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Biomedical subjects

R Harada

Publications and source records attributed to R Harada.

At least 19 recordsLinked to original sources

[Thoracic surgery for the penetrating lung or tracheal trauma].

Seven cases suffered from a chest trauma (stab wound in 6 and impalement injury in 1) were emergently transferred to our hospital. Open thoracotomy was performed for the intolerable bleeding immediately after admission. Injured lung was treated by lobectomy in 1 patient, lingual segmentectomy in 2, lower basal segmentectomy in 2, partial resection in 4 and direct suture in 2. The penetrating trachea was carefully repaired by direct suture with additional midsternal thoracotomy. To accomplish appropriate partial resection of the injured lung, a metallic straight suction tube inserted into a pulmonary stab wound was retracted and a stapling instrument was applied underneath the suction tube. With the segmentectomy and the partial resection, the volume of the residual lung was maximally saved. As a result, all 7 patients were successfully alive.

Adult↗

Streptococcus anginosus infection in oral cancer and its infection route.

OBJECTIVE: To elucidate a possible involvement of Streptococcus anginosus in oral cancer, we assessed the frequency of S. anginosus infection in oral cancer tissues, and investigated its infection route. MATERIALS AND METHOD: The tissue specimens were obtained from 46 oral cancer and three precancerous leukoplakia subjects. Frequency of S. anginosus infection was assessed by a species-specific polymerase chain reaction (PCR) assay. The genotype of the clinical isolates taken from cancer tissue and dental plaque samples was analyzed using pulsed-field gel electrophoresis (PFGE). RESULTS: S. anginosus DNA was frequently detected in squamous cell carcinoma (19/42), but not in other types of cancer (lymphoma and rhabdomyosarcoma) or leukoplakia samples. A subject-based analysis revealed that S. anginosus was solely detected in dental plaque and not in saliva from all 19 S. anginosus-positive squamous cell carcinoma cases. Further, the genotype of S. anginosus isolated from cancer tissue was identical to that from dental plaque of the same patients. CONCLUSION: Infection of S. anginosus could occur frequently in oral squamous cell carcinoma and that dental plaque could be a dominant reservoir of the S. anginosus.

Aged↗

[Prevention of acute exacerbation of interstitial pneumonia in the patients operated for lung cancer].

Eight patients with interstitial pneumonia (IP) underwent pulmonary surgery for lung cancer. The first patient died due to postoperative exacerbation, but the subsequent 7 patients had good postoperative course without exacerbation by the following careful management. 1) Avoidance of administration of high concentration of oxygen keeping the PO2 about 100 mmHg during the operation. 2) Short-term administration of low-dose steroid before the operation. 3) Administration of erythromycin, tocopherol acetate, and inhalation of N-acetylcysteine before and after the operation. 4) Long-term drainage of the postoperative thoracic discharge to release the local cytokines. These treatments inhibit secretion of the inflammatory cytokines which influence exacerbation of IP.

Aged↗

[Removal of the intrapleural hematoma after extrapleural pneumonectomy].

Three cases of pleuropneumonectomy, which have been performed in our institution between 1996 and 2003, are studied. All of them received re-thoracotomy to remove intrapleural hematoma for prolonged high fever, anemia and high level of CRP. Post re-operative courses were satisfactory without any signs of infection. The residual intrapleural hematoma sometimes causes pyothorax and would be an obstacle to the intrapleural instillation of anticancer medications. The removal of the hematoma should be scheduled at an early period after the pleuropneumonectomy.

Hematoma↗

Autocrine motility factor enhances hepatoma cell invasion across the basement membrane through activation of beta1 integrins.

