Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 649 records · Page 36Linked to original sources

PubMed1994

Analysis of acute myeloid leukemia cells by flow cytometry, introducing a new light-scattering classification.

A combined flow-cytometric evaluation of light scattering and the immunophenotype of acute myeloid leukemia (AML) cells from 71 newly diagnosed consecutive patients was conducted. Light-scattering characteristic of AML cells examined by flow cytometry and multiple surface markers were also analyzed using the same samples, to enable a comparison with the French-American-British (FAB) classification. Our AML cases could be classified into three light-scattering classification (LSC) types according to their physical properties on flow cytometry. These were type A, where forward light scattering (FSC) of the leukemic cell population was larger than that of lymphocytes, while side light scattering (SSC) was the same or larger than that of lymphocytes but smaller than that of monocytes; type B, where FSC of the leukemic cell population was larger than that of lymphocytes and SSC spread toward that of monocytes; and type C, where both FSC and SSC of the leukemic cell population spread beyond those of monocytes. Although a clear relationship between the FAB classification and LSC classification by the light-scattering profile of AML was not established, we observed the following findings. The majority of cases were classified as type A (58%), while type B comprised 25% and type C comprised 17%. While CD7 expression on AML cells is considered to be an immature characteristic, CD7 was expressed more frequently among LSC type A cases. Furthermore, all but one of the FAB M1 cases were classified as type A. On the other hand, CD7 was not expressed on type C leukemic cells. The percentage of cases in which more than 60% of leukemic cells possessed another immature surface antigen, CD 34ö, was 13/18 (72%) among FAB M1 cases, much higher than among FAB M2 (35%) or FAB M4 (27%) cases. A negative correlation was observed between mature antigen CD33 and CD34 among the FAB M2 cases. The frequency of CD7 expression was 25% among the total cases, and CD7-positive cases were frequent among FAB M1 and M2, but not among FAB M3 cases. These findings concerning LSC and immunophenotyping indicate that the scattergram pattern analysis may contribute towards more precise immunophenotyping, in that it reflects the maturation stage of each AML case.

Acute Disease↗

PubMed1994

Generation of tumor-specific cytotoxic T lymphocytes in vivo by combined treatment with inactivated tumor cells and recombinant interleukin-2.

In order to search for a new therapy that would maximize the effect of interleukin-2 (IL-2) in evoking antitumor immunity in vivo, the therapeutic effect of a combination of mitomycin-C(MMC)-treated tumor cells and recombinant IL-2 was examined for its induction of antitumor activity against established melanoma metastasis. In C57BL/6 mice intravenously (i.v.) injected with B16 melanoma cells on day 0, the combined treatment with an intraperitoneal (i.p.) injection of MMC-treated melanoma cells on day 6 and 2500 U rIL-2 (twice daily) on days 7 and 8 markedly reduced the number of pulmonary metastases. This antitumor activity was more effective than that in untreated controls and mice that were injected with MMC-treated melanoma cells alone or rIL-2 alone. When the i.p. injection of MMC-treated tumor cells was replaced by other syngeneic tumor cells, antitumor activity against metastatic melanoma was not induced. The antitumor activity induced by this treatment increased in parallel with an increase in the dose of rIL-2 injected. In contrast, an i.p. injection of soluble tumor-specific antigens alone could induce only a marginal level of antitumor activity, and this activity was not augmented by subsequent i.p. injections of rIL-2. In vivo treatment with anti-CD8 monoclonal antibody (mAb), but not with anti-CD4 mAb or anti-asialo-GM1 antibody, abrogated the antitumor activity induced by this combined therapy. This suggests that the antitumor effect was dependent on CD8+ T cells. Lung-infiltrating lymphocytes from mice that had been i.v. injected with melanoma cells 11 days before and were treated with this combined therapy, showed melanoma-specific cytolytic activity. This combined therapy also showed significant antitumor activity against subcutaneously inoculated melanoma cells. These results demonstrate that the combined therapy of an i.p. injection of MMC-treated tumor cells and subsequent and consecutive i.p. administration of rIL-2 increases antitumor activity against established metastatic melanoma by generating tumor-specific CD8+ CTL in vivo.

