Effects of Zinc on Production of Active Oxygen Species by Rat Neutrophils

Abstract: The effects of zinc on the production of active oxygen species were investigated in rat neutrophils by chemilumi-nescence and spectrophotometric assays. The luminol-dependent chemiluminescence in unstimulated neutrophils showed a single peak. Zinc at concentrations lower than 0.1 mM augmented the intensity of chemiluminescence and showed a bimodal pattern, the first peak of which was inhibited by superoxide dismutase and catalase, while the second peak disappeared in the presence of catalase, but was unaffected by superoxide dismutase. At the same concentrations of zinc, O₂^? and H₂O₂ production increased, but secretion and activity of myeloperoxidase were not affected. Zinc at 0.1 mM enhanced the second peak of luminol-dependent chemiluminescence, and concomitantly O₂^? and H₂O₂ production of neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine. Homogenized neutrophils showed a bimodal pattern on induction by zinc, the second peak of which was inhibited slightly by catalase and completely by sodium azide, but was not inhibited by superoxide dismutase. Zinc-induced O₂^? production was inhibited by pertussis toxin, but was not significantly inhibited by a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), or a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). These results suggest that zinc can augment luminol-dependent chemiluminescence by increasing O₂^? production through the classical signal transduction pathway, and by increasing H₂O₂ not via O₂^?.     

A case of pulmonary embolism following acute respiratory failure with hypercapnia]

A 18-year-old boy was admitted to hospital in an unconsciousness state as a result of taking a large dose of several psychotropic drugs simultaneously in an attempt to commit suicide. Blood studies revealed hypoxia (55.7 mmHg) and hypercapnia (59.7 mmHg). Hypoxia (74.3 mmHg) and hypercapnia (46.7 mmHg) were still present on the fourth day after admission, and the patient was becoming lethargic. Reduced vascular markings in the right upper lung field on chest roentgenogram in spite of hypercapnia suggested that the persistent hypoxia was the result of a pulmonary embolism. This diagnosis was supported by a perfusion defect on 99mTc-MAA scintigram and arterial obstruction in right pulmonary angiogram. Hypercapnia is an unusual finding in pulmonary embolism, and in this case was considered due to depression of respiration by psychotropic drugs.     

Universal applications of sentinel node technology

The sentinel node (SN) concept was originally proposed by several pioneers in the middle of the last century. After Donald Morton and his colleagues demonstrated the clinical significance of the SN concept in melanoma, it attracted vast attention in surgical oncology. At recent international conferences, a number of new approaches in this field for various solid tumors have been reported. Now, there are several possible applications with different technological aspects, such as individualized surgical management of solid tumors, multidisciplinary treatments, and novel therapeutic approaches. This article provides an overview of the future potential of SN technology.     

A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

A case of Sweet's syndrome (acute febrile neutrophilic dermatosis) associated with mixed connective tissue disease]

Sweet's syndrome (acute febrile neutrophilic dermatosis) is an unusual condition characterized by fever, polymorphonuclear neutrophil leukocytosis of the blood, thick painful plaques on the face, neck and limbs, and a dense dermal infiltrate of mature neutrophils seen histologically. Recently, this disease has also been reported in association with various malignant neoplasms and chronic inflammatory disorders. In the literature, seven cases of Sweet's syndrome associated with collagen diseases have been reported, but no cases with mixed connective tissue disease (MCTD). The first case of Sweet's syndrome associated with MCTD was herein described and discussed. A 49-year-old man was admitted to our hospital with the complaints of high fever and painful erythema on his face, neck and limbs. Six months ago, MCTD was suspected, with the presence of limited cutaneous sclerosis of the hands, Raynaud's phenomenon, polyarthralgia, an elevation of CPK value and a positive anti-RNP antibody. Just before hospitalization, he suffered a prodromal infection of the upper respiratory tract for two weeks. He was diagnosed as Sweet's syndrome by the clinical and histological features. He began receiving corticosteroid therapy (prednisolone 60 mg/day), and within a week he showed dramatic improvement in the above symptoms.     

