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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 37 records · Page 2Linked to original sources

Tubulointerstitial macrophage infiltration in a patient with hypokalemic nephropathy and primary Sjögren's syndrome.

We report a case of hypokalemic nephropathy associated with primary Sjögren's syndrome (SS). The patient presented with profound and persistent hypokalemia secondary to distal renal tubular acidosis (RTA). A renal biopsy exhibited tubular degeneration, marked interstitial fibrosis and intense macrophage infiltration. Hypokalemia has been reported to induce macrophage infiltration in experimental animal models but not in humans. This is the first report of intense tubulointerstitial macrophage infiltration in a patient with hypokalemic nephropathy associated with SS.

Adult↗

CyberKnife radiosurgery for vestibular schwannoma.

OBJECTIVE: The CyberKnife is newly developed equipment for radiosurgery and fractionated radiosurgery. The authors report on their experience using the CyberKnife in 38 patients with vestibular schwannoma who were treated between 1998 to 2002. METHODS: During this period, 38 patients with vestibular schwannoma were treated using CyberKnife fractionated radiosurgery. Before undergoing fractionated radiosurgery, 14 patients had Gardner Robertson classes I or II hearing (the serviceable hearing group), and 24 patients had classes III to V hearing (the non-serviceable hearing group). The treatment volumes of these two groups were 0.5 to 24.0 cm (3) (mean 4.7 cm (3)), and 0.5 to 41.6 cm (3) (mean 8.2 cm (3)). Target irradiation was administered in 1 - 3 fractions (mean 2.5 fractions). The total marginal radiation doses were 15.0 to 20.5 Gy (mean 17.0 Gy), and 11.9 to 20.1 Gy (mean 16.9 Gy), respectively. RESULTS: After a mean follow-up period of 31.9 months (range 12 to 59 months, median 27 months), 94 % of the tumors were controlled. Only one patient in the group with non-serviceable hearing underwent additional surgical resection for a presumed increase in tumor size. The hearing preservation rate was 93 %. Facial weakness did not develop in any of the patients in the serviceable hearing group. New trigeminal symptoms did not develop in any patients in either group. CONCLUSION: Although a longer and more extensive follow-up is needed, CyberKnife fractionated radiosurgery is considered to be safe and effective, even in patients with large tumors.

Adolescent↗

Impairment of gastrointestinal motility by nitrate administration: evaluation based on electrogastrographic changes and autonomic nerve activity.

BACKGROUND: Nitrates decrease the tone of the lower oesophageal sphincter, and may thus induce gastro-oesophageal reflux. AIM: In the present study, we evaluated electrogastrographic changes and heart-rate variability before and after the administration of nitrates. METHODS: In 15 patients with chest pain treated with nitrates, electrocardiography and percutaneous electrogastrography were performed before and after administration of nitrates. Autonomic nervous system function was evaluated by spectral analysis of heart-rate variability and serial changes in low frequency and high frequency power, and the low frequency/high frequency ratio were compared. Electrogastrograms were analysed by obtaining peak power amplitudes and their dominant frequencies. RESULTS: After the administration of nitrates (isosorbide dinitrate), high frequency power, an index of parasympathetic nervous activity, was significantly decreased, whereas the low frequency/high frequency ratio, an index of sympathetic nervous activity, was significantly increased. The mean peak amplitude of the electrogastrogram significantly increased postprandially both before and after treatment. After isosorbide dinitrate treatment, however, mean peak amplitudes after a meal were significantly lower than those obtained before treatment. The mean dominant frequency of the electrogastrogram did not vary before and after treatment. CONCLUSIONS: The present study suggests that nitrates inhibit gastrointestinal motility by decreasing autonomic nervous activity.

Aged↗

Inherited cardiomyopathies as a troponin disease.

