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Biomedical subjects

K Nagai

Publications and source records attributed to K Nagai.

At least 37 records · Page 2Linked to original sources
PubMed2003

Involvement of vacuolar H+ -ATPase in incorporation of risedronate into osteoclasts.

Although osteoclasts incorporate bisphosphonates during bone resorption, the mechanism of this incorporation by osteoclasts is not known. We previously reported that bisphosphonates disrupt the actin rings (clear zones) formed in normal osteoclasts, but did not disrupt actin rings in osteoclasts derived from osteosclerotic oc/oc mice, which have a defect in the gene encoding vacuolar H(+)-ATPase (V-ATPase). The present study showed that V-ATPase is directly involved in the incorporation of risedronate, a nitrogen containing bisphosphonate, into osteoclasts. Treatment of osteoclasts with risedronate disrupted actin rings and inhibited pit formation by osteoclasts on dentine slices. Bafilomycin A(1), a V-ATPase inhibitor, inhibited the pit-forming activity of osteoclasts but did not disrupt actin rings. Risedronate failed to disrupt actin rings in the presence of bafilomycin A(1). E-64, a lysosomal cysteine proteinase inhibitor, showed no inhibitory effect on the demineralization of dentine by osteoclasts but inhibited the digestion of dentine matrix proteins without disrupting actin rings. Risedronate disrupted actin rings even in the presence of E-64. Treatment of osteoclasts placed on plastic plates with risedronate also disrupted actin rings. Bafilomycin A(1) but not E64 prevented the disruption of actin rings in osteoclasts treated with risedronate on plastic plates. Inhibition of V-ATPase with bafilomycin A(1) also prevented disruption of actin rings by etidronate, a non-nitrogen-containing bisphosphonate. These results suggest that V-ATPase induced acidification beneath the ruffled borders of osteoclasts and subsequent bone demineralization triggers the incorporation of both nitrogen-containing and non-nitrogen-containing bisphosphonates into osteoclasts.

Actins↗
PubMed2003

Destruxins, cyclodepsipeptides, block the formation of actin rings and prominent clear zones and ruffled borders in osteoclasts.

Bone-resorbing osteoclasts exhibit polarized morphological structures such as actin rings, clear zones, and ruffled borders. To gain insight into the mechanism of bone-resorbing activity of osteoclast and to discover new types of anti-resorptive agents, we have screened for natural compounds that inhibit the bone-resorbing activity of osteoclast-like multinucleated cells (OCLs). Destruxin B (DestB) and E (DestE), cyclodepsipeptides, were found to inhibit pit formation without affecting osteoclast differentiation and survival. Destruxins reversibly induced morphological changes in OCLs in a dose-dependent manner (DestB, 0.2-1 microM; DestE, 0.01-0.05 microM) and inhibited pit formation. Destruxin-induced morphological changes were accompanied by disruption of the actin rings in OCLs. The formation of actin rings in OCLs after adhesion was also inhibited by destruxins. Electron microscopical analysis revealed that destruxin-treated OCLs on dentine slices have no prominent clear zones and ruffled borders. The effective concentrations of destruxins on the morphological changes were almost the same as those that inhibited bone resorption in organ culture system. These results suggest that the anti-resorptive effects of destruxins result from induction of a disorder of the morphological structures in polarized OCLs.

Acid Phosphatase↗
PubMed2003

Pneumocystis carinii pneumonia in HIV/AIDS patients at an urban district hospital in Kenya.

