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Biomedical subjects

N Hara

Publications and source records attributed to N Hara.

At least 181 records · Page 10Linked to original sources

[Clinical efficacy of imipenem/cilastatin sodium for respiratory infections in patients with lung cancer].

Imipenem/cilastatin sodium (IPM/CS) was administered to 102 patients with respiratory tract infections and lung cancer. Patients with other serious diseases were excluded and a total of 73 patients were enrolled. They were divided into 12 patients who underwent surgery (operated group) and 61 who did not (non-operated group); the latter group included 28 patients treated with anticancer agents or radiation therapy (treated group) and 33 untreated patients (untreated group). IPM/CS was effective in 75% of the patients, both with and without surgery. The drug was effective in 81% of the treated group, although many of the patients had Stage III or more advanced cancer, as well as bronchial occlusion. IPM/CS was also effective in 69% of the untreated group, although many of the patients have serious infections and a PS (Performance Status) of 3 or greater. Thus, IPM/CS treatment achieved good results. Bacteriological studies showed that 3 out of 4 strains in the operated group and 16 out of 18 in the non-operated group were eliminated. Safety was evaluated in all patients. Two patients (2%) experienced side effects and two others (2%) showed abnormal clinical findings, but the symptoms were mild and resolved after discontinuation or completion of therapy. In conclusion, IPM/CS was very effective for treating respiratory infections in patients with lung cancer.

Adenocarcinoma↗

[Spontaneous recovery from cytomegalovirus pneumonia].

A 30-year-old woman with systemic lupus erythematosus was admitted to our hospital because of a slight fever and diffuse interstitial shadows on a chest X-ray film. She had taken prednisolone (60 mg per day) at another hospital for six weeks. At the time of admission to our hospital, she had been treated with antituberculosis drugs (streptomycin, isoniazid, and rifampicin) for two weeks because of suspected miliary tuberculosis. Chest radiography on admission revealed diffuse nodular and micronodular shadows in the middle and lower lung fields on both sides. Examination of transbronchial lung biopsy specimens revealed intranuclear viral inclusion bodies in infected alveolar epithelial cells, which suggested the diagnosis of cytomegalovirus infection. The elevation of serum IgM antibody to cytomegalovirus and positive results of in situ hybridization for cytomegalovirus DNA supported this diagnosis. The symptoms and radiographic abnormalities resolved completely without ganciclovir. Although we cannot exclude the possibility that the antituberculosis drugs caused the resolution of the cytomegalovirus pneumonia, it appears most probable that the cytomegalovirus pneumonia resolved spontaneously.

Adult↗

[Delayed traumatic hernia diagnosed with magnetic resonance imaging].

A 30-year-old man was admitted to the hospital 7 years after an automobile accident during which a lumbar vertebra was fractured. Immediately after the accident he had neither thoracic nor abdominal symptoms. An X-ray film obtained 4 years after the accident showed elevation of the left side of the diaphragm. That elevation progressed over the next 3 years, although the patient had no symptoms. On admission, a chest X-ray film showed blunting of the left costo-phrenic angle and mobility of the shadow, which simulated a pleural effusion. A chest CT scan and barium studies showed that portions of the small intestine, transverse colon and descending colon were in the left side of the thorax, but the diaphragm was not seen. The patient was given a diagnosis of delayed traumatic diaphragmatic hernia after T1-weighted sagittsal magentic resonance images revealed the whole diaphragm and the hernial orifice. Magnetic resonance imaging can be very useful in the evaluation of diaphragmatic hernia.

Adult↗

[Intrapulmonary hematoma diagnosed by magnetic resonance imaging].

We report a case of intrapulmonary hematoma in which magnetic resonance imaging was useful in establishing the diagnosis. A 53-year-old man had bronchial asthma that was well controlled with inhaled beclomethasone dipropionate and salbutamol, and with oral theophylline. A spherical mass was found in the right lower lung field on a chest radiograph taken during a regular physical examination. A CT scan showed a well circumscribed spherical mass, which was attached to an intrapulmonary bullae. Magnetic resonance imaging showed a well-circumscribed mass in the superior segment of the right lower lobe. On a T1-weighted image the mass was hyperintense and had a higher-intensity rim. On a T2-weighted image the mass was hyperintense and had some hypointense areas. We therefore diagnosed intrapulmonary hematoma. Chest radiography 6 months later revealed a substantial decrease in the size of the mass, which supported the diagnosis. As in this case, intrapulmonary hematoma can be difficult to diagnose because of the lack of a history of injury and because of the slow regression. In this case, magnetic resonance imaging was useful in making the diagnosis.

