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Biomedical subjects

K Hamada

Publications and source records attributed to K Hamada.

At least 343 records · Page 19Linked to original sources

[Neuropathological study of autosomal dominant ataxia linked to loci on chromosome 6p (SCA 1)].

We reported an autopsy case of hereditary OPCA genetically proved to be SCA 1. Clinically, he showed cerebellar ataxia from beginning to the end stage, and was characterized by slow eye movement with external ophthalmoplegia, pyramidal tract signs, generalized amyotrophy including facial muscle, mild bulbar paresis, mild dementia, and urinary disturbance. Neuropathologically, the degeneration and loss of neurons with gliosis were seen in the Purkinje layer, dentate nucleus of the cerebellum, inferior Olive nucleus, motor nucleus of cranial nerve, anterior horn of the spinal cord, and column of the Clarke. And the myelinpallor was revealed in the connecting nerve fiber of these lesions, posterior column and spinocerebellar tract of the spinal cord.

Brain↗

[A case of eosinophilic pneumonia with histologically proven mediastinal lymph node involvement].

Intrathoracic lymphadenopathy in eosinophilic pneumonia is very rare and few cases have been confirmed histologically. This is the first case of eosinophilic pneumonia with mediastinoscopic lymph node biopsy reported in Japan. The case is a 42-year-old man who was admitted to our hospital complaining of cough, general fatigue and dyspnea of one month's duration. Chest X-ray demonstrated bilateral hilar and mediastinal lymph node enlargement with interlobar pleural thickening and infiltrative shadows in right lower lung field. Computed tomography revealed infiltrative shadows at right S4, S5, S8 and S9 and S10 segments and #2, #3, #5, #6 lymph node enlargement. Biopsy of the lymph node via mediastinoscopy demonstrated that the architecture was preserved, sinusoids were filled with histiocytes and eosinophils, and lymphoid follicles were compressed. Immunohistochemical technique using monoclonal antibody EG2 which reacts with the secreted form of Eosinophilic Cationic Protein (ECP), demonstrated that eosinophils infiltrating the mediastinal lymph nodes were activated. The pathogenesis of mediastinal lymphadenopathy in eosinophilic pneumonia remains to be determined, but our case suggests that mediastinal lymph nodes may play a role in eosinophilic pneumonia.

Adult↗

[A case of Jordans' anomaly].

A 71 year-old female with jordans' anomaly was described. Fat-containing vacuoles were observed in neutrophils, eosinophils, basophils, monocytes and lymphocytes of the peripheral blood, but not in erythrocytes and platelets. In the bone marrow they were also observed in myeloid cells including myeloblasts, erythroblasts and megakaryocytes. In the granulocyte series, numbers of vacuole-containing cells and numbers of vacuoles increased as leukocytes matured. Histochemically, vacuoles were thought to contain neutral fat based on staining with Sudan III. However serum lipids showed no abnormalities. Both the reduction rate of NBT and the phagocytic activities for Candida albicans were normal.

Aged↗

Variant von Willebrand disease with defective binding to factor VIII: the first case from Japan.

This is the first case of variant von Willebrand disease (vWD) with defective binding of von Willebrand factor (vWF) to factor VIII (F.VIII) to be diagnosed in Japan. An 8-year-old Japanese girl, who had had recurrent episodes of subcutaneous hematomas, showed a prolonged A-PTT, low F.VIII (F.VIII:C 4 U/dl, FVIII:Ag 4 U/dl), and normal level of vWF (RCof 80 U/dl, vWF:Ag 60 U/dl). The patient's vWF-multimeric structure on SDS agarose gel electrophoresis was similar to that in normal subjects. A F.VIII binding assay was performed, as described by Nishino et al. (1989). F.VIII binding (y) of vWF was expressed as a function of the amount of immobilized vWF (x) on the wells of a polystyrene plate. Regression lines from normal subjects and the patient had a high correlation coefficient. F.VIII binding capacity was estimated by the slope of the regression lines. The slope for normal subjects showed y = 0.002 + 0.653x, while, in contrast, the slope for the patient showed y = 0.005 + 0.009x, indicating that the capacity of vWF from the patient to bind F.VIII was markedly decreased. Exons 18-20 of the vWF gene, covering the first 132 amino acids of mature vWF subunit from the patient, were sequenced, using the PCR amplification method. A point mutation C-->T at codon 816 in exon 19, predicting a substitution of Trp for Arg(53), was characterized; this was inherited by the patient from her mother.

