Hemopoietic growth factors regulate the survival of human basophils in vitro.

Human basophils were purified from normal peripheral blood, using density gradient followed by negative panning selection. We tested the effects of hemopoietic growth factors on the survival of these basophils in vitro. In the absence of exogenous factors, basophils (purity greater than 90%) decreased in number rapidly. At day 7 only 11% of the cells remained alive in cultures; less than 1% of cells survived at day 14. Interleukin (IL)-3 maintained numbers of viable cells; cell viability was 67% at day 7 and 45% at day 14. Granulocyte-macrophage (GM)-colony-stimulating factor (CSF) exhibited slight effect on the survival; 33% of cells remained at day 7. Other growth factors including granulocyte (G)-CSF, macrophage (M)-CSF, and IL-4 had no significant effect on the survival of basophils at all. Morphological and functional characterization of cells maintained by IL-3 revealed that they belonged to the basophil lineage. These observations indicate that normal basophils possess functional receptors for IL-3 and GM-CSF and that both factors modulate immediate- and delayed-type hypersensitivity reactions by prolonging the life span of basophils.     

Fundamental morphological changes in human olivary hypertrophy.

Morphological features of neurons in human inferior olivary nuclei were studied in 6 autopsied patients with dentato-olivary pathway lesions, who had survived for between 6 days and 15 months. Central chromatolysis-like neuronal enlargements were already present in the acute cases. Electron microscopy revealed round, homogeneous and electron-dense granules, varying in diameter from 0.15 micron to 2.5 microns, occurring frequently within the rough endoplasmic reticulum (ER) in the chromatolytic neurons of all 6 patients. No similar granules were observed in 6 controls. The vacuoles were due to dilatation of the rough ER, and often contained floccular materials. Neurofilamentous hyperplasia in the neurons was more frequently seen in the chronic cases. These findings suggest that the fundamental changes in the neurons in olivary hypertrophy occur within the rough ER.     

Alpha 1-antichymotrypsin has a trophic effect on hippocampal neurons in vitro

alpha 1-Antichymotrypsin (ACT) has been reported to be present in senile plaques, and ACT level is elevated in the sera of patients with Alzheimer's disease. We found that ACT has a neurotrophic activity in vitro, i.e., it enhanced neuronal survival under the culture conditions used. Hippocampal neurons were cultured in chemically defined medium containing ACT at various concentrations. In order to evaluate the number of surviving neurons semiquantitatively, enzyme immunoassay for microtubule-associated protein2 (MAP2) was carried out using anti-MAP2 antibody. Cells cultured in medium containing 4 micrograms/ml of ACT showed 1.8-fold more neurotrophic activity than those cultured without ACT.     

An autopsy case of acquired immune deficiency syndrome (AIDS) with preceding aplastic anemia

A case of acquired immunodeficiency syndrome (AIDS) with preceding aplastic anemia is reported. The patient was a 36 year old female who had been diagnosed as having aplastic anemia 10 years before and thereafter had received multiple transfusions. Human immunodeficiency virus (HIV)-seropositivity was revealed 10 months prior to her death, but no particular clinical signs indicating HIV infection, pre-AIDS or onset of AIDS were recognized before serological diagnosis, although the slow progression of leukopenia was noted along with thrombocytopenia. Her general condition deteriorated during the last 10 months accompanied by an acute decrease In the CD4/CD8 ratio. Autopsy revealed full-blown AIDS: systemic aspergillosis, progressive multifocal leukoencephalopathy, Epstein-Barr virus-related B cell lymphoma arising in the diaphragm and severe lymphocyte depletion in the lymph nodes and spleen. Markedly hypo-plastic bone marrow was considered to be primarily attributable to the aplastic anemia but the affection of AIDS was not excluded. The possible transmission route of HIV and the effect of the preceding aplastic anemia on the infection and clinical course of AIDS are discussed.     

Polymer conformation and NMR chemical shifts, 9. Poly(α-methylene-γ-butyrolactone)

The conformational energies of poly(α-methylene-γ-butyrolactone) are calculated and compared with those of poly(methyl methacrylate). In spite of the structural resemblance of these two polymers, the patterns of the energy contour maps are clearly distinguishable from each other; the energy barriers between rotational isomeric states are appreciably higher in the former than in the latter polymer. The calculation indicates large non-bonded interactions between the protons in one lactone ring and those in the adjacent lactone rings. The broad NMR spectrum of poly(α-methylene-γ-butyrolactone) apparently reflects its rigid conformational structure. ¹H and ¹³C NMR chemical shifts are calculated by theoretical shielding calculations based on conformational analysis. Much lower magnetic field resonances of the O? CH₂ and α-CH₂ carbons in poly(α-methylene-γ-butyrolactone) as compared with those of the O? CH₃ and α-CH₃ carbons in poly(methyl methacrylate) are well reproduced by the calculation. The shift to lower magnetic field is mainly attributed to paramagnetic shielding derived from the interaction between O? CH₂ carbon and α-CH₂ carbon. Tacticity- and conformation-dependent ¹H and ¹³C NMR chemical shifts of poly(α-methylene-γ-butyrolactone) are well interpreted on the basis of the conformational analysis.     