Autocrine motility factor/phosphohexose isomerase (AMF/PHI) is a cytokine that is linked to tumor invasion and metastasis. In hepatocellular carcinoma (HCC) tissues, hepatoma cells produce AMF/PHI and its receptor, Mr 78,000 glycoprotein (gp78), is strongly detected in hepatoma cells invading into the stroma and tumor thrombi in the portal vein. Here, we investigated the mechanism of hepatoma cell invasion through Matrigel induced by AMF/PHI using 3 hepatoma cell lines. Production of AMF/PHI, phosphorylation of MEK1/2, and Rho activity were investigated by immunoblotting. Expression of AMF/PHI and gp78 was observed by confocal fluorescence microscopy. The influence of AMF/PHI on activated integrin beta1 subunit expression was evaluated by flow cytometry. Changes in invasion, adhesion, and motility induced by AMF/PHI were evaluated using chemoinvasion, adhesion, and phagokinetic track motility assays. The effect of AMF/PHI on matrix metalloproteinase (MMP) secretion was evaluated by gelatin zymography. Hepatoma cells produced AMF/PHI and expressed gp78. Although AMF/PHI was ubiquitously detected, gp78 was strongly expressed in migrating cells. AMF/PHI induced up-regulation of activated integrin beta1 subunit expression. AMF/PHI stimulated hepatoma cell invasion through Matrigel, and stimulated the adhesion, motility, and MMP-2 secretion of hepatoma cells. The latter effects were suppressed by the function-blocking antibody for integrin beta1 subunit. AMF/PHI also enhanced Rho activity and the phosphorylation of MEK1 and MEK 2. Our results indicate that AMF/PHI enhances hepatoma cell invasion through Matrigel in an autocrine manner by stimulating the adhesion, motility, and MMP-2 secretion of these cells through activation of beta1 integrins.

Basement Membrane↗

Aryl radical cyclizations: one-Pot syntheses of protoberberine and pavine alkaloids.

Treatment of 2-(2'-bromo-beta-phenethyl)isocarbostyrils 7 with AIBN-Bu(3)SnH in boiling benzene gave 8-oxoberbines 3 in good yields. A similar treatment of 2-(2'-bromo-beta-phenethyl)isoquinolinium bromides 6 and their nor- and homoanalogues (10,11) induced 6-, 5-, and 7-exo radical closures in a one-pot manner to give protoberberines 2, dibenzo[b,g]indolizidine 14a and, dibenzo[a, h]-1-azabicyclo[5.4.0]undecane 15a, respectively. A one-pot radical cyclization of 1-(2'-bromobenzyl)isoquinoline methiodide 18a gave a pavine alkaloid, (+/-)-algemonine (19a).

Alkaloids↗

A Facile Route to Indolo

Treatment of 1-(2'-bromobenzyl)-3,4-dihydroisoquinolines 2 in the presence of K(2)CO(3) in boiling DMF efficiently provided a variety of alkoxy-substituted indolo[2,1-a]isoquinolines 3. Application of this cyclization to 7-benzyloxyisoquinoline derivatives, followed by further elaboration of the resultant 2-benzyloxy-5,6-dihydroindolo[2,1-a]isoquinolines 16a,b, led to the formal synthesis of dibenzopyrrocoline alkaloids, (+/-)-cryptaustoline (1a) and (+/-)-cryptowoline (1b).

Journal Article↗

Aryl radical cyclizations of 1-(2'-bromobenzyl)isoquinolines with AIBN-Bu3SnH: formation of aporphines and indolo

[reaction: see text] Radical cyclization of alkoxy-substituted 1-(2'-bromobenzyl)-3,4-dihydroisoquinolines 1 with AIBN-Bu3SnH gave 6a,7-dehydroaporphines 2 preferentially. A steric repulsion between the respective alkoxy groups at the 7- and 3'-positions gave 5,6-dihydroindolo[2,1-a]isoquinolines 3 in a "disfavored" 5-endo cyclization mode. Radical cyclizations of the related substrates, such as 1-(2'-bromobenzoyl)isoquinolines or 1-(2'-bromo-alpha-hydroxybenzyl)isoquinolines, were also found to give the corresponding oxoaporphines or oxyaporphines.

Journal Article↗

Epidemiological study of human herpesvirus-6 and human herpesvirus-7 in pityriasis rosea.