Troponin, one of the sarcomeric proteins, plays a central role in the Ca(2+) regulation of contraction in vertebrate skeletal and cardiac muscles. It consists of three subunits with distinct structure and function, troponin T, troponin I, and troponin C, and their accurate and complex intermolecular interaction in response to the rapid rise and fall of Ca(2+) in cardiomyocytes plays a key role in maintaining the normal cardiac pump function. More than 200 mutations in the cardiac sarcomeric proteins, including myosin heavy and light chains, actin, troponin, tropomyosin, myosin-binding protein-C, and titin/connectin, have been found to cause various types of cardiomyopathy in human since 1990, and more than 60 mutations in human cardiac troponin subunits have been identified in dilated, hypertrophic, and restrictive forms of cardiomyopathy. In this review, we have focused on the mutations in the genes for human cardiac troponin subunits and discussed their functional consequences that might be involved in the primary mechanisms for the pathogenesis of these different types of cardiomyopathy.

Cardiomyopathy, Dilated↗

Tei index determined by tissue Doppler imaging in patients with pulmonary regurgitation after repair of tetralogy of Fallot.

The myocardial performance index (Tei index) determined by the pulsed Doppler method is a simple and noninvasive measurement for assessing global right ventricular (RV) function. This index can also be obtained by tissue Doppler imaging (TDI). The effects of significant pulmonary regurgitation (PR) on the determination of the Tei index by these two methods have not been investigated. We examined 15 patients (6.3 +/- 2.2 years) with significant PR after repair of tetralogy of Fallot (TOF) and 24 age-matched healthy children. Myocardial wall motion velocities at the tricuspid annulus were assessed during systole (Sa), early diastole (Ea), and late diastole (Aa) from a four-chamber view. Pulsed Doppler-Tei index and TDI-Tei index were measured as reported previously. The Tei index obtained by the pulsed Doppler method in TOF patients did not differ from that in normal children (0.30 +/- 0. 12 vs 0.32 +/- 0.07, p = not significant). TDI showed that TOF patients had significantly decreased Ea, Aa, and Sa velocities compared to those of normal children. Both isovolumic contraction time and isovolumic relaxation time in TOF patients were significantly longer than those in normal children (88 +/- 18 vs 62 +/- 23 msec and 46 +/- 11 vs 21 +/- 12 msec, respectively; p < 0.0001), although the duration of Sa did not differ between the two groups. Consequently, the Tei index as measured by TDI was significantly greater in TOF patients than in normal children (0.48 +/- 0.07 vs 0.30 +/- 0.07, p < 0.0001). The Tei index measured by the pulsed Doppler method is limited in its ability to assess RV function in patients with significant PR. However, the Tei index determined by TDI is a sensitive indicator of RV function in these patients, and it appears to be a promising new means of assessing global RV function in patients with significant PR.

Blood Flow Velocity↗

Perfluorooctane sulfonate concentrations in surface water in Japan.

Perfluorooctane sulfonate (PFOS) is a class of specialty chemicals used in a variety of applications, and has been found to be globally distributed in many living organisms including humans. Several analytical methods have been developed for determination of PFOS in environmental samples and biological matrices. However, these methods employ liquid chromatography/tandem mass spectrometry (LC/MS/MS), an instrumentation which has limited accessibility because it is expensive to use and maintain. In the present study we present the development of a robust analytical method using liquid chromatography/mass spectrometry (LC/MS) in combination with solid phase extraction. The high yield and concentration of the present method enabled us to quantify PFOS as low as 0.1 ng/L. This method was applied to the determination of PFOS in 142 surface water samples collected from various geographic locations around Japan. The geometric mean (geometric standard deviation) (ng/L) for river samples (n = 126) was 2.37 (4.13), with a median of 1.68 and a range of 0.3-157 ng/L, and for coastal sea water samples (n = 16) was 1.52 (4.14), with a median of 1.21 and a range of 0.2-25.2 ng/L. However, the concentrations in most of the samples were much lower than the values reported in the US, except for those from the Jinzu (135.0 ng/L) and Tama (157 ng/L) Rivers. Because surface waters in the Ara (13.0-38.5 ng/L), Tama (0.7-157.0 ng/L), and Yodo (0.9-27.3 ng/L) Rivers, sources of drinking water for more than eight million people, were moderately contaminated with PFOS, more work is needed to assess exposure to PFOS.

