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Biomedical subjects

M Murai

Publications and source records attributed to M Murai.

At least 37 records · Page 2Linked to original sources

Integrin alpha3beta1 engagement disrupts intercellular adhesion.

During tissue morphogenesis and tumor invasion, epithelial cells must undergo intercellular rearrangement in which cells are repositioned with respect to one another and the surrounding mesenchymal extracellular matrix. Using three-dimensional aggregates of squamous epithelial cells, we show that such intercellular rearrangements can be triggered by activation of beta1 integrins after their ligation with extracellular matrices. On nonadherent substrates, multicellular aggregates (MCAs) formed rapidly via E-cadherin junctional complexes and over time became compacted spheroids exhibiting a more epithelial phenotype. After MCAs were replated on culture substrates, the spheroids collapsed to yield tightly arranged cell monolayers. Cell-cell contact induced rapid elevation in E-cadherin levels, which was due to an increase in the metabolic stability of junctional receptors. During MCA remodeling of cell-cell adhesions, and monolayer formation, their E-cadherin levels fell rapidly. Similar behavior was obtained regardless of which ECM ligand-collagen type I, fibronectin, or laminin 1-MCAs were seeded on. In contrast, when seeded onto a matrix elaborated by squamous epithelial cells, cells in the MCA attached, spread, lost cell-cell junctions, and dispersed. Analysis identified laminin 5 as the active ECM ligand in this matrix, and MCA dispersion required functional beta1 integrin and specifically alpha3beta1. Furthermore, substrate-immobilized anti-integrin antibody effectively reproduced the epithelial-mesenchymal-like transition induced by the laminin 5 matrix. During the early stages of aggregate rearrangement and collapse, cells on laminin 5 substrates, but not those on collagen I substrates, exhibited intense cortical arrays of F-actin, microspikes, and fascin accumulation at their peripheral surfaces. These results suggest that engagement of specific integrin-ligand pairs regulates cadherin junctional adhesions during events common to epithelial morphogenesis and tumor invasion.

Antibodies, Monoclonal↗

Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease.

We have studied the recruitment and roles of distinct dendritic cell (DC) precursors from the circulation into Propionibacterium acnes-induced granulomas in mouse liver. During infection, F4/80(-)B220(-)CD11c(+) DC precursors appeared in the circulation, migrated into the perisinusoidal space, and matured within newly formed granulomas. Recruited DCs later migrated to the portal area to interact with T cells in what we term "portal tract-associated lymphoid tissue" (PALT). Macrophage inflammatory protein 1alpha attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT. Anti-SLC antibody diminished PALT expansion while exacerbating granuloma formation. Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.

Animals↗

Detection of IL-2 receptor gene expression in peripheral blood from renal transplant patients.

Cytokine monitoring is a potentially useful tool in the management of transplant patients. This study was conducted to analyze interleukin (IL)-1, tumor necrosis factor (TNF), IL-2, and IL-2 receptor gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in peripheral whole blood from healthy volunteers and patients who underwent laparotomy or renal transplantation. In the patients who underwent laparotomy, IL-1 and TNF expression was detected postoperatively, but IL-2 and IL-2 receptor expression was not. IL-1, TNF, and IL-2 receptor gene expression was detected in all the renal transplant patients, including those with signs of rejection. No cytokine gene expression was detected preoperatively, pretransplant, or in the healthy volunteers. We were able to discriminate transplantation from laparotomy by the cytokine profile. These results indicate that our method may be a useful tool for the immunological monitoring of transplant patients.

Adult↗

Genomic analysis of a mouse model of immunoglobulin A nephropathy reveals an enhanced PDGF-EDG5 cascade.

The molecular mechanism of immunoglobulin A nephropathy (IgAN), the most common primary renal glomerular disease worldwide, is unknown. HIGA (high serum IgA) mouse is a valid model of IgAN showing almost all of the pathological features, including mesangial cell proliferation. Here we elucidate a pattern of gene expression associated with IgAN by analyzing the diseased kidneys on cDNA microarrays. In particular, we showed an enhanced expression of several genes regulating the cell cycle and proliferation, including growth factors and their receptors, as well as endothelial differentiation gene-5 (EDG5), a receptor for sphingosine 1-phosphate (SPP). One of the growth factors, platelet-derived growth factor (PDGF) induces a marked upregulation of EDG5 in proliferative mesangial cells, and promotes cell proliferation synergistically with SPP. The genomic approach allows us to identify families of genes involved in a process, and can indicate that enhanced PDGF-EDG5 signaling plays an important role in the progression of IgAN.