Base Sequence↗

Synthesis and antiulcer activity of N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas: histamine H2-receptor antagonists with a potent mucosal protective activity.

As an aim toward developing new antiulcer agents, new N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas were synthesized and evaluated for histamine H2-receptor antagonistic, gastric antisecretory, and gastric mucosal protective activities. A QSAR study showed that the most favorable N-substituents were electron-donating straight-chain alkyl groups of short length such as ethyl group from the viewpoint of dual action, i.e., gastric antisecretory and mucosal protective actions. Among the ureas studied, compounds 4, 5, and 8-10 were selected as candidates for further study.

Animals↗

Crystal structure of an electron-transfer complex between methylamine dehydrogenase and amicyanin.

The crystal structure of the complex between the quinoprotein methylamine dehydrogenase (MADH) and the type I blue copper protein amicyanin, both from Paracoccus denitrificans, has been determined at 2.5-A resolution using molecular replacement. The search model was MADH from Thiobacillus versutus. The amicyanin could be located in an averaged electron density difference map and the model improved by refinement and model building procedures. Nine beta-strands are observed within the amicyanin molecule. The copper atom is located between three antiparallel strands and is about 2.5 A below the protein surface. The major intermolecular interactions occur between amicyanin and the light subunit of MADH where the interface is largely hydrophobic. The copper atom of amicyanin and the redox cofactor of MADH are about 9.4 A apart. One of the copper ligands, His 95, lies between the two redox centers and may facilitate electron transfer between them.

Bacterial Proteins↗

[Results of radiation therapy for squamous cell carcinoma of the uterine cervix using high dose-rate intracavitary irradiation].

We retrospectively analyzed 216 previously untreated patients with cervical cancer treated by high dose-rate intracavitary irradiation between 1978 and 1986. Cumulative 5-year survivals in stage Ib, IIa, IIb, IIIa, IIIb and IVa were 72.3%, 88.9%, 68.9%, 75.0%, 64.0% and 16.7%, respectively. Cause-specific 5-year survivals in stage Ib, IIa, IIb, IIIa, IIIb and IVa were 93.3%, 88.9%, 74.7%, 75.0%, 68.9%, and 18.8%, respectively. Recurrences outside the pelvis in stage IIb and IIIb (14.9% and 24.0%) were more common than loco-regional recurrences (10.3% and 12.0%). However, loco-regional recurrences (50%) were most frequent in stage IVa. Thirteen patients (6.0%) required surgical management for intestinal complications (severe). Six patients (2.7%) died due to intestinal complications (fatal). These fatal and severe complications were closely correlated with the dose of external radiation. These data suggest that intracavitary irradiation using a high dose-rate system is useful for the treatment of uterine cancer; however, further efforts to reduce intestinal complications by lowering the dose of external radiation will be necessary. It is also suggested that a combined modality, such as chemotherapy, is necessary for controlling metastases outside the pelvis in stage IIb and IIIb, and for local control in stage IVa.

Adult↗

Direct induction of tetraploids or homozygous diploids in the industrial yeast Saccharomyces cerevisiae by hydrostatic pressure.

