Androgens and the hair follicle. Cultured human dermal papilla cells as a model system.
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Androgen-Insensitivity Syndrome↗
Biomedical subjects
K Hamada
Publications and source records attributed to K Hamada.
A new method of gene transfer into hematopoietic progenitors using liquid culture with interleukin-3 and interleukin-6.
The technique of gene transfer into hematopoietic cells is expected to offer a new form of therapeutics. As a result of studies on a gene-delivery system using granulocyte-macrophage colony-forming units (CFU-GM), a type of hematopoietic progenitor, we have established a technique for efficient gene transfer into CFU-GM. DGL, a retrovirus vector containing the SV40 promoter and the neomycin resistance gene, was constructed and found to transfer genes effectively into murine CFU-GM, which subsequently expressed the neomycin resistance gene. After gene transfer of murine non-adherent bone marrow cells precultured in liquid culture with recombinant murine IL-3 (rmIL-3) and recombinant human IL-6 (rhIL-6) for 6 days, gene transferred CFU-GM in bone marrow cells were able to proliferate 5-10-fold and the ratio of gene transferred CFU-GM to total CFU-GM reached 70-100% from less than 1% in the liquid culture with rmIL-3, rhIL-6 and neomycin for 6 days. Using this protocol, we have been able to obtain large amounts of highly concentrated gene-transferred CFU-GM for fundamental research on CFU-GM gene-delivery systems.
Animals↗
Aseptic meningitis in children: correlation between fever and interferon-gamma level.
We studied the correlation between interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in cerebrospinal fluid (CSF) and clinical/laboratory findings in children with aseptic meningitis. In 19/27 patients (70%), the CSF IFN level was high at initial diagnosis, and reduced to a low or undetectable level during the convalescent phase (5-14 days later) of the disease. There were no differences in IL-1 beta and TNF-alpha levels between the acute and convalescent phase of the patients. The serum IFN-gamma levels in the patients, which were simultaneously examined were undetectable in the acute phase. When we compared the clinical/laboratory findings between the 29 patients with detectable CSF IFN-gamma level and the 21 patients with an undetectable CSF IFN-gamma level in the acute phase, the former demonstrated higher body temperature (P less than 0.01), and higher cell number and protein level in the CSF (P less than 0.05) than the latter. On the other hand, there were no significant differences in the duration of meningeal signs, the titre of C-reactive protein, and the peripheral leucocyte count between the two groups. By the Spearman's rank sum test, the CSF IFN-gamma levels correlated more definitively with the severity of febrile episode (maximal body temperature, duration of fever and body temperature at the first lumbar tap), and the cell number and protein level in the CSF. These results suggest that IFN-gamma produced in the inflamed intrathecal space may be associated with the pathogenesis of aseptic meningitis, especially the production of fever.
Child↗
Accumulation of CD16-CD56+ natural killer cells with high affinity interleukin 2 receptors in human early pregnancy decidua.
Most human peripheral blood natural killer (NK) cells express the phenotype CD16+CD56+. However, a very minor subset of NK cells express CD16-CD56+, and these NK cells bear both interleukin 2 receptor (IL-2R)alpha (p55) and IL-2R beta (p75) (high affinity IL-2 receptors). In this report, we demonstrate that in human early pregnancy decidua--an interface between maternal immunocompetent cells and fetus (placenta)--abundant (approximately 83%) CD16-CD56+ NK cells with high affinity IL-2 receptors were present, and these cells responded to low amounts of IL-2 (4.5 pM). These CD16-CD56+ NK cells significantly expressed an early activation antigen, CD69, in vivo, whereas peripheral CD16-CD56+ NK cells did not express CD69. These findings suggest that CD16-CD56+ NK cells in early pregnancy decidua may be activated in vivo, and may play an important role in immunoregulation during early pregnancy. Also, decidual lymphocytes may be useful materials to study the mechanism of MHC-unrestricted cytotoxicity of this type of NK cells.
Antigens, CD↗
The effects of diltiazem on hepatic drug metabolizing enzymes in man using antipyrine, trimethadione and debrisoquine as model substrates.