Animals↗

Age-related prevalence of erectile dysfunction in Japan: assessment by the International Index of Erectile Function.

BACKGROUND: The effects of age and concomitant chronic illness on male sexual function were investigated to obtain insight into the prevention of erectile dysfunction (ED). METHODS: A questionnaire from the International Index of Erectile Function (IIEF) was given to 2311 non-institutionalized men aged 23-79 years along with a survey of health status. The study sample consisted of 1517 men who provided complete responses to the questionnaire. For statistical analysis, ANOVA was conducted to evaluate the effect of aging on the sexual functions and a logistic regression model was used to identify significant independent risk factors for ED. RESULTS: There was a significant correlation between age and the scores for erectile function, orgasmic function, sexual desire and intercourse satisfaction. The prevalence of moderate and severe cases of ED were 1.8% and 0% for ages 23-29; 2.6% and 0% for ages 30-39; 7.6% and 1.0% for ages 40-49; 14.0% and 6.0% for ages 50-59; 25.9% and 15.9% for ages 60-69; and 27.9% and 36.4% for ages 70-79 years, respectively. Hypertension, diabetes mellitus, heart disease, chronic hepatitis, disc herniation and cerebral infarction under treatment with anticoagulants were significant independent risk factors for ED. CONCLUSIONS: The results obtained indicated a significant association between aging and chronic diseases and erectile function. Further epidemiologic research and analysis of individual risk factors are required to allow more effective future strategies for the treatment and prevention of ED.

Adult↗

Transurethral needle ablation of the prostate: an initial Japanese clinical trial.

OBJECTIVES: Transurethral needle ablation of the prostate is a new alternative endoscopic thermal therapy that uses a low-energy radio frequency delivered into the prostatic adenoma. Herein is reported the initial clinical experience by multiple institutes in Japan of transurethral needle ablation of the prostate for the treatment of symptomatic benign prostatic hyperplasia. METHODS: A total of 93 patients were treated with this technique. Transurethral needle ablation of the prostate was generally performed under low-spinal anesthesia. Before and after the procedure, international symptom score (IPSS), quality of life (QOL) score, peak urinary flow rate (Qmax), postvoid residual urine volume and prostate size were evaluated. RESULTS: There was a reduction of IPSS of more than 50% when compared with that of pretreatment, being 51.3% (57/93 patients) and 60.2% (56/93 patients) at 3 months and 6 months after the procedure, respectively. Sixty-seven patients who were available for a 12-month follow-up period demonstrated a markedly decreased mean IPSS when compared with that measured before the treatment for a statistically significant difference (P < 0.01). Fifty-eight patients who were available for uroflowmetric study at 12 months exhibited a notably increased mean Qmax of 11.2 +/- 4.5 mL/s, which was a statistically significant increase when compared with that found before treatment (P < 0.05). Although all patients suffered some degree of gross hematuria after the procedure, none of them required any specific treatment for complications. CONCLUSION: Transurethral needle ablation technique for the treatment of symptomatic benign prostatic hyperplasia is safe and effective. However, a much longer follow-up study is essential for fully evaluating the extended effectiveness of this technique.

Aged↗

Brachytherapy for prostate cancer in Japan.