Hydrostatic pressure and a dye plate method were used to investigate the direct induction of tetraploids or homozygous diploids from the industrial diploid or haploid yeast Saccharomyces cerevisiae. Above 200 MPa, hydrostatic pressure greatly inactivated the strains HF399s1 (alpha haploid), P-540 (a/alpha diploid), and P-544 (a/alpha diploid). At the same time, when pressure-treated cells of these strains were spread on a dye plate, some of the visible colonies were stained red/blue or dark blue (variant colonies); the rest stained violet, similar to colonies originating from diploid cells or haploid cells that were not pressure-treated. In addition, above 100 MPa, the formation of variant colonies increased with increasing pressure, and maximized (1 x 10(-1)) at 200 and 250 MPa, respectively. The size of almost all variant cells from P-544, P-540, and HF399s1 was visibly increased compared with that of untreated cells and the measured cellular DNA content of P-540 and HF399s1 was double that of untreated cells. Furthermore, based on random spore analysis and mass-matings, induced variants in the diploid strains were found to be tetraploid with an a/a/alpha/alpha genotype at the mating-type locus or, in the haploid strains, homozygous diploid with an alpha/alpha genotype. From these results we conclude that pressure treatment in combination with a dye plate is a useful method for strain improvement by direct induction of tetraploids or homozygous diploids from industrial strains whether diploid or haploid.

Crosses, Genetic↗

Short-term treatment with synchronized coronary venous retroperfusion before full reperfusion significantly reduces myocardial infarct size.

The efficacy of short-term synchronized coronary venous retroperfusion (SRP) before full arterial reperfusion was studied in a canine model. A control group (n = 6) was subjected to 90 minutes of occlusion of the left anterior descending coronary artery, which was followed by 6 hours of reperfusion. In another group (n = 6) the left anterior descending coronary artery was occluded for 2 hours followed by 5.5 hours of reperfusion. In this group SRP was applied for 30 minutes before full reperfusion. Myocardial regional blood flow was measured with the use of colored microspheres. During occlusion of the left anterior descending coronary artery, there was severe myocardial ischemia in both groups. Blood flow in the subendocardial area was, however, significantly better in the SRP group (0.51 +/- 0.17 ml/min/gm after 3.5 hours of reperfusion) than in the control group (0.29 +/- 0.16 ml/min/gm) after 4 hours of reperfusion (p less than 0.05). Left ventricular function was assessed as global ejection fraction from a left ventriculogram. Ejection fraction was reduced during ischemia in both groups (control = 38% +/- 3%, SRP = 32% +/- 8%). This dysfunction remained after 4 hours of reperfusion. Infarct size was assessed by means of triphenyltetrazolium chloride staining. The myocardial area at risk was similar in the two groups (control = 33.1% +/- 5.3%, SRP = 30.6% +/- 6.5%). Infarct size, which was expressed as the percent of the area at risk, was significantly smaller in the SRP group (17.2% +/- 14.6%) than in the control group (36.0% +/- 8.1%; p = 0.0197).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

MRI findings of multiple sclerosis with acute transverse myelopathy.

We classified clinically definite multiple sclerosis (MS) patients who underwent brain MRI with superconductive magnet into 2 subgroups: group A, consisting of 14 patients who had shown acute transverse myelopathy (ATM) during the course of illness; and group B, 35 patients without ATM, and the same neuroradiologist, blinded to clinical profiles of the patients, investigated the MR scans. We analyzed some parameters such as distribution, size, shape and number of the lesions. Although the total number of lesions were similar in each group, and the number of small size or patchy shape solitary lesions were not different, the moderate, large, ovoid or confluent lesions were lower in number in group A, compared with group B. The degree of cerebral white matter lesions and periventricular lesions were higher in group B. Brainstem lesions were significantly less common in group A. These results show characteristic differences in MR-detected, possibly pathological, changes between these 2 groups, and support our previous report that group A may constitute a distinct subgroup in patients with MS.

Adult↗

Analysis of chromosome aberrations induced by U5 RNA.

