Clinical study on long-term cinoxacin therapy for outpatients with chronic complicated urinary tract infections

Cinoxacin was administered to 30 outpatients with chronic complicated urinary tract infection for 57.3 days (average) and the following results were obtained. Clinical efficacy based on decrease of pyuria were "excellent" in 44.8%, "good" in 31.0%, "fair" in 24.1%, and "poor" in 0%; and, overall effectiveness rate reached 75.9%. As for side effect, diarrhea and nausea were observed in 2 and 1 patients, respectively. GOT and GPT elevation was also seen in one case. Cinoxacin long term therapy seems to be effective and useful to chronic complicated urinary tract infections.     

Positron CT imaging using a high resolution PCT device (Positologica-I),11CO,13NH3, and18FDG in clinical evaluation of cerebrovascular diseases

Positron computed tomography (PCT) was performed in 3 normal volunteers and 21 patients with cerebrovascular diseases using a high resolution PCT device Positologica-I and three tracers¹¹CO,¹³NH₃, and¹⁸FDG. Relatively early lesions showed various accumulation patterns, and metabolism and perfusion mismatches were clearly shown by this measurement. One type of mismatch is luxury perfusion which had a slight increase of blood volume. Another type of uncoupling is misery perfusion. Remote effects of ischemic lesions also appeared on PCT with¹⁸FDG and¹³NH₃. From our clinical results, the PCT method with a high resolution device and radiopharmaceuticals such as¹¹CO,¹³NH₃, and¹⁸FDG is very useful in the assessment of cerebrovascular diseases and in defining circulatory dysfunction in man.     

CD98 regulates the phosphorylation of HER2 and a bispecific anti-HER2/CD98 antibody inhibits the growth signal of human breast cancer cells

Human epidermal growth factor receptor (HER) family proteins are currently major targets of therapeutic monoclonal antibodies against various epithelial cancers. However, the resistance of cancer cells to HER family-targeted therapies, which may be caused by cancer heterogeneity and persistent HER phosphorylation, often reduces overall therapeutic effects. We herein showed that a newly discovered molecular complex between CD98 and HER2 affected HER function and cancer cell growth. The immunoprecipitation of the HER2 or HER3 protein from lysates of SKBR3 breast cancer (BrCa) cells revealed the HER2-CD98 or HER3-CD98 complex. The knockdown of CD98 by small interfering RNAs inhibited the phosphorylation of HER2 in SKBR3 cells. A bispecific antibody (BsAb) that recognized the HER2 and CD98 proteins was constructed from a humanized anti-HER2 (SER4) IgG and an anti-CD98 (HBJ127) single chain variable fragment, and this BsAb significantly inhibited the cell growth of SKBR3 cells. Prior to the inhibition of AKT phosphorylation, BsAb inhibited the phosphorylation of HER2, however, significant inhibition of HER2 phosphorylation was not observed in anti-HER2 pertuzumab, trastuzumab, SER4 or anti-CD98 HBJ127 in SKBR3 cells. The dual targeting of HER2 and CD98 has potential as a new therapeutic strategy for BrCa.     

Repeat liver resection for recurrent colorectal liver metastases

BACKGROUND: This study aimed to delineate the role of surgery for recurrent colorectal cancer in the liver and to identify prognosticators for better patient selection and outcome. METHODS: Data from 90 repeat hepatectomies (second = 75; third = 12; fourth = 3) for recurrent colorectal cancer were collected. RESULTS: After the second hepatectomy, the 3-and 5-year survival rates were 48% and 31%, respectively. Twenty-seven percent (20 of 75) of patients are alive without recurrence after a median follow-up of 27 months, and 9 survived more than 5 years. Four or more tumors, positive regional lymph node metastases, concomitant extrahepatic disease, and residual tumor were independent poor prognostic factors after the second hepatectomy. CONCLUSIONS: Repeat hepatectomy should be applied for recurrent colorectal cancer, when curative removal of the tumor is possible, although the benefit from treatment was limited in a patient with regional lymph node metastases, 4 or more metastases, or extrahepatic disease.     

