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Biomedical subjects

M L Hsu

Publications and source records attributed to M L Hsu.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cell source and biological characteristics of murine bone marrow-derived colony-promoting activity.

A murine colony-promoting activity (CPA) was found in the supernatants of Dexter long-term bone marrow cultures (LTBMC). This activity itself failed to stimulate in vitro granulocyte-macrophage colony (CFU-GM) formation but could increase the number of colonies induced by colony-stimulating factors (CSFs). CPA was produced by the adherent stromal cells but not by the nonadherent cells. No CPA could be detected in cultures of pure marrow fibroblasts, nor was it secreted by the stromal cells following macrophage depletion. In contrast, a large amount of CPA was found in cultures of isolated macrophages, suggesting that marrow macrophages may be the main cell source of CPA. Although colony formation was augmented by adding CPA in combination with various CSFs, the colony type induced by CPA plus CSF was no different from that of CSF alone. Preincubation of bone marrow (BM) cells with CPA at 37 degrees C for 24 hours before using in clonal culture assay resulted in a marked colony enhancement. Furthermore, colony formation by 5-fluorouracil (5-FU)-treated marrow cells could be induced by granulocyte-macrophage (GM)-CSF plus CPA but not by GM-CSF alone. These results suggest that CPA may act on early developing hematopoietic stem cells to induce them to differentiate into more mature myeloid progenitor cells capable of responding to CSF stimulation. CPA was nondialyzable and stable under heat (56 degrees C for 30 minutes) and freeze/thawing (3 times). Its activity was acid-labile (pH 2.0) but relatively alkaline-resistant (pH 11.0). When treated with enzymes, CPA was sensitive to trypsin and bacterial protease but not to neuraminidase. In addition, the activity of CPA could be abrogated by anti-CPA antiserum but remained unchanged after treatment with antibodies to other murine hematopoietic synergizing/stimulating factors, including interleukin-1 (IL-1), IL-3, IL-4, IL-6, and stem cell factor (SCF).

Animals↗
PubMed1992

Public opinion about AIDS policies. The role of misinformation and attitudes toward homosexuals.

In an effort to better understand the cognitive and attitudinal factors underlying public opinion on AIDS-related issues, this article proposes and empirically tests a model of the relationships between (1) knowledge of HIV transmission, specifically the misinformation that AIDS can be transmitted easily through casual contact with HIV-infected persons; (2) attitudes toward homosexuals, the most prominent of the social groups presently affected by the AIDS crisis; and (3) support for restrictive public policies aimed at HIV-infected persons. Data from two nationally representative surveys conducted in December of 1985 (N = 2,308) and in July of 1987 (N = 2,095) provide evidence that misinformation about AIDS transmission and negative attitudes toward homosexuals are strong predictors of support for stringent restrictions of persons with AIDS. The findings also suggest that several background factors, in particular, education and political liberalism, may also play decisive roles in influencing levels of support for restricting those infected with the AIDS virus.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Pathogenesis of hair infection and black dots in tinea capitis caused by Trichophyton violaceum: a histopathological study.

The majority of tinea capitis in southern Taiwan occur in adult women and are caused by Trichophyton violaceum. We report the histopathological findings of a series of 10 cases of tinea capitis caused by T. violaceum, the largest such study to date. Our study provides new information regarding the process of hair infection, mechanism of black dot formation, and chronicity of infection caused by this fungus. The cuticle remains intact. The fungi enter the proximal cortex where the cuticle is immature. They then colonize the proximal keratinized cortex and generate septate hyphae which transform gradually into arthrospores as they are carried upwards by the growing hair. At the infundibular level, the hair cortex is almost completely replaced by spores and swells, impeding further exit of the growing hair and causing the already weakened hair to coil up inside the infundibulum, forming a black dot. In one patient who had infection for more than 20 years, there were changes suggestive of cyclic reinfection of the same follicles which might contribute to the chronicity of the infection.

Adolescent↗
PubMed1992

Cutaneous alternariosis in association with scabies or iatrogenic Cushing's syndrome.

Cutaneous alternariosis is rare. Most infections occur in immunocompromised hosts. We report the first three cases in Taiwan. The patients were elderly farmers residing in Tainan. They developed indolent, erythematous, ulcerated or crusted papules, plaques or pustules over the extensor aspect of the forearms or hands. Pure colonies of Alternaria sp were isolated from biopsy specimens in each case. The diagnosis was confirmed by detecting pleomorphic fungal elements in the dermis within suppurative, granulomatous infiltrates. All three patients were immunocompromised. They showed a negative reaction to an intradermal test of seven common antigens. Cases 2 and 3 had iatrogenic Cushing's syndrome. Cases 1 and 3 had extensive scabies, which in Case 1 was of the Norwegian type. To the best of our knowledge, scabies associated with alternariosis has not been reported previously. The infection showed spontaneous regression in Case 1; in Case 2, it resolved after seven weeks of intralesional amphotericin B at a dose of 1 mg/mL twice a week.

