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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 595 records · Page 33Linked to original sources

Hypertriglyceridemia associated with tumor necrosis factor-alpha in hamster cheek-pouch carcinogenesis.

We demonstrated for the first time that 9,10-dimethyl-1,2-benzanthracene (DMBA)-treated hamsters showed hypertriglyceridemia followed by cachexia. Hypertriglyceridemia is believed to be caused in part by the decreased lipoprotein lipase (LPL) activity, and by cytokines such as tumor necrosis factor (TNF)-alpha. In addition, TNF-alpha action is associated with the LPL activity. Therefore, we determined the content of triglyceride (TG), LPL, and TNF-alpha in the serum from DMBA-treated hamsters. Elevated TG concentration in the serum of tumor-bearing hamsters was more remarkable and preceded the increase in other lipids, whereas the activity of LPL, the key enzyme of TG metabolism in vivo, was drastically reduced. TNF-alpha, known as an endogenous inhibitor of LPL activity, was detected in both the sera and the extract of tumors from DMBA-treated hamsters, whereas it was not detectable in any control samples. Pre-incubation of control sera with exogenous recombinant human TNF-alpha resulted in a potent inhibition of endogenous LPL activity in a dose-dependent manner in vitro. Therefore, the presence of TNF-alpha might lead to the increase in plasma TG mediated by LPL in tumor-bearing hamsters.

9,10-Dimethyl-1,2-benzanthracene↗

Intravascular ultrasound imaging of peripheral arteries as an adjunct to atherectomy: preliminary experience.

12 atherosclerotic lesions in nine patients, including four restenoses after balloon angioplasty, were treated by atherectomy under the guidance of intravascular ultrasound (US). Echogenicities of the plaques and morphological alterations in the arterial walls produced by atherectomy were evaluated. The two-layered appearance of post-angioplasty restenoses was found to be inner fibrous intimal thickening with proliferation of smooth muscle cells and outer residual collagen-rich plaque. The deep cut surfaces were shown as concave U-shaped defects. Medial tissues were present in all cases where intravascular US demonstrated the disruption of a thin hyperechoic layer of the internal elastic lamina. Intravascular US imaging may provide valuable information on the degree, eccentricity and histological type of stenosis, the presence of calcification before atherectomy, and on the extent of excision and the morphological changes in the arterial wall after atherectomy.

Aged↗

OK-432 induces production of neutrophil chemotactic factors in malignant pleural effusion.

We investigated the changes in cellular components and neutrophil chemotactic factors in pleural fluid from 19 lung cancer patients who received intrapleural injection of OK-432 to treat malignant pleurisy. Not only neutrophil chemotactic activity (NCA) but also neutrophil count and percentage were increased significantly at 6 hours after OK-432 injection. The neutrophil count was significantly correlated with NCA level. The levels of C5a and IL-8 in pleural fluid were increased significantly after OK-432 injection. The increased IL-8 level was associated with a increase of both NCA and neutrophil count. OK-432 treatment also induced a marked increase of IL-1 beta and IL-6 in pleural fluid. Thus, intrapleural injection of OK-432 induced production of neutrophil chemotactic factors (IL-8 and C5a) and cytokines (IL-1 beta and IL-6), which eventually attracted neutrophils into the pleural space. These observations suggest that neutrophil migration mediated by these factors and cytokines may contribute to the sclerosing effects of OK-432 treatment.

Adult↗

Relapsing polychondritis associated with subclinical Sjögren's syndrome and phlegmon of the neck.

A 25-year-old woman, diagnosed with Sjögren's syndrome at age 20, presented with painful edema of her left neck. Three days later, she additionally complained of bilateral auricular pain, and her nasal cartilage was tender to palpation. She was diagnosed as having phlegmon on the basis of her neck findings. Anti-human cartilage antibodies were demonstrated by indirect immunofluorescence, and the diagnosis of relapsing polychondritis was established. The patient was administered antibiotics and a non-steroidal anti-inflammatory drug, and her symptoms gradually improved. Relapsing polychondritis is one of the possible complications of autoimmune diseases, and infection might be a precipitating factor for this disease.

Adult↗

Concomitant immunity against tumor development is enhanced by the oral administration of a kampo medicine, Hochu-ekki-to (TJ-41: Bu-Zhong-Yi-Qi-Tang).

