Lobular panniculitis terminating in acute myeloid leukemia.
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Acute Disease↗
Biomedical subjects
S Itami
Publications and source records attributed to S Itami.
Influences of gonadal and adrenal androgens on the side glands of Suncus murinus.
In order to know the contribution of adrenal and gonadal androgens to the development of the side gland of Suncus murinus, we studied the effects of gonadectomy and adrenalectomy on gland thickness and the plasma levels of testosterone, androstenedione (delta 4-dione) and dehydroepiandrosterone (DHA). In males, castration decreased gland thickness to 71% of the control. The plasma levels of delta 4-dione and testosterone were also decreased from 4.16 +/- 0.50 and 0.65 +/- 0.10 ng/ml to 1.44 +/- 0.17 and 0.12 +/- 0.02 ng/ml, respectively. Adrenalectomy following castration caused no notable additional decrease in gland thickness, although the plasma levels of delta 4-dione and DHA were further decreased by this treatment. In females, ovariectomy affected neither gland thickness nor plasma androgen levels, except for a peculiar rise in the plasma concentration of delta 4-dione. In contrast, adrenalectomy in addition to ovariectomy decreased gland thickness to 63% of the control and the plasma concentrations of delta 4-dione and DHA from 1.43 +/- 0.26 and 0.43 +/- 0.05 ng/ml to 0.37 +/- 0.11 and 0.10 +/- 0.04 ng/ml, respectively. Therefore, testicular androgens are required for the male side gland to fully develop, whereas in the female adrenal androgens are important for the maintenance of sebaceous gland activity and delta 4-dione is quantitatively more important than DHA. One hour after the intraperitoneal administration of [3H]delta 4-dione, dihydrotestosterone was found to be the major androgen bound to nuclei of the side gland. Thus, the side gland can utilize delta 4-dione as a precursor of a more active androgen.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Glands↗
Evaluation of prognostic factors for 233 patients with recurrent advanced breast cancer.
We analyzed possible prognostic factors in 233 patients with recurrent advanced breast cancer treated primarily by adriamycin, cyclophosphamide and ftorafur (ACF) therapy and ACF modifications. The patients were in the Cancer Institute Hospital from 1977 to 1986, and were followed-up until 1989. In terms of chemotherapeutic response, complete and partial responses were observed in 31 (13%) and 100 (43%) patients, respectively. The overall median survival from the beginning of chemotherapy was 20.3 months. The factors evaluated were response to chemotherapy, performance status (PS), age, disease-free interval (DFI), menopausal status, number of metastatic sites (step classification), presence or absence of liver metastasis, presence or absence of malignant effusion, and presence or absence of prior radiotherapy. Out of the nine factors, response to chemotherapy, PS, age, DFI and liver metastasis were significant factors affecting survival in univariate analysis, and multivariate analysis of these five factors revealed the survival to be markedly affected by response to chemotherapy (P less than 0.00001), PS (P = 0.00001) and DFI (P less than 0.00001).
Adult↗
[Combination chemotherapy of advanced Hodgkin's disease with vincristine, cyclophosphamide, procarbazine, and prednisolone].
Thirty-three patients with advanced Hodgkin's disease were treated with a combination chemotherapy consisting of vincristine 1 mg/m2 iv on day 1, 8, cyclophosphamide 500 mg/m2 iv on day 1, procarbazine 100 mg/m2 p.o. day 1-7, and prednisolone 40 mg/m2 p.o. day 1-7. Twenty patients received this regimen every 4 weeks (VCPP II regimen). Furthermore, we conducted higher dose intensive VCPP II-2 regimen which was repeated every two weeks for thirteen patients. Complete response rate of both regimens was 63% (VCPP II 45%, VCPP II-2 85%). The median duration of CR was 37 + months. Leukopenia, neurotoxicity and gastrointestinal toxicity were commonly observed but were clinically manageable. These results indicate that high dose intensive chemotherapy is effective for achieving high CR rate for advanced Hodgkin's disease.
Adolescent↗
[Phase I-II study of hepatic intraarterial one-shot administration of adriamycin in patients with metastatic liver cancer].