BACKGROUND: Pneumocystis carinii pneumonia has generally been regarded to be an uncommon opportunistic infection in HIV infected individuals in sub-Saharan Africa. The reason for this has not been clear but postulates included a lack of suitable pathogenic types in the African environment, diagnostic difficulties and the more commonly held belief that African HIV infected individuals were dying early from common non-opportunistic pathogens before severe degrees of immunosuppression occured. Recently a trend has emerged at the Mbagathi district hospital whereby an increasing number of HIV infected patients are empirically treated for Pneumocystis carinii pneumonia (PCP) based on clinical and radiological features. OBJECTIVE: To determine the prevalence of PCP and clinical outcomes of HIV infected patients presenting at the Mbagathi District Hospital, Nairobi with the presumptive diagnosis of PCP. SETTING: Mbagathi District Hospital, a 169-bed public hospital in Nairobi, Kenya. METHODS: Patients presenting with a sub-acute onset of cough and dyspnoea were eligible for the study if they were found to have bilateral pulmonary shadows and had negative sputum smears for AFBS. Consenting patients who had no contraindication to fiberoptic bronchoscopy had a clinical evaluation which was followed with a fiberoptic bronchoscopy procedure where bronchoalveolar lavage fluid (BALF) was obtained. BALF was examined for cysts of P. carinii using toluidine blue stain and immunofluorescent antibody test (IFAT). BALF was also processed for fungi, bacteria and mycobacteria using routine procedures. Standard treatment with high dose cotrimoxazole was offered to all patients who were then followed up until discharge from hospital or death whichever came first. RESULTS: Between June 1999 and August 2000 a total of 63 patients were referred for bronchoscopy. Of these four declined to undergo the fiberoptic bronchoscopy procedure, four died before the procedure could be done, one was judged too sick to undergo the procedure and three had been on cotrimoxazole for longer than five days. Thus 51 patients underwent bronchoscopy. Pneumocystis carinii stain was positive in 19 (37.2%) while death occured in 16 (31.4%) of the 51 patients. There were more deaths in those without PCP but this difference was not statistically significant (odds ratio 0.68 (95% CI 0.35-1.32; P=0.2). CONCLUSION: PCP was found to be common in HIV infected patients presenting with clinical and radiological features of the disease. The mortality rate for patients with a presumptive diagnosis of PCP is high. This study suggests that cotrimoxazole preventive therapy may be a useful intervention in symptomatic HIV infected patients in Kenya for the prevention of PCP and may avert deaths from this disease.

AIDS-Related Opportunistic Infections↗
PubMed2002

Transverse sound in liquid-3He-aerogel system.

Transverse sound in normal liquid 3He in aerogel is studied on the basis of the Landau transport equation taking into account the simultaneous oscillation of the aerogel. We show that the nature of transverse sound is strongly modified if aerogel is immersed in the liquid. Scattering of 3He quasiparticles by the aerogel molecules causes friction between the liquid and the aerogel, giving rise to coupled motion of the two systems. There exists a low-attenuation transverse sound mode in this coupled system. The high-temperature behavior of its attenuation alpha is given by alpha proportional, variant const+T-2, which is in contrast to alpha proportional, variant T in pure liquid 3He in the hydrodynamic regime.

Journal Article↗
PubMed2002

Proposed double-layer target for the generation of high-quality laser-accelerated ion beams.

In order to achieve a high-quality, i.e., monoenergetic, intense ion beam, we propose the use of a double-layer target. The first layer, at the target front, consists of high-Z atoms, while the second (rear) layer is a thin coating of low-Z atoms. The generation of high-quality proton beams from the double-layer target, irradiated by an ultraintense laser pulse, is demonstrated with three-dimensional particle-in-cell simulations.

Ions↗
PubMed2002

A case of cancer on the pharyngoesophageal junction treated by ambulatory endoscopic mucosectomy.

A 52-year-old man underwent endoscopy because of discomfort in the hypopharyngeal region, and a 1.5-cm tumor was found on the pharyngoesophageal junction. In 1992, the patient was treated for advanced cervicothoracic esophageal cancer by preoperative chemotherapy and esophagectomy with radical lymph adenectomy and right thoracotomy. Reconstruction with a gastric substitute by cervical esophagogastrostomy was performed and postoperative adjuvant radiotherapy followed. Histologically, the esophageal tumor had invaded the adventitia and showed metastases to regional lymph nodes and vascular involvement with a free surgical margin. Hypopharynx was also included in the irradiation field. Therefore, we tried to resect another primary tumor on the pharyngoesophageal junction by the endoscopic mucosectomy technique with an esophageal multipurpose tube (np-EEM). The tumor was resected on August 21, 1996, but follow-up endoscopy revealed residual or another primary tumor on the pharyngoesophageal junction in October 1996. The first resected specimen revealed a positive cut margin that might indicate incomplete resection. Three months later we performed a second mucosectomy. No problems occurred during or after tumor resection. Both treatments were performed without hospitalization, and the patient returned to his normal daily life on the day following tumor resection. Follow-up examinations have shown no sign of cancer recurrence on the pharyngoesophageal junction for more than 4 years.

Ambulatory Surgical Procedures↗
PubMed2002

A new neuromodulatory pathway with a glial contribution mediated via A(2a) adenosine receptors.

