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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 91 records · Page 5Linked to original sources

Angiotensin converting enzyme polymorphism is associated with severity of coronary heart disease and serum lipids (total cholesterol and triglycerides levels) in Japanese patients.

BACKGROUND: Much past research has concerned the relationship between coronary heart disease and the angiotensin converting enzyme (ACE) genotype, with many lines of evidence demonstrating polymorphism to be an independent risk factor for myocardial infarction. Interestingly, however, association of ACE polymorphism and severity of coronary artery stenosis according to racial background has recently been proposed. OBJECTIVE: To clarify the relationship between the ACE genotype and severity of coronary artery stenosis in Japanese patients. METHODS: In 36 consecutive patients undergoing coronary catheterization, comparative examination of coronary angiography findings with the ACE genotype was conducted. RESULTS: The severity of coronary artery stenosis indeed showed a relationship with the ACE genotype, with more severe coronary artery stenosis associated with the deletion (D) allele (P < 0.05). The serum lipids, total cholesterol and triglycerides levels, were also elevated in patients with the D allele (P < 0.05). CONCLUSION: We have provided further evidence that ACE polymorphism is associated with severity of coronary heart disease in a Japanese population. A possible relationship between serum lipids and the ACE genotype is also suggested.

Biomarkers

Paraneoplastic pemphigus: report of a case.

A 56-year-old male with chronic lymphocytic leukemia developed extensive erosive mucocutaneous lesions with histologic acantholysis. Immunopathologic studies showed IgG deposition at the intercellular space, C3 deposition at both the intercellular space and the dermo-epidermal junction, and reactivity of the serum to rat urinary bladder epithelium. Autoantibodies in the serum to human epidermal proteins of 210 kD and 190 kD were shown by Western blotting and to proteins of 250 kD, 210 kD, and 190 kD by immunoprecipitation. All these data suggest the diagnosis of paraneoplastic pemphigus. Repeated plasmapheresis resulted in re-epithelialization of the mucocutaneous lesions and reduction in antibody titer from 1:1280 to 1:20. Although this mucocutaneous disease was established as a new autoimmune bullous disease by Anhalt et al. (1990), cases have rarely been reported from Japan. The present patient demonstrates the major characteristics of paraneoplastic pemphigus.

Autoantibodies

Human T-lymphotropic virus type II in Japan.

Serum specimens were assayed for human T-lymphotropic virus type II(HTLV-II) infection in 1,500 individuals known to be seropositive for HTLV-I and 30,000 blood donors in Japan. All HTLV-I-positive individuals were negative for HTLV-II. However, one of the blood donors was clearly seropositive for HTLV-II. Further, the donor was shown to be positive for HTLV-IIb. Here we report at least one case with HTLV-II in Japan and discuss the origin of the infection.

Adult

Multiple primary cancers with microsatellite instability: report of a case.

We report here a patient who developed a variety of tumors both synchronously and metachronously over a 2-year period. The involved organs were the uterus, ureter, and small and large intestines. The patient underwent open surgery 3 times and polypectomies 6 times. Postoperative histopathologic analysis showed 2 adenomas and 8 carcinomas. Genetic analysis revealed microsatellite instabilities at the tested loci in all 10 tumors, indicating that replication errors played an essential role in the tumorigenesis. Early identification of microsatellite instability could be useful for predicting development of additional primary cancers.

DNA, Neoplasm

Clinical features of measles in immunocompromised children.