For the purpose of obtaining the optimal dose of adriamycin (ADM) in hepatic intraarterial one-shot administration, phase I-II study was conducted in 14 patients with various liver cancers. The starting dose of ADM was 20 mg/m2 (4 patients) and the doses were escalated to 40 mg/m2 (5 patients), 60 mg/m2 (4 patients) and 80 mg/m2 (3 patients). One patient with salivary gland cancer showed PR for the liver metastasis. Major toxicity was leukopenia. With a dose of 40 mg/m2, 3 out of 4 patients showed nadir of WBC counts below 4,000/mm3 (2,400, 2,900, 3,100), 60 mg/m2 (1,100, 1,500, 2,200 and 2,700), and 80 mg/m2 (900, 1,200, and 1,400). Nadirs of WBC counts were observed from 9 to 15 days after the one-shot administration, and recovered above 4,000/mm3 in 1 to 3 weeks. Plasma concentrations of ADM from the peripheral vein were determined by HPLC in 12 patients, 14 courses. The curves of ADM plasma levels after 20 and 40 mg/m2 bolus injections were almost the same, and in patients treated with 60 and 80 mg/m2 the curves were also quite similar, but higher in the plasma levels, comparing with in patients with 20 and 40 mg/m2. There might be a limit of ADM tissue absorption, and above the doses 60 mg/m2, ADM might be overflowed, followed by side effects, especially leukopenia. Upon these data of venous plasma concentrations of ADM and leukopenia, the optimal dose of ADM in the hepatic intraarterial one-shot administration seemed to be 40 mg/m2.
Adult↗
Intranuclear androgen and cytosolic receptor concentrations in the axillary skin of osmidrosis.
5 alpha-Dihydrotestosterone (DHT) and testosterone were measured by radioimmunoassay in the crude nuclear and cytoplasmic fractions of the axillary skin of both male and female patients with osmidrosis and the levels compared with those of nongenital skin. The intranuclear levels of DHT were 1.44 +/- 0.22 and 1.77 +/- 0.38 pg/micrograms DNA in men and women, respectively. Those of testosterone were about 10% of DHT levels. In the skin of nontarget regions nuclear DHT was much scarcer or undetectable. Cytosolic androgen receptors in isolated apocrine glands were also measured using 3H-R1881 as a ligand. Typical androgen receptors were present in all of eight patients (KD = 1.32 +/- 0.24 X 10(-9)M, Bmax = 10.3 +/- 0.51 fmol/mg protein). Neither the intranuclear androgen concentrations nor the cytosolic androgen receptor levels were significantly different between the two sexes. These data indicate clearly that the apocrine gland of patients with osmidrosis is a typical androgen target organ, irrespective of sex, and suggest that nuclear DHT in the axillary skin of women is derived from not only testosterone but also other precursors, especially in consideration of the very low serum concentrations of testosterone in females.
Adolescent↗
5 alpha-reductase activity in cultured human dermal papilla cells from beard compared with reticular dermal fibroblasts.
The activity of 5 alpha-reductase was assessed in cultured human beard dermal papilla cells and reticular dermal fibroblasts to elucidate the mechanism of androgen action in promoting the growth of beards in men. The monolayer was incubated with 50 nM of [1,2-3H]-testosterone. Steroids were extracted from the medium and analyzed by thin layer chromatography. The major metabolite in the beard dermal papilla cells was dihydrotestosterone (DHT), the most potent androgen in the androgen target tissue. By contrast, the amount of DHT formed was similar to that of androstenedione in reticular dermal fibroblasts. The 5 alpha-reductase activity in beard dermal papilla cells was three to five times as high as that in the reticular dermal fibroblasts from the same skin sample. The apparant Michaelis constant of 5 alpha-reductase in the beard dermal papilla cells was 1.0 X 10(-6) M, which was virtually equivalent to that of genital skin fibroblasts, typical androgen target cells. It was 4.0 X 10(-5) M in reticular dermal fibroblasts. By contrast, the activities of 5 alpha-reductase in dermal papilla cells from occipital scalp hair follicles were similar to those of reticular dermal fibroblasts of the same skin samples. These results strongly suggest that the beard dermal papilla cell is an androgen target cell, and that DHT plays a role in the growth of beards in men.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
[Combination chemotherapy of ifosfamide, cisplatin and vindesine for non-small cell lung cancer].