A low concentration (10 nM) of adenosine potentiated hippocampal neuronal activity via A(2a) adenosine receptors without affecting presynaptic glutamate release or postsynaptic glutamatergic conductance. Adenosine inhibited glutamate uptake through the glial glutamate transporter, GLT-1, via A(2a) adenosine receptors. In addition, adenosine stimulated GLT-1-independent glutamate release from astrocytes, possibly in response to a rise in intracellular Ca(2+), via A(2a) adenosine receptors involving PKA activation. Those adenosine actions could lead to an increase in synaptic glutamate concentrations responsible for the potentiation of hippocampal neuronal activity. The results of the present study thus represent a novel neuromodulatory pathway with a glial contribution, bearing both inhibition of GLT-1 function and stimulation of glial glutamate release, as mediated via A(2a) adenosine receptors.

Adenosine↗
PubMed2002

Dechlorination and destruction of PCDD, PCDF and PCB on selected fly ash from municipal waste incineration.

The potential of fly ash to dechlorinate and destroy PCDD, PCDF and PCB was tested under oxygen deficient conditions in the laboratory. Specifically, two types of fly ash were compared, originating either from a fluidized bed incinerator using Ca(OH)2 spray (FA1), or a stoker incinerator without Ca(OH)2 impact (FA2). Results from the present study indicate that on FA2 type fly ash, the degradation processes of OCDD, OCDF and D10CB occurred primarily via dechlorination/hydrogenation up to temperature settings of 340 degrees C. In contrast, FAI type fly ash was found to effect both dechlorination and destruction of these compounds already at temperature settings of 260 degrees C. The dechlorination velocity of PCDD and PCDF did not differ significantly. However, the first dechlorination step of OCDF in the 1,9-position occurred faster compared to the first dechlorination step of OCDD. The isomer pattern resulting from the dechlorination processes was quite similar on both FAI and FA2, indicating that differences in alkalinity or elemental composition of the two types of fly ashes do not have a significant influence on the position of dechlorination. PCDD and PCDF dechlorination of the 2,3,7,8-positions was not favoured over dechlorination of the 1,4.6,9-positions on either type of fly ash. In contrast, dechlorination of PCB occurred predominantly on the toxicological relevant 3- and 4-positions. The dechlorination/destruction processes were completed on both types of fly ash at 380 degrees C within one hour, which correlates well with results obtained from actual plant operation practices.

Air Pollution↗
PubMed2002

Effects of selected metal oxides on the dechlorination and destruction of PCDD and PCDF.

OCDD and OCDF spiked silica/graphite based model fly ash containing various copper compounds and metal oxides were thermally treated under oxygen deficient conditions. All copper compounds tested showed a considerable dechlorination/hydrogenation reaction at 260 degrees C. After 30 min at 340 degrees C, less than 1% of the spiked OCDD and OCDF was recovered as T4CDD/F to OCDD/F. Other compounds tested demonstrated a lower rate of dechlorination compared to the copper compounds. However, all other metal oxides showed a small dechlorination effect at 260 degrees C, which was considerably increased at 340 degrees C. The model fly.ash containing the different copper compounds or metal oxides showed comparable PCDD and PCDF isomer patterns after thermal treatment. However, small differences were observed among the different tested compounds. The PCDD and PCDF isomer patterns on the model fly ashes were similar to patterns found during dechlorination experiments on fly ashes from waste incineration processes. Model fly ash containing Ca(OH)2 exhibited the highest destruction potential, but a low dechlorination potential. In contrast, model fly ash containing any of the remaining compounds tested, was found to predominantly dechlorinate the spiked OCDD and OCDF.

Benzofurans↗
PubMed2002

Single- and multistep selection study of the antipneumococcal activity of BMS-284756 compared to ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin.

Single- and Multi-step selection studies were used to test the ability of BMS-284756, ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin to yield resistant clones from 12 quinolone-susceptible and -resistant Streptococcus pneumoniae strains. Although all quinolones selected, to a greater or lesser degree, for resistant clones with mutations usually in parC or gyrA, BMS-284756 tended to select for resistant clones at a lower rate than other quinolones studied.

Anti-Infective Agents↗
PubMed2002

Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture of superficial esophageal carcinoma.

