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Biomedical subjects

D Ma

Publications and source records attributed to D Ma.

At least 253 records · Page 14Linked to original sources

High dose chemotherapy and autologous bone marrow transplantation in advanced Hodgkin's disease.

OBJECTIVE: To present the use of high dose chemotherapy with autologous bone marrow transplantation as salvage therapy for advanced Hodgkin's disease in Australia. DESIGN: A prospective open study for patients whose disease was resistant to conventional treatment. SETTING: The bone marrow transplantation units of four Australian tertiary hospitals. PATIENTS: Seventeen patients (median age 30 years) entered and completed the study. The stage of the disease at initial diagnosis was I or II (seven patients), III (seven patients) and IV (three patients). Histological types were lymphocyte predominant (one), nodular sclerosis (12), mixed cellularity (three) and unknown (one). Therapy before consideration for transplantation included radiotherapy (13), mustine, vincristine, procarbazine and prednisone (MOPP--17 patients) or doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD--13 patients) and other chemotherapy regimens (five). The median interval from diagnosis to transplantation was 29 months (range, 9-178 months). The patient's disease was classified as sensitive (nine) or resistant (eight) to treatment, depending on the response to the most recent course of chemotherapy. INTERVENTIONS: Morphologically normal autologous bone marrow was harvested and cryopreserved. The conditioning regimen given was cyclophosphamide, carmustine and etoposide (14) or busulphan and cyclophosphamide (three). The marrow was then infused. MAIN OUTCOME MEASURES: Remission (complete or partial), disease-free survival and overall survival. RESULTS: Over all, 10 of 17 patients (59%) entered or remained in complete remission and four of 17 (24%) achieved partial remission. The overall actuarial survival at 30 months was 70%. Eight of the nine patients with treatment-sensitive disease (89%) remain disease-free at a median of 22 months (range, 18-29 months) after transplantation. Two of the eight patients with resistant disease (25%) are disease-free at 20 and 28 months. There was one procedure-related death from haemorrhage and four disease-related deaths at six, seven, eight and 13 months after transplantation. CONCLUSION: Autologous bone marrow transplantation may provide an effective salvage therapy in advanced Hodgkin's disease, particularly for patients with treatment-sensitive disease and a low tumour burden.

Adult↗

Third ventricular subependymal oxytocin-like immunoreactive neuronal plexus in the rat.

In a previous retrograde tracing study, a dense subependymal neuronal plexus was found along the anterior ventral third ventricle that projects to the posterior pituitary. In the work reported here, the oxytocin-like immunoreactive neurons of this plexus were studied in detail. It has a population of about 650 cells with a great wealth of dendrites. The neurons are of magnocellular neurosecretory type with long straight dendrites running parallel to the ependyma. The plexus is composed of a dorsal and a ventral part. The dorsal part consists of about 75% of the whole population and is most dense at the levels of the anterior and medial magnocellular paraventricular nuclei. Their dendrites appear vacuous in immunohistochemically stained sections and have a tendency to form fascicles. The ventral part is more sparse. The dendrites of the subependymal plexus are well organized so the anteriorly located ones tend to be directed rostrally and the posteriorly ones caudally. The functional significance of the plexus is discussed.

Animals↗

2-Aryl-3-indoleacetamides (FGIN-1): a new class of potent and specific ligands for the mitochondrial DBI receptor (MDR).

The 2 aryl-3-indoleacetamides (FGIN-1) are a new class of compounds that potently (nM) and selectively bind to glial mitochondrial diazepam binding inhibitor (DBI) receptors (MDR), previously called peripheral benzodiazepine receptors, and increase mitochondrial steroidogenesis. The high-affinity binding of FGIN-1 to MDR derivatives depends on the following chemical characteristics: 1) the dialkylation of the amide; 2) the chain length of this alkyl substitution; and 3) the halogenation of aryl groups appended to the indole nucleus. FGIN-1 derivatives do not bind to gamma-aminobutyric acid (GABAA), GABAB, glycine, glutamate, dopamine, serotonin, opiate, cholecystokinin, beta adrenergic, cannabinoid or sigma receptors. FGIN-1-27 [N, N-di-n-hexyl 2-(4-fluorophenyl)indole-3-acetamide] enters the brain, and for this reason, this FGIN-1 compound is potent and efficacious behaviorally. Like the neurosteroid 3 alpha-5 alpha tetrahydrodeoxycorticosterone (THDOC), FGIN-1-27 delays the onset of isoniazid-induced convulsions, but fails to delay the onset of bicuculline-induced convulsions. However, differently from THDOC, the FGIN-1-27 anticonvulsant action is blocked by the isoquinoline carboxamide PK 11195. In the elevated plus maze test, FGIN-1-27 inhibits neophobia manner that is antagonized by PK 11195 but not by flumazenil. Because FGIN-1-27 binds to MDR and does not bind to the GABAA receptors, it is inferred that FGIN-1-27 may act on GABAA receptors indirectly, presumably via a stimulation of neurosteroid synthesis and release from glial cells.