Twenty patients with advanced non-small cell lung cancer were treated with a combination chemotherapy consisting of ifosfamide (IFX), cisplatin (CDDP) and vindesine (VDS). The treatment schedule was IFX 1.3 g/m2 i.v., on days 1-5, CDDP 20 mg/m2 i.v., on days 1-5, and VDS 3 mg/m2 i.v., on days 1 & 8, and, in principle, the regimen was repeated every 4 weeks. Of 19 evaluable patients, there were 1 CR, 7 PR, 10 NC and 1 PD, with an overall response rate of 42.1%. The median duration of responses was 7.45 months, and the median survival time of all patients was 13.2 months. The major toxicities occurring were hematologic toxicity, alopecia, gastrointestinal toxicity and peripheral neuropathy. Hematologic toxicity was severe and was judged to be dose limiting, but clinically manageable. These results indicate that this combination chemotherapy is active against non-small cell lung cancer and deserves further studies.
Adult↗
[Treatment of cancer in the elderly--cancer chemotherapy].
A retrospective analysis was made of elderly cancer patients (pts) who were treated with cancer chemotherapy in our Department of the Cancer Inst. Hosp. There were 180 pts above age 70 years at the start of chemotherapy between July of 1974 and December of 1988. Characteristics of these 180 pts were as follows: (1) 73 years of age in median (70-89 years), (2) 67 pts with malignant lymphoma (37%); 40 with lung ca. (22%), 20 with breast ca. (11%), stomach ca., colorectal ca., multiple myeloma and other; (3) Combination chemotherapy given to 174 pts; (4) OUTCOME: 41 pts (23%) were alive as September of 1989, and autopsy performed in 66 out of 87 pts who died in the hospital (76%). There were no special chemotherapeutic regimens only for elderly pts. Intensity of adequate chemotherapy based on therapeutic protocols was evaluated, dividing pts into two groups: full-dose group and reduced-dose group. Most pts (96%) with small cell lung cancer (SCL) were treated on protocols. For example, 12 elderly pts with SCL were treated with VEC regimen (VCR.VP-16.CTX); eight pts with full-dose and four reduced-dose, and their response rate (CR/PR) of 50%/38% and 25%/75%, respectively, and in 23 younger pts; 20 full-dose and three reduced-dose, and response rate 35%/35% and 33%/33%, respectively. There were 40 pts with acute non-lymphocytic leukemia over 60 years old, treated at Jikei University and in our Department. CR rates of these pts according to age showed a lower percentage with advancing age. Elderly pts with malignancies responsive to chemotherapy should be treated with the same regimen used in younger pts. But doses of each drug have to be adjusted to organ functions of each pt. patients with unresponsive malignancies, must be enrolled in clinical trials, and their responses and toxicities evaluated by age-stratified analysis.
Aged↗
Side gland of Suncus murinus as a new model of sebaceous gland: 5 alpha-reductase, androgen receptor, and nuclear androgen content in male and female animals.
The side gland of Suncus murinus is composed of well-developed sebaceous glands in both males and females. We measured the 5 alpha-reductase activity, androgen receptor content, and the intranuclear concentrations of testosterone and dihydrotestosterone in this side gland taking it as a new experimental model of human sebaceous glands. Lineweaver-Burk plot analysis suggested the presence of two classes of 5 alpha-reductase with different Km for testosterone in the homogenate. The enzyme activity was slightly higher in males than in females in the presence of a high concentration of testosterone. The levels of androgen receptors were approximately 40 and 30 fmol/mg protein in the cytosol and nuclei, respectively. The values did not differ significantly between males and females. The intranuclear concentration of dihydrotestosterone in the side gland was higher than that of testosterone in each sex. The intranuclear level of each of these two androgens in the female side gland was comparable to that in the male side gland despite the fact that the serum level of testosterone was much lower in the female. These data clearly indicate that the side gland is a typical target tissue for androgens in the female as well as in the male. Androgens other than testosterone may serve as precursors of dihydrotestosterone in the female side gland.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Mongolian spots associated with cleft lip.
