strabismus showed no disparity stereopsis, or position stereopsis, in spite of the presence of DFM. The MPA appeared to be closely related to early-onset esotropia regardless of age, while it disappeared and motion perception became symmetric 4 to 5 months after birth in normal infants. The DFM seemed to play an important role in maintaining good motor alignment for several years after surgery. I developed a checkerboard pattern stimulator in 1978. This method proved to be useful in developing binocular functions and motor alignment by applying simultaneous bifoveolar stimulation and anti-suppression. Extensive exposure to the stimulation was essential for therapeutic success.

Adolescent↗
PubMed1997

[Significance of residual renal functions of patients with end-stage renal failure undergoing continuous ambulatory peritoneal dialysis].

It is generally accepted that residual renal function remains well-preserved longer with CAPD than with hemodialysis. However, consideration and impact of the contributory effects of residual renal function on the adequacy of renal replacement therapy has not been well defined. In this report, creatinine clearance (Ccr), Kt/V, normalized protein catabolic rate (nPCR) and urinary excretion of uremic solutes were studied in 26 stable CAPD patients with a four-bag exchange. Weekly Ccr, weekly Kt/V and nPCR were 62.3 +/- 20.2 l/week/1.73 m2, 1.77 +/- 0.35, and 0.90 +/- 0.13 g/kg/day, respectively. These parameters correlated significantly with the daily urine volume. The weekly Ccr and Kt/V of anuric patients seemed to be inadequate. Urinary excretion of urea nitrogen, Cr, Na, Cl, Pi and beta 2-microglobulin (beta 2-MG) were dependent upon the daily urine volume. Significant phosphorus and beta 2-MG excretion seemed to have an effect on the prevention of bone and joint complications, because serum iPTH and beta 2-MG levels increased after the patients fell into an anuric state. It was suggested from this study that CAPD should be started before the patient loses residual renal function because four bag exchange as the standard CAPD prescription might not be adequate once the patient loses urine excretion.

Adult↗