Acetamides↗

Immune effect of tumor-infiltrating lymphocytes and its relation to the survival rate of patients with ovarian malignancies.

Tumor-infiltrating lymphocytes (TIL) in histological sections from 94 patients with ovarian malignancies were quantitated for their relation to the prognosis of the patients. It was found that the degree of lymphocyte infiltration directly affected the patients' survival rate and also related to clinical staging of the patients, as well as grading and histologic typing of the tumor. T lymphocytes characterized by alpha-naphthyl acetate (ANAE) staining were the major cells in the stroma of ovarian malignancies. Ultrastructural study of TIL and cancer cells suggested that tumor cell degeneration is related to the effect of TIL.

Carcinoma↗

[Experiment on stability of total flavones in guanshu tablet].

This paper reports the study on the stability of total flavones in guanshu tablet by heating and accelerating method. Taking the total flavone contents of the tablet as the index, the time of validity of guanshu tablet at room temperature 25 degrees C is calculated to be 9.6 years by chemical kinetic analysis.

Drug Stability↗

Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group.

Previously untreated patients with acute nonlymphocytic leukemia (ANLL) aged 15 to 70 years were randomized to either cytosine arabinoside 100 mg/m2/d continuous intravenous (IV) infusion days 1 through 7, daunorubicin 50 mg/m2/d IV days 1 through 3 (7-3), or the same drugs intensified with etoposide 75 mg/m2/d IV days 1 through 7 (7-3-7) as induction therapy. Patients achieving complete remission (CR) received two courses of consolidation therapy (5-2 or 5-2-5) followed by maintenance therapy. Of 264 eligible patients, CR occurred in 56% of 7-3 and 59% of 7-3-7 patients; 7-3-7 significantly improved remission duration (P = .01). The median remission duration was 12 months for 7-3 and 18 months for 7-3-7. Survival was similar when the two arms were compared overall. Subset analysis performed to identify patients with the most benefit showed that etoposide significantly prolonged remission duration in younger patients (less than 55 years) with a median of 12 months for 7-3 and 27 months for 7-3-7 (P = .01). Survival appeared to be prolonged with 7-3-7 in patients aged less than 55 years, with a median of 9 months for 7-3 as compared with 17 months for 7-3-7 (P = .03). In older patients (aged greater than or equal to 55 years), 7-3-7 was more toxic, with significantly more severe [World Health Organization (WHO) grade 3 or 4] stomatitis (P = .02) and no additional clinical benefit. Hematologic toxicity for induction courses was similar, with granulocytopenia less than 0.5 x 10(9)/L for a median of 16 days per course for 7-3 and 15 days for 7-3-7. Hematologic toxicity was more severe for 5-2-5 consolidation courses (P = .003). Induction and consolidation therapy intensified with etoposide resulted in significantly improved remission duration but not survival.

Adolescent↗

A preliminary study on natural killer activity in patients with gynecologic malignancies.

A release assay of 125IUdR-labelled K562 cells as target cells was performed for measuring natural killer (NK) activity of mononuclear cells in the peripheral blood of 92 cases, including 42 healthy women, 22 patients with gynecological benign tumors, and 28 patients with gynecological malignancies. The NK activity of malignant tumor group was obviously lower than that of healthy women and of benign tumor group, suggesting that a defective NK activity was present in the patients with gynecological malignancies. The NK activity in patients with ovarian malignant tumors was much lower than in those with cervical cancer, the difference being of statistical significance. In this study the leukocyte interferon was investigated for its effects on the NK activity of peripheral blood mononuclear cells from 4 cases of gynecological malignancies. The level of NK activity ascended significantly in every case nearly to normal. The augmentation of NK activity by interferon may be used as a new immunotherapy for gynecological malignancies.