Six healthy male subjects were given single oral doses of antipyrine (7 mg kg-1), trimethadione (4 mg kg-1) and debrisoquine (10 mg) before and during diltiazem treatment (30 mg three times daily orally for 8 days). Antipyrine clearance decreased from 33.7 +/- 9.1 to 22.5 +/- 4.9 ml min-1 (P less than 0.05, mean +/- s.e. mean) after diltiazem treatment without any significant change in apparent volume of distribution (0.59 +/- 0.06 to 0.60 +/- 0.04 1 kg-1), resulting in an increase in antipyrine elimination half-life from 13.4 +/- 4.8 to 19.7 +/- 3.2 h (P less than 0.05). The formation clearance of antipyrine to 4-hydroxyantipyrine was decreased significantly from 10.8 +/- 2.7 to 6.6 +/- 2.7 ml min-1 (P less than 0.05), while that to 3-hydroxymethylantipyrine and norantipyrine was not altered by diltiazem. The metabolic ratio of debrisoquine (urinary excretion of debrisoquine/4-hydroxydebrisoquine) was increased significantly from 0.70 +/- 0.05 to 1.95 +/- 0.20 (P less than 0.05), while that of trimethadione (serum concentration of dimethadione/trimethadione) was not changed significantly (0.48 +/- 0.08 vs 0.41 +/- 0.06) after diltiazem treatment. Diltiazem selectively inhibits cytochrome P-450 isoenzymes.
Adult↗
HTLV-1 associated myelopathy combined with chronic thyroiditis.
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Human T-lymphotropic virus 1↗
[The study on bacterial infection in chronic lower respiratory tract infection--from the viewpoints of acute and chronic infection].
Using mainly changes in the amount of sputum as an index of the infectious course of chronic lower respiratory tract infection associated with purulent sputum over years, the disease was divided into stable and acute exacerbated phases and a bacteriological investigation using transtracheal aspiration (TTA) conducted. TTA was performed 107 and 45 episodes during stable phases and acute exacerbated phases respectively. Monomicrobial and polymicrobial infection were detected most frequently during the stable and acute exacerbated phases respectively (p less than 0.01). During the stable phases, the single organisms detected most frequently were H. influenzae (26 episodes) and P. aeruginosa (20 episodes), while in the cases in which multiple organisms were detected during stable phases, combination including H. influenzae were most common (19 episodes). H. influenzae was the most frequently detected organism in cases showing single organisms during acute exacerbated phases (7 episodes). In the cases in which multiple organisms were detected as well, H. influenzae was the most commonly detected organism assumed to predispose to exacerbation (7 episodes), while P. aeruginosa was not found. These results suggest that in chronic lower respiratory tract infection. H. influenzae and P. aeruginosa are important as persistent infective organisms, while H. influenzae are important in acute exacerbation.
Acute Disease↗
Two cases of neoplastic angioendotheliomatosis presenting with myelopathy.
We describe two patients with autopsy-proven neoplastic angioendotheliomatosis (NAE) presenting only as a transverse myelopathy for 10 to 12 months, followed by disseminated intracranial manifestations. Postmortem examination disclosed a vasculocentric distribution of neoplastic cells in various organs that stained positively with B-lymphocyte-specific monoclonal antibody. These cases were unusual because they manifested as an isolated myelopathy for many months.
Brain↗
Quantitative lymphoscintigraphy using 99Tcm human serum albumin in patients with previously treated uterine cancer.
To evaluate the clinical usefulness of lymphoscintigraphy using 99Tcm human serum albumin (99Tc-HSA) in assessing lymphoedema in the lower extremities, lymphoscintigraphy was performed by subcutaneous injection of 7.4 MBq of 99Tcm-HSA in 26 patients with uterine cancer, previously treated by operation (OP) and/or radiation therapy (RT), and in five controls. Radioactivity at the injection site in the lower extremities was counted for 3 min at 10 min (A) and at 3 h (B) after injection, and clearance of 99Tcm-HSA was defined as (1-(B)/(A)) x 100(%). Clearance in controls was 46.8 +/- 3.9%, which was significantly more than those in the other treatment groups. Clearances in patients treated with both OP and RT were less than those in patients treated with either OP or RT alone (30.1 +/- 11.4 vs. 41.9 +/- 8.9, 43.7 +/- 9.6%, respectively; p less than 0.01). The clearance in legs with lymphoedema was less than those without lymphoedema in patients treated with both OP and RT (16.6 +/- 7.7 vs. 34.9 +/- 9.3%; p less than 0.01) and in patients treated with RT (33.1 +/- 7.4 vs. 48.0 +/- 5.6%; p less than 0.01). There was a significant difference between clearance in controls and clearance in non-oedematous patients' legs treated with OP and RT (p less than 0.01). In patients treated with RT alone, radiation dose was closely correlated with 99Tcm-HSA clearance and with the development of lymphoedema. These data suggest that lymphoscintigraphy using 99Tcm-HSA is useful in evaluating lymphoedema and that radiation dose is one of the factors in the development of lymphoedema.
