Studies concerning carcinogenesis of diesel particulate extracts following intratracheal instillation, subcutaneous injection, or skin application.
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Biomedical subjects
Publications and source records attributed to K Shimamura.
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Latamoxef (LMOX, Siomarin) at a dose of 2 g was intravenously administered to each of 23 patients undergoing the open heart surgery and the concentrations in serum, pericardial fluid and auricle of heart were measured. Pharmacokinetic observations are summarized below. The peak serum concentration (t = 0) was 227.3 micrograms/ml and the serum half-life (T1/2 beta) was 1.74 hours. In pericardial fluid, LMOX reached the peak concentration of 28.44 micrograms/ml at 4.9 hours and the half-life was 9.99 hours. In auricle of heart, LMOX reached the peak concentration of 42.78 micrograms/g at 6.9 minutes and the half-life was 1.74 hours. It was shown that LMOX penetrates well into the pericardial fluid and the auricle of heart, and it is considered that their levels exceed the minimal inhibitory concentration against a majority of clinical isolates except Pseudomonas aeruginosa.
We hereby report light and electron-microscopic (EM) studies on an unusual case of molluscum contagiosum occurring in an epidermal cyst. It was considered that the pre-existing cyst was inoculated with molluscum contagiosum viruses, which were confirmed electron-microscopically. We also would like to re-emphasize the usefulness of formalin fixed tissue for EM confirmation of viruses.
Effects of sodium vanadate on electrical and mechanical activities of smooth muscle of the guinea-pig vas deferens were investigated. Sodium vanadate of concentrations higher than 5 X 10(-6) M caused an elevation of basal tension and, at concentrations higher than 5 X 10(-4) M, initiated spontaneous contractions. These effects were not blocked by treatments with reserpine, tetrodotoxin or phentolamine. Treatment with ouabain also did not block the tension development by sodium vanadate. Sodium vanadate caused slight depolarization of membrane and potentiated spike activities. The phasic contraction of potassium contracture was potentiated by sodium vanadate in a similar manner to pretreatment with 15 mM K+ or with ouabain, both treatments occasioning slight depolarization. Sodium vanadate also caused tension development in K-depolarized preparetions. Contrastingly, drug-induced contractions were not significantly affected by sodium vanadate. It is suggested that sodium vanadate acts directly on smooth muscles and causes tension development without relation to Na, K-ATPase activity. Changes in the membrane electrical activities may be part of the cause of contraction. However, it can also initiate tension development without membrane potential changes, presumably acting on intracellular Ca binding sites.
Two types of peroneal island-flap transfer were used in fourteen patients with a large defect in the soft tissues of the lower extremity. The peroneal artery and vein and their cutaneous branches form the pedicle, and an extensive transfer of skin is possible either from above the knee or from the lateral side of the leg to as far distal as the foot. Two methods were used: in the first we severed the peroneal artery and vein distally, with an island of skin attached, and elevated them proximally, and in the second we severed the proximal portions of the peroneal vessels, with an island of skin attached, and elevated them distally. The largest flap that we used in this series measured fourteen by 16.5 centimeters and the smallest, 2.5 by five centimeters. All fourteen transfers healed, with no necrosis of the flap.
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Physiological functions of natural killer (NK) cells in the development of bone marrow cells into the cells expressing B cell characteristics were examined in recipient mice expressing different allotype immunoglobulins (Ig) or in mutants defective in lipopolysaccharide (LPS) response. When the irradiated BALB/c nude mice (Igha) were injected with bone marrow cells of C57BL/6N (B6,Ighb), the level of donor-type serum Ig (Ighb) was about 10 fold higher in the mice with NK activity depleted by injecting anti-asialo GM1 compared to that of mice with the normal NK activity on day 21 after bone marrow transplantation. In the irradiated C3H/HeJ (low responder) which received bone marrow cells of C3H/HeN (high responder), augmentation of polyclonal antibody response and of the cell proliferation with LPS was demonstrated in the NK depleted mice. However, the difference in the level of donor-type Ig or LPS response between the NK-depleted and intact mice disappeared in 3 to 4 weeks. In normal mice without irradiation and marrow cell transplantation, NK cell elimination from spleen cells did not give rise to distinctly enhanced responses to in vitro LPS stimulation, whereas mice with augmented NK activity by poly I:C demonstrated a suppressed response to LPS when the mice were immunized with LPS. Collectively, these observations suggested that NK cells are involved in the suppressive regulation of developing B cell lineage as well as activated B cells in vivo.