The oral administration of a kampo herbal medicine, Hochu-ekki-to (TJ-41: Bu-Zhong-Yi-Qi-Tang) using a water-supplying bottle resulted in a slight but significant inhibition of Meth A growth. The oral administration of TJ-41 with gastric gavage significantly enhanced the specific antitumor activity against Meth A at rechallenge on day 9. In a tumor-neutralizing assay, the tumor draining LN cells of the TJ-41 administered mice showed an antitumor activity against Meth A. In a cytolytic assay, the anti-Meth A specific cytolytic T lymphocyte activity was not detected in the spleen cells of the Meth A bearing and TJ-41 administered mice. The oral administration of TJ-41 enhanced the natural killer (NK) activity of the spleen cells in naive mice but could not improve the decreased NK activity of spleen cells from the tumor bearing mice. In a cytostatic assay, the peritoneal exudate cells from the Meth A bearing and TJ-41 administered mice showed a significantly higher amount of cytostatic activity against Meth A than that from either Meth A bearing or TJ-41 administered mice. These results indicate that the oral administration of TJ-41 into the tumor bearing mice may thus be able to enhance concomitant antitumor immunity through the augmentation of the cytostatic activity.

Adjuvants, Immunologic↗

Minamata disease: methylmercury poisoning in Japan caused by environmental pollution.

Minamata disease (M. d.) is methylmercury (MeHg) poisoning that occurred in humans who ingested fish and shellfish contaminated by MeHg discharged in waste water from a chemical plant (Chisso Co. Ltd.). It was in May 1956, that M. d. was first officially "discovered" in Minamata City, south-west region of Japan's Kyushu Island. The marine products in Minamata Bay displayed high levels of Hg contamination (5.61 to 35.7 ppm). The Hg content in hair of patients, their family and inhabitants of the Shiranui Sea coastline were also detected at high levels of Hg (max. 705 ppm). Typical symptoms of M. d. are as follows: sensory disturbances (glove and stocking type), ataxia, dysarthria, constriction of the visual field, auditory disturbances and tremor were also seen. Further, the fetus was poisoned by MeHg when their mothers ingested contaminated marine life (named congenital M. d.). The symptom of patients were serious, and extensive lesions of the brain were observed. While the number of grave cases with acute M. d. in the initial stage was decreasing, the numbers of chronic M. d. patients who manifested symptoms gradually over an extended period of time was on the increase. For the past 36 years, of the 2252 patients who have been officially recognized as having M. d., 1043 have died. This paper also discusses the recent remaining problems.

Disease Outbreaks↗

[Comparisons of histological grading between biopsy and radical prostatectomy specimens in prostatic adenocarcinoma].

PURPOSE: To examine how accurately biopsy specimens reflect the corresponding excised specimens in terms of histologic grades of prostatic adenocarcinoma, histologic grades of biopsy specimens were compared to those of radical prostatectomy specimen in 29 patients who underwent radical prostatectomy without any prior treatment. METHODS: For the assessment of histological grading, Japanese General Rule for Prostatic Cancer (JGRPC), in which adenocarcinoma was graded as being either well, moderately or poorly differentiated, and Gleason's system were applied. RESULTS: According to JGRPC, histologic grades of biopsy specimens were identical to those of the prostatectomy specimens in 83% of cases, with biopsy specimens given higher grades than those of the prostatectomy specimen in 4 (14%), and lower grades in 1 (3%). According to Gleason score histological grade of biopsy specimens were identical to those of the prostatectomy specimens in only 52%. However, the grouping category of Gleason score (2 to 5, 6, 7 and 8 to 10) assigned to the biopsy was lower than that of prostatectomy specimen in only 3 cases (10%) and was greater than that of prostatectomy specimen in 5 cases (17%). CONCLUSION: These results suggest that histological grades based upon biopsy specimens will predict those of the corresponding prostatectomy specimens in the majority (72% to 83%) but not all of the cases.

Adenocarcinoma↗

[Evaluation by proton magnetic resonance spectroscopy of carotid-cavernous fistula with cortical venous drainage].

Cases with carotid-cavernous fistula (CCF) associated with cortical venous drainage through the sylvian veins are rather rare. However, such cases involve risk for subarachnoid hemorrhage, subcortical hemorrhage and venous infarction due to venous hypertension in the brain. Even without these symptoms, CCF under these conditions provokes disturbance in cerebral metabolism. We report two cases of CCF associated with cortical venous drainage evaluated by proton magnetic resonance spectroscopy (1H-MRS). Case 1: A 56 year-old female suffered from a right CCF associated with cortical venous drainage through the sylvian veins after trauma. Before embolization with a detachable balloon catheter, the ratios of N-acetyl-aspartate (NAA)/Choline (Cho) and NAA/Creatine (Cr) in 1H-MRS on the right temporo-basal ganglia were lower than those in normal volunteers. After curative balloon embolization of the CCF, serial 1H-MRS still demonstrated laterality (NAA/Cho and NAA/Cr ratios on the right side were lower than those on the left). Six months after embolization, these ratios on the right became closer to those on the left. Case 2: A 48 year-old female suffered from spontaneous CCF associated with cortical venous drainage. Before embolization of the CCF, ratios of NAA/Cho and NAA/Cr on the temporo-basal ganglia of the drainage side (left side) were lower than those on the contralateral side. After partial embolization of the CCF, which caused the angiographical disappearance of the cortical venous drainage, NAA/Cho and NAA/Cr ratios on the affected side increased to almost the same levels as those on the contralateral side. We consider that 1H-MRS is noninvasive and is a useful method to generate data evaluation of affected brain metabolism by venous reflux in cases of CCF associated with cortical venous drainage.