Reduction of tumorigenicity by an interferon-γ-gene-transduced tumor on another syngeneic tumor in a murine model

To evaluate the effect of interferon-γ-genetransduced cells, DS mice were inoculated into their footpads with syngeneic mammary adenocarcinoma SC42 admixed with interferon-γ producing mammary adenocarcinoma SC115Kγ, which had been established by an interferon-γ-gene transduction in another syngeneic mammary adenocarcinoma SC115 using retroviral vectors. These mice rejected both tumor cells and developed resistance to subsequent challenges with either SC115 or SC42 cells inoculated into their opposite posterior footpads. These results thus indicate that systemic immunological memory to each of the independent tumor cell lines developed in these mice. Although the SC42 cells admixed with irradiated SC115Kγ cells were rejected by these mice, the SC42 cells admixed with irradiated SC115neoR, in which the neo-gene had been transduced, were observed to proliferate. Tumor rejection was reversed by an in vivo administration of anti-interferon-γ antibody, thus suggesting that locally produced interferon-γ plays an important role in tumor elimination and immunological memory induction. In conclusion, interferon-γ-gene-transduced tumor cells are therefore considered to have a therapeutic potential for other types of malignant tumor cell lines.     

Clinical, immunological and MRI features of myelitis with atopic dermatitis (atopic myelitis)

In order to clarify the characteristic features of myelitis with atopic dermatitis (AD), we compared the clinical, immunological and MRI findings between 14 myelitic patients with AD and 12 myelitic patients without AD. The myelitic patients with AD showed the following distinct features, compared with those without AD. (1) A preferential involvement of the cervical cord, as shown by neurologic as well as MRI examinations (14/14 vs. 5/12; P=0.0012), (2) paresthesia/dysesthesia as the predominant symptoms and a rare occurrence of definite muscle weakness (0/14 vs. 5/12; P=0.0120) and dysuria (1/14 vs. 8/12; P=0.0029), (3) a lower Expanded Disability Status Scale score (mean, 1.5 vs. 3.5; P=0.0018), (4) normal cerebrospinal fluid (CSF) findings including those for the IgG index and oligoclonal IgG bands and (5) a persistence of neurologic symptoms and MRI lesions during the follow-up periods (mean, 17 months). In addition, both the serum total IgE level and the frequency of specific IgE to Dermatophagoides farinae were significantly higher in the myelitic patients with AD (median IgE=1266 U/ml, specific IgE 14/14) than in those without AD (145 U/ml, P=0.0034 and 8/12, P=0.0331, respectively) and in 40 healthy controls (86 U/ml, P<0.0001 and 12/40, P<0.0001, respectively). Since myelitis with AD has distinct features and atopy to mite antigens appears to be the underlying cause of this condition, it may therefore be a distinct subtype of myelitis.     

Anterior Transhepatic Approach for Isolated Resection of the Caudate Lobe of the Liver

RID=" ID=" <E5>Correspondence to:</E5> J. Yamamoto, M.D.     

Induction of erythroleukemia cell adhesion by plant diterpene tumour promoters: a quantitative study and correlation with in vivo activities