Measles is often fatal for immunocompromised hosts. Protective immunity against measles has been studied but is still not completely understood. Recently, five cases of measles were encountered in immunocompromised children. Two of these were allogeneic bone marrow transplanted cases (one common variable immunodeficiency and one severe aplastic anemia) in remission, one Wilms' tumor case in remission, one hepatoblastoma case after cytotoxic therapy at disease onset and one exaggerating hemophagocytic syndrome case with suppressed natural killer cell activity. Clinical symptoms, laboratory findings and the immunologic backgrounds of these five patients were investigated. One of the patients, an 8 year old boy with hemophagocytic syndrome, died of giant cell pneumonia which was confirmed in the section of necropsy lung specimen. Two other patients who received allogeneic bone marrow transplants were not immune to measles, despite their own and their donors' immunizations. Their clinical symptoms were rather severe but both patients recovered and have remained seropositive for as long as 13 months. This fatality from measles is the first reported in a patient with hemophagocytic syndrome. Suppressed natural killer cell activity may be a poor prognostic factor. Also, secondary immunization failure for measles can occur in bone marrow transplanted patients with rather severe clinical symptoms.

Adult

Oestradiol-induced relaxation of rabbit basilar artery by inhibition of voltage-dependent Ca channels through GTP-binding protein.

1. Effects of oestradiol on the electrical and mechanical properties of the rabbit basilar artery were investigated by use of microelectrode, patch-clamp and isometric tension recording methods. 2. Oestradiol (10 nM-100 microM) relaxed arterial tissue pre-contracted by excess [K]o solution (30 mM) in a concentration-dependent manner. In Ca-free solution, histamine (10 microM) and caffeine (20 mM) each produced a phasic contraction, but oestradiol (10 microM) did not significantly affect their amplitude. 3. Oestradiol (< or = 100 microM) did not change the resting membrane potential of the artery whether in the presence or absence of TEA (10 mM). Action potentials observed in the presence of 10 mM TEA were abolished by oestradiol (100 microM). 4. Oestradiol (1 microM-100 microM) inhibited the voltage-dependent Ba current in a concentration-dependent manner. Oestradiol (100 microM) inhibited the Ba current observed in the presence of nicardipine (1 microM) more than that in the absence of nicardipine (to 31.0% vs 62.0% of control). 5. GTP gamma S (30 microM) in the pipette enhanced the inhibitory actions of oestradiol on the Ba current. On the other hand, with GDP beta S (1 mM) in the pipette, oestradiol failed to inhibit the Ba current. Pertussis toxin (PTX 3 micrograms ml-1) in the pipette totally prevented the inhibitory action of oestradiol on the Ba current. 6. Oestradiol (< or = 100 microM) had no significant effect on the outward K currents evoked by a membrane depolarization. 7. These results strongly suggest that oestradiol relaxes arterial tissue by inhibition of voltage-dependent Ca channels and that it inhibits both nicardipine-sensitive and -resistant Ca currents via a PTX-sensitive GTP-binding protein. The main target of oestradiol among the arterial Ca channels seems to be the nicardipine-resistant Ca channel, rather than the nicardipine-sensitive one.

Animals

Analysis of the critical sites for protein thermostabilization by proline substitution in oligo-1,6-glucosidase from Bacillus coagulans ATCC 7050 and the evolutionary consideration of proline residues.

To identify the critical sites for protein thermostabilization by proline substitution, the gene for oligo-1,6- glucosidase from a thermophilic Bacillus coagulans strain, ATCC 7050, was cloned as a 2.4-kb DNA fragment and sequenced. In spite of a big difference in their thermostabilities, B. coagulans oligo-1,6-glucosidase had a large number of points in its primary structure identical to respective points in the same enzymes from a mesophilic Bacillus cereus strain, ATCC 7064 (57%), and an obligately thermophilic Bacillus thermoglucosidasius strain, KP1006 (59%). The number of prolines (19 for B. cereus oligo-1,6-glucosidase, 24 for B. coagulans enzyme, and 32 for B. thermoglucosidasius enzyme) was observed to increase with the rise in thermostabilities of the oligo-1,6-glucosidases. Classification of proline residues in light of the amino acid sequence alignment and the protein structure revealed by X-ray crystallographic analysis also supported this tendency. Judging from proline residues occurring in B. coagulans oligo-1,6-glucosidase and the structural requirement for proline substitution (second site of the beta turn and first turn of the alpha helix) (K. Watanabe, T. Masuda, H. Ohashi, H. Mihara, and Y. Suzuki, Eur. J. Biochem. 226:277-283, 1994), the critical sites for thermostabilization were found to be Lys-121, Glu-290, Lys-457, and Glu-487 in B. cereus oligo-1,6-glucosidase. With regard to protein evolution, the oligo-1,6-glucosidases very likely follow the neutral theory. The adaptive mutations of the oligo-1,6-glucosidases that appear to increase thermostability are consistent with the substitution of proline residues for neutrally occurring residues. It is concluded that proline substitution is an important factor for the selection of thermostability in oligo-1,6-glucosidases.