BACKGROUND AND STUDY AIMS: In this study we clarify the microvascular architecture of superficial esophageal carcinoma as observed by ultra-high magnification endoscopy and stereoscopic microscopy with Microfil injection. PATIENTS AND METHODS: We observed two surgically resected specimens of superficial esophageal cancer under stereoscopic microscopy with Microfil injection. In addition, in the histological investigation, we measured the caliber of the vessels at the surface of the tumor. We carried out ultra-high magnification before treatment in 82 patients with superficial esophageal neoplasms. We classified the depth of tumor penetration of superficial esophageal carcinoma into four categories: m1 to m3 (mucosal cancer) and sm (submucosal cancer). RESULTS: By observing the normal esophageal mucosa under a stereoscopic microscope and an ultra-high magnification endoscope, we were able to visualize the intrapapillary capillary loops (IPCL). In cancer lesions, we observed characteristic changes in the superficial microvascular architecture according to the depth of tumor invasion. In m1 invasion, there was dilatation of the IPCL; in m2 invasion, there was dilatation and elongation of the IPCL; in m3, there was a mixed appearance of the IPCL and tumor vessels; and in sm invasion, complete replacement by tumor vessels. On the basis of the above criteria, ultra-high magnification endoscopic observation before treatment showed a rate of agreement between histological depth of invasion and magnified appearance of 60/72 cases (83.3 %) for which satisfactory pictures were obtained. The histological investigation showed the caliber of the IPCL of the m1 cancer lesions (12.9 +/- 3.9 microm) to be significantly greater than that of the normal esophageal mucosa (6.9 +/- 1.5 microm) (P < 0.0001). CONCLUSIONS: Observation of the microvascular architecture of superficial esophageal carcinoma is useful in the diagnosis of the depth of invasion.

Carcinoma↗
PubMed2002

kdsA mutations affect FtsZ-ring formation in Escherichia coli K-12.

No one has, as yet, addressed the relationship between the nature of the outer membrane and cell division. kdsA encodes 3-deoxy-D-manno-octulosonic acid (KDO) 8-phosphate synthetase which catalyses the first step in the synthesis of KDO, the linker between lipid A and oligosaccharide of lipopolysaccharide (LPS). Seven temperature-sensitive mutants containing missense mutations in kdsA were affected in the production of KDO and all mutants stopped dividing at 41 degrees C and formed filaments with either one or no FtsZ ring. All observed defects were reversed by the plasmid-borne wild-type kdsA gene. Western blotting analysis, however, demonstrated that the amount of FtsZ protein was not affected by the mutation. The mutants were more susceptible to various hydrophobic materials, such as novobiocin, eosin Y and SDS at 36 degrees C. Methylene blue, however, restored kdsA mutant growth. Plasmid-borne wild-type msbA, encoding a lipid A transporter in the ABC family, partially suppressed kdsA mutation. A mutation of lpxA, functioning at the first stage in lipid A biosynthesis, inhibited both cell division and growth, producing short filaments. These results indicate that the instability of the outer membrane, caused by the defect in KDO biosynthesis, affects FtsZ-ring formation.

Aldehyde-Lyases↗
PubMed2002

Cloning and mapping of platypus SOX2 and SOX14: insights into SOX group B evolution.

Group B SOX genes, the closest relatives to the sex-determining gene SRY, are thought to have evolved from a single ancestral SOX B by a series of duplications and translocations. The two SOX B genes SOX2 and SOX14 co-localize to chromosome 3q in humans. SOX2 and SOX14 homologues were cloned and characterized in the platypus, a monotreme mammal distantly related to man. The two genes were found to co-localize to chromosome 1q in this species. Proximity of the two related genes has therefore been conserved for 170 Myr, since humans and platypus diverged. The sequence similarity and conserved synteny of these group B genes provide clues to their origin. A simple model of SOX group B gene evolution is proposed.

Amino Acid Sequence↗
PubMed2002

Mycoplasma pneumoniae in children with pneumonia at Mbagathi District Hospital, Nairobi.

OBJECTIVE: To determine the prevalence of mycoplasma pneumoniae in nasopharyngeal aspirates of children under five years of age suffering from pneumonia. DESIGN: Cross-sectional survey. METHODS: Two primer sets targeting the genes coding for adhesion protein and 16S rRNA were used in PCR and M. pneumoniae specific antibodies were detected using commercial article agglutination kit. Microbiological investigations to isolate common acute respiratory infectious pathogens were also carried out. RESULTS: M. pneumoniae was detected in nasopharyngeal aspirates of 33.7% of the cases by PCR while serology was positive in only 4.1%. M. pneumoniae alone (single detection) was detected in 25% of the cases while 75% occurred with other acute respiratory infectious (ARI) pathogens. However, the results did not correlate with clinical outcome or the severity of pneumonia. No significant aetiology was found in 28% of the cases investigated, however microbiological investigations by culture revealed the presence of other aetiological agents as follows: Streptococcus pneumoniae (26%), Klebsiella pneumoniae (1%), Staphylococcus aureus (3%), E. coli (2%), parainfluenza viruses (5%), Salmonella(1%), adenovirus (4%), RSV (22%) and Candida spp(13%), Mycoplasma pneumoniae was more prevalent in children aged between six months and three years. Cases of M. pneumoniae PCR positive and S. pneumoniae exhibited similar seasonal distribution with peaks in May and September. However, there was no relationship between M. pneumoniae PCR positive and the severity of pneumonia. CONCLUSION: More investigation is required to establish the significance of atypical pathogens in respiratory infections in Kenya.

