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Biomedical subjects

M Johno

Publications and source records attributed to M Johno.

At least 37 records · Page 2Linked to original sources

Activated protein C attenuates endotoxin-induced pulmonary vascular injury by inhibiting activated leukocytes in rats.

We investigated the effect of activated protein C (APC) on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats to investigate the possible usefulness of APC as a treatment for adult respiratory distress syndrome. Intravenously administered LPS (5 mg/kg) significantly increased pulmonary vascular permeability. APC prevented the LPS-induced increase in pulmonary vascular permeability observed at 6 hours. Heparin plus antithrombin III (ATIII) and active site-blocked factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, inhibited LPS-induced coagulopathy but did not prevent LPS-induced pulmonary vascular injury. LPS-induced pulmonary vascular injury was significantly attenuated in rats with nitrogen mustard-induced leukocytopenia and in rats treated with ONO-5046, a potent granulocyte elastase inhibitor. Administration of LPS also increased pulmonary accumulation of leukocytes, as evaluated by measurement of myeloperoxidase activity in the lungs. APC significantly reduced LPS-induced increases in pulmonary accumulation of leukocytes at 1 hour. Neither ATIII plus heparin nor DEGR-Xa inhibited leukocyte accumulation. Active site-blocked APC (DIP-APC) prevented neither the LPS-induced pulmonary accumulation of leukocytes nor the LPS-induced increase in pulmonary vascular permeability. These results suggest that the mechanism of APC inhibition of LPS-induced pulmonary vascular injury was independent of its anticoagulant activity and was related to its ability to inhibit accumulation of leukocytes. In addition, these findings suggest that the serine protease activity of APC may be essential to its inhibitory effect on LPS-induced pulmonary accumulation of leukocytes and subsequent pulmonary vascular injury.

Amino Acid Chloromethyl Ketones↗

Giant basal cell carcinoma associated with systemic amyloidosis.

A large basal cell carcinoma, 39 x 26 cm in size, is presented as second in size only to the largest basal cell carcinoma documented (40 x 30 cm), reported by Beck and co-workers (1). A 61-year-old Japanese male visited our clinic with a huge ulcerating tumor on the back. He had hidden the tumor for the previous 30 years. The tumor was histologically confirmed as basal cell carcinoma. The condition was associated with anemia, hypoproteinemia, and dyspnea, and with systemic amyloidosis in the skin, in the lymph nodes, and in the intestinal canal. On admission, the tumor had metastasized to the regional lymph nodes, and, about two years after the first operation, there were metastases to bone and lung, leading to death due to respiratory failure.

Amyloidosis↗

Recombinant thrombomodulin prevents endotoxin-induced lung injury in rats by inhibiting leukocyte activation.

Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis. Thrombomodulin, an important endothelial anticoagulant, binds thrombin to generate activated protein C (APC). We have previously demonstrated that APC prevents endotoxin (ET)-induced pulmonary vascular injury by inhibiting activated leukocytes. We therefore examined whether recombinant human soluble thrombomodulin (rhs-TM) prevents activated leukocyte-induced pulmonary vascular injury in rats receiving ET. Intravenous administration of rhs-TM prevented ET-induced pulmonary accumulation of leukocytes and increase in pulmonary vascular permeability, as well as ET-induced histological changes, such as leukocyte infiltration and pulmonary interstitial edema. Dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, did not prevent these effects of ET. rhs-TM did not prevent ET-induced pulmonary accumulation of leukocytes and pulmonary vascular injury in rats pretreated with DEGR-Xa. These results suggest that rhs-TM prevents ET-induced pulmonary vascular injury by inhibiting pulmonary accumulation of leukocytes and that this effect may be mediated primarily by APC generation.

Animals↗

A novel platelet activating factor antagonist, SM-12502, attenuates endotoxin-induced disseminated intravascular coagulation and acute pulmonary vascular injury by inhibiting TNF production in rats.