Animals↗

PubMed1994

Th1 type CD4+ T cells may be a potent effector against poorly immunogenic syngeneic tumors.

We examined the possibility that Th1 type CD4+ T cells may be an effector against three kinds of syngeneic tumors such as highly immunogenic B16 melanoma (B16) and two poorly immunogenic lines of MCA fibrosarcoma (MCA) and 3LL carcinoma (3LL). In a proliferation assay, the Th1 type CD4+ T cell clone (MH2) recognized the purified protein derivatives (PPD) derived from Mycobacterium tuberculosis. In a tumor-neutralizing assay, MH2 showed anti-tumor activity against both B16 and MCA. In a model of pulmonary metastasis, MH2 also showed anti-tumor activity against both B16 and 3LL. In an assay of cytolysis, MH2 showed a moderate level of tumor necrosis factor-dependent cytolytic activity only against MCA. In a cytostasis assay, MH2 showed a high level of interferon gamma-dependent cytostatic activity against the three tumors in the presence of macrophages. The anti-tumor activity of MH2 against B16 and 3LL was suggested to be, at least in part, attributable to the augmented natural killer activity. Taken together, these findings suggest that we may potentially be able to utilize Th1 type CD4+ T cells as an effector for immunotherapy against poorly immunogenic tumors.

Animals↗

PubMed1994

Increased beta 2-microglobulin in both parotid and submandibular/sublingual saliva from patients with Sjögren's syndrome.

Samples of unstimulated saliva from patients with sialoadenopathy were collected by microcapillary tube (1 microliter), and their beta 2-microglobulin (B2-MG) content determined by a sandwich enzyme immunoassay. A higher than normal (control) concentration of the globulin was present in both parotid and submandibular/sublingual saliva from the patients with Sjögren's syndrome but not in the samples from the patients with sialoadenitis or diabetes mellitus. The increase in B2-MG in saliva from patients with Sjögren's syndrome may reflect that immunolopathological events are important in the degeneration of both glands in this disease. Therefore, the determination of B2-MG in saliva may be a simple, non-invasive technique for confirming the diagnosis of Sjögren's syndrome as an autoimmune disease.

Autoimmune Diseases↗

PubMed1994

Brain abscess observed by localized proton magnetic resonance spectroscopy.

We encountered a case of brain abscess that was difficult to differentiate from glioblastoma. Localized 1H-MRS was found to be useful for obtaining information on the biochemical status of brain abscess. The peak of lipid and high residual peak of NAA (N-acetyl-aspartate) were observed in the cystic lesion of the brain abscess by 1H-MRS. The NAA/Cho (Choline-containing compounds) ratio in brain parenchyma showing an edematous lesion before therapy gradually increased with the relief of inflammation.

Aspartic Acid↗

PubMed1994

Phototoxicity and photoallergenicity of quinolones in guinea pigs.

Clinical reports indicate that the fluoroquinolone group of antibiotics can induce cutaneous photosensitivity reactions. In the present study, phototoxicity and photoallergenicity of quinolones including nalidixic acid (NA) norfloxacin (NFLX), ofloxacin (OFLX), enoxacin (ENX), ciprofloxacin (CPFX), lomefloxacin (LFLX), and tosufloxacin (TFLX) were experimentally examined in an in vivo system using the guinea pig. Phototoxicity of all quinolones tested was demonstrated after a single, oral administration of the drugs and subsequent exposure to long-wave ultraviolet (UVA) at a dose of 30 J/cm2. The phototoxic potencies were: ENX, LFLX > OFLX > NA, TFLX > NFLX, CPFX. Photoallergic reaction was also induced to LFLX and NA by pretreatment with cyclophosphamide, an immunoadjuvant. No cross-reactions in photoallergy were observed among quinolones. The photo-ingestion test was positive in photoallergically sensitized animals, while the photopatch test was negative. This is the first report which demonstrated experimentally the photoallergenicity of quinolones. Clinical features of the photosensitivity due to quinolones can be explained by the results of the present experiments.

4-Quinolones↗

PubMed1994

Renal and hormonal responses to repeated treatment with enalapril in non-azotemic cirrhosis with ascites.