Of the present series comprising 66 newborns with cleft lip, 13 (20%) had pigmented macules in the labial skin on the lateral side of the cleft. Histological examination using serial sections were performed on 47 cases and showed evidence of dermal melanocytosis in 40 cases (85%) consisting of 33 (70%) without clinically detectable macules and 7 (15%) with obvious pigmented macules. The fusiform cells in the dermis were positive for dopa reaction and anti-melanocyte antibody. The high incidence of dermal melanocytosis is comparable to that of common Mongolian spots in Asian babies.
Cleft Lip↗
[A study to overcome drug resistance using high-dose chemotherapy with autologous bone marrow transplantation].
Drug resistant phenomenon to antitumor agents remains a major problem in cancer chemotherapy. In this study, we attempted to overcome drug resistance using high-dose chemotherapy with autologous bone marrow transplantation (ABMT). The main regimen consisted of Cyclophosphamide 60 mg/kg/day and thio-TEPA 6 mg/kg/day which were infused for 3 consecutive days. Three patients with malignant lymphoma, four with breast cancer, two with gastric cancer and one with ovarian cancer. All of whom were refractory to conventional chemotherapies were treated. The overall response rate was 70%. Severe bone marrow suppression, mucositis and diarrhea were observed in all patients, but these were not life-threatening and clinically manageable. Furthermore, the administration of granulocyte colony stimulating factor (G-CSF) has significantly (p less than 0.05) shortened the duration of leukopenia, and has been judged to be useful for reducing severe infections and for shortening the period stayed in clean room. Our results indicates that high-dose chemotherapy with ABMT is an effective method for overcoming drug resistance.
Adult↗
[4'-(9-acridinylamino)-methanesulfon-m-aniside (AMSA) combination salvage therapy in refractory acute non-lymphocytic leukemia in adults].
Eight patients with acute non-lymphocytic leukemia in adults refractory to Daunomycin (DM)-based conventional regimens were treated with AMSA-based regimens. Complete remission (CR) was obtained in 4 (50%) and partial remission (PR) in 2 (25%). The median time to CR was 26.5 days and 3 cases achieved CR in the first cycle. The median duration of CR was 8.3 months. Hematologic toxicity was severe and the nadir (median) of leukocytes and platelets was 0.15 x 10(3)/microliters and 15.5 x 10(3)/microliters, respectively. Other adverse effects were mucositis, nausea.vomiting and hepatotoxicity which occurred over 50%, while cardiac toxicity was not observed. This study indicates that AMSA is clinically non-cross-resistant to DM and considered to be an active drug for salvage therapy.
Adolescent↗
[Follow-up study on cytophagic histiocytic panniculitis with abnormal immunologic findings].
A 41-year-old patient suffering from multiple subcutaneous nodules of 9 years' duration subsequently left a well-demarcated region of atrophy. Histiocytic panniculitis was observed in biopsy specimens with cytophagocytosis. Histiocytosis was found in the bone marrow. These histiocytes were positive for lysozyme and platelets. He later developed fever and hepatomegaly. Laboratory examination revealed leukocytopenia, mild anemia, and liver disfunction as well as abnormal immunologic findings such as positive LE test and ANA, and an increase of serum IgA and complement levels. The patient was successfully treated with systemic administration of prednisolone and azathiopurine++.
Adult↗
Estrogen binding component in the pilosebaceous tumor developed in Suncus murinus.
We transplanted a pilosebaceous tumor developed on the sidegland of Suncus murinus to male nude athymic (BALB/c-nu/nu) mice. This tumor can be transplanted to female hosts as well, with a lower rate of graft-taking and slower growth rate. In this study we demonstrated the presence of macromolecules which specifically bind to estrogen. Measurement of 17 beta-estradiol (E2) binding by a dextran-coated charcoal assay revealed that the number of binding sites and the dissociation constant were 22.3 +/- 4.6 fmol/mg protein and 1.4 +/- 0.24 X 10(-9) M, respectively. This binding was specific for E2 and diethylstilbestrol (DES). Sucrose gradient centrifugation of the [3H]E2-labeled cytosol yielded a sharp peak of radioactivity at 3.5S-4S under high salt conditions and a 9S peak with a shoulder at 3.5S under low salt conditions. This 3.5S shoulder was due to dissociation of [3H]E2 from the 9S peak during the centrifugation, since only the 9S peak was obtained by postlabeled density gradient analysis. An assay of the in vivo binding of [3H]E2 showed significant radioactivity in the nuclear extract from the tumor. This nuclear uptake was markedly decreased by simultaneous administration of 100-fold excess of E2. In tumor-bearing castrated nude mice, 1-100 micrograms/day of E2 did not affect tumor growth, whereas it counteracted the stimulative effect of testosterone propionate.