A small nuclear RNA, U5, was reported previously to induce chromosome aberrations. This was further analyzed in the present study. An in vitro transcript from a synthetic DNA template, which corresponds to the 3' half of the first stem of U5, induced chromosome aberrations upon transfection of a rat fibroblast, 3Y1 cells. Introduction of an expression vector construct carrying the same part of the U5 sequence resulted in morphological transformation of the cells. A cytological analysis of the transformed cells showed chromosome abnormalities similar to those induced by the RNAs. It was also shown that the frequency of chromosome aberrations in the transformed cells increased by elevating the level of the transcript. A possible mechanism of chromosome aberrations by the RNAs is discussed.

Animals↗

Results of the combination of external-beam and high-dose-rate intracavitary irradiation for patients with cervical carcinoma.

We retrospectively analyzed 220 patients with squamous cell carcinoma of the uterine cervix treated by the combination of external-beam and high-dose-rate intracavitary brachytherapy between 1978 and 1986. Five-year survivals for Stage Ib (n = 15), IIa (n = 18), IIb (n = 107), IIIb (n = 50), and IVa (n = 18) were 72.3, 88.9, 68.9, 64.0, and 16.7%, respectively. The incidences of recurrence outside the pelvis in Stage IIb and IIIb patients (15.0 and 24.0%) were higher than those of local recurrences (10.3 and 12.0%). Eighteen patients (8.2% of the total) had serious intestinal complications. These serious complications were closely correlated with the external-beam dosages. External-beam therapy was performed at 1.8-2.0 Gy/day, and high-dose-rate brachytherapy using a remotely controlled afterloading system (RALS) was performed once a week with 6.0-7.5 Gy at points A/fraction. Treatment dosages to the whole pelvis (WP), with central shieldings (CS), and with RALS according to FIGO stage were as follows: Stages Ib, IIa, 30-40 Gy (WP) plus 24-30 Gy (RALS); Stages IIb, IIIb, 40 Gy (WP) plus 10-20 Gy (CS) plus 24-30 Gy (RALS); Stage IVa, 40-50 Gy (WP) plus 10-20 Gy (CS) plus 20-30 Gy (RALS). From these data, the combination of external-beam and high-dose-rate intracavitary irradiation is an effective therapy for cervical cancer. It is also suggested that an additional combined chemotherapy is necessary to control metastic lesions outside the pelvis for Stages IIb and IIIb.

Adult↗

In vivo expression of CD69 on lung eosinophils in eosinophilic pneumonia: CD69 as a possible activation marker for eosinophils.

The antigen, CD69, has been demonstrated to be expressed on activated T cells and natural killer cells. There have been no studies concerning the expression of CD69 on eosinophils. In this article, we demonstrate that lung eosinophils obtained from the bronchoalveolar lavage fluid of patients with eosinophilic pneumonia expressed significant levels of CD69, whereas peripheral blood (PB) eosinophils did not express CD69. We also activated PB eosinophils in vitro using phorbol myristate acetate and cytokines to determine whether CD69 was expressed. PB eosinophils expressed CD69 after short-term culture with phorbol myristate acetate and eosinophil hemopoietic cytokines (interleukin-3, granulocyte-macrophage--colony-stimulating factor, and interleukin-5). These findings suggest that CD69 may be a useful marker for activated eosinophils at inflammatory sites.

Antigens, CD↗

Patterns of failure and survival in locally advanced carcinoma of the uterine cervix treated with high dose-rate intracavitary irradiation system.

We retrospectively analyzed 71 patients with locally advanced carcinoma of the uterine cervix treated by irradiation using high dose-rate intracavitary brachytherapy between 1978 and 1985. Seven patients were Stage IIIa, 46 Stage IIIb, and 18 Stage IVa. Five-year survivals for Stage IIIa, IIIb, and IVa were 71.4, 60.9, and 16.7%, respectively. An analysis of patterns of failure demonstrated that loco-regional recurrences were observed in 1 (14.3%) for Stage IIIa, 6 (13.0%) for Stage IIIb, and 9 (50.0%) for Stage IVa. The incidence of recurrence outside the pelvis observed in Stage IIIb patients (7 para-aortic nodes, 5 distant metastases) was much higher than that of local recurrence. Five patients (7.0% of the total: 1 with Stage IIIa, 3 with Stage IIIb, 1 with Stage IVa) required surgery to manage the complications. These data suggest that a high dose-rate intracavitary irradiation system is an effective tool for the treatment of cervical cancer. Further efforts to control metastatic lesions outside the pelvis are required for patients with Stage IIIb. To increase a loco-regional control rate for patients with Stage IVa disease, it is important to give additional treatment such as chemotherapy in conjunction with radiation therapy.