Since a single dose of the angiotensin-converting enzyme inhibitor enalapril was shown to cause natriuresis in cirrhosis in a previous study, we investigated whether repeated doses of this substance would sustain a favorable renal effect in cirrhosis. Ten milligrams of enalapril maleate were administered once a day for 8 days to ten patients with non-azotemic cirrhosis and ascites. Enalapril reduced blood pressure significantly at 4 to 12 h (systolic blood pressure) and 2, 6, and 8 h (diastolic blood pressure) on day 2, compared to pretreatment (day 0) values, but this depressor effect decreased on day 8. No change in heart rate could be detected. Enalapril significantly suppressed serum angiotensin-converting enzyme activity and plasma aldosterone concentration (p < 0.001 to 0.01), which were elevated prior to treatment, with pretreatment values of 25.8 +/- 1.8 IU/l for serum angiotensin-converting enzyme activity and 241 +/- 67 pg/ml for plasma aldosterone concentration. This drug caused a 12 to 24% increase (p < 0.05 to 0.01) in mean daily urinary volume and a 40 to 54% increase (p < 0.001 to 0.01) in mean daily urinary sodium excretion from the respective pretreatment baselines during the 8-day period. Creatinine clearance was improved (p < 0.05) by the treatment, with mean improvement values from 24 to 34% above the pretreatment value of 47.4 +/- 4.3 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Ultrastructure of the intracellular membranous system of rat hepatocytes in intrahepatic cholestasis induced by phalloidin.

To investigate the effect of a thickened pericanalicular ectoplasm in tubulovesicular transport and biliary excretion, we examined the ultrastructure of the intracellular membranous system in rat hepatocytes with and without phalloidin treatment, by transmission electron microscopy and scanning electron microscopy combined with the Aldehyde prefix Osmium-Dimethyl Sulfoxide-Osmium method. Hepatocytes possessed elaborate networks of tubules around bile canaliculi, and some of them extended to the bile canaliculi in control rats. Vesicles were also present around the bile canaliculus. Treatment of rats with phalloidin produced a thick pericanalicular ectoplasm around the bile canaliculus visualized by transmission electron microscopy, and the density of vesicles (p < 0.001) and tubules (p < 0.001) within 0.5 microns around the bile canaliculus significantly decreased in phalloidin-treated rats. The number of lysosomes in hepatocytes apparently increased in phalloidin-treated rats; however, they were rarely observed around the bile canaliculus. The Aldehyde prefix Osmium-Dimethyl Sulfoxide-Osmium method produced an organelle-free space around the bile canaliculus by removing the thick pericanalicular ectoplasm in scanning electron microscopic examination, and the thickened pericanalicular ectoplasm inhibited the approach of intracellular membranes to the canalicular membrane in the transmission electron microscopic examination. In some pathological cholestatic conditions, the thickened pericanalicular ectoplasm may inhibit not only bile canalicular contraction but also biliary excretion of substances, which is mediated by the tubulovesicular transport system.

Animals↗

PubMed1994

A study of the deep ascending cervical artery (new definition) and its relation to some other arteries in the human cervical region.

A minute study of cervical arteries in 67 Japanese bodies, totalling 130 sides, revealed that a small twig arose from the second part of the subclavian artery and ascended under the scalenus anterior muscle, sending spinal branches and muscular branches to scalenus muscles in 77% of cases. Judging from its course and distribution, it is reasonable to consider that this ascending twig is a precostal anastomosis of cervical intersegmental arteries and has the same morphological significance as the ascending cervical artery. The authors therefore propose the name "deep ascending cervical artery (Ca-p)" for this twig. The Ca-p may also be the source artery of the costocervical trunk or the transverse cervical artery from the second part of the subclavian artery. In 22 cases the deep cervical artery or the costocervical trunk from the first part had disappeared and was compensated by a branch from the Ca-p. On the other hand, there were some cases in which the lateral branch to the scalenus medius muscle from the Ca-p had developed into the transverse cervical artery or its deep branch. This artery arose from the second part of the subclavian artery and ran laterally under the scalenus anterior muscle, passing through the brachial plexus. In the remaining 23% of cases a typical Ca-p did not exist, but a similar branch from the costocervical trunk was found instead. Since this branch has the same course and distribution as the Ca-p, we have called it the costocervical type of Ca-p (Ca-pc).