FUT-175 (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulphonate), a new synthetic protease inhibitor, was administrated to (NZB x NZB) F1 mice in order to examine its influence on the development of autoimmune diseases. A dose (400 mg/kg of body weight) of FUT-175 has both prophylactic and curative effects on the development of lupus nephritis: mice showed a significantly low percentage of proteinuria, a marked decrease in BUN levels, and the lowest degree of glomerular damages. Dexamethasone had almost the same effect as FUT-175 (400 mg/kg), but it was slightly less effective than FUT-175. These results suggest that the administration of FUT-175 may become a viable strategy for the treatment of human autoimmune diseases.
An autopsy case of a malignant granular cell tumor of the right sciatic nerve was reported. The surgically excised malignant granular cell tumor of a 43-year-old women showed a close relationship with the sciatic nerve, and postmortem examination disclosed extensive metastases. Electron microscopic observations of the material obtained at surgery revealed many diagnostic granules containing myelin figures, as well as basement membrane-like structures around some of the tumor cells. Electron microscopic acid phosphatase staining suggested that the granules could be of a lysosomal origin. Immunohistochemical investigation showed the presence of S-100 protein in the tumor cells, a finding which is believed to be specific for the nervous system. And, focally, the cytoplasmic processes accompanied by basement membrane mimicked Schwann cells. This evidence suggested the highly malignant nature of the malignant granular cell tumor of probable Schwann cell origin.
Leu 7 immunoreactivity was demonstrated with the indirect peroxidase-labelled antibody method on frozen and paraffin-embedded tissue sections of human digestive organs. Anti-Leu 7 monoclonal antibody, which allegedly detects mononuclear cells with natural killer or killer activity, recognized lymphoid cells among intestinal epithelial cells and in the germinal centres of solitary lymphoid follicles of small and large intestine, and a few in gallbladder, liver and the lamina propria of the intestine. In addition, peripheral nerve fibres, endocrine cells in the gut and pancreas and carcinoid and islet cell tumours were also positively stained. At the ultrastructural level, Leu 7 antigen was localized on the plasma membrane of granulated lymphoid cells in the gut mucosa and on the secretory granules of intestinal endocrine cells. In normal pancreas, Leu 7 immunoreactivity was demonstrated in most cells containing pancreatic polypeptide and in many cells containing somatostatin or glicentin. Insulin-containing cells, however, lacked Leu 7 immunoreactant. These findings were obtained in both frozen sections and paraffin-embedded sections. The possible cross-reactivities of monoclonal antibodies are discussed as they raise an important caveat in immunohistochemical studies using these antibodies.
A composite graft of skin and attached vein was taken from the dorsal aspect of the foot and used in the replantation of 6 amputated digits in 5 patients which were complicated by loss of skin and blood vessels and with exposed bone and tendon. The 5 replanted digits survived in 4 patients. Complete survival of the skin graft was achieved in two digits and partial necrosis occurred in three digits. The technique is put forward as a possible method of vascular reconstruction in which skin loss is complicated by exposure of the deeper structures i.e., bone, tendon and/or joint.