Adult respiratory distress syndrome and disseminated intravascular coagulation are important pathologic conditions affecting the outcome of patients with sepsis. To elucidate the possible therapeutic efficacy of SM-12502, a novel platelet activating factor antagonist, on acute lung injury and disseminated intravascular coagulation in sepsis, we investigated the effect of SM-12502 on an endotoxin (ET)-induced septic model in rats. SM-12502 prevented ET-induced increases in pulmonary vascular permeability and ET-induced histologic changes, such as leukocyte infiltration and pulmonary interstitial edema, 6 h following the administration of ET (5 mg/kg). SM-12502 also inhibited the decrease in fibrinogen and the increase in fibrin and fibrinogen degradation products observed following ET administration. SM-12502 prevented increases in the serum concentration of tumor necrosis factor (TNF) 90 min following ET administration in vivo, and significantly inhibited the production of TNF-alpha by ET-stimulated monocytes in vitro. These findings suggest that SM-12502 attenuates the actions of endotoxin by the inhibition of TNF production.

Animals↗

Metastatic skin cancer; a case with signet ring cell histology.

We report a 64-year-old Japanese man who developed metastatic skin cancer, in the form of 1-3 cm diameter dome-shaped tumours on his face and head. Histopathological examination demonstrated diastase-resistant periodic acid--Schiff and Alcian blue-positive signet ring cells, suggesting gastric carcinoma. Immunohistochemical staining showed that these cells were positive for carbohydrate antigen CA19-9.

Antigens, Neoplasm↗

Differences in IL-2 receptor levels between mycosis fungoides and cutaneous type adult T-cell leukemia/lymphoma in the early stages of the disease.

Skin lesions in mycosis fungoides (MF) and cutaneous-type adult T-cell leukemia/lymphoma (c-ATL) are sometimes difficult to differentiate. Our previous investigations showed that the alpha-chain of interleukin-2 receptor (IL-2R alpha) secretion is enhanced in both acute and chronic type ATL. This finding suggested increased levels of IL-2R alpha in c-ATL that might differentiate it from MF. In this study, we report several observations on IL-2R alpha levels in MF and c-ATL. 1) Plasma levels of IL-2R alpha determined by enzyme-linked immunosorbent assay were higher in patients with c-ATL (tumor group, 17,571 +/- 5,919 U/ml; non-tumor group, 4,546 +/- 1,788 U/ml) than those of patients with MF (tumor group, 2,352 +/- 861 U/ml; plaque group, 530 +/- 174 U/ml). 2) The percentages of IL-2R alpha-positive cells in skin lesions of c-ATL were 30.5 +/- 13.4% in the non-tumor group and 62.7 +/- 12.0% in the tumor group, which were significantly higher than those of MF, plaque group (12.7 +/- 5.9%), and tumor group (3.4 +/- 2.3%). 3) Further, there was a significant correlation between plasma IL-2R alpha levels and the number of IL-2R alpha-positive cells in skin lesions in patients with c-ATL (r = 0.654, p < 0.0001) and MF (r = 0.537, p < 0.01) on an individual basis; whereas no increased IL-2R alpha levels in peripheral blood mononuclear cells were observed in patients with either MF or c-ATL. 4) Skin lesions of c-ATL had much higher levels of IL-2R alpha genomic RNA than those of MF in their initial stages when measured by DNase/reverse transcription/polymerase chain reaction and liquid hybridization analysis. These findings suggest that increased plasma IL-2R alpha levels in patients with either MF or c-ATL may be linked to cellular IL-2R alpha levels in the skin lesions, and thus reflect the difference between MF and c-ATL.

Adult↗

Langerhans cell histiocytosis presenting as a varicelliform eruption over the entire skin.

A boy with skin eruptions resembling varicella and specific for Langerhans cell histiocytosis (LCH) is reported. At his initial visit when he was four months old, vesiculopustular lesions were present over the entire body; these had first appeared on the third day post partus. Histopathological, immunohistochemical, and electron microscopical examination confirmed the Langerhans cell phenotype and Birbeck granules in the responsible cells. He also had hydronephrosis, recurrent fever, and cutaneous bacterial infections. His parents refused further medical treatment and he died of diarrhea with cachexia about two years later. LCH may present diagnostic difficulties by manifesting as a skin eruption which resembles varicella.