The temporary implantation of iridium-192 (Ir-192) is available in Japan if the patient is isolated in a radiation control area during the treatment. In this study, brachytherapy for prostate cancer was preceded by using low-dose rate Ir-192. Twenty-six patients with localized prostate cancer were treated with brachytherapy since December 1997. The age of patients ranged from 61 to 82 (median 76) years and the initial serum prostate-specific antigen (PSA) level ranged from 4.3 to 141 (median 17.4) ng/ml. Ten to 14 needles with Teflon sheaths were introduced into the prostate via a transperineal approach and an Ir-192 wire was placed in each sheath. The dose-distribution curve based on computed tomography imaging was drawn and the irradiation time was calculated for the whole prostate to receive over 70 Gy. During the 1-22-month follow-up period, all cases with an initial PSA level of less than 25 ng/ml showed continuous PSA decrease without biochemical failure. Magnetic resonance imaging demonstrated tumor regression in all cases within 6 months after the treatment. One-year biopsy specimens from patients with PSA failure demonstrated viable tumor cells, and the specimens from patients with favorable progress revealed fibrosis replacement without any variable tumor cells. Characterization of nocturnal penile tumescence data and IIEF 15 score proved the minimal effect of the treatment on erectile function. No major side effects or complications were observed. Brachytherapy using Ir-192 is a less invasive and safe procedure, which is expected to become a standard treatment for localized prostate cancer patients with relatively low PSA levels.

Aged↗

Aging and erectile dysfunction: the role of aging and concomitant chronic illness.

Erectile dysfunction (ED) can have a strong negative effect on the well-being and quality of life of the sufferer. Many factors may contribute to the development of this disorder; age in particular and also concomitant chronic illnesses including neurological, hormonal, arterial and cavernosal factors. An understanding of the prevalence and characteristics of risk factors for ED is required, in order to establish effective therapeutic strategies. However, the prevalence of ED depends on the definitions used and the use of an internationally established scale for the assessment of male sexual function is necessary to facilitate the comparison of data between different countries. Further epidemiologic research and analysis of individual risk factors is required. Such studies will clarify the interactive effects of organic factors and their probable etiology with the general physical, sociocultural and psychologic status of patients. These efforts will make it possible to design more effective future strategies for the treatment and prevention of ED.

Aged↗

Re-evaluation of the latent period of bladder cancer in dyestuff-plant workers in Japan.

BACKGROUND: The carcinogenesis of benzidine (BZ) and beta-naphthylamine (BNA) for bladder is well known. Although it was thought to be rare to develop occupational bladder cancer more than 20 years after the exposure to these chemicals, there are still new clinical cases even 30 years after exposure. The purpose of this study was to re-evaluate the latent carcinogenic period of BZ and BNA, in order to set the safety period after exposure for the health surveillance system. METHODS: The subjects were 236 dyestuff-plant workers in Tokyo, who had been exposed to these dyestuffs. The incidence of bladder cancer and its histopathology in this group was surveyed in the period from 1962 to 1996. RESULTS: Nineteen workers (8.1%) were found to have bladder cancers. The exposure period for these 19 patients was 82.0 +/- 50.2 months. The mean +/- SD latent period from the subjects' initial and final exposure until tumor development was 29.5 +/- 8.2 years and 20.1 +/- 10.6 years, respectively. Significantly, a negative correlation (Pearson) was observed between the exposure period and the latent period from the end of exposure to cancer onset (R = -0.544, P < 0.05). All tumors except one were transitional cell carcinoma. Flow cytometric analysis was performed in 11 patients and all of these patients had DNA aneuploidy. CONCLUSIONS: The latent periods of bladder cancer caused by BZ and BNA were longer than previously expected. It is necessary to survey the onset of bladder cancer in exposed workers more than 30 years after the initial exposure.

2-Naphthylamine↗

Establishment of a testicular carcinoma cell line producing alpha-fetoprotein.