Age Distribution↗
PubMed2002

[Salvage operation for esophageal cancer after radical chemoradiotherapy].

We reviewed salvage surgery cases for esophageal cancer following radical chemoradiotherapy. From January 1998 through January 2001, 6 patients (4 men, 2 women) underwent salvage operation at our department. Mean age was 56 years (range: 46-66). According to the Japanese Society for Esophageal Diseases localization schema, there was one case in the upper third of the thoracic esophagus, 3 cases in the middle third and 2 cases in the lower third. The histology was squamous cell carcinoma in all cases. Our radical chemoradiotherapy regimen for esophageal cancer was fluorouracil (5-FU) 400 mg/m2/24 hours i.v. on days 1 to 5 and 8 to 12, cisplatin (CDDP) 40 mg/m2/2 hours i.v. on days 1 and 8, and concurrent radiation therapy (2 Gy/day on days 1 to 5, 8 to 12 and 15 to 19). This regimen was repeated in 5 weeks, followed by 5-FU 800 mg/m2/24 hours i.v. on days 1 to 5 and CDDP 80 mg/m2/2 hours i.v. on day 1, which was repeated in 4 weeks. After these chemoradiotherapy, patients who were confirmed to have local recurrence or esophagobronchial fistula underwent salvage operation. Postoperative complications were anastomosis leakage in 1 patient, and anastomosis stenosis in 2 and esophagobronchial fistula in 1. Although no postoperative hospitalized death occurred, 1 patient died because of empyema 3 months after salvage operation. Another patient died due to respiratory failure 15 months later. The salvage operation outcomes are not acceptable. Salvage procedure and indication for salvage intervention need to be changed.

Aged↗
PubMed2002

Quantitative assessment of harmonic power Doppler myocardial perfusion imaging with intravenous Levovist in patients with myocardial infarction: comparison with myocardial viability evaluated by thallium-201 single-photon emission computed tomography and coronary flow reserve.

BACKGROUND: Intravenous myocardial contrast echocardiography with harmonic power Doppler imaging is a novel technique for assessing myocardial perfusion. AIMS: The aim of this study was to quantitatively assess myocardial perfusion by harmonic power Doppler imaging in patients with a previous myocardial infarction and compare myocardial contrast echocardiography results with myocardial viability evaluated by thallium-201 single-photon emission computed tomography ((201)Tl-SPECT) and the results of Doppler flow measurement of coronary flow velocity reserve. METHODS: Twenty-three patients with anterior myocardial infarction who were scheduled for adenosine stress (201)Tl-SPECT underwent myocardial contrast echocardiography with harmonic power Doppler imaging. Harmonic power Doppler imaging was performed at rest and during adenosine infusion (0.15 mg/kg/min) using an intravenous infusion of Levovist. The peak colour pixel intensity ratios of the risk area to the control area were used for quantitative analysis of myocardial perfusion by harmonic power Doppler imaging. Coronary blood flow velocity was measured using Doppler-tipped guidewire in the distal portion of left anterior descending artery and coronary flow velocity reserve was calculated. RESULTS: In patients with myocardial viability assessed by (201)Tl-SPECT, pixel intensity ratios both at rest and during hyperaemia were significantly higher compared with those in patients without myocardial viability (at rest: 0.62 +/- 0.28 vs 0.37 +/- 0.17, P=0.038, during hyperaemia 0.72 +/- 0.19 vs 0.40 +/- 0.18, P=0.003). Coronary flow velocity reserve was significantly different between two groups (2.35 +/- 0.43 vs 1.49 +/- 0.53, P <0.01). CONCLUSIONS: Quantitative assessment of microvascular integrity by harmonic power Doppler imaging corresponds to the evaluation of the microcirculation by coronary flow velocity reserve.

Adenosine↗