Hematoma↗

Possible role of indoor environment and coal combustion emission in lung carcinogenesis in Fuyuan County, China.

Fuyuan Country, in Yunnan Province, China has an extremely high lung cancer mortality both in males and non-smoking females. Out of 5768 deaths, 588 patients died of malignant diseases. Lung cancer was the number one cause of death among malignant diseases both in males and females. The rate of lung cancer death to the whole of malignant diseases was 56.2% for males and 55.0% for females. Indoor soot and combustion emission derived from smoky coal produced in northern Fuyuan exhibited high mutagenic activities against Salmonella typhimurium TA98 strain in Ames test. Resected lung tissues derived from the patients with lung cancer in Fuyuan contained significantly higher concentrations of benzo(a)pyrene than those in Japan, both in males and females (i.e., 608.7 +/- 477.1 pg/dry weight for samples of the patients in Fuyuan, 180.1 +/- 104.5 for Japanese non-smokers, and 207.5 +/- 98.8 for Japanese heavy smokers, respectively). These results suggest that mutagenic chemicals contained in coal as well as indoor environment may have a great influence on lung carcinogenesis in Fuyuan, Yunnan Province, China.

Air Pollution, Indoor↗

[Multiple brain metastasis of bronchial atypical carcinoid: unusual MR imaging, case report].

We reported a case of a 76-year-old male who suffered from gait disturbance. His first MR image showed multiple masses in the cerebellum and cerebrum. After 50Gy of whole brain irradiation the masses downsized, but, after 8 months the patient was readmitted because of general convulsions. MRI on his second admission showed an enlargement of the multiple masses and reinforcement of the perifocal edema. One year after the onset, MRI revealed the unusual appearance of multiple obscure-marginated cystic masses, intratumoral hemorrhage, and intraventricular hemorrhage. Soon he died of complications from pneumonia. In the autopsy, a mass 4 x 5 cm in size was found in the right lung and multiple metastatic foci were found in the CNS, small intestine, and lymph nodes. The case was diagnosed as bronchial atypical carcinoid with multiple metastases.

Aged↗

[Interstitial pneumonia caused by manidipine HCl].

A 62-year-old woman was given a diagnosis of rheumatoid lung in 1993. She began receiving manidipine HCl (10 mg per day) on June 19, 1996 to treat hypertension. The next day fever, coughing and dyspnea developed. She was admitted to our hospital on June 28. A chest radiograph showed diffuse reticulo-nodular shadows in all lung fields and arterial blood gas analysis revealed severe hypoxemia. Administration of manidipine HCl was stopped and treatment with methylprednisolone was started. The symptoms and the radiographic evidence of infiltrates disappeared. A drug lymphocyte stimulation test for manidipine HCl was positive. We know of no previous report of pneumonia caused by manidipine HCl.

Antihypertensive Agents↗

[Paraneoplastic syndrome].

Treatment for the paraneoplastic syndrome associated with lung cancer was reviewed. The principle of the treatment of paraneoplastic syndrome is to control cancer as an underlying disease. Therefore, the standard therapy for Cushing's syndrome associated with lung cancer is surgical treatment if the tumor is operable. There is no standard therapy for Cushing's syndrome associated with advanced small-cell lung cancer. Metyrapone is used in combination with systemic chemotherapy. The effects of ketoconazole and octreotide are under investigation. To control hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion, fluid restriction is standard. When hyponatremia cannot be controlled with fluid restriction, demeclocycline can be used. For life-threatening hyponatremia, hypertonic saline with intravenous furosemide is administered under careful monitoring. Followed by hydration with saline, pamidronate is effective for the control of symptomatic hypercalcemia. Combined use of calcitonin facilitates rapid normalization of serum calcium for critically ill cases. Heparin is used for patients with recurrent episodes of thrombosis resulting from chronic disseminated intravascular coagulation, although the efficacy is controversial. Thrombocytes and coagulation factors are combined with heparin for patients with uncontrollable bleeding, although the efficacy is not established.

Alendronate↗

[Expression of CD44 standard and CD44 variant 6 in human lung cancer].