Adult↗
[Localization of alpha 1-adrenoceptors in hypertrophic prostate].
In order to determine the localization of alpha 1-adrenoceptors in human hypertrophied prostates, in vitro autoradiography was performed on the frozen specimens from 13 enucleated hypertrophied prostates with [125I]-HEAT (iodo-2-[beta-(4-hydroxyphenyl)-ethylaminomethyl] tetralone) and [3H]-prazosin. In vitro autoradiograms showed macroscopically the specific binding site on the areas seemed to the nodular area for [125I]-HEAT, but not so clear specific binding sites for [3H]-prazosin. Microscopic autoradiograms seemed to show binding sites located mainly on the interstitial beneath the gland, and partly on the basement membrane and epithelium of the prostatic gland. Further studies are needed to show clearer specific binding sites of alpha 1-adrenoceptors.
Aged↗
Interferon-gamma inhibition of interleukin 4-induced hyperproliferation of resting B cell from NZB/NZW F1 mice.
To characterize B cell hyperactivity in autoimmune NZB/NZW (B/W) F1 mice, we studied the effects of murine recombinant interferon gamma (IFN-gamma) on interleukin 4 (IL-4) induced resting B cell growth and differentiation. The number of resting B cells of B/W F1 mice were decreased, with more sensitivity to IL-4 than normal mice. Thus, resting B cell hyperresponsiveness to IL-4 was in a dose-dependent manner suppressed by IFN-gamma. This action was most noticeable when IFN-gamma was added to the culture system simultaneously with IL-4. As well, IFN-gamma did not exhibit cytotoxicity. These results suggest that IFN-gamma may have regulatory effects on IL-4 mediated B cell triggering.
Animals↗
[A case of prolonged eosinophilic pneumonia with pulmonary emphysema and bronchial asthma diagnosed by open lung biopsy].
A 65-year-old man was admitted to our hospital complaining of productive cough, dyspnea and stridor. Chest X-ray disclosed overinflation with micronodular infiltrates. Blood examination showed mild eosinophilia and IgE elevation. Pulmonary function test disclosed severe airway obstruction and diffusion capacity impairment. Although clinical improvement was achieved after bronchodilator therapy, laboratory abnormalities continued. Open lung biopsy demonstrated mononuclear cellular and eosinophilic infiltration at alveolar lumen and vessel walls without prominent fibrosis, which was compatible for prolonged eosinophilic pneumonia. From above findings, this case was thought as a prolonged eosinophilic pneumonia combined with pulmonary emphysema and bronchial asthma.
Aged↗
[Clinical study of respiratory infections complicating bronchial asthma].
We conducted a clinical study on respiratory infections complicating bronchial asthma. Transtracheal aspiration (TTA) was performed 37 times in 22 patients. The most frequently isolated organism was H. influenzae. The patients in whom organisms were isolated on TTA had a high incidence of fever and evidence of inflammation. Antimicrobial therapy caused a decrease in indices of inflammation (white blood cell count and ESR), but was less effective against the asthmatic symptoms. Respiratory infection may play a complex role in the clinical picture of bronchial asthma.
Aged↗
[A case of recurrent cranial neuropathy presenting as recurrent Tolosa-Hunt syndrome].
A 64-year-old woman, with history of hypertension and arteriosclerosis, developed left painful ophthalmoplegia in July, 1988. Neurological examination proved abnormality of the third cranial nerve innervation, otherwise normal. No systemic illness was present. With corticosteroid therapy, the symptoms regressed and completely disappeared in 3 months. In January, 1990, right painful ophthalmoplegia appeared. Neurological examination revealed involvement of right sixth nerve and first branch of the right fifth nerve. With corticosteroid therapy, the symptoms completely regressed in several weeks. In April, 1990, she developed severe pain in the right side of the face. The facial pain disappeared rapidly with corticosteroid therapy, but reappeared following quit of steroid. She complained of severe pain of the right face, the territory of first and second branch of the right fifth nerve, but neurological examination was negative. With corticosteroid therapy, the pain disappeared remaining with mild tingling sensation on the right face, but during the tapering of corticosteroid in August, a severe peripheral type right facial palsy developed. Corticosteroid therapy resumed and the facial palsy regressed almost completely in ten days. Our case suggests that THS might be a variant of so-called recurrent cranial neuropathy.