Adult↗

The effect of dnaA protein and n' sites on the replication of plasmid ColE1.

The role of the dna A protein in the replication of plasmid ColE1 and its derivatives was examined. Wild-type and mutant ColE1 plasmids were compared as to their ability to replicate in an in vitro replication system supplemented with ammonium sulfate fractionated extracts from a dnaA-overproducing strain. Synthesis on plasmid templates containing the wild-type origin of replication was stimulated 1.3-fold by addition of the dnaA-overproducing extract. A larger effect was observed after deletion of the primosome assembly site, the n' site, on the leading strand. On the latter template, synthesis was only about one-half that observed with the wild-type templates, but synthesis could be restored to normal levels by addition of the dnaA-overproducing fractions. When the n' site on the lagging strand of pBR322 was deleted, synthesis in the in vitro replication system was reduced to less than 10% of levels seen with intact templates. dnaA-overproducing extract did not restore activity since the dnaA site was also deleted on these plasmids. To verify that the observed stimulation of wild-type and leading strand n' site mutants was due to the dnaA protein, dnaA protein was purified to greater than 50% homogeneity, and antiserum was prepared. The purified protein stimulated synthesis on the plasmid templates to the same extent as the overproducing extracts, and dnaA antiserum blocked stimulation both by extracts and by the purified protein. Thus, dnaA protein, and, by inference, the dnaA recognition site at the ColE1 origin of replication seem to be important for ColE1 replication. The effect of dnaA protein is enhanced when the n'site is defective, suggesting that the dnaA protein plays a role similar to that of the proteins i, n, n', and n'' in directing primosome assembly, as proposed by Seufert, W., and Messer, W. ((1987) Cell 48, 73-78).

Bacterial Proteins↗

A noninvasive technique to assess completeness of spinal cord lesions in humans.

The effect of scalp stimulation delivered through electrodes overlying the motor cortex was evaluated in five healthy subjects and six patients with traumatic spinal cord injury. The latency to the onset of the electromyographic response was measured in the biceps brachii and abductor pollicis brevis muscles. In all the patients, latencies to the muscle (biceps brachii) whose innervation originated above the lesion were in the normal range; whereas, latencies to the muscle (abductor pollicis brevis) whose innervation originated below the lesion were prolonged. Electromyographic signals were recorded in muscles which showed no voluntary motor activity. No lateral differences in latencies were found in healthy subjects; however, in the patients, significant differences were obtained between the right and left abductor pollicis brevis muscles. The results of this study demonstrate that the spinal cord of patients with a lesion deemed to be clinically complete, contains nerve fibers which descend through the lesion and are capable of conveying impulses leading to muscle contraction.

Adolescent↗

Expression of polypeptide segments of the human complement component C3 in E. coli: genetic and immunological characterization of cDNA clones specific for the alpha-chain of C3.

The third component of complement C3 and its fragments have a central role in a variety of host defense mechanisms. The identification of functionally relevant C3 domains is important because of the marked functional versatility of the C3 molecule. Several human C3 cDNA clones from a human liver cDNA library were isolated and characterized. A bacterial expression vector system was used to express cDNA clones that were identified by an immunological screening procedure. The C3 cDNA clones produced in E. coli the hybrid proteins consisting of cro-beta-galactosidase and polypeptide segments of human C3, as revealed by Western blotting with antisera to human C3. The C3 moiety of the hybrid proteins had a m.w. of up to 46.000. Polyclonal antibodies against the C3 segments expressed by one of the C3 cDNA clones (ReC3-1) have been raised in mice and rabbit, and in addition, a monoclonal antibody was produced. The antisera and the monoclonal antibody reacted in Western blotting analysis selectively with the alpha-chain, but not the beta-chain of human C3. Restriction mapping of the different cDNA clones was performed, and revealed that the different clones were partially overlapping. The ReC3-1 cDNA clone included a 0.7 kb noncoding region at the 3' terminal end of the C3 cDNA. One of the restriction sites (Hind III) identified in the ReC3-1 cDNA clone was not present in the recently published sequence of human C3 cDNA. This difference in nucleotide sequence provides direct evidence for C3 polymorphism at the DNA level. The combination of immunologic procedures with recombinant DNA methodology should facilitate additional analysis of the structure-function relationship of the C3 molecule.