Aged↗
PubMed1991

Inhibition of microtubule assembly is a possible mechanism of action of mitoxantrone.

We have found that mitoxantrone can inhibit the polymerization of brain tubulin in a dose dependent manner. MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosine-triphosphatase (GTPase) activity nor could it compete with vinblastine (VB) and colchicine (Col) for tubulin binding sites. Furthermore, MXT (0.1-10 microM) is antiproliferative to cold-treated (0 degree C) epithelial cells after only brief exposure (30 min). These results indicated that MXT is a microtubule inhibitory agent and can exert its anticellular effect through modulation of microtubule assembly.

Animals↗
PubMed1991

Tinea capitis in adults in southern Taiwan.

We report the clinicomycologic study of 27 culture-proven cases of tinea capitis from southern Taiwan during the years 1988 to 1990. The series is notable for its predominance of adults (63%), of women (89%), and of Trichophyton violaceum infection (74%). The age distribution was clearly bimodal; the median age was 6 years for children and 56 years for adults (older than 18 years). Whether or not these findings represent a new trend of tinea capitis in southern Taiwan remains to be determined. Clinically, our cases of black-dot ringworm caused by T. violaceum often presented with subtle changes of scaling, hair loss, and black dots. The keys to the correct diagnosis are (1) a high clinical index of suspicion with careful inspection of the scalp for the presence of black dots, and (2) microscopic examination and culturing of the black dots or plucked hairs.

Adolescent↗
PubMed1991

Alopecia syphilitica, a simulator of alopecia areata: histopathology and differential diagnosis.

Alopecia syphilitica (AS) may be "moth-eaten" or diffuse, clinically, and be confused with alopecia areata (AA) or other alopecias. The English language literature contains scant information regarding the histopathology of AS, and the resemblance between AS and AA has not been given adequate recognition. We report the histopathological findings of AS from nine patients with secondary syphilis and acute hair loss. The alopecia was moth-eaten in four patients and diffuse, but slightly moth-eaten, in five. Microscopically, the dermoepidermal interface was not involved. The numbers of hair follicles were diminished, with increased numbers of catagens and telogens. Lymphocytic infiltration was present around the hair bulbs and fibrous tracts in eight cases. Plasma cells were present in four biopsies. Other less common findings included lymphocytes in the isthmus, parabulbal lymphoid aggregates, and granulomatous infiltrate in the upper dermis. The findings, save for the follicular changes, resembled those of macular/maculopapular syphilides outside the scalp. With the follicular changes, the overall patterns resembled AA closely. The modified Steiner stain did not reveal spirochetes in any of our cases and failed to differentiate between AS and AA. Comparing the AS cases to 13 cases of AA, we found only a few differentiating features. The presence of peribulbal eosinophils strongly suggests AA. Without peribulbal eosinophils, the presence of plasma cells, abundant lymphocytes in the isthmus, or parabulbal lymphoid aggregates suggests AS.

Adult↗
PubMed1991

In vivo stimulation of myelopoiesis in cyclophosphamide-treated mice by purified human GM-CSF.

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) secreted by a hepatoma cell line, HA22T/GVH, was purified and assessed for its effects in vivo on blood leukocytes and bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in ICR mice pretreated with a sublethal dose of cyclophosphamide (cytoxan). The hGM-CSF preparations were natural and had no detectable endotoxin. Five days after the administration of 300 mg/kg cytoxan, severe leukopenia with marked myelopoietic suppression was induced. The cytoxan-treated mice were then injected intraperitoneally with 10,000 units of purified hGM-CSF/mouse daily for three days. Leukopenia was totally abrogated and the leukocyte number greatly increased to a level 2- to 3-fold higher than in GM-CSF-uninjected mice. Differential white cell count showed that the subpopulations of leukocytes responsive to hGM-CSF stimulation were mainly of neutrophils and monocytes, while the lymphocytes remained unaffected. Meanwhile, in the bone marrow, hGM-CSF administration induced an apparent (3-fold) increase in the number of myeloid progenitor cells, CFU-GM. However, the effect in vivo of a single hGM-CSF injection could only maintain for 48 hrs. In addition, the loss in body weight caused by cytoxan was less in the mice with subsequent hGM-CSF than those without CSF. These results suggest that injection of GM-CSF can effectively reconstitute the cytotoxic drug-damaged myelopoiesis without apparent in vivo toxic reaction.