Alkanesulfonic Acids↗

A new 68Ge/68Ga generator system using an organic polymer containing N-methylglucamine groups as adsorbent for 68Ge.

A macroporous styrene-divinylbenzene copolymer containing N-methylglucamine groups was selected for a new 68Ge/68Ga generator system. This resin packed into a column effectively adsorbed the parent nuclide 68Ge. The daughter 68Ga was eluted from the resin with a solution of a low-affinity gallium chelating ligand such as citric or phosphoric acid. The 68Ge leakage was less than 0.0004% of the 68Ge adsorbed on the resin. By simple mixing of transferrin and desferoxamine conjugated HSA and IgG with the eluate from the column, 68Ga-labeling was completed in high yield.

Adsorption↗

Cisplatin induces apoptosis in oral squamous carcinoma cells by the mitochondria-mediated but not the NF-kappaB-suppressed pathway.

Cisplatin (CDDP) is a potent DNA-damaging anticancer agent, and its cytotoxic action is exerted by the induction of apoptosis. However, activation of the transcription factor NF-kappaB results in protection against apoptosis. We examined the molecular mechanisms involved in the induction of apoptosis by CDDP as regards both suppression of NF-kappaB and activation of caspases. Human oral squamous carcinoma cells (B88) were employed in this study. We found that CDDP treatment affected neither NF-kappaB activity nor the expression levels of antiapoptotic proteins, including TRAF-1, TRAF-2, and cFLIP, in B88 cells. However, two apoptosome molecules, cytochrome c and Apaf-1, were significantly augmented in the cytoplasm by CDDP treatment. Further, the activation of caspase-9 and caspase-3, downstream molecules leading to mitochondria-mediated apoptosis, were detected after treatment with CDDP. Finally, apoptosis was also clearly observed, as evidenced by cleavage of PARP through the activation of caspase-3. These findings suggest that CDDP exerts its apoptotic action by the mitochondria-mediated activation of caspases but not by the activation of caspases due to the inhibition of NF-kappaB activity that follows the suppression of antiapoptotic proteins.

Antineoplastic Agents↗

Hepatic 'stem cell' malignancies in adults: four cases.

AIMS: Combined hepatocellular/cholangiocarcinomas have been explained by some investigators as bidirectional differentiation of neoplastic progenitor cell populations. The presence of hepatic progenitor cells has now been confirmed in humans, though whether they can give rise to malignant tumours has not been confirmed. We report four cases of small tumours identified in livers with features of chronic hepatitis which may suggest a role for malignant transformation of hepatic stem cells in hepatic malignancies. METHODS: Tumour samples were studied from four patients by histochemistry and immunohistochemistry. RESULTS: Two patients had chronic hepatitis B, one had chronic hepatitis C and chronic alcoholic liver injury, and one had non-B non-C chronic hepatitis. Stages of disease ranged from portal fibrosis to cirrhosis. All tumours contained undifferentiated cells with morphological and immunohistochemical features that would be expected of hepatic progenitor cells. These cells merged with both hepatocellular carcinoma and cholangiocarcinoma components as well as with mature appearing hepatocytes within the tumours. CONCLUSION: We suggest that these tumours are of hepatic progenitor cell origin, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells and that such a process may underlie development of some mixed hepatocellular/cholangiocarcinomas and dysplastic nodules.

Aged↗

Long-term follow-up of large flat colorectal tumors resected endoscopically.