Amino Acid Sequence

Inhibition of aldosterone production by adrenomedullin, a hypotensive peptide, in the rat.

Recently, we conducted in vitro studies and reported that adrenomedullin, a novel hypotensive peptide, inhibits aldosterone secretion by dispersed rat adrenal zona glomerulosa cells. To assess the physiological role of this inhibitory effect, we investigated the effect of adrenomedullin on aldosterone production in vivo. Male Sprague-Dawley rats were fed a normal sodium diet before the experiments. To begin the experimental procedure, we stimulated aldosterone production with a sodium-deficient diet or bilateral nephrectomy. After 3 days of sodium depletion or immediately after nephrectomy, we injected synthetic human adrenomedullin (2.5 nmol/kg SC) and repeated the injection three times at 6-hour intervals. Two hours after the last injection, the rats were decapitated and adrenal capsular tissue was collected. Adrenomedullin had no effect on plasma and adrenal aldosterone concentrations in the rats fed a normal sodium diet. Rats fed a sodium-deficient diet had significantly increased aldosterone concentrations in both plasma (4770.1 +/- 364.3 pmol/L) and adrenal gland (57.34 +/- 3.27 pmol per adrenal). Subsequently, injection of adrenomedullin significantly inhibited increases in concentrations (plasma, 2648.9 +/- 313.2 pmol/L; adrenal, 44.28 +/- 4.94 pmol per adrenal). In nephrectomized rats, increased aldosterone concentrations in plasma and adrenal gland were also significantly inhibited by adrenomedullin. In the second part of the study, plasma renin concentration, adrenal renin activity, plasma corticosterone concentration, serum potassium concentration, and plasma immunoreactive adrenomedullin concentration were examined for adrenomedullin effects. The first four were unaffected, and the last, plasma immunoreactive adrenomedullin, was elevated 15% to 30%. These in vivo results, together with our in vitro data, suggest that adrenomedullin may indeed play a physiological role in the control of blood pressure and electrolyte balance.

Adrenomedullin

Plasma adrenomedullin concentration in patients with heart failure.

We measured plasma concentrations of adrenomedullin (AM), a novel bioactive peptide with potent vasodilator activity, in 21 patients with chronic congestive heart failure due to various heart diseases and compared them to levels in age- and sex-matched healthy subjects to examine the pathophysiological role of plasma AM in heart failure. In addition, the relationship between plasma AM and other hormones known to control the cardiovascular system was examined in these patients. The plasma AM level in the patients with heart failure was significantly (P < 0.01) higher than that in the control subjects (mean +/- SEM, 2.94 +/- 0.15 fmol/mL; n = 16), with a significantly (P < 0.05) higher concentration in patients in class III or IV (11.82 +/- 1.81 fmol/mL; n = 5) of the New York Heart Association functional classification than in those in class I or II (8.74 +/- 0.44 fmol/mL; n = 16). There were no significant correlations between plasma AM and catecholamine levels, whereas the plasma AM level was significantly correlated with the concentrations of plasma atrial natriuretic peptide (r = 0.58; P < 0.01), brain natriuretic peptide (r = 0.47; P < 0.05), and PRA (r = 0.77; P < 0.01) in the patients. Thus, the plasma AM concentration increased in proportion to the severity of heart failure along with the hormones known to modulate the development of congestive heart failure. The present findings suggest a possible role for AM as a circulating hormone participating in the defense mechanism against further deterioration of congestive heart failure in patients with heart disease.