Animals↗
PubMed1991

Quantitative and morphological changes of Langerhans cells in Bowen's disease from patients with chronic arsenicism.

Langerhans cells (LCs) are considered to be responsible for the immunologic presentation of tumor-associated antigens and play a role in the elimination of neoplastic clones. Ultraviolet light B can cause dysfunction and loss of LCs. Both the number and dendritic morphology of LCs are known to be diminished in squamous cell carcinomas from sun-exposed skin. The effects of arsenics on LCs are unknown. Using an OKT-6 monoclonal antibody to stain intraepithelial LCs, we compared their number and morphology in Bowen's lesions and in the perilesional skin from sun-protected sites in ten patients with chronic arsenicism. There was a significant reduction in the numbers of LCs in the Bowen's lesions as compared to the perilesional skin specimens. Loss of dendrites was observed in all Bowen's lesions and in seven of the perilesional skin specimens. Ultrastructurally, the LCs showed an absence of dendrites, but the Birbeck granules were preserved. Since the specimens were not from sun-exposed skin in our study, the findings may be related to chronic arsenic intoxication. The morphologic alteration of LCs observed in the perilesional skin further suggests an arsenic-related systemic dysfunction of the LCs, which in turn may contribute to the development of skin cancers in these patients.

Aged↗
PubMed1991

Effect of lipopolysaccharide on the production of colony-stimulating factors by the stromal cells in long-term bone marrow culture.

The production of colony-stimulating factors (CSFs) by murine bone marrow stromal cells was studied with Dexter long-term bone marrow culture (LTBMC). For induction of CSF release, various concentrations (0.5-40.0 microgram/ml) of bacterial lipopolysaccharide (LPS) were added to nonrecharged 3-week-old LTBMCs consisting of an intact or macrophage-depleted adherent cell layer. The depletion of monocytes/macrophages from freshly prepared bone marrow cell suspension was performed by carbonyl-iron incorporation before establishment of LTBMC. The supernatants (Sup) of normal LTBMCs contained a low level of macrophage colony-stimulating factor (M-CSF) that was produced by the adherent cells but not by the nonadherent cell elements. No colony inhibitor was found in the Sup of LTBMCs, whereas a colony-promoting activity (CPA) was detected in medium conditioned by the adherent marrow cells (AC-CM). CPA could enhance the colony formation of myeloid progenitor cells when used in combination with recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF). The production of CSFs peaked at about 24 h after refeeding, but it then declined to only half the optimal activity at the end of the week. Addition of LPS to the intact LTBMC invariably increased the production of a GM-CSF-like cytokine. The release of this cytokine was dose dependent and peaked at a dosage of 20 micrograms/ml of LPS at 24 h after treatment. In contrast, macrophage-depleted marrow-adherent cells failed to respond to LPS for CSF secretion. These results suggest that LPS can stimulate marrow macrophages to directly release CSF or to potentiate the production of CSF by other stromal cells.

Animals↗
PubMed1990

Induction of thymidine kinase activity and clonal growth of certain leukemic cell lines by a granulocyte-derived factor.

Normal polymorphonuclear neutrophils (PMNs) constitutively secrete a mediator designated granulocyte-derived factor (GDF) that can enhance the uptake of 3H-thymidine (3- to 20-fold) by the molt-3, CTV-1, and K562 leukemic cell lines in a dose-dependent manner. GDF is heat labile (56 degrees C for 30 minutes) and acid labile (pH 2.0) and is sensitive to treatment with bacterial protease type IV. Our preliminary studies suggest that GDF is non-dialyzable (molecular weight cutoff, 12,000), binds to diethylaminoethyl (DEAE), and has an apparent molecular weight (mol wt) of about 40 Kd. Production of GDF is unaffected by treatment of PMN with activating agents (interferon gamma, OK432, phorbol ester, calcium ionophore, poly I:C) or metabolic inhibitors (actinomycin-D and cyclohexamide), suggesting that GDF is constitutively secreted. Despite the marked enhancement of 3H-thymidine uptake, cell number and the rate of DNA synthesis in GDF responsive cultures remain unchanged. In contrast, the clonogenic efficiency of the responsive cells is greatly increased in the presence of GDF. These phenomena occur in parallel to an amplification of the level of thymidine kinase activity in the sensitive cells. GDF is distinct from a panel of different lymphokines and monokines in antigenicity and biochemical and functional characteristics, and is possibly a novel cytokine that can alter the pattern of DNA synthesis and growth characteristics of certain hematopoietic cells. However, its biologic and physiologic significance remains to be determined.

Biological Transport↗
PubMed1989

Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor.