Animals↗
Immunohistochemical study of beta-adrenergic receptors in the psoriatic epidermis using an anti-alprenolol anti-idiotypic antibody.
In order to study the beta-adrenergic receptor-cyclic AMP system in the human skin, we have developed a monoclonal antibody against the receptor binding site in two fusion steps. We produced an anti-alprenolol monoclonal antibody using a hybridoma technique after the immunization of a mouse with alprenolol-BSA conjugate. This antibody was then used to immunize mice, whose splenocytes were used for the second fusion. Colonies were screened by enzyme linked immunosorbent assay (ELISA) using turkey erythrocyte membrane as an antigen. One of the positive colonies was grown in mice to obtain ascites fluids. This antibody showed the ability to compete with [125I]-iodocyanopindolol for the binding to beta-adrenergic receptors of turkey erythrocytes. The binding of the antibody to the turkey erythrocytes was prevented by the existence of the anti-alprenolol antibody and also L-alprenolol. This antibody showed a prominent inhibition of the adrenaline-stimulated adenylate cyclase activity of the turkey erythrocyte membrane. The data indicate that the anti-idiotypic monoclonal antibody against alprenolol binds to the beta-adrenergic receptors and acts like an antagonist. We further studied the localization of the beta-adrenergic receptors with this antibody in the normal human skin as well as in the psoriatic skin using immunohistochemical technique. A prominent decrease of the beta-receptors was observed in the psoriatic epidermis.
Alprenolol↗
Epidermal cell culture using Sephadex beads coated with denatured collagen (cytodex 3).
Epidermal cell culture using microcarriers of Sephadex beads coated with denatured collagen (cytodex 3) was performed. Epidermal basal cells (above 95%) obtained from human skin by trypsinization were cultivated statically on the beads in 96-well culture plates. Proliferation was rapid and great in synchronous waves during 2-7 days after inoculation. The growth rate depended on the inoculation cell population densities. When cells were inoculated at 7.75 X 10(4)/well, the maximum increase was 3.6-fold and at 1.69 X 10(4)/well and 0.32 X 10(4)/well, 2.5-fold and 2.1-fold, respectively. Differentiation was assessed visually on a hemocytometer. The percentage of basal cells of the total cells present in each well was reduced from 98% (on inoculation) to approximately 25% in a week and thereafter. In 1 month after inoculation, cells with keratohyaline-like granules were observed at 12%. The attachment of cells to the beads was rather loose. Cells were supposed to be attached to denatured collagen on the beads via fibronectin contained in the serum of the medium, because denatured collagen had the property to bind strongly to fibronectin. Loose attachment made it possible to harvest intact cells without the use of trypsin. This cell culture system with such new characteristics will be a useful tool for studying epidermal cell biology and biochemistry.
Aged↗
Monoclonal antibodies to the beta-adrenergic receptor: modulation of catecholamine-sensitive adenylate cyclase by the antibody.
We have developed two types of hybridomas producing monoclonal antibodies to the turkey erythrocyte beta 1-adrenergic receptor in order to study the beta-adrenergic-cAMP system of epidermis. Splenic cells from BALB/c mice immunized with partially purified turkey erythrocyte beta 1-receptors were fused with mouse myeloma cell line SP2/0-Ag14. Five hybridomas of 17 positive cells producing antibodies which could precipitate soluble turkey erythrocyte beta 1-receptors were cloned by the limiting dilution method. The antibodies cross-reacted with beta 1- and beta 2-adrenergic receptors and stained epidermal basal cells with immunocytochemical techniques. Neither type of antibody interfered with the antagonist binding, i.e., all antibodies bound to sites other than the ligand binding site on the surface. One type of antibody inhibited epinephrine-stimulated adenylate cyclase activity in our "leaky" epidermal cell system. The data suggest that the antibody interferes with the coupling of the receptor to the regulatory protein.
Adenylyl Cyclases↗