Aged↗
[Gene-transfer into bone marrow cells].
We have intended to improve gene-transfer technique into hematopoietic stem cells for somatic gene therapy. 1) We have developed a new packaging cell line, ampGPE for retroviral production. LTR-less gag, pol or env genes from Moloney murine leukemia virus were separately inserted into BMGNeo vector. Packaging cell lines containing 20-50 copies of these two kinds of plasmid were obtained. Retrovirus stock for gene-transfer have been produced at a high titer (10(5)-10(6) cfu/ml) and without replication-competent viruses by using ampGPE. 2) Retrovirus-transduced murine CFU-GM have been found to selectively proliferate (5-10 fold/week) in liquid capture with recombinant murine IL-3, human IL-6 and G418 to consequently obtain enough amount of, highly concentrated (70-100%), and gene-transferred murine CFU-GM for gene-delivery system.
Animals↗
[Differentiation of intestinal candidial colonization from invasive candidiasis by measuring serum level of D-arabinitol in combination with oral administration of low dose amphotericin B].
The measurement of D-arabinitol in serum has been reported to be useful for the diagnosis of invasive candidiasis. However, excessive proliferation of Candida species in intestinal tract often leads false positive result of serum D-arabinitol. Based on the evidence that amphotericin B (AMPH) is scarcely absorbed from intestinal tract and inhibits the proliferation of Candida species only in intestinal tract, we have developed a simple differentiation method of intestinal candida colonization from invasive candidiasis by measuring serum level of D-arabinitol in combination with oral administration of low dose AMPH. AMPH, 600 mg/day for 2 days was orally administered to five patients with hematological malignancies who showed more than 1.7 mumol/mg of D-arabinitol/creatinine ratio (D/C ratio) in serum without any evidence of invasive candidiasis. D/C ratios were markedly decreased and normalized after the oral administration of low dose AMPH. While, in a patient with invasive candidiasis in whom Candida species was detected by blood cultures, D/C ratio remained unchanged in spite of oral administration of AMPH. These observations suggest that this method is a simple and reliable diagnostic method to distinguish intestinal candida colonization from true invasive candidiasis.
Administration, Oral↗
[The early changes in bone mineral metabolism due to radiation--measurement of bone mineral density in lumbar vertebra by quantitative computed tomography].
Osteosclerosis, osteonecrosis and compression fracture are commonly observed several years after radiation. Since lumbago usually occurs several months after radiation, the possibility that bone mineral metabolism is disturbed during and immediately after radiation cannot be ruled out. However, there have been no reports concerning early changes in bone mineral metabolism due to radiation. The bone mineral density was measured by QCT (Quantitative Computed Tomography) in 30 normal non-radiated cases and 14 radiated cases to investigate the changes in bone mineral metabolism due to radiation. The bone mineral density (QCT-Value: QCT-V) in the 3rd lumbar vertebra (L3) of normal non-radiated subjects decreased linearly with age (Y = 291.114447-3.01473X). The QCT-V of the 5th lumbar vertebra (L5) of normal cases also decreased linearly with age (Y = 309.641397-3.03986X), resembling that of L3. The ratio of the QCT-V of L5 to L3 (L5/L3, expressed as a percentage) definitely increased with age (Y = 86.5657441 + 0.58885064X). In radiated cases, the QCT-V of L3 in the non-radiated field did not change appreciably. The QCT-V of L5 in the radiated field was decreased from 20GY and reached 53.08 +/- 17.37% of the pre-radiation value after 50GY. The L5/L3 ratio was also decreased from 20GY and reached 55.47 +/- 15.32% of the pre-radiation value after 50GY. It becomes apparent that the QCT-V of the radiated lumbar vertebra is decreased during radiation. It is suggested that bone mineral metabolism may be disturbed in the early phase of radiation.
Bone Density↗
[Clinical evaluation of cefuzonam for bacterial pneumonia].
Ten patients with moderate or severe bacterial pneumonia with underlying diseases or complications were treated with cefuzonam (CZON) at a daily dose of 2 g to 4 g. The clinical effectiveness was good in 9 patients. No side effects or abnormal laboratory test results were observed in any patient. These results suggest that CZON may be useful in the treatment of bacterial pneumonia.
Aged↗