Chickenpox↗

Radiation therapy of adult T-cell leukemia.

Between January, 1983 and December, 1991, 30 adult patients with T-cell leukemia (ATL) and lymph node or skin lesions resistant to chemotherapy were treated by irradiation. Thirty Gy of high energy x-rays, 60Co gamma rays or electrons was delivered to 22 lymph node lesions in 17 patients, for focal cutaneous lesions in 6 patients, and as total skin irradiation in 7 patients. Irradiation therapy was effective in all patients with skin lesions and in 12 of 17 patients with lymph node lesions. Symptoms such as pain or itching diminished in all cases and no severe side effects were observed. Radiation therapy thus achieved good control of ATL associated focal lesions resistant to chemotherapy. Even if the prognosis of ATL is poor, radiation therapy should be considered as a palliative therapy.

Adult↗

Serum levels of interleukin 6 in patients with pustulosis palmaris et plantaris.

Serum interleukin 6 (IL-6) was measured in patients with pustulosis palmaris et plantaris by a fluorescent sandwich enzyme-linked immunosorbent assay (ELISA) method. Increased production of IL-6 was observed in 8 cases out of 10 showing numerous pustules in their active stage. Six cases were measured before and after tonsillectomy, and statistically significant reduction in the levels of IL-6 paralleled an improvement in the disease activity. It is suggested that IL-6 may be one of the mediators which link tonsillectomy to the activity of pustulosis palmaris et plantaris.

Adult↗

A case of adult T cell leukemia with bullae in the palmoplantar regions followed by a crisis.

A 48-year-old Japanese female who had had chronic ATL for 4 years suddenly developed vesicles on the palms and soles. Histologically, these bullae were specific lesions of ATL. After a tendency toward improvement, a crisis appeared with increases in the following: peripheral white blood cells, atypical lymphocytes, CD25 positive cells, serum LDH, and soluble IL-2R. Palmoplantar bullae, a rather rare finding, may be indicative of a following crisis.

Female↗

BCC-associated amyloidosis with a peculiar pattern of deposition.

An 83-year-old Japanese woman with lepromatous leprosy had been treated in a leprosarium. More than 10 years ago, she developed a dome-like brown tumor on the dorsum of the nose which showed the histology of basal cell carcinoma. The lesion was a well bordered, rounded tumor with tumor cell nests on its periphery extending toward the center as cords of tumor nest and with amyloid depositions between the cords. The tumor nests and amyloid lessened toward the center of the tumor, being replaced by collagen fibers. Amyloidosis showing this peculiar pattern of transition was reported with a review of published cases.

Aged↗

Spontaneous regression in Merkel cell (neuroendocrine) carcinoma of the skin.

In two Japanese women, 68 and 88 years old, Merkel cell (neuroendocrine) carcinoma of the face developed. Their tumors regressed after biopsy was performed, a rare occurrence. Histological and electron microscopic examination showed apoptosis, cellular necrosis, and an infiltration composed mainly of lymphocytes in the tumors. These changes may have been related to the mechanism of regression. It is interesting that our two patients were women, as was another patient described with Merkel cell carcinoma regression, in light of the fact that the prognosis of this tumor is sex dependent.

Aged↗

Anticonvulsant syndrome with multiple symptoms, including porphyria, IgA deficiency, and liver dysfunction.

A 19-year-old Japanese female who had been treated for epilepsy with a combined phenytoin-phenobarbital preparation for the past three years presented with increasing skin pigmentation and hirsutism. She had suffered two attacks of loss of consciousness after bilateral partial oophorectomy at the age of 16. Investigations revealed a marked increase in coproporphyrin levels in the urine and feces, a marked decrease in her serum IgA level, and liver dysfunction. All these manifestations gradually improved upon the withdrawal of her antiepileptic treatment. In vitro studies revealed B cell dysfunction producing IgA deficiency, which normalized within one year after discontinuation of the antiepileptic therapy. It was assumed that her treatment had worsened preexisting porphyria, which was misdiagnosed as epilepsy because of abnormal EEG findings. The type of porphyria appeared to be hereditary coproporphyria, despite the lack of a family history.

Adult↗