OBJECTIVE: To characterize a newly established human testicular carcinoma cell line that continuously produces alpha-fetoprotein (AFP), and to investigate the effects of retinoic acid on AFP production. MATERIALS AND METHODS: A 24-year-old man underwent a radical orchidectomy for a right testicular tumour and was found to have two separate metastatic lesions in the lungs, both of which were removed surgically. The cancer cells were isolated from one of the tumours, which was composed of undifferentiated germ cells and produced AFP; the cells were cultured in a monolayer. This cell line was designated as KU-MT. RESULTS: The cell line was successfully maintained both in athymic nude mice and in culture. Histological examination showed that the xenografted tumours were composed of cells in the reticular, solid and glandular patterns of a yolk sac tumour, and of embryonal carcinoma cells. These cells immunostained positively for AFP. On electron microscopy, the extracellular deposition of a basement lamina-like substance, a typical feature of yolk sac tumour, was detected. The AFP production in mice correlated well with the tumour weight of the xenograft. The cultured KU-MT cells were oval to polygonal in morphology and grew exponentially, with a population doubling time of approximately 2 days. Chromosomal analysis showed a modal number of 57 with consistent structural abnormalities of +add(1)(p13), del(1)(q32), del(2)(q31), add(6) (q21), +add(9)(p22), add(11)(p15), and add(14)(p11). Reverse-transcription polymerase chain reaction analysis showed that the retinoic acid receptors (RAR)-alpha, RAR-gamma, and retinoid X receptor-alpha were present in the cells. The expression of AFP mRNA was up-regulated in response to all-trans-retinoic acid; treatment with this agent caused morphological changes and induced apoptosis in the cells. CONCLUSIONS: This newly established cell line provides a reproducible model system that should offer a good insight into the differentiation of testicular carcinoma.

Adult↗

Retroperitoneoscopic radical nephrectomy by the posterior lumber approach for renal-cell carcinoma associated with chronic renal failure.

PURPOSE: To evaluate the efficacy and invasiveness of retroperitoneoscopic radical nephrectomy for renal-cell carcinoma (RCC) in patients with chronic renal failure (CRF), a group known to have relatively high surgical risk. PATIENTS AND METHODS: Between May 1996 and September 1999, six CRF patients maintained on hemodialysis underwent retroperitoneoscopic radical nephrectomy for clinically localized RCC by the posterior lumber approach. The excised kidneys were evacuated via a posterior skin incision (5 cm) between two port sites; the muscle layers were not incised. RESULTS: The procedure was completed in all patients with no major complications. The mean operative time was 162 (range 135-210) minutes, and the estimated blood loss was 58 (15-100) mL; none of the patients required a blood transfusion. Regular hemodialysis was restarted on postoperative day 2 or 3. CONCLUSIONS: This procedure seems to be minimally invasive and suitable for the treatment of small RCC in atrophic kidneys, especially in patients with CRF.

Atrophy↗

Expression of estrogen receptor (ER-alpha and ER-beta) mRNA in human prostate cancer.

OBJECTIVE: The distribution of the two estrogen receptors (ER-alpha, ER-beta) in human prostate tissue have not been fully clarified, so the present study investigated the mRNA expression of the receptors to explain the broad spectrum of estrogen activity in prostate cancer. MATERIALS AND METHODS: Four human prostate cancer cell lines (LNCap, JCA-1, DU-145 and PC-3) and 24 pairs of untreated prostate cancer tissue and noncancerous tissue from resected prostate glands were subjected to RT-PCR testing. RESULTS: Both LNCap and JCA-1 expressed the mRNA of both receptors, but DU-145 and PC-3 only expressed ER-beta mRNA. In the human prostate tissue samples, 20 of the 24 prostate cancer tissues expressed ER-alpha, and 23 of the 24 expressed ER-beta. Of the 24 noncancer tissues, 14 expressed ER-alpha mRNA and 17 expressed ER-beta mRNA. The incidence of ER-beta mRNA expression between the paired cancer and noncancer tissues was statistically significantly different (p<0.05). CONCLUSIONS: A higher incidence of ER-beta mRNA expression in untreated prostate cancer tissues was observed. Furthermore, the absence of ER-alpha mRNA and the presence of ER-beta mRNA expression in hormone-independent and/or untreated prostate cancer cells leads to a tentative speculation of the mechanism of the hormone refractory feature of prostate cancer.

Estrogen Receptor alpha↗

Aldosterone-producing adenoma with prolonged amelioration by dexamethasone.

Secretion of aldosterone from aldosterone-producing adenoma (APA) is to some degree under the control of ACTH and the suppressible effect of glucocorticoid on plasma aldosterone concentration (PAC) and blood pressure has been reported to be transient. We report a rare case of aldosteronism due to APA in which PAC and blood pressure were well controlled with small dose dexamethasone for over one year. No chimeric gene of glucocorticoid-remediable aldosteronism (GRA) was found in DNA of APA and leukocytes from peripheral blood and 17alpha-hydroxylase deficiency (17-OH-D) was ruled out by endocrinological examinations, this case indicates the possibility of an unknown mechanism of ACTH-dependent APA.