Animals↗

Human B cell development. I. Phenotypic differences of B lymphocytes in the bone marrow and peripheral lymphoid tissue.

The phenotype of B lineage cells (TdT+, pre-B, IgM+, IgD-, and IgM+,IgD+) in infant and adult human bone marrow was compared with that of B cells seen in peripheral tissues such as tonsil and blood. The range of B cell-associated antibodies used included four reagents with greater than 90% reactivity on peripheral B cells: RFB4 and To15 (both p135, corresponding to CD22), RFB6 (p140 corresponding to CD21), and Y29/55, a unique B cell-specific antibody. In addition, AL-1, an antibody with virtually no reactivity against peripheral B cells was also used. The BM cell subpopulations were heterogeneous in respect of antibody reactivity. The TdT+, pre-B and IgM+, IgD- cells were AL-1+ but did not express membrane antigens recognized by the antibodies To15, RFB4 (CD22), and RFB6 (CD21). TdT+, pre-B cells, and 50% of IgM+, IgD- BM B cells were also unreactive with antibody Y29/55, the other 50% being Y29/55+. In contrast, the IgM+,IgD+ BM B cells, like peripheral B cells, were positive with antibodies To15, RFB4, RFB6, and Y29/55, but reacted only in small numbers with AL-1. The orderly differentiation-linked display of these antigens was also suggested by the findings that normal TdT+, pre-B, and IgM+,IgD- cells expressed the To15 and RFB4 (CD22) antigens in their cytoplasm (in the Golgi region). This observation was confirmed in malignant common acute lymphoblastic and pre-B blast cells, as well as in the corresponding permanent cell lines KM3 and NALM-6. In these lines the membrane expression of To15 and RFB4 could be induced by phorbol ester during a 48 to 72 hr culture period.

Adolescent↗

cis-acting mutations that affect rop protein control of plasmid copy number.

A number of pMB1 derivatives provide a trans-acting function that can suppress lethal runaway replication of a temperature-sensitive copy-number mutant of NTP1. Deletion analysis indicates that the region of the pMB1 genome that contains the rop gene is required for this suppression. Mutant derivatives of the temperature-sensitive copy-number mutant plasmid whose conditional lethal phenotype is not suppressed in trans by the region encoding the rop gene have been isolated. These rop-insensitive derivatives contain single nucleotide changes within the RNA I coding region.

Bacterial Proteins↗

Iodine trapping and organification in patients with chronic renal failure.

In vitro thyroid function tests were studied in 30 patients on regular hemodialysis. In addition, 8 patients (one not yet dialyzed) underwent perchlorate discharge testing and the salivary to plasma ratio of 131I was measured to identify defects in iodine uptake or organification. When compared with 35 healthy controls, uremic patients had lower total T4 (5.8 +/- 0.4 vs 8.6 +/- 0.3 micrograms/100 ml) and total T3 (81 +/- 6 vs 124 +/- 5 ng/100 ml) but T3RU was higher in dialysis patients (35.5 +/- 0.9 vs 28 +/- 0.5%, P less than 0.01). The TSH levels were not different from those of controls. The RAI uptake 1 h after perchlorate was significantly higher than the control valve (0.6 +/- 0.14 vs 0.06 +/- 0.04, P less than 0.05). Similarly, the salivary to plasma ratio of 131I was higher in patients with chronic renal failure (70 +/- 10:1 vs 40 +/- 4:1). It is concluded that there is altered iodine trapping in CRF patients but iodine organification appears to be normal.

Adult↗

In vitro dissolution of dapsone.

Los normal samples of dapsone (DDS) were prepared in which the geometric mean diameter ranged from 20 to 50 micron while the geometric standard deviation was in the range 1.62 to 1.88. Using a simple in vitro flow-through dissolution cell at 37 degrees C, the data obtained were found to fit the Hixson-Crowell cube root dissolution law up to a critical time, Tc, where a distinct break occurred. Such a biphasic phenomenon has been predicted by other workers and is related to the time at which the smallest particles present have undergone dissolution. The initial slopes of the cube root dissolution plots were shown to be directly related to the reciprocal of the geometric mean diameter.

Dapsone↗