We immunohistochemically examined the expression of CD44 standard (CD44 st) and CD44 variant 6 (CD44 v6) in 112 cases of primary lung cancer, and their relationship to the clinical milieu, including the clinical stage. In 46 cases of squamous cell carcinoma, expression of CD44 st was observed in 45.7% of the cases, and expression of CD44 v6 was observed in 60.9%. In 43 cases of adenocarcinoma, positive staining of CD44 st and CD44 v6 was seen in 2.3% and 4.7% of the cases, respectively. None of 21 small cell carcinomas was positive for CD44 st or CD44 v6. In squamous cell carcinomas, the expression of CD44 st and CD44 v6 was observed at a rate significantly higher than in other histologic type. Most specimens positive for CD44 st stained positively for CD44 v6. Therefore, it seems likely that the CD44 expression observed in squamous cell carcinoma of the lung was a variant CD44 containing the domain encoded by variant exon 6. The expression of CD44 v6 was not related to the clinical stage. Significant association between CD44 v6 and differentiation of squamous cell carcinoma was seen; 2/7 (28.6%) for poorly differentiated, 19/31 (61.3%) for moderately differentiated, and 7/8 (87.5%) for well differentiated squamous cell carcinomas (p = 0.02 by trend test). It was previously reported that CD44 st and CD44 v6 were expressed in both normal bronchial epithelium and squamous cell metaplasia. These results suggest that the expression of CD44 v6 in squamous cell carcinoma of the lung may reflect the immunohistochemical characteristics of the tissue from which such carcinoma emerge.

Adenocarcinoma↗

The utility of p53 immunostaining of transbronchial biopsy specimens of lung cancer: p53 overexpression predicts poor prognosis and chemoresistance in advanced non-small cell lung cancer.

There are few reports on the p53 status of small cell lung cancer (SCLC) and advanced non-SCLC (NSCLC) because surgically resected specimens are generally not available. Therefore, we evaluated p53 immunostaining in 175 transbronchial biopsy (TBB) specimens obtained from patients with all stages of lung cancer and retrospectively evaluated the relationship between p53 status and clinical parameters. All of the specimens were obtained prior to therapy. Formalin-fixed, paraffin-embedded TBB specimens were immunostained using an anti-p53 antibody (DO-1). p53 protein was detected in 55% (61 of 111) of NSCLCs and 58% (37 of 64) of SCLCs. The rate of positivity increased significantly with increasing stage (stages I and II, 45%; stage III, 54%; stage IV, 66%), but not with other clinical parameters. Ninety-five patients were evaluated for their response to chemotherapy. Positive staining for p53 correlated significantly with unresponsiveness to chemotherapy in NSCLC (response rate of 13 versus 60%; P = 0.006), but not in SCLC (80 versus 57%; P = 0.22). p53 positivity was a statistically significant negative prognostic factor for stage III and stage IV NSCLC (P = 0.02), but not for stage I and stage II NSCLC (P = 0.79). There was no survival difference relative to p53 status in SCLC (P = 0.35). These results indicate that p53 overexpression in TBB specimens predicts poor prognosis and chemoresistance in advanced stage NSCLC.

Aged↗

Glutamic acid 207 in rodent T-cell RT6 antigens is essential for arginine-specific ADP-ribosylation.

A rat T-cell antigen RT6.1 catalyzes NAD glycohydrolysis but not ADP-ribose transfer, even though the antigen has significant amino acid identity with eucaryotic arginine-specific ADP-ribosyltransferases. Since a highly conserved Glu in the catalytic region of these transferases is substituted with Gln at position 207 in RT6.1, we replaced the Gln with Glu, Asp, or Ala, by site-directed mutagenesis. The Glu-207 mutant produced ADP-ribosylarginine during incubation with NAD and L-arginine. The Asp-207 mutant but not the Ala-207 mutant produced ADP-ribosylarginine, but at a lower rate. In contrast, these mutations affected NAD glycohydrolase activity of RT6.1 to a much lesser extent. Kinetic studies of transferase reaction revealed that kcat of the Glu-207 mutant increased compared to findings with the Asp-207 mutant. Moreover, the mouse homologue of rat RT6 lost arginine-specific ADP-ribosyltransferase activity when Glu-207 was replaced with Gln. Thus, Glu-207 in rodent T-cell RT6 antigens is essential for transfer reaction of ADP-ribose to arginine.

ADP Ribose Transferases↗

Immunohistochemical expression of glutathione S-transferase-Pi can predict chemotherapy response in patients with nonsmall cell lung carcinoma.