Adenoma↗

[Clinical efficacy of leuprolide acetate and combined treatment with estramustine for advanced prostate cancer].

BACKGROUND/PURPOSE: Twenty-two institutes have organized Keio University Prostate Cancer Study Group to study clinical efficacy and safety of Leuprolide acetate (Leuplin) for the treatment of advanced prostate cancer (clinical stage D1 and D2). Cotreatment of Leuplin and Estramustine phosphate disodium (Estracyt) has been performed to investigate its clinical efficacy. MATERIALS AND METHODS: One hundred and two cases of advanced prostate cancer were treated either with Leuplin alone (group I), Leuplin and Estracyt (group II) or Estracyt alone (group III). After 12 weeks treatment, clinical effects against subjective symptoms (pain, voiding difficulty, performance status and body weight), serum testosterone level, tumor size and serum PSA level were examined to investigate short-term effect of each treatment. The treatment had been continued for 24 months and the treatment effects including progression free survival and overall survival were analyzed. RESULTS: Clinical efficacy after 12 weeks treatment were examined among 97 cases (group I; 35 cases, group II; 36 cases, group III; 26 cases). The background of those patients in each group was statistically equal. Treatment effects against subjective symptoms and serum testosterone level statistically revealed no significant difference among 3 groups. Treatment effects against primary tumor, bone metastatic lesion, lymphnode metastatic lesion and serum PSA level were investigated and anti-tumor effect was characterized by total efficacy rate (complete remission rate plus partial remission rate) of each treatment group. Treatment efficacy rates for each lesion and PSA demonstrated no statistical difference among 3 treatment groups. Total efficacy rate of group I, II and III were 88.2%, 84.0% and 78.3%, respectively, which statistically revealed no significant difference. Total efficacy rate of each group after completing 24 months treatment was; group I 80.0%, group II 55.6% and group III 83.3%, which statistically showed no significant difference among 3 treatment groups. The median day for progression free survival of group I, II and III were 661, 731 and 517, respectively. The overall survival rate of group I, II and III after completing 24 months treatment were 77.5%, 83.0% and 72.4%, respectively. Both progression free survival rates and overall survival rates revealed no significant difference among 3 groups. Side effects during 24 months treatment were seen in 8.6% of group I, 47.2% of group II and 26.9% of group III, and these occurrence rates were significantly different among the groups (p = 0.0013). CONCLUSION: Although number of the cases had not been able to continue the treatment for their side effects, the statistical characterization demonstrated that cotreatment of Leuplin and Estracyt had no greater treatment effect than monotreatment of each drug.

Aged↗

Immunotherapy of bladder cancer using autologous dendritic cells pulsed with human lymphocyte antigen-A24-specific MAGE-3 peptide.

Recent investigations have demonstrated the efficacy of autologous dendritic cells (DCs) pulsed with tumor antigens to generate tumor-specific CTLs against cancer cells. Melanoma antigens (MAGE) are a family of tumor-specific antigens shown to be expressed in various tumors, including bladder cancers and melanoma, but not in normal tissues except for the testis. Because invasive bladder cancers are frequently reported to express MAGE, we explored the possibility of establishing a new immunotherapeutic modality against advanced bladder cancer using autologous DCs pulsed with one of the MAGE-3 epitope peptides (IMPKAGLLI), which is synthesized to bind specifically to HLA-A24. A MAGE-3-expressing bladder cancer cell line, FY, was newly established from a lymph node metastasis of bladder cancer in a HLA-A24+ patient. The FY cell-specific CTL response was significantly higher when CTL was induced by autologous DCs pulsed with IMPKAGLLI than by FY cells alone or by nonpulsed DCs in vitro. A total of four HLA-A24+ patients with advanced MAGE-3+ bladder cancers were treated with s.c. injections of autologous DCs pulsed with IMPKAGLLI every 2 weeks for a minimum of 6 and a maximum of 18 times. Three of four patients showed significant reductions in the size of lymph node metastases and/or liver metastasis. No significant untoward side effects were noted in these patients. This study indicated that, at sometime in the future, tumor-specific DC-based cancer immunotherapy may be useful as an additional treatment modality against advanced bladder cancer.