Results of definitive radiotherapy with concurrent chemotherapy for maxillary sinus carcinomas with neck lymph node metastasis

The purpose of this study was to describe the results of definitive radiotherapy (RT) with concurrent chemotherapy for maxillary sinus carcinomas (MSCs) with neck lymph node metastasis to clarify its limitation. Local control (LC), progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan–Meier method and were compared between subgroups using the log rank test. Toxicity was classified using common terminology criteria of adverse events version 5.0. Eighteen patients with inoperable MSC with neck lymph node metastasis including 12 men and 6 women with a median age of 67 years were analyzed. The histologic diagnoses were as follows: 16 patients had squamous cell carcinomas and 2 had other histology. Four patients had stage T3 MSC, 6 had T4a and 8 had T4b. Among 18 patients, 7 received concurrent systemic chemotherapy and 11 received selective arterial chemo-infusion. The median follow-up period was 17 months. The 2-year LC, PFS and OS rates for the entire cohort were 34, 31 and 46%, respectively. No significant differences were observed for LC, PFS and OS rates between systemic chemotherapy and selective arterial chemo-infusion cohorts. Grade 3 or higher acute toxicity, including both non-hematological and hematological, was observed in nine patients (50%), while no grade 3 or higher late toxicity was observed. In conclusion, we described the results of definitive RT for MSCs with neck lymph node metastasis. Local recurrence of primary tumor was a frequent pattern of failure and it should be addressed in future study.     

Infiltration and tissue concentration of intravesically instilled (2"R)-4'-O-tetrahydropyranyladriamycin or adriamycin in rat bladder tumor induced by BBN

Rats with bladder tumor induced by BBN were treated by intravesical instillation of 0.8 mg of (2"R)-4'-O-tetrahydropyranyladriamycin (THP) (9 rats) or adriamycin (ADM) (8 rats) dissolved in 0.2 ml of distilled water. Thirty minutes later, the bladder was removed surgically. Rats without the tumor received the same treatment of THP (8 rats) or ADM (9 rats). THP and ADM infiltrations to the normal bladder tissue and the tumor were estimated by the use of the photonic microscope system, since both drugs were known to emit characteristic fluorescence. It was found that infiltration of THP to the tumor tissue was more prominent in amounts and deeper than that of ADM, while smaller amounts of THP infiltrated into the normal mucosa compared to ADM. The fact might explain the clinical finding that THP instilled intravesically in half a concentration of ADM showed the same effect on the tumor as ADM. Subsequently, tissue concentrations of THP and ADM were estimated by high performance liquid chromatography. Either THP or ADM was instilled intravesically for 30 minutes to 6 rats with bladder tumor. Similarly, either THP or ADM was instilled in 5 rats without the tumors. Contrary to the result of the photonic microscope system, the tissue concentration of THP was not different from that of ADM not only in the tumor tissues but also in the normal bladder ones. Furthermore, the tissue concentration of both drugs in the normal bladder was higher than that in the bladder tumor.(ABSTRACT TRUNCATED AT 250 WORDS)     

A clinicopathologic evaluation of "depth" in cases of endometrial adenocarcinoma

A total of 573 cases of endometrial adenocarcinomas, composed of patients that had been hysterectomized from 1949 to 1985 at the Cancer Institute Hospital in Tokyo, have been clinicopathologically investigated to evaluate the degree of the myometrial invasion, meaning the "Depth" as a postoperative prognostic factor of this type of cancer. These patients were classified into groups, depending on the depth of the invasion. The Depth d group, showing a myometrial invasional depth of over two-thirds of the uterine wall, revealed a rate of 61.3% of the lymph node metastasis positive cases, and accounted for 50.0% of the postoperative survivals. These values were statistically worse, when compared to those of the Depth a to c groups, which showed less invasional depth. Thus it was concluded that "Depth" is an important prognostic factor in cases of an endometrial adenocarcinoma.     

Induction of apoptosis in ovarian carcinoma cell line by glucocorticoids, and sex steroid hormones

We investigated the interactions in the KOC-2s human ovarian cancer cells on the effect of glucocorticoids, and sex steroid hormones in ovarian carcinomas. At 10(-8) M to 10(-5) M, dexamethasone (Dex) decreased the number of cells by 75-80% (p<0.001). At 10(-8) M and 10(-7) M, hydrocortisone (HC) decreased the number by 50% (p<0.01); at 10(-6) M and 10(-5) M, the decrease in number of cells was 65%. The E-2 decrease in number was not statistically significant. Progesterone (PG) showed at 10(-8) to 10(-6) M an increase in number of cells, however, at 10(-5) M it was decreased by 70% with a significant difference (p<0.001). Dex (10(-8)-10(-5) M), HC (10(-8)-10(-5) M) and PG (10(-5) M) produced internucleosomal cleavage of DNA into fragments with multiples of 180 to 200 bp. The TNF-alpha with addition of Dex (10(-8)-10(-5) M) and HC (10(-8)-10(-5) M) was increased after 24 h, 48 h (p<0.001); however, gradually decrease after 72 h. When PG (10(-8)-10(-5) M) was added, PG (10(-5) M) increased the secretion of TNF-alpha after 72 h. Our findings demonstrate that glucocorticoids, and PG directly induce apoptotic DNA fragmentation of KOC-2s cells. However, the secretion of TNF-alpha and expression of Fas antigen were totally different in these substances. These data provide a basis for future studies on the mechanisms of apoptotic effect of glucocorticoids, and PG and the therapeutic effects of these substances.