T lymphocytes are predisposed to recognition of foreign protein fragments bound to cell-surface molecules encoded by the major histocompatibility complex (MHC). There is now compelling evidence that this specificity is a consequence of a selection process operating on developing T lymphocytes in the thymus. As a result of this positive selection, thymocytes that express antigen receptors with a threshold affinity for self MHC-encoded glycoproteins preferentially emigrate from the thymus and seed peripheral lymphoid organs. The specificity for both foreign antigen and MHC molecules is imparted by the alpha and beta chains of the T-cell antigen receptor (TCR). Two other T-cell surface proteins, CD4 and CD8, which bind non-polymorphic regions of class II and class I MHC molecules respectively, are also involved in these recognition events and play an integral role in thymic selection. In order to elucidate the developmental pathways of class II MHC-restricted T cells in relation to these essential accessory molecules, we have produced TCR-transgenic mice expressing a receptor specific for a fragment of pigeon cytochrome c and the Ek (class II MHC) molecule. The transgenic TCR is expressed on virtually all T cells in mice expressing Ek. The thymuses of these mice contain an abnormally high percentage of mature CD4+CD8- cells. In addition, the peripheral T-cell population is almost exclusively CD4+, demonstrating that the MHC specificity of the TCR determines the phenotype of T cells during selection in the thymus.

Animals↗
PubMed1989

Uterine malignancy developing after long term use of IUCD additional report of 2 cases: endometrial stromal sarcoma and leiomyosarcoma.

In our 2 previous papers published in this Journal, we had 5 cases of uterine malignancies developing after long term use of IUCD's. In the present paper 2 cases of such association are to be added. One case ATH with right adnexectomy was performed for persisting vaginal bleeding after 22 years of Lippes Loop application and recurrence 8 years after the first operation. Pathological diagnosis is endometrial stromal sarcoma. The other case is a leiomyosarcoma developing after 25 years of Lippes Loop application. Although no cause and effect relationship between IUCD use and uterine malignancy in human beings has been proved, the increase in such cases suggests to us that long term application should be avoided, particularly in view of the positive animal experiments. The successive detection of such cases in a relatively short period of time prompts us to make further studies to gain a deeper insight into such associations.

Female↗
PubMed1989

The skin manifestation of acute graft-versus-host disease: clinical and pathological analysis.

We report 11 cases of acute graft-versus-host disease (GVHD); 10 occurred after bone marrow transplantation (BMT) and one following transfusion of nonirradiated whole blood in a patient with severe combined immunodeficiency (SCID). According to the Seattle Classification, 5 cases were of Grade III, 2 Grade II, and 4 Grade I. The skin rash developed between the 6th to 47th day (22 +/- 12 day) after transplantation or transfusion, and was usually manifested initially as erythematous macules or papules in the neck or upper chest. The rash resolved in scaling or became purpuric, pigmented or erythrodermic in severe cases. The grading of skin pathology correlated well with clinical severity of GVHD. Four of the five who had advanced GVHD (Grade III) died. In all 4 cases but one (the SCID case), the skin pathology showed extensive basal vacuolization and multiple dyskeratotic cells. None of the others with mild or focal basal vacuolization and few dyskeratotic cells progressed into advanced GVHD. Three of the 5 cases with advanced GVHD received an underdose of cyclosporin A. These results suggest that severe GVHD carries a poor prognosis and an adequate dose of cyclosporin A is important in alleviating the severity of GVHD and reducing the mortality. The sero-virologic study performed during the skin rash period was negative, suggesting that the skin rash following BMT is mainly caused by GVHD and always precedes intestinal or hepatic manifestations.

Adolescent↗
PubMed1988

Selection of amino acid sequences in the beta chain of the T cell antigen receptor.

The induction of an immune response in mammals is initiated by specifically reactive T lymphocytes. The specificity of the reaction is mediated by a complex receptor, part of which is highly variable in sequence and analogous to immunoglobulin heavy- and light-chain variable domains. The functional specificity of the T cell antigen receptor is, however, markedly different from immunoglobulins in that it mediates cell-cell interactions via the simultaneous recognition of foreign antigens and major histocompatibility complex-encoded molecules expressed on the surface of various lymphoid and nonlymphoid cells. The relation between the structure of the receptor and its functional specificity was investigated by analyzing the primary sequences of the receptors expressed by a series of T lymphocyte clones specific for a model antigen, pigeon cytochrome c. Within this set of T lymphocyte clones there was a striking selection for amino acid sequences in the receptor beta-chain in the region analogous to the third complementarity-determining region of immunoglobulins. Thus, despite the functional differences between T cell antigen receptors and immunoglobulin molecules, analogous regions appear to be important in determining ligand specificity.

Amino Acid Sequence↗