A potent tumour promoter on mouse skin, phorbol-9-myristate-9a-acetate,induces certain clones of Friend erythroleukemia cells to becomeadhesive to the surface of tissue culture dishes, whereas inthe absence of this compound, these cells grow in suspension.We have quantitatively tested 20 other phorbol esters and relatedcompounds for this effect. When the results are expressed asthe concentrations of compounds which show half-maximum effecton cell adhesion, the decreasing order of potency is: phorbol-9-myristate-9a-acetate(3.6 x 10^–10M) gnilatimacrin > milliamine A phorbol-9,9a-didecanoate mezerein gnidilatin ingenol-3,20-dibenzoate > phorbolol-9-myristate-9a-acetate> phorbol-9,9a-dibutyrate phorbol-9,9a-dibenzoate > 4a-O-methyl-phorbol-9-myristate-9a-acetate> phorbol-9-myristate-9a-acetate-3-aldehyde > phorbol-9,9a-diacetate> 2,3-dihydrophorbol-9-myristate-9a-acetate. Phorbol, 4a-phorbol-9,9a-didecanoate,phorbol-3,9,9a-triacetate, phorbol-9-myristate, phorhol-9-monoacetateand phorbol-9a-monoacetate were inactive in this assay whentested at concentrations as high as 1 µg/ml (10^–6M).None of these 20 compounds induced adhesion when they were testedwith a variant clone of Friend erythroleukemia cells which isresistant to the induction of adhesion and several other effectsof phorbol-myristate-acetate. When the relative potencies ofthese compounds in the adhesion assay were compared to availablein vivo data on tumour promoting activity on mouse skin, therewas, in general, a good qualitative correlation. A better butnot perfect quantitative correlation was obtained when the resultsfrom the adhesion assay were compared with reported inflammatoryactivity on mouse ear. When several other tumour promoters andcocarcinogens which differ structurally from the phorbol estersand related plant diterpenes were tested, none of these inducedadhesion in this assay.     

Vergence disorders in patients with spinocerebellar ataxia 3/Machado-Joseph disease: a synoptophore study

Diplopia, a common symptom in spinocerebellar ataxia 3/Machado-Joseph disease (SCA3/MJD) cases, is not always due to asymmetric ophthalmoplegia. We found a Japanese SCA3/MJD family, in which three patients clearly had an impairment of divergence eye movement. We thus quantitatively examined the vergence ranges in eight Japanese SCA3/MJD cases using the synoptophore test. An impairment of the vergence eye movements was found in all patients, and the vergence impairment pattern, but not the ophthalmoplegia pattern, was found to be compatible with the diplopia pattern. The diplopia in SCA3/MJD cases is, therefore, attributed, at least in part, to the impairment of the vergence eye movements.     

Flow cytometric differentiation of Asian and Western types of multiple sclerosis, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and hyperIgEaemic myelitis by analyses of memory CD4 positive T cell subsets and NK cell subsets

We examined the alterations of memory CD4(+) T cell subsets bearing surface receptors linked to either Th1 or Th2 cytokine production as well as natural killer (NK) cell subsets by three color flow cytometry in the peripheral blood from 36 patients with clinically definite multiple sclerosis (MS), 27 patients with HAM/TSP, 13 patients with hyperIgEaemic myelitis who had mite antigen-specific IgE and 25 healthy controls (HC). The patients with MS were clinically classified into an optico-spinal form of MS (Asian type, MS-A) and the conventional form of MS (Western type, MS-W). MS-A showed a significant increase of CD4(+)CD45RA(-)CCR5(+) cells (Th1 cells) through the relapse and remission phases in comparison to HC, while MS-W showed a significant increase of CD4(+)CD45RO(+)CD62L(-) cells (Th1 cells) only at the relapse phase. HAM/TSP showed a significant increase of CCR5(+) and CD62L(-) memory CD4(+) T cells as well as CD30(+) memory CD4(+) T cells (Th2 cells) in comparison to HC. On the other hand, a selective increase of CD4(+)CD45RO(+)CD30(+) cells was found in hyperIgEaemic myelitis. The percentage of mature NK cells (CD3(-)CD16(+)CD56(+) cells) as well as double negative T cells (CD3(+)CD4(-)CD8(-) cells) decreased significantly in HAM/TSP in comparison to HC. Our findings therefore suggest a flow cytometric analysis of Th1/Th2-associated markers on memory CD4(+) T cells as well as NK cell subsets to be useful for differentiating various inflammatory neurologic conditions.