BACKGROUND: Resistance to chemotherapy agents is a major problem in the treatment of patients with nonsmall cell lung carcinoma (NSCLC). Recent studies have indicated that glutathione S-transferase-Pi (GST-Pi) may play an important role in the resistance of cancer cells to alkylating agents, including cisplatin compounds. METHODS: The expression of GST-Pi in tissues obtained by bronchoscopic biopsy from 38 NSCLC patients was investigated immunohistochemically. These patients were treated with a combination of cisplatin-based chemotherapy and were evaluated to determine the relationship between GST-Pi expression and chemotherapy response. RESULTS: Of the 38 patients, 25 (66%) were GST-Pi-positive and 13 (34%) were negative. There was no significant correlation between GST-Pi expression and the clinicopathologic factors examined (age, sex, performance status, histology, differentiation grade, and stage). Of the 38 patients treated with cisplatin-based chemotherapy, 12 patients responded to chemotherapy (overall response rate, 32%). For the patients with negative GST-Pi expression, the response rate was 69% (9 of 13 patients). In the patients with positive GST-Pi expression, the response rate was 12% (3 of 25 patients). This difference was statistically significant (P=0.0012). CONCLUSIONS: The expression of GST-Pi in NSCLC patients was significantly related to response to cisplatin-based chemotherapy, and may be a useful predictor of chemotherapy response.

Aged↗

Granulocyte-colony stimulating factor promotes invasion by human lung cancer cell lines in vitro.

The effects of exogenous and endogenous granulocyte colony-stimulating factor (G-CSF) on invasion by cancer cells were studied, using lung cancer cell lines that produce G-CSF (NCI-H157) and lines that do not (PC-9 and NCI-H23). The invasive capacity of NCI-H157 cells was 26- to 27-fold higher than that of PC-9 and NCI-H23 cells. The invasiveness of PC-9 cells was stimulated by exogenous G-CSF, while that of NCI-H157 cells was not. Antibodies against G-CSF blocked the stimulation of PC-9 cell invasiveness by exogenous G-CSF. Anti G-CSF antibodies also inhibited invasion by NCI-H157 cells in the absence of exogenous G-CSF. These results suggest that endogenous and exogenous G-CSF both stimulate invasion by lung cancer cells.

Antibodies↗

Tuberculosis following liver transplantation: report of a case and review of the literature.

We report on a 44-year-old man who developed tuberculosis 4 months after liver transplantation. The diagnosis was confirmed using a polymerase chain reaction (PCR) technique in bronchial alveolar lavage (BAL) fluid, and the patient was successfully treated by reducing his immunosuppression and administering antituberculous drugs. The patient became afebrile 20 days after starting antituberculous therapy and remains well at home. A review of the literature revealed that tuberculosis after liver transplantation is a rare complication with a reported mortality rate of as high as 40%. The mortality is highest for patients who become symptomatic within 3 months after transplantation (83% vs 0%, P < 0.01; Fisher's exact test) and for those with an interval between the initial symptom and diagnosis of more than 2 weeks (71% vs 0%, P < 0.05). Early diagnosis is, therefore, essential for successful resolution of tuberculosis after liver transplantation.

Adult↗

Reversal effect of itraconazole on adriamycin and etoposide resistance in human leukemia cells.

Itraconazole is a triazole antifungal agent that inhibits cell membrane serol biosynthesis. Currently, itraconazole is a potent candidate for in vivo use to revert multidrug resistance in acute leukemias, with the added benefit of its antifungal effect. As previously reported, itraconazole, as well as verapamil, reversed adriamycin-resistant K562 cells (K562/ADR) and HL60 cells (HL60/ADR) in dosages compatible to the plasma levels achieved by the therapeutic dosages used for the treatment of fungal infections. By RT-PCR analysis of mdr1, mdr3, and mrp mRNA, these adriamycin-resistant cells showed a higher expression of the transcript of these genes than those of the parent cells. By FACS analysis, both the adriamycin-resistant cells showed a higher expression of P-glycoprotein on their cell surfaces. These results suggested the involvement of itraconazole in the mdr gene and/or mrp gene product-associated resistance. Furthermore, itraconazole partially reversed etoposide resistance in both the K562 and K562/ADR cells. The present study suggests that itraconazole may reverse multidrug resistance, at least in part, via a classical MDR-associated mechanism.

Antibiotics, Antineoplastic↗

Modulatory effect of roxithromycin on human neutrophil function.

Neutrophils are thought to play a key role in tissue injury. We investigated the effect of roxithromycin, a 14-membered ring macrolide, on human neutrophil functions. The drug inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide (O2-) production and Ca2+ influx of human neutrophils. The inhibition was overcome by adding an inhibitor of cyclic AMP-dependent protein kinase (PKA), H-89. These results suggest that the drug affects O2- production and intracellular Ca2+ concentration of neutrophils via the action of PKA. Moreover, roxithromycin ameliorated endothelial cell injury induced by neutrophils, which may be, in part, due to the effect of the drug on neutrophils. Thus, roxithromycin may contribute to the treatment of diseases worsened by the excessive action of neutrophils.

Anti-Bacterial Agents↗