BACKGROUND: Pityriasis rosea (PR) is a common papulosquamous skin disorder that is suspected to have an infectious aetiology. OBJECTIVES: We aimed to study the role of human herpesvirus (HHV)-7 and HHV-6 in the pathogenesis of PR. METHODS: We performed seroepidemiological studies (indirect immunofluorescence test) and polymerase chain reaction (PCR) analysis for HHV-6 and HHV-7 in patients with PR. Seventy-two serum samples and 37 samples of peripheral blood mononuclear cells (PBMC) from 44 patients with PR were obtained. Twenty-five patients with other skin disorders such as drug eruption, urticaria or herpes zoster were studied as controls in the PCR analysis. RESULTS: HHV-7 DNA was detected in 13 of 30 (43%) samples of PBMC of the patients with PR and 14 of 25 (56%) samples of PBMC of controls. HHV-6 DNA was detected in six of 29 (21%) patients with PR and nine of 23 (39%) controls. Thus there was no difference in the prevalence of HHV-6 or HHV-7 in PBMC between patients with PR and those with other skin disorders. In the seroepidemiological study, two cases of at least a fourfold rise in titre and five cases of a fourfold decrease in titre to HHV-7 antibody, and two cases of a fourfold rise in titre and two cases of a fourfold decrease in titre to HHV-6 antibody, were observed in 24 patients with PR. This seroepidemiological study revealed antibody responses consistent with active infection in several PR patients, but the greater proportion of the patients had no definite increase in the antibody titres. CONCLUSIONS: We conclude that HHV-7 and HHV-6 may play a part in some patients with PR, but that other causative agents may exist. Further analyses are needed to determine the causative agents of PR.

Adolescent↗

Regulation of granulocyte colony-stimulating factor and parathyroid hormone-related protein production in lung carcinoma cell line OKa-C-1.

Previously we have established a clonal squamous cell carcinoma cell line OKa-C-1 derived from lung cancer of a patient with marked leukocytosis and hypercalcemia. OKa-C-1 cells simultaneously produce granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) at the single cell level and cause paraneoplastic syndromes in nude mice bearing the tumor. It is known that the production of G-CSF and PTHrP is individually regulated by inflammatory cytokines in various malignant cells. To investigate the common factors in the regulation of G-CSF and PTHrP production in OKa-C-1 cells, we examined the effects of some inflammatory agents [lipopolysaccharide (LPS), phorbol-12-myristate-13-acetate (PMA), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) beta and IL-6] on G-CSF and PTHrP production, by means of enzyme-linked immunosorbent assay (ELISA), immunoradiometric assay (IRMA) and quantitative reverse transcription-polymerase chain reaction (RT-PCR). TNF-alpha or IL-1beta induced both G-CSF and PTHrP production in the conditioned medium. TNF-alpha synergized with IL-1beta to significantly increase G-CSF production. In addition, TNF-alpha and IL-1beta strongly induced G-CSF mRNA with peaks at 2 and 6 h respectively. Although PTHrP production was also strongly induced by TNF-a PTHrP mRNA expression was more strongly induced by PMA than by TNF-alpha. Thus, TNF-alpha and IL-1beta could be common factors that individually and synergistically regulate G-CSF and PTHrP production in OKa-C-1 cells. Moreover, G-CSF and PTHrP production could be not only transcriptionally, but also posttranscriptionally regulated by other factors.

Animals↗

[Two cases of Trichophyton mentagrophytes infection contracted from a hamster and a chinchilla].

We report two cases of Trichophyton mentagrophytes infection. Case 1: A 10-year-old girl visited Tokyo Electric Power Hospital in June 1994 for evaluation of an erythematous lesion on her head. Three months of topical steroid therapy exacerbated the lesion with pustular formation. Histopathological and mycological examination revealed that the patient had tinea capitis caused by T. mentagrophytes. T. mentagrophytes was also isolated from her pet, a hamster. Case 2: A-14-year-old girl was referred to Shonan Clinic in January 1996 with scaly erythema on her face. She had been treated with neticonazole hydrochloride at another clinic, but the lesion became worse. Direct microscopic examination of the scale was negative at that time, so treatment with topical steroid was started. After 10 days, the lesion was almost cured, but one month later it recurred with an annular distribution. KOH preparation of the scale revealed mycelia and T. mentagrophytes was isolated on culture. T. mentagrophytes was also isolated from her pet, a chinchilla. In both cases, the oral administration of itraconazole at 50 mg/day was effective. The isolated pathogen was identified as Arthroderma vanbreuseghemii with species-specific primers of chitin synthase 1 gene. T. mentagrophytes is one of the most common dermatophytes isolated from man and animals. Rodents like the hamster and the chinchilla have recently become popular as pets in Japan. We should be aware that rodents may carry this kind of fungal pathogen as they become even more popular as pets.