Single units of the adrenal sympathetic nerve (n = 46) were dissected and characterized with respect to tonic discharge and response to cutaneous and baroreceptor stimulation. The frequency of tonic discharge averaged 1.6 Hz and cardiovascular rhythmic modulation was observed in 53% of the units. The stimuli employed in the present study included phenylephrine-induced increases in blood pressure and pinching or brushing of lower chest skin. Mean unit activity increased 27% on lower chest pinching stimulation, decreased 12% on lower chest brushing stimulation and decreased 62% on phenylephrine-induced baroreceptor stimulation. Although there was a tendency for units with higher tonic firing frequency to have a greater response to stimulation, this relationship was not significant for pinching or brushing of lower chest skin. The close correlation between tonic activity and response to phenylephrine was explicable on the basis of a near total depression of many units, which resulted in a larger decrease in firing frequency for units with initially high spontaneous discharge rates. As might be expected, units with cardiovascular rhythmicity manifested greater responses to baroreceptor activation. This correlation was independent of tonic rate of discharge since rhythmic and non-rhythmic units did not significantly differ in tonic activity. While a majority of units responded in a typical fashion to all three stimuli (i.e. with increases to pinching and decreases to brushing and phenylephrine administration), there was little correlation between the response magnitude of individual units to any two of the stimuli employed. We conclude, therefore, that most adrenal sympathetic units receive convergent reflex input from cutaneous noxious and non-noxious afferents as well as from baroreceptor afferents, although for any individual unit the quantitative significance of each input varies.
The peroneal flap has many advantages, such as thin subcutaneous tissue, availability of a large-diameter artery and vein for anastomosis, a long pedicle, and freely designed size and shape. This technique is introduced because it has many outstanding features that allow it to be used to meet a variety of specific needs, such as a free peroneal flap, a peroneal island flap, a free vascularized fibular graft with skin, and a monitoring flap in free vascularized fibular grafts. We have found the peroneal flap to be especially useful.
Passive cutaneous anaphylaxis (PCA) was produced in the rat with mouse IgE-rich antiserum. The effect of drugs on the PCA-induced skin histamine decrease and leakage of protein-bound dye was studied. Salbutamol (0.5 mg/kg i.v. or 1.0 mg/kg s.c.) and cromoglycate (10 mg/kg i.v.) significantly inhibited the skin histamine decrease. A combination of salbutamol (0.5 mg/kg i.v. or 1.0 mg/kg s.c.) and aminophylline (25 mg/kg i.v. or 75 mg/kg s.c.) had an additive or greater than additive effect on the histamine decrease. Salbutamol (1.0 mg/kg s.c.) inhibited the dye leakage markedly, and aminophylline (75 mg/kg s.c.) slightly. These results indicate that the decrease in the skin histamine content is useful as an index of the in vivo inhibitory effect of antiallergic drugs on the antigen-induced histamine release.
A 71-year-old male presenting high fever, pancytopenia, liver dysfunction and jaundice died without a confirmed diagnosis. Microscopically, histiocytes with marked atypia and erythrophagocytosis had infiltrated the spleen, enlarged lymph nodes, liver, and bone marrow. From the above features this case was diagnosed as malignant histiocytosis. The infiltrating histiocytes were classified into three categories: 1) phagocytic cells, 2) atypical, mostly non-phagocytic cells, and 3) bizarre cells including multinucleated giant cells. An immunohistochemical study of histiocyte markers demonstrated that lysozyme was positive in the atypical cells and some phagocytic cells, whereas alpha-l-antitrypsin tended to be localized in the phagocytic cells. Bizarre cells were negative for both markers. No S-100 protein was demonstrated in the neoplastic cells. These immunohistochemical features suggested monocyte-phagocytic origin of the tumor in this case.
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Findings are reported in three members of a Japanese family with a chronic familial disease characterized by signs of marked cerebellar dysfunction, mild pyramidal and extrapyramidal dysfunction, and loss or decrease of the knee and ankle jerks. Although the clinical features suggested olivopontocerebellar atrophy, postmortem study of one patient with obvious dementia revealed massive multiform plaques of Kuru type as well as multicentric, senile, and primitive types throughout the central nervous system, most prominent in the cerebellar and cerebral cortices and caudate nucleus. There was degeneration of the spinocerebellar and pyramidal tracts, posterior columns, superior cerebellar peduncles, cerebellar cortex, dentate nucleus, and vestibular nuclei as well as gliosis of the inferior colliculus and cerebellar foliar white matter. There were no cerebral spongiform changes, although slight spongy alteration without glial reaction was present. The clinical and neuropathological characteristics were consistent with those reported as Gerstmann-Sträussler-Scheinker's disease in an Austrian family.