Aorta, Thoracic↗

PubMed1994

Spontaneous non-traumatic rupture of the thoracic aorta.

Spontaneous non-traumatic rupture of the aorta is a very rare condition that requires immediate surgery. However, correct preoperative diagnosis is difficult or impossible to establish. We report a case of spontaneous aortic rupture which was successfully treated by emergency surgical exploration following a transesophageal echographic diagnosis of hemopericardium. This case, as well as other reports, suggests that hemopericardium along with symptoms which suggest aortic dissection or rupture (e.g., acute chest or back pain) should raise a strong suspicion of spontaneous aortic rupture even in the absence of intimal flap or aortic dilatation, and the emergency surgery may be life-saving.

Aorta, Thoracic↗

PubMed1994

The effect of night-time naps on recovery from fatigue following night work.

A questionnaire was performed in order to investigate the effect of naps during duty on recovery from fatigue. Studies were performed on 12 male computer operators in each of two chemical plants working a four-team three-shift system. In one of the plants, the shift workers were able to take a 2 h nap during the night shift (nap group). In the other plant, no nap was taken (no-nap group). Before and after the two consecutive night shifts, both the nap and no-nap groups greatly extended their night sleeps, but the daytime sleep taken by the no-nap group during this period was significantly longer than that of the nap group on both the first and second days. No significant difference was found when comparing the length of the day sleep of the no-nap group with the total sleeping time (night-time nap plus subsequent day sleep) of the nap group. Therefore a night-time nap enables part of the essential sleep to be taken in advance of the day sleep following night work. During night work, both the nap and no-nap groups exhibited an increase in the sleepiness scores and also in the subjective feelings of fatigue concerning the complaints related to drowsiness, dullness and difficulty in concentration. However, it was found that for the no-nap group these effects continued for a large part of the recovery period following night work. It can therefore be surmised that naps taken during night-time work can be to a certain extent aid recovery from the fatigue caused by that work.

Adult↗

PubMed1994

Treatment of ureteral stones by extracorporeal shock wave lithotripsy: with ureteral catheter or in situ?

Many authors recommend that stone manipulation or catheter placement be attempted before SWL of ureteral stones. We tried to insert ureteral catheters before SWL on the unmodified Dornier HM3 machine in all patients treated for solitary ureteral stones between April 1986 and December 1991, succeeding in 77.5% (n = 395) of those for whom adequate follow-up is available for analysis. The stone-free rates with SWL alone in the series of 510 patients were 93% in patients with catheters and 75% in patients without catheters. An additional 6% of the patients in both groups became stone free with the aid of ureteroscopy. Eventually, only 0.5% of the patients with a catheter and 1.7% of the patients without a catheter had residual fragments. Among patients with a ureteral catheter after any procedure, 58.7% had no need for pain relief medication and no fever; the figure in the patients treated without a catheter was 74.4%. Although the success rate of SWL for ureteral stones is higher with a ureteral catheter in place, the incidence of complications also is higher. We recommend trying in situ SWL initially for patients with a ureteral stone.

Body Temperature↗

PubMed1994

Immunohistochemical distribution of CD44 and desmoplakin I & II in Hailey-Hailey's disease and Darier's disease.

The cell-surface glycoprotein CD44 is found on a wide variety of cells including epidermal cells. It is involved in cell to cell adhesion. Desmoplakin I & II are important components of the attachment plaque of desmosomes. In this study, we compared the distribution patterns of anti-CD44 and anti-desmoplakin I & II in Hailey-Hailey's disease and Darier's disease. In the normal skin, anti-CD44 stained the entire periphery of epidermal keratinocytes while anti-desmoplakin I & II produced dotted staining patterns along the periphery of epidermal keratinocytes. In Hailey-Hailey's disease and Darier's disease, the staining pattern of anti-CD44 on acantholized keratinocytes did not change, but anti-desmoplakin I & II lost their peripheral, dotted patterns and stained diffusely in the cytoplasm in most acantholytic cells. These results suggest that, in Hailey-Hailey's disease and Darier's disease, CD44 may be intact even in acantholytic cells but abnormalities of desmoplakin exist in such cells.