Adolescent↗

Endometrial expression of cellular protooncogene c-ski and its regulation by estradiol-17beta.

The expression of the cellular protooncogene c-ski was examined in the rat uterus. In situ hybridization revealed that c-ski mRNA was expressed in the uterus of the adult rat on the day of estrous and localized mainly in the luminal and glandular epithelia. To test the possibility that the expression of c-ski mRNA is induced by estrogen, rats were ovariectomized and estradiol-17beta (E2) was injected. The expression of c-ski mRNA was upregulated 3 h after E2 treatment, reaching the highest level at 6 h and this persisted until 24 h; the E2-induced expression of c-ski mRNA was restricted to the luminal and glandular epithelia. These results suggest that the c-ski gene plays a role in uterine epithelial cell proliferation and mediates the proliferative action of E2.

Animals↗

Inhibition of tissue factor pathway during intermittent pneumatic compression: A possible mechanism for antithrombotic effect.

Intermittent pneumatic compression (IPC) devices are an effective prophylaxis against lower extremity deep vein thrombosis. Their antithrombotic effect has been attributed to a reduction in venous stasis and enhanced fibrinolysis. The initiating mechanism for blood coagulation is the tissue factor (TF) dependent pathway, which is inhibited by tissue factor pathway inhibitor (TFPI). We have investigated the effect of IPC on the TF pathway in 6 normal subjects and 6 patients with postthrombotic venous disease undergoing IPC for 120 minutes; all subjects were studied with each of 5 IPC devices. In normal subjects and patients, plasma factor VIIa (FVIIa) activity (the activated form of factor VII [FVII]) declined from mean values ranging 51 to 65 and 50 to 53 mU/mL before IPC with different devices to 10 to 13 and 20 to 22 mU/mL at 180 minutes, respectively (P<0.001 for all groups). FVII antigen levels were unchanged. Plasma TFPI (P<0.001) rose from mean baseline values ranging 69 to 79 and 57 to 61 ng/mL to 76 to 123 and 71 to 79 ng/mL at 180 minutes in normal subjects and patients, respectively (P<0. 001 for all groups). Plasma prothrombin fragment F1.2 levels showed minimal changes. There was an inverse relationship between TFPI and FVIIa in normal subjects (r=-0.31, P=0.001) and patients (r=-0.37, P<0.001). IPC results in an increase in plasma TFPI and decline in FVIIa. Inhibition of TF pathway, the initiating mechanism of blood coagulation, is a possible mechanism for the antithrombotic effect of IPC.

Adult↗

[A case of human infection with Clinostomum sp].

The genus Clinostomum is a cause of parasitic laryngo-pharyngitis. We report the 15th case of Clinostomum sp. infection in Japan. A 29-year-old female visited our hospital because of throat discomfort and expectoration of a worm by sneezing on November 17, 1997. The pharyngitis was caused by the worm. The worm was morphologically identified as the adult of the genus Clinostomum.

Adult↗

Nine patients with hepatocellular carcinoma surviving for more than six years after treatment, including two patients who have survived without recurrence after hepatic lobectomy.

Of patients treated for hepatocellular carcinoma (HCC) accompanied by liver cirrhosis at our University Hospital between 1985 and 1990, clinical background factors in nine patients (7.0% of all patients) who survived for more than six years were examined to clarify the conditions that facilitate long-term survival. In particular, we describe two cases among these patients who have survived without the recurrence of a liver tumor for more than six years after hepatic lobectomy. In eight of nine patients, surgery was performed as the initial treatment. In seven patients, HCC was solitary and there was no portal invasion. Six patients were evaluated as Stage I according to clinical staging. Furthermore, the two patients without recurrence after treatment have been taking immunostimulators since their initial treatment until the present. The above observations suggest that surgical treatment should be considered in patients in whom hepatic reserve capacity is well maintained despite a tumor size greater than 2 cm. Subsequent recurrence should be detected earlier, and percutaneous ethanol injection therapy (PEIT) with a focus on maintaining liver function should be repeated. In addition, multi-disciplinary treatment including medication with immunostimulators is beneficial.