Arteriovenous Fistula↗

[Induction chemotherapy followed by adjuvant surgery (IC-AS) in patients with stage I-II small cell lung cancer (SCLC)].

Ten patients with stage I-II SCLC received IC-AS between 1984 and 1993. As induction chemotherapy, COMP-VAN alternating chemotherapy and CAV-PVP hybrid chemotherapy were administered. The former consisted of a 4-drug combination of cyclophosphamide (CPA), vincristine (VCR), methotrexate (MTX) and procarbazine alternated with a 3-drug combination of etoposide (ETP), adriamycin (ADM) and nimustine every 4 weeks. In the latter, a 3-drug combination of CPA, ADM and VCR given on day 1, and a 2-drug combination of ETP and cisplatin on day 8, were repeated every 4 weeks. All the patients had an objective response, including one complete response by induction chemotherapy. Post-operative pathology revealed SCLC in 4 patients, adenocarcinoma in 2 and no tumor (pathological CR) in 4. Four patients relapsed, and a intrathoracic relapse was experienced in only 2 patients. Six patients have died: 3 from relapsing SCLC, 2 from stomach cancer, and 1 from squamous lung cancer, who was salvaged from relapsing SCLC. The median survival time was 27.5 months, and the 3-year survival rate 37.5%. These results indicate that IC-AS is highly effective for stage I-II SCLC and warrant additional studies comparing IC-AS with chemo-radiotherapy.

Aged↗

Relationship of infused CFU-GM and CFU-Mk mobilized by chemotherapy with or without G-CSF to platelet recovery after autologous blood stem cell transplantation.

Although hematologic reconstitution is usually rapid after autologous blood stem cell transplantation (ABSCT), there is an occasional delay in platelet recovery. We studied the hematologic recovery of 27 adult patients with hematologic malignancies who received marrow-ablative chemotherapy and ABSCT to determine whether or not the numbers of infused mononuclear cells (MNC), colony-forming units granulocyte/macrophage (CFU-GM), and colony-forming units megakaryocyte (CFU-Mk) were related to the speed of platelet recovery after ABSCT. Peripheral blood stem cells were collected using chemotherapy-induced mobilization with or without cytokine therapy. While the number of MNC infused did not show a significant correlation with time to platelet recovery as well as granulocyte and reticulocyte recovery, the logarithmic number of CFU-GM-infused did (p < 0.01). We also found a significant correlation between the logarithmic number of CFU-Mk-infused and the time to platelet recovery (p < 0.01). These findings suggest that the number of CFU-GM-infused is a reliable indicator of hematopoietic recovery and that the number of CFU-Mk-infused is no more reliable than CFU-GM for predicting platelet recovery after ABSCT.

Adolescent↗

Role of cytoskeleton and acidification of endocytic compartment in asialoglycoprotein metabolism in isolated rat hepatocyte couplets.

The process of receptor-mediated endocytosis is common to a variety of species and cell types. One of the best characterized receptor-ligand systems is the hepatocyte receptor for asialoglycoproteins. We investigated the morphological features of the uptake and intracellular transport of gold-conjugated asialofetuin in isolated rat hepatocyte couplets. We assessed the effects of colchicine, lumicolchicine, cytochalasin B, and chloroquine on the uptake and intracellular transport of asialoglycoproteins. Isolated rat hepatocyte couplets were incubated with gold-conjugated asialofetuin, and transmission electron micrographs of these cells were analyzed to determine the density and distribution of gold particles in the peripheral and pericanalicular areas. Results were analyzed morphometrically. Colchicine significantly inhibited the uptake and intracellular transport of asialoglycoproteins, but did not affect membrane fusion of endocytic compartments in the peripheral area. Lumicolchicine and cytochalasin B had minimal effects on these processes. Chloroquine inhibited the uptake of asialoglycoproteins, but did not affect the intracellular transport of asialoglycoproteins. Results suggest that the microtubule is essential for intracellular movement of endocytosed asialoglycoproteins and receptor recycling, and that endocytic structures in the peripheral regions can fuse in the absence of intact microtubules. We also found that uptake and intracellular transport of asialoglycoproteins were independent of the microfilaments, and the pH gradient in endocytic compartments was important in receptor-mediated endocytosis of asialoglycoproteins.

Acids↗

Junctional proteins of keratinocytes in Grover's disease, Hailey-Hailey's disease and Darier's disease.