Carrier Proteins↗

PubMed1994

Role of increased DNA synthesis activity of hepatocytes in multicentric hepatocarcinogenesis in residual liver of hepatectomized cirrhotic patients with hepatocellular carcinoma.

To examine whether the marked increase in DNA synthesis of hepatocytes in cirrhotic liver might elicit multicentric hepatocarcinogenesis, we examined the relationship between new development of hepatocellular carcinoma (HCC) and the bromodeoxyuridine (BrdU) labeling index (LI) of hepatocytes in the residual liver of hepatectomized patients with liver cirrhosis (LC) and HCC. Eighteen hepatectomized patients with LC and HCC, whose resected liver revealed neither portal nor hepatic vein invasion by histologic examination, were studied (to exclude cases with intrahepatic metastasis). DNA synthesis activity of hepatocytes from the residual cirrhotic liver was measured by a BrdU/anti-BrdU in vitro method. The incidence of HCC recurrence was studied during a 3-year follow-up period. Among 18 patients, 9 patients had recurrence and 9 did not. The average BrdU LI in the recurrent patients was 2.6 +/- 1.3% and was significantly higher than that in patients without recurrence (1.4 +/- 0.5%, P < 0.05). All five patients who had a BrdU LI of 2.4% or above showed recurrence within 3 years, as compared with 4 of 13 (30.8%) patients with BrdU LI of less than 2.4% (P < 0.05). Our data indicate that abnormally high DNA synthesis in hepatocytes in the background cirrhosis might lead to the development of multicentric carcinogenesis in human cirrhotic liver, and in the residual cirrhotic liver of hepatectomized patients with HCC and LC, it may be a predictor of new development of HCC.

Adult↗

PubMed1994

Cytomegalovirus (CMV) antigenaemia for rapid diagnosis and monitoring of CMV-associated disease after bone marrow transplantation.

A technique for the rapid detection of cytomegalovirus (CMV) antigen-positive blood leucocytes (CMV antigenaemia) was evaluated in 15 marrow transplant patients as a means of diagnosis and for monitoring CMV-associated disease. CMV antigenaemia was determined by direct immunoperoxidase staining of leucocytes with a peroxidase-labelled monoclonal antibody, HRP-C7, which binds an immediate-early antigen of human CMV. CMV antigenaemia occurred in 7/15 marrow transplant patients (47%) and was initially detected between 4 and 6 weeks after transplantation. CMV-associated diseases developed in 3/15 patients (20%). All patients with CMV-associated disease had a relatively large number of CMV antigen-positive leucocytes, exceeding 10 per 50,000 white blood cells (WBCs). In the remaining 12 patients, CMV antigen-positive leucocytes were less than 10 per 50,000 WBCs or were undetectable. CMV-associated disease did not develop in these patients during the period of monitoring. CMV antigen-positive leucocytes were detected more frequently in patients who developed acute graft-versus-host disease (GVHD) or haemorrhagic cystitis than in those without such complications. CMV antigens were detectable from 1 to 4 weeks before the onset of CMV-associated disease which allowed initiation of ganciclovir treatment at an early stage. The degree of CMV antigenaemia paralleled the clinical symptoms and signs, higher degrees of antigenaemia being associated with more significant disease. Thus, the detection of CMV antigen-positive blood leucocytes is useful for the diagnosis and monitoring of CMV-associated disease following bone marrow transplantation.

Acute Disease↗

PubMed1994

A comparative study of partial primary structures of the catalytic region of mammalian protein C.

Protein C (PROC) is a plasma vitamin K-dependent zymogen of a serine protease which regulates blood-clotting cascade through proteolytic inactivation of the non-enzymatic cofactors of blood coagulation, Va and VIIIa. We characterized the partial nucleotide and amino acid sequences for the catalytic domain of PROC in six mammalian species, rhesus monkey, dog, cat, goat, horse and mouse, and compared these sequences with known ones from humans, the bovine and rat. By using a pair of primers based on the nucleotide sequences from human and bovine PROC cDNA, the PROC gene fragments were enzymatically amplified from their genomic DNAs and were sequenced by the dideoxy-termination method. The cloned PROC gDNA encoded a part of the heavy chain of PROC including the lesions of active site residues corresponding to human PROC Asp-257 and Ser-360. Comparison of the sequences from these species revealed that there was a high degree of homology at the nucleotide and amino acid levels; from 69% to 96% of the amino acids in the catalytic region were identical among the nine species including humans, the bovine and rat. The locations of five Cys residues as well as the putative carbohydrate attachment sites were evolutionally conserved. All the amino acids recognized in the human abnormal PROC variants were conserved across species, suggesting their functional importance, and a comparison of the conserved residues among PROC from multiple species will provide considerable information in the investigations of PROC functions.