Aged↗

[Prognosis and prognostic factor after extended lymphadenectomy in lung cancer].

From 1984 to 1994, 418 patients were received surgery for the lung cancer in our center. Of them, 178 patients were underwent extended lymphadenectomy. Fifty six of the 178 were histologically proven N2 of N3 alpha disease after surgery. Extended lymphadenectomy means R2b lymphadenectomy including the left tracheobronchial node dissection for the right lung cancer and R3 (bilateral mediastinal lymphadenectomy through a median sternotomy) for the left. In the 56 patients, we examined the location and frequency of metastases to the mediastinal lymph nodes and the relationship between some clinical factors (pT, number of metastatic station, clinical staging of the lymph node (CN), histological type, contralateral mediastinal lymph nodes metastases) and prognosis. Most of the pN2 patients of the right lung cancer showed ipsilateral mediastinal lymph nodes metastases and 25 percent of the patients showed the spread to N2b mediastinal modes. The patients of the left lung cancer showed higher incidence of contralateral mediastinal lymph nodes metastases than the patients of the right lung cancer. The five years survival rate of all pN2 patients (N = 39) was 48%, and T1 or T2-N2 patients (N = 22) was 67%. On the other hand, all T4 N2 patients (N-9) died within 3 years after operation. There was no significant difference in postoperative survival between the patients with single station metastasis (N = 20) and multistation metastases (N = 30, including 11 cases with N3 alpha). The five years survival rate of all the patients with multistation metastases was 45%, and that of T1 or T2 multilevel (N = 20) was 65%. There was significant difference in postoperative survival between the patients with CN0-pN2 and CN2-pN2 (p < 0.05). The five years survival of CN0-pN2 patients (N = 14) was 85% and four years survival rate of CN2 pN2 patients (N = 19) was 30%. Among the patients with T1 or T2 tumor, however, there was no significant differences in postoperative survival between CN0-pN2 patients and CN2 pN2 patients. There was no difference in postoperative survival between adenocarcinoma and squamous cell carcinoma (5 years survival: 56%, 43%). In conclusion, extended lymphadenectomy has brought a good prognosis in the patient with T1 or T2 in spite of presence of CN2 or multistation N2. The patients with contralated mediastinal metastases (N3 alpha) showed good prognosis after R3 (5 years survival: 100%) in the patients with the left lung cancer (N = 6). But the N3 alpha patients of right lung cancer showed poorer prognosis (3 years survival: 30%) after R3 (N = 5) than the left. It suggested that R3 lymphadenectomy was significant and beneficial for the left lung cancer patients with N3 alpha but controversial for the right.

Aged↗

Etiology and prognosis of cryptogenic liver cirrhosis: possible contribution of hepatitis B virus.

Three female patients without type B or type C viral hepatitis, alcoholic, metabolic or autoimmune liver disease, were selected from 250 cases with histologically proven liver cirrhosis (M:F = 183:67). All three cases showed at least one positive aspect among three parameters of serum anti-HBc (RPHA, x1), HBV-DNA (gene S, nested PCR) and liver HBs and/or pre-S2 antigen (immunoperoxidase methods). Two cases may suggest a spontaneous disappearance of HBV from sera. Another case may suggest a contribution of mutant HBV which can not be detected by the routine tests. These HBV-related cirrhotic patients have done well clinically and have not been associated with hepatocellular carcinoma during the period from 6 to 12 years of follow-up when compared with 59.6% and 65.4% prevalence of hepatocarcinogenesis in type B and type C hepatitis-associated cirrhosis during the observation period of six and seven years on average, respectively.

Aged↗