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.     

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.     

Two cases of gastrointestinal stromal tumor (GIST) of the stomach and a consideration of its malignancy potential and treatment strategy - report of two cases

We report two cases of large gastrointestinal stromal tumor (GIST) of the stomach both of which were assessed as highly malignant, but took different clinical courses. Case 1: A 72-year-old male. Case 2: A 63-year-old female. The tumor size of Case 1 was suggestive of high malignancy, but only a partial gastrectomy was selected because it did not show any invasive findings. This patient has been followed up for 3 years post-operatively and no recurrence or metastasis has been noted. Case 2 had liver and lymph node metastases, which was consistent with high malignancy. We performed a total gastrectomy with distal pancreatosplenectomy and segmental liver resection. But after surgery, liver metastasis recurred therefore, imatinib mesylate was administered as adjuvant chemotherapy and since then, the tumor has been diminishing in size. No definitive evidence for adjuvant therapy has been established so far, but we suggest that post-operative adjuvant therapy is effective for high-risk GIST.     

A case undergoing repeated anaphylactic shock after systemic administration of vinorelbine

We here describe a 49-year-old man who suffered repeated anaphylactic shock after systemic chemotherapy with vinorelbine for stage IV left lung adenocarcinoma (S1+2). He was treated using a combination of cisplatin and weekly irinotecan (CPT-11) as the first line; however, the regimen was changed to a combination of vinorelbine (VNR) and gemcitabine (GEM) because of his progressive disease. He was admitted to our hospital for examination of the unknown cause of hypotension and loss of consciousness.The second shock occurred after eating pistachios, and the third one at cancerous pain. After pain control, the shock no longer occurred. Anaphylactic shock may show two peaks and late symptoms. In patients with a history of anaphylactic shock, we should pay attention to foods, drugs, and various stresses which might cause anaphylaxis.     

Circadian rhythms in the CNS and peripheral clock disorders: function of clock genes: influence of medication for bronchial asthma on circadian gene

Bronchial asthma is a chronic inflammatory disorder of the airways, in which inflammation causes bronchial hyper-responsiveness and flow limitation in the presence of various stimuli. Pulmonary function in asthmatic patients frequently deteriorates between midnight and early morning, which has suggested a role for chronotherapy. Although relationships between bronchial asthma and the function of clock genes remain unclear, some medications given for asthma such as glucocorticoids or beta(2)-adrenoceptor agonists may influence clock genes in vivo. In our studies of clock gene mRNA expressions in human bronchial epithelial cells in vitro and peripheral blood cells in vivo, we demonstrated that glucocorticoid or beta(2)-adrenoceptor agonist treatment strongly induced human Per1 mRNA expression both in vitro and in vivo. Human peripheral blood cells provide a useful indication of peripheral clock gene mRNA expression in vivo.     

Organ-specific endoglin (CD105) expression in the angiogenesis of human cancers

Some markers of angiogenic endothelial cells are emerging as targets for cancer therapy. The present study compared the expression of CD105 with that of other endothelial markers in cancers from various organs. Surgically resected cancer tissues from 188 patients comprising brain (n = 17), lung (n = 38), breast (n = 30), stomach (n = 30), colon (n = 31), liver (n = 32), and kidney (n = 10) cancers were immunohistochemically analyzed on tissue microarrays using a panel of eight endothelial markers. CD31 was expressed in vascular endothelial cells in cancer lesions as well as in non-cancerous areas (30-100%) in all core tissue samples. CD105 expression was intense and restricted to capillary endothelial cells in cancer lesions (>73%). In contrast, positive expression of CD105 was seen in <20% of non-cancerous areas in the same organs. However, no significant difference in CD105 expression in vascular endothelial cells between cancer lesions and non-cancerous areas from liver and renal cancer samples was found. Vascular endothelial growth factor (VEGF), Flt1, and Flk1 were also expressed, but only sporadically and in few samples (<30%), and transforming growth factor (TGF)-beta1 and TGF-betaRII were negative in vascular endothelial cells but generally positive in cancer cells. CD44 was strongly expressed in sinusoidal endothelial cells of the liver (90-100%). These results show that CD105 is expressed specifically in the tumor angiogenesis of brain, lung, breast, stomach, and colon cancers.     

Role of non-protein amino acid L-canavanine in autoimmunity

Association of SLE and alfalfa was first reported in a volunteer who developed lupus-like autoimmunity while ingesting alfalfa seed for a hypercholesterolemia study. This was corroborated with studies in monkeys fed with alfalfa sprout that developed SLE. Re-challenge with L-canavanine relapsed the disease. Arginine homologue L-canavanine, present in alfalfa, was suspected as a cause. L-canavanine can be charged by arginyl tRNA synthetase to replace L-arginine during protein synthesis. Aberrant canavanyl proteins have disrupted structure and functions. Induction or exacerbation of SLE by alfalfa tablets reported in a few cases remains controversial. Epidemiological studies on the relationship between alfalfa and SLE are sparse. In mice, NZB/W F1, NZB, and DBA/2 mice fed with L-canavanine show exacerbation/triggering of the SLE, however, BALB/c studies were negative. L-canavanine incorporation may be more efficient in the presence of inflammation or other conditions that can cause arginine deficiency. The L-canavanine induced apoptotic cells can be phagocytosed and a source of autoantigens processed by endosomal proteases. Endogenous canavanyl proteins are ubiquitinated and processed via proteasome. Incorporation of L-canavanine into proteasome or endosome can also cause disruption of antigen processing. Alfalfa/L-canavanine-induced lupus will be an interesting model of autoimmunity induced by the modification of self-proteins at the translational level.