Amino Acid Sequence↗

PubMed1994

Involvement of interferon-gamma and macrophage colony-stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults.

We investigated the role of monocyte/macrophage-activating cytokines in pathogenesis of haemophagocytic lymphohistiocytosis (HLH) in 21 adult patients. Sera from patients with active HLH contained extremely high levels of macrophage colony-stimulating factor (M-CSF) and of interferon-gamma (IFN-gamma). These levels returned to almost normal during remission. Neither interleukin-4 nor granulocyte/macrophage colony-stimulating factor could be detected. Active HLH sera also contained high concentrations of inflammatory monokines, such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). Serum concentrations of soluble CD8 and soluble interleukin-2 receptor were extremely high during active HLH, and returned to virtually normal levels during remission. Circulating CD2+ T-cells obtained from patients with active HLH spontaneously secreted M-CSF and IFN-gamma in vitro, whereas circulating monocytes did not produce detectable levels of both M-CSF and IFN-gamma, but produced high levels of IL-6 and TNF-alpha. These findings suggest that IFN-gamma and M-CSF at least partly from T-cells, such as CD8+ T-cells, might contribute to activation of monocytes or histiocytes, resulting in the up-regulated monokine production and haemophagocytosis in HLH.

Adolescent↗

PubMed1994

Contribution of thromboxane A2 to the antigen-induced immediate asthmatic response mediated by IgG1 antibody by augmentation of bronchial responsiveness in guinea-pigs.

1. IgG1-mediated anaphylactic bronchoconstriction was elicited by intravenous administration of antigen to guinea-pig 2 days after passive sensitization with IgG1-rich serum, and this response was not affected by heating the serum (at 56 degrees C, for 4 h). IgE-mediated bronchoconstriction, provoked 14 days after passive sensitization with IgE-rich serum, was completely abolished by the heating of the serum. 2. S-1452 (10 mg kg-1, p.o.), a selective thromboxane (Tx) A2 antagonist, significantly but incompletely suppressed the IgG1-mediated bronchoconstriction, but did not affect the IgE-mediated one, while diphenhydramine (5 mg kg-1, i.v.), a histamine antagonist, almost completely inhibited both IgG1- and IgE-mediated bronchoconstriction. 3. Pretreatment with propranolol (1 mg kg-1, i.v.), a beta-adrenergic blocker, in addition to diphenhydramine, caused a long-lasting bronchoconstriction following antigen challenge in both animal models. This histamine-independent bronchoconstriction was markedly suppressed by S-1452 at a low dose of 0.1 mg kg-1. 4. A significant increase in bronchial responsiveness to i.v. acetylcholine (ACh), compared to the prechallenge value, occurred as early as 3 min and persisted for 24 h after antigen challenge in the IgG1 model, but was not observed in the IgE model. S-1452 (10 mg kg-1, p.o.) inhibited the IgG1-mediated bronchial hyperresponsiveness, as assessed 60 min after antigen challenge. 5. A marked elevation of TxB2 levels was observed in bronchoalveolar lavage fluid (BALF) 3 min after antigen challenge in the IgG1 model, while levels were not changed in the IgE model. In contrast, the plasma TxB2 level assessed 1 min after antigen challenge was increased in both the IgGI and IgE models.6. The results indicate that the inhibition of IgGl- but not IgE-mediated bronchoconstriction by higher doses of S-1452 may result from the suppression of increased bronchial responsiveness to allergic mediators such as histamine, which is probably due to TxA2 generated in the airway lumen rather than in plasma. In both the IgGI and IgE models, plasma TxA2 appeared to contribute directly to the bronchoconstriction, its action being almost completely masked by histamine-mediated bronchoconstriction.

6-Ketoprostaglandin F1 alpha↗