Study of the duration of antimicrobial chemotherapy in mycoplasmal pneumonia]

We assessed the period of administration of antibiotics required for cases of mycoplasmal pneumonia. The subjects were 38 patients with mycoplasmal pneumonia admitted to our hospital. These patients were treated with 100 mg minocycline or 500 mg erythromycin by intravenous infusion twice a day. They were divided into a 6 day-administration group (Group A; 16 cases) and a 9 day-administration group (Group B; 17 cases). Administration was discontinued on the 4th day or earlier in 5 cases due to side effects. A comparative assessment was made between Groups A and B with respect to body temperature, WBC, erythrocyte sedimentation rate, CRP, and chest X-ray on the 3rd, 6th, and 9th days of treatment, but no significant difference was observed. Residual shadows at the end of treatment were present in 100% of Group A and in 47% of Group B, but they disappeared gradually in both groups. No cases of recurrence were observed in either Group A or B within 1 month after the completion of treatment. Regarding the treatment period for mycoplasmal pneumonia by intravenous infusion of minocycline or erythromycin, no significant clinical difference was observed between the 6 day-administration group and the 9 day-administration group, suggesting that 6 days of administration is sufficient for treatment.     

Applications of DNA Flow Cytometry and Fluorescence In situ Hybridization Using a Chromosome-specific DNA Probe on Paraffin-embedded Tissue Sections of Primary Malignant Melanomas

We have applied DNA flow cytometric analysis to paraffin-embedded tissue sections of primary malignant melanomas. Conventionally, flow cytometric analysis of paraffin-embedded tissue sections has been done by the method of Hedley et al. We added ultrasound treatment to the method of Hedley et al. and a lower value of coefficient of variation was shown. Furthermore, a new technique, fluorescence in situ hybridization with a chromosome-specific repetitive DNA probe, was used for the analysis of chromosomal numerical aberrations in the same paraffin-embedded tissue sections. The DNA flow cytometric analysis showed that in 8 cases six primary malignant melanomas were of the aneuploid pattern and two cases of lentigo maligna (melamona in situ) were of the diploid pattern. By fluorescence in situ hybridization, the two cases with the diploid pattern had spots/nucleus of 1.28 and 1.12, and those with the aneuploid pattern had spots/nucleus from 2.01 to 2.27. Only one nodular melanoma in an aneuploid case showed spots/nucleus of 1.71. These data indicate that fluorescence in situ hybridization with chromosome-specific repetitive DNA probes can serve as a cytogenetic tool for the analysis of interphase nuclei of solid human tumors and may be useful for the study of tumor cell heterogeneity.     

Neuropathology of progressive multifocal leukoencephalopathy]

Progressive multifocal leukoencephalopathy (PML) is caused by opportunistic infection of JC virus which belongs to Papovavirus, and presents with progressive demyelinating lesion in the central nervous system. PML was originally reported as a rare complication of hematologic disorders, but later greatly increased in number in association with acquired immunodeficeincy syndrome (AIDS). Original neuropathological features of PML consist of demyelination lacking inflammatory reaction or necrosis, accompanying oligodendroglial nuclear inclusions in the periphery of demyelination. The lesion is preferentially localized to gray-white junction of the cerebral hemisphere and manifests as characteristic demyelinating lesion, called scallopping. Detection of JC virus is essential for the final diagnosis of PML and is achieved via immunohistochemical detection of JC virus with antibodies raised against their components, ultrastructural demonstration of virions characteristic of JC virus, or detection with in-situ hybridization of the genome of JC virus. JC virus can replicate only in oligodendroglial cells, but astrocytes are frequently infected by the virus. The resume of immunological function through therapeutic intervention develops new pathology in PML, exhibiting severe inflammatory reaction with edema and necrosis. This new pathological feature is called immune reconstruction syndrome and clinically presents with severe progression in symptoms of the central nervous system. Nevertheless, treatment of PML is directed for the elimination of the viruses by host immune system. The modification of the above immune reconstruction syndrome is essential for successful outcome of such therapeutic trial.