Aged↗

Treatment of human renal cell carcinoma by a conditionally replicating herpes vector G207.

PURPOSE: Surgical removal remains the only potentially curative therapy for renal cell carcinoma. In this study we evaluated the inhibitory effect of the replication competent engineered herpes simplex virus type 1, G207, for renal cell carcinoma in vitro and in vivo. MATERIALS AND METHODS: The nature of G207 enables it to replicate within cancer cells, thus, causing cytolysis, but replication is restricted within normal cells. The susceptibility of the human renal cancer cell lines ACHN and A498 to G207 at a multiplicity of infection of 0.1 was examined. In addition, the growth characteristics of G207 was assessed. In vivo athymic mice bearing subcutaneous tumors were inoculated with 1 x 10(7) plaque forming units of G207 intra-neoplastically. For pathological analysis subcutaneous tumors were stained with X-gal. RESULTS: Two cell lines were efficiently destroyed by G207 within 1 week. The viral yields of G207 increased in a time dependent manner. In vivo the intra-neoplastic inoculation of G207 caused significantly decreased tumor growth in athymic mice harboring subcutaneous human renal cancer cells. On day 14 the mean growth ratio of ACHN and A498 lesions was significantly inhibited in G207 treated compared to control tumors (p <0.005 and <0.0001, respectively). CONCLUSIONS: These results suggest that G207 should be considered another potential therapeutic agent for renal cell carcinoma.

Animals↗

[Angiographic findings of hemodialysis access insufficiency].

One hundred forty-six angiographic findings of malfunctioning internal arteriovenous fistulas without any history of interventional procedures were reviewed. Angiographies demonstrated 110 cases of stenosis, 72 of occlusion, 5 of venous varicosity, and 13 of venous aneurysm. Of 182 stenotic lesions, 118 (65%) lesions (74 venous stenoses: 67%; 44 venous occlusions: 61%) were revealed within five centimeters of anastomoses. In 4 of 5 cases of varicosity, proximal venous occlusions were demonstrated. On the other hand, interventional procedures were performed in 81 cases of stenoses and 14 of occlusions in the manner of PTA and fibrinolysis. The initial success rate was 90% in stenotic lesions and 71% in occlusive lesions, not a statistically significant difference. Furthermore, there was no statistically significant difference in initial success rates according to anatomical location and lesion length. Although there was no statistically significant difference according to the angiographic findings of lesions, we would like to emphasize the importance of correct understanding of anatomical changes in the dialysis shunt and of early intervention to improve the initial success rate of PTA.

Adolescent↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). I. Susceptibility distribution].

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the susceptibilities of them to many kinds of antimicrobial agents were investigated. The number of them were 499 strains. The breakdown of these strains was Gram-positive bacteria as 31.3% and Gram-negative bacteria as 68.7%. Susceptibilities of these bacteria to antimicrobial agents were as follows; vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) showed strong activities against Enterococcus faecalis. The increase of low-susceptible strains which was noticed in the former year showed a slight recovery in this year. VCM showed a strong activity against MRSA preventing growth of all strains with 1 microgram/ml. In addition, the activity of arbekacin (ABK) was also strong with the MIC90 of 2 micrograms/ml against MRSA. However, MSSA and MRSA showing low susceptibilities were detected in one strain each (MIC: 16 micrograms/ml and 32 micrograms/ml, respectively). Carbapenems showed high activities against Citrobacter freundii and Escherichia coli. Meropenem (MEPM) prevented growth of all strains within 0.125 microgram/ml. Quinolone resistant E. coli decreased in this year compared with those in the last year, that percentage was less than 5%. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis. MEPM and carumonam (CRMN) prevented growth of all strains within 0.125 microgram/ml. On the other hand, one strain of K. pneumoniae showing resistance to cefaclor (CCL) and one strain of P. mirabilis showing low susceptibility to most of cephems were detected. Against Pseudomonas aeruginosa, almost drugs were not so active. The MIC90s of carbapenems were 8 micrograms/ml and those of all other drugs were more than 16 micrograms/ml.

Anti-Bacterial Agents↗