Alterations of junctional structures in non-immune mediated acantholytic diseases (Grover's, Hailey-Hailey's and Darier's diseases) were examined using monoclonal antibodies against desmosomal attachment constituents (desmoplakin I & II and plakoglobin), desmosomal intercellular cement glycoprotein (desmoglein), protein of adherens junction (vinculin), and protein of gap junction (43Kd connexin). Universal cell surface (transmembrane) glycoprotein CD44 was also studied. In acantholytic foci of these diseases, attachment plaque proteins had dissolved and diffused into the acantholytic cells. The normal dotted linear pattern of immunostaining on the cell membrane was totally lost. In contrast, CD44 was well preserved on the cell membranes of acantholytic cells. Adherens junction and gap junction proteins were mostly preserved. Acantholytic cells of pemphigus vulgaris were similarly studied. In these cells, desmosomal attachment plaque proteins were very well preserved, while intercellular cement substance (desmoglein), adherens junctional proteins (vinculin), and gap junction protein (connexin) were totally absent, either on the cell membrane or in the cytoplasm. Electron microscopy confirmed an early dissolution of attachment plaque. Internalized desmosomal structures were seldom found in acantholytic cells of non-immune diseases. It was concluded that the primary event in acantholysis in these three diseases is the dissolution of desmosomal attachment plaque.

Acantholysis↗

[Autopsy cases of cytomegalovirus interstitial pneumonitis following bone marrow transplantation].

We investigated the relevance of cytomegalovirus (CMV) to interstitial pneumonitis (IP) using formalin-fixed and paraffin-embedded lung tissues obtained from 12 autopsy cases who died following bone marrow transplantation (BMT) from May 1985 to March in 1992. The lung tissues were examined by hematoxylin and eosin (H.E.) staining, immunohistochemistry with monoclonal antibodies (DDG9, CCH2) and polymerase chain reaction (PCR) for amplifying human CMV DNA. Eight of 12 cases were clinically diagnosed as IP. The 4 cases showed no signs of IP, and their tissues were used as controls. H.E. staining revealed inclusion bodies in two of the eight and only severe fibrosis in the other six. In 4 of the 6 cases, however, CMV was identified by immunohistochemistry or PCR. We concluded that the relevance of CMV in the genesis of IP is often overlooked by H.E. staining alone. Immunohistochemistry and PCR are useful in examining tissues which are suspected of CMV-IP.

Adolescent↗

[Proliferative cystitis forming tumorous lesion: a case report].

A 66-year-old woman was admitted with asymptomatic macrohematuria. Cystoscopy revealed bladder tumor with a diameter of about 1.5 cm and smooth surface. Transurethral resection was performed and histological examination showed proliferative cystitis, mainly consisting of cystitis glandularis. Proliferative cystitis is not so rare, but tumorous formation of it seems to be unusual.

Aged↗

Granulocyte colony-stimulating factor mobilizes primitive hematopoietic stem cells in normal individuals.

We studied the hematopoietic activity of peripheral blood stem cells (PBSC) mobilized by recombinant human granulocyte colony-stimulating factor (G-CSF) using semisolid and long-term culture systems (LTC) in 5 normal individuals. Following 2 or 3 daily subcutaneous injections of G-CSF (filgrastim; 1.5 micrograms/kg), not only committed progenitors including CFU-GM, BFU-E, and CFU-Mix, but also long-term culture initiating cells (LTC-IC) were increased in the peripheral blood. When the cells derived from CFU-GM, BFU-E and CFU-Mix colonies were replated for secondary colony formation, a minor fraction of CFU-GM and CFU-Mix colonies formed after 3 days of G-CSF stimulation in vivo could produce secondary colonies. Moreover, the replating capacity of primary colonies from 5-week-old LTC initiated after 3 days of G-CSF stimulation was increased compared to that from 5-week-old LTC initiated in a 'steady-state'. These observations indicate that G-CSF can mobilize very primitive progenitors (LTC-IC) along with committed progenitors into the circulation and suggest that some of these G-CSF-mobilized progenitors may retain self-renewal capacity.

Adult↗

[A comparative study of DNA measurement of bladder cancer from image cytometry and chromosome aberration in in situ hybridization].

The relationship between interphase cytogenetics and the DNA index measuring SCM of bladder cancer was investigated in 17 patients with bladder tumor. By in situ hybridization, the copy number of chromosomes 1, 7, 10, 11, 17, 18, X and Y was detected. The percentage of hyperdiploid cells for chromosomes 7 and 17 was highly correlated with the increasing DNA index. Since a high DNA index is both indicative of more aggressive tumor behavior and a worse prognosis, these findings suggest that the percentage of hyperdiploid cells, especially for chromosome 7 and 17, may be highly predictive of bladder tumor aggressiveness.

Carcinoma, Transitional Cell↗