BACKGROUND AND STUDY AIM: When a large flat colorectal tumor is excised by piecemeal endoscopic resection, it is not possible to obtain suitable specimens for histopathological examination to assess whether the resection has been complete. We prospectively analysed follow-up colonoscopy examinations of endoscopic polypectomy resection sites for residual lesions. PATIENTS AND METHODS: A total of 24 patients with large flat colorectal tumors were treated using an endoscopic submucosal saline injection technique. The resection site was prospectively examined for residual lesions using a magnifying colonoscope, at 3, 6, 12 and 24 months postoperatively. RESULTS: None of the 5 patients who underwent en bloc resection exhibited residual lesions postoperatively. Of the 19 patients who underwent piecemeal resection, one died of an asthma attack and 18 were followed up. Residual lesions were detected in four of these 18 patients (three adenomas and one cancer), which were resected endoscopically. When the tumor was resected endoscopically en bloc and was judged histologically to be completely resected, residual lesions were not detected at follow-up. However, residual lesions were detected in 22.2 % of patients 3 months after initial resection when polyps were resected piecemeal. After treatment, residual lesions were detected in two patients (11.1 %) at 24 months. CONCLUSION: After piecemeal endoscopic resection for large flat colorectal tumors, it is necessary to follow-up and remove residual lesions endoscopically every 3 months until they all are removed.

Adenocarcinoma↗

Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death.

OBJECTIVE: To investigate the clinical outcome, ECG characteristics, and optimal treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), a malignant and rare ventricular tachycardia. PATIENTS AND METHODS: Questionnaire responses and ECGs of 29 patients with CPVT were evaluated. Mean (SD) age of onset was 10.3 (6.1) years. RESULTS: The initial CPVT manifestations were syncope (79%), cardiac arrest (7%), and a family history (14%). ECGs showed sinus bradycardia and a normal QTc. Mean heart rate during CPVT was 192 (30) beats/min. Most cases were non-sustained (72%), but 21% were sustained and 7% were associated with ventricular fibrillation. The morphology of CPVT was polymorphic (62%), polymorphic and bidirectional (21%), bidirectional (10%), or polymorphic with ventricular fibrillation (7%). There was 100% inducement of CPVT by exercise, 75% by catecholamine infusion, and none by programmed stimulation. No late potential was recorded. Onset was in the right ventricular outflow tract in more than half the cases. During a follow up of 6.8 (4.9) years, sudden death occurred in 24% of the patients, 7% of whom had anoxic brain damage. Autosomal dominant inheritance was seen in 8% of the patients' families. beta Blockers completely controlled CPVT in only 31% of cases. Calcium antagonists partially suppressed CPVT in autosomal dominant cases. CONCLUSIONS: CPVT may arise in certain distinct areas but the prognosis is poor. The onset of CPVT may be an indication for an implanted cardioverter-defibrillator.

Adolescent↗

Intrahepatic bile duct loss in immune-mediated ductopenic biliary diseases with an emphasis on biliary epithelial apoptosis.

The biliary epithelial apoptosis is thought to be a major pathogenic process of bile duct loss in a number of immune-mediated ductopenic biliary diseases, though its exact mechanism and process seem still speculative. Clarification of pathologic microenvironments around the bile ducts as well as pathobiology of biliary epithelial cells undergoing apoptosis in these diseases are mandatory. Several steps and mechanisms during induction and progression of biliary epithelial apoptosis followed by bile duct loss are now being proposed in immune-mediated ductopenic biliary diseases: 1) the presentation of target antigens including autoantigen(s) in biliary epithelial cells; 2) network of cytokine and its imbalance around the damaged bile ducts; 3) migration of immune-competent cells into the biliary layer followed by cell-to-cell and cell-to-matrix interaction and antibody-mediated cell dysfunction of biliary epithelial cells; and 4) increased susceptibility and decreased threshold for biliary epithelial apoptosis and aggravation of biliary epithelial apoptosis by infectious agents. We review here the pathogenetic processes of immune-mediated ductopenic biliary diseases.

Journal Article↗