Adrenomedullin

Chronic effect of beta-adrenoceptor blockade on plasma levels of brain natriuretic peptide during exercise in essential hypertension.

Many factors have been reported to stimulate the release of brain natriuretic peptide (BNP) as well as atrial natriuretic peptide (ANP). In hypertensive patients, however, little is known about whether these factors differ from those in normotensive subjects or if they are influenced by antihypertensive treatment. We measured the plasma concentrations of BNP and ANP in 12 hypertensive patients and examined the chronic effects of beta-adrenoceptor blockade on BNP secretion during exercise with a bicycle ergometer. The exercise raised both plasma BNP and ANP with concomitant increases in systolic blood pressure, heart rate (HR) and plasma norepinephrine (NE) and epinephrine (Epi) before and after treatment. Before treatment, the changes in ANP and BNP correlated with that in HR (p < 0.05). After treatment 4 wk of treatment, the change in ANP correlated with those in NE and Epi as well as HR. Multivariate regression analysis indicated that only NE was a significant stimulus for ANP secretion during the treatment period. As for BNP, HR was the only significant stimulant for its secretion both before and after treatment. In essential hypertension, beta-adrenergic receptor blockade affected the factors stimulating exercise-induced ANP release but not those stimulating BNP release. BNP release, therefore, seems to be stimulated by similar but distinct factors from those that stimulate ANP release.

Adrenergic beta-Antagonists

The differences in the expressions of visual pigments and transducin in photoreceptor cell differentiation.

The distribution and accumulation of visual pigments, i.e., rod pigment, rhodopsin and red sensitive cone pigment, iodopsin, and transducin in the retina of chicken and chicken embryo were investigated immunohistochemically using their specific antibodies. The immunoreactivities of these proteins appeared at the early stage of photoreceptor differentiation (embryonal day 15) and increased in the photoreceptor cells appeared to reach maximum at the end of the embryonal period (embryonal day 20). On the other hand, although the immunoreactivity of beta gamma subunit of transducin (T beta gamma) was detected at embryonal day 15, the expression level of T beta gamma still remained in low level during the embryonal period. These observations suggest that both T beta gamma and visual pigments are expressed during the embryonic period in chicken photoreceptor cells, but their accumulations in the cells are different.

Animals

Early gastric cancer in young adults.

The clinicopathological features of 31 young patients with early gastric cancer, defined as under 40 years of age, were reviewed retrospectively from hospital records between 1969 and 1993. The results were compared with those for 549 patients 40 years of age or older. Early gastric cancer was found in 36.0% of the younger patients with gastric cancers and in 36.3% of the older patients with those. The gender ratio of m/f was 1.21 for the younger patients and 2.37 for the older patients. The macroscopic characteristics of early gastric cancer for the younger patients were superficial depressed lesions and a larger tumor size. The distinguished histologic features of early gastric cancer for the younger patients were a diffuse type of cancer and infiltrative tumor growth with a scirrhous stroma. More extensive lymph node dissection was performed on the younger patients than on the older patients. The younger patients had a prognosis similar to that of the older patients. We conclude that early gastric cancer in young patients possesses histological aggressiveness, but those patients rather show a similar survival to older patients.

Adult

Fight against infectious diseases.