Adult↗

The anti-inflammatory effect of erythromycin in zymosan-induced peritonitis of mice.

The anti-inflammatory effect of erythromycin was investigated using zymosan-induced peritonitis in mice. When mice were given erythromycin 10 mg/kg/day po for 28 days, a marked suppression of inflammatory responses, including the reduced influx of leucocytes, plasma exudation and prostaglandin E2 synthesis, was observed. However, neither a 7-day treatment with erythromycin nor a 28-day treatment with clindamycin suppressed the response. The anti-inflammatory activity induced after a 28-day treatment with erythromycin was comparable to the anti-inflammatory effect conferred by a 2-day treatment with dexamethasone 40 microgram/mouse/day. Thus, these data confirm previous studies which show that erythromycin can exert an anti-inflammatory effect when used over long periods of time.

Animals↗

Mechanism of androgen action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo.

Androgens are major regulators of human hair growth, but their effects vary: many follicles are stimulated by androgens, e.g., beard; some remain unaffected, e.g., eyelashes; whereas scalp follicles undergo regression and balding in genetically disposed individuals. Because the dermal papilla controls many aspects of the hair follicle, androgens may act via the dermal papilla, affecting the other follicular components indirectly. In this hypothesis androgens would alter dermal papilla cell production of regulatory substances, e.g., growth factors and/or extracellular matrix components. To test this theory the mechanism of androgen action has been compared in primary lines of dermal papilla cells cultured from androgen-dependent follicles and relatively androgen-independent non-balding scalp. Androgen receptor levels were assayed by saturation analysis (9-10 points; 0.05-10 nmol/l) using the synthetic androgen [3H]-mibolerone and specificity was confirmed by competition studies. Androgen metabolism was investigated both intracellularly and in the media after a 2-h incubation with 5 nM [3H]-testosterone. Carrier and [14C] steroids were added to the extracts before separation by thin-layer chromatography; steroid identity was confirmed by recrystallization. Dermal papilla cells from androgen-dependent follicles contained higher levels of specific, high-affinity, low-capacity androgen receptors than non-balding scalp cells. Testosterone metabolism also varied with beard, public and scalp cells containing testosterone and androstenedione intracellularly, but only beard cells producing 5 alpha-dihydrotestosterone, in line with the scanty beard growth found in 5 alpha-reductase deficiency. Elsewhere we have shown that cultured dermal papilla cells produce extracellular matrix components and mitogenic factors. These results all concur with our original hypothesis and suggest that further studies of such cells may elucidate the paradoxical effects of androgens on human hair follicles.

Androgens↗

Effects of gamma-interferon and FK506 on resting B cell proliferation of New Zealand black/white F1 mice.

We examined the effects of gamma-interferon (gamma-IFN) and the new immunosuppressant FK506 on resting B cell proliferation of New Zealand black/white F1 hybrid (B/W F1) mice, an animal model of human systemic lupus erythematosus (SLE). gamma-IFN and FK506 inhibited in a dose-dependent manner both B cell proliferation and autoantibody production of resting B cells respectively. There was a synergistic interaction between gamma-IFN and FK506 in their inhibition and they did not exhibit cell cytotoxicity. This in vitro synergism of gamma-IFN and FK506 may have clinical application in that low doses of gamma-IFN and FK506 combinations may be effective to correct polyclonal B cell activation of patients with SLE.

Animals↗