During early Meiji era in Japan, there were frequent epidemics of fatal acute communicable diseases such as cholera, dysentery and smallpox, and preventive measures and preparations for acute infectious diseases were urgently needed. Together with improvement of scientific preparations, the Communicable Disease Prevention Law was promulgated in 1897. Then gradually until 1940's, the focus of preventive measures have been shifted from acute infectious diseases to chronic ones, particularly tuberculosis. After the World War II, except the short period of social confusion, major legally-defined communicable diseases had been decreasing rapidly mainly due to the use of antibiotics and improvement of environmental sanitation. At the same time, the introduction of preventive vaccination marked a new era for the prevention of infectious diseases and was largely responsible for the remarkable decrease of infant mortality in Japan. Recently the concept of defense by vaccination against infectious diseases has evolved from group-oriented to individual-oriented, so that the Preventive Vaccination Law was drastically revised in 1994. Currently, effective counter-measures against newly emerged infectious diseases, as viral hepatitis, institution-acquired infection, viral hemorrhagic fever etc., have been implemented. For the future, improvement of infections disease surveillance, vaccine development and expansion of vaccination coverage along with monitoring side-effects, preventive health education on AIDS/STDs, addressing the special needs of foreigners living in Japan and international collaboration for disease control abroad are all vital to the success of protection of the public's health from infectious diseases in Japan.

Communicable Disease Control

Mitochondrial DNA mutation at nucleotide 1555 in a patient with bilateral sensorineural hearing loss of unknown etiology.

A mitochondrial DNA mutation at nucleotide 1555 in the ribosomal RNA gene was recently reported as a cause of maternally inherited non-syndromic sensorineural deafness. We assumed that the 1555 mutation is also associated with sporadic non-syndromic deafness and screened for the mutation in seven randomly selected sporadic cases with bilateral sensorineural hearing loss of unknown etiology. The mutation was found in one patient, who first noticed hearing loss when she was in her early teens with subsequent gradual progression. The results suggest that the 1555 mutation may contribute to the etiology of idiopathic bilateral sensorineural hearing loss in some cases.

Adult

Adrenomedullin: changes in circulating and cardiac tissue concentration in Dahl salt-sensitive rats on a high-salt diet.

Adrenomedullin (AM), a novel hypotensive peptide, is suggested to be involved in defense mechanisms against hypertension, however, the detail mechanisms have not been clarified. To elucidate whether AM synthesis would be altered in a salt dependent hypertension, we have investigated the AM concentration and AM messenger RNA (mRNA) level in tissues of Dahl salt-sensitive rats on either low- or high-salt intake. The AM concentration in cardiac ventricle of the high-salt group was significantly higher than that of the low-salt group. The plasma AM concentration was also significantly higher in the high-salt group than in the low-salt group. Furthermore, the plasma AM concentration correlated well with the weight of left ventricle. RNA blot analysis revealed that the AM mRNA level in cardiac ventricle of the high-salt group was higher than that of the low-salt group. These results suggest that AM participates in the pathophysiology of salt dependent hypertension and plays a role in cardiac hypertrophy.

Adrenomedullin

[Chemotherapy with low-dose consecutive cisplatin (CDDP) for patients with recurrent and distant metastasis of head and neck cancer].

Treatment with low-dose consecutive cisplatin (CDDP) was performed on six patients with recurrent and distant metastasis of head and neck squamous cell carcinoma. All patients were men, and their ages ranged from 64 to 86 years with an average of 75. Primary treatments were radiotherapy and surgery in three patients, chemotherapy and radiotherapy in two patients, and radiotherapy, regional chemotherapy and surgery in one patient. Two patients had laryngeal recurrent carcinomas, one patient had nasopharyngeal recurrent carcinoma, one patient had recurrent metastatic neck lymph node and two patients had distant metastasis (lung and brain). CDDP was administered over consecutive seven days, with a daily dose of 10mg/m2 as continuous drip infusion for 148 hours from day 1 to day 7. Four patients received two courses, while two patients received one course. The overall response rate was 33%, which was restricted to a partial response in two patients. These patients were still alive about one year after treatment. No toxic effect was observed. The present study indicated that low-dose consecutive CDDP was safe and efficacious for patients with recurrent head and neck squamous cell carcinoma.

Aged