Immunoexpression of the α subunit of a guanine nucleotide-binding protein (Go) in pulmonary neuroendocrine cells and neoplasms

The α subunit of a GTP-blndlng protein, Go, was investigated in pulmonary neuroendocrine neoplasms and fetal tissues of the lung by an immunohistochemlcal method. Positive immunostaining for the α subunit of Go (Goα) was found predominantly on the cell membrane and found occasionally in the cytoplasm. Typical carcinoids were all positively stained (9/9), and small cell carcinoma showed weaker and less frequent staining (5 positive cases in 10). Atypical carcinoids were variously stained (3/4). The tendency for obvious neuroendocrine differentiation to be immunohistochemically determined in typical carcinoids and not in small cell carcinoma is also true of staining for neuron specific enolase (NSE), chromogranin A (CG-A) and synaptophysin. In the lung, Goα-immunostaining was positive not only in nerve tissues but also in the airway epithelium. In the fetal lung, serial sections immunostained for NSE, CG-A and Goα confirmed that Goα-immunoreactive cells belong to the neuroendocrine cell population. The biological significance of Goα is unclear in normal and neoplastic lung tissues, but Goα is a useful marker of neuroendocrine cells and neoplasms of the lung.     

Measurements of cerebral blood flow and metabolism in patients with Alzheimer's disease

Positron emission tomography (PET) was used to measure cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and cerebral metabolic rate of glucose (CMRglc) in patients with Alzheimer's disease. In the patients, values for CBF, CMRO2, and CMRglc have been shown to drop by 30-50% in comparison to age-matched normal controls. In the early stage (stage I), reductions in CBF and CMRO2 are prominent in the temporal and the temporoparietal cortices. In stage II, reduction in the parietal cortex also become quite prominent, and in the late stage (stage III) reduction begins prominently in the frontal cortex as well. These PET findings in Alzheimer's disease differ from those in vascular dementia, Pick's disease, and Huntington's disease. In the interrelationship among CBF, CMRO2 and higher brain function, CBF and CMRO2 decrease especially in the left frontal, the left temporal and the left parietal cortices in patients with marked language disability. On the contrary, CBF and CMRO2 decrease in the right temporal and the right parietal cortices in patients with marked apraxia and visuospatial deficits. Cerebral blood flow and metabolism are closely related to the functioning of nerve cells. Therefore we can isolate the region responsible for higher brain dysfunction and similarly evaluate the effects of treatment using cerebral blood flow and metabolism measurements.     

Correlation between the number of apoptotic cells and expression of the apoptosis-related antigens Fas, Ley and bcl-2 protein in non-Hodgkin's lymphomas

The relationship between the number of apoptotic cells and the expression of apoptosis-related antigens was examined In 56 cases of non-Hodgkin's lymphomas and in 10 cases of reactive hyperplastic lymph nodes (RHL). Apoptosis was visually quantified by the in situ end-labeling (ISEL) method, and the expression of Fas, Le^y antigens and bcl-2 protein was examined by Immunohistochemistry. The expression of Le^y antigen was observed in germinal centers of RHL and 45% of non-Hodgkin's lymphomas. The apoptotic cell count (AC) in follicular lymphomas was significantly less than that in diffuse lymphomas. The distribution pattern of apoptotic cells In follicular lymphomas was inverse to that in RHL. In follicular lymphomas, AC was lower in follicles than in inter-follicular areas. In contrast, AC was higher in follicles than in Interfollicular areas in RHL. Le^y antigen-positive lymphomas showed a significantly higher AC than the negative cases. The Fas antigen-positive lymphomas showed a higher AC than the negative cases. However, AC in bcl-2 protein-positive and negative cases was not significantly different. These results suggest that Le^y and Fas antigens appear to be involved in the apoptotic tendency of tumor cells in non-Hodgkin's lymphomas, whereas bcl-2 does not necessarily.     

Pulmonary adenoma and endocrine cell hyperplasia in Syrian golden hamster treated with 4-nitroquinoline 1-oxide

Chronic effects of 4-nitroquinoline 1-oxide (4 NQO) on the lungs of Syrian golden hamsters were studied. 4 NQO was subcutaneously injected weekly for 3 weeks at a dose of 20 mg/kg body weight. The animals were sacrificed at the 65th and 80th experimental weeks. Two cases of pulmonary adenomas were demonstrated in the 10 4 NQO-treated animals at the 80th week, and the tumor cells contained cytoplasmic lamellar inclusion bodies. In a previous study, we reported 4 NQO- induced pulmonary endocrine cell hyperplasias in the 4 NQO-treated hamster after the 20th experimental week (Jpn. J. Cancer Res., 77, 1986). In the present study, 12 pulmonary endocrine cell hyperplasias were recognized in serial sections of the 24 treated animals. The hyperplastic lesions showed positive immunoreactivity to calcitonin. The hyperplastic lesion did not develop to pulmonary endocrine cell neoplasm.     

PULMONARY ADENOMA AND ENDOCRINE CELL HYPERPLASIA IN SYRIAN GOLDEN HAMSTER TREATED WITH 4-NITROQUINOLINE 1-OXIDE

Chronic effects of 4-nitroquinoline 1-oxide (4 NQO) on the lungs of Syrian golden hamsters were studied. 4 NQO was subcutaneously injected weekly for 3 weeks at a dose of 20 mg/kg body weight. The animals were sacrificed at the 65th and 80th experimental weeks. Two cases of pulmonary adenomas were demonstrated in the 10 4 NQO-treated animals at the 80th week, and the tumor cells contained cytoplasmic lamellar inclusion bodies. In a previous study, we reported 4 NQO- induced pulmonary endocrine cell hyperplasias in the 4 NQO-treated hamster after the 20th experimental week (Jpn. J. Cancer Res., 77,1986). In the present study, 12 pulmonary endocrine cell hyperplasias were recognized in serial sections of the 24 treated animals. The hyperplastic lesions showed positive immunoreactivity to calcitonin. The hyperplastic lesion did not develop to pulmonary endocrine cell neoplasm. ACTA PATHOL JPN 38 : 1097∼1104, 1988.     

Induction of lymphokine-activated killer cells with low-dose interleukin 2 and interferon-γ in oral cancer patients

Lymphokine-activated killer (LAK) cells were induced with low-dose recombinant interleukin 2 (rIL-2) and recombinant interferon- (IFN-) in 28 oral carcinoma patients. The patients received daily intravenous injections of rIL-2 (1.2×10⁵ U/m²) and rIFN- (7.0×10⁴ U/m²), and both natural killer (NK) and LAK activities were periodically examined. A significant increase in CD16⁺CD57⁺ and CD16⁺CD57^– NK subsets was observed after the induction. An increase in the T-cell population was also found, with a significant increase in CD3⁺HLA-DR⁺, CD8⁺Leu8^–, and CD4⁺Leu8^– cells. Significant increases in NK activity, from the original level of 32.0±13.7 to 49.9±15.2%, and LAK activity, from 4.8±3.5 to 11.0±6.1%, at Day 7 were observed. Both activities were maintained at high levels during the cytokine injections, but greater enhancement of the killing activities could not be obtained subsequently. When NK and LAK activities were investigated in each subpopulation of CD3^– and CD16^– cells, no remarkable cytotoxic activity could be observed before induction in any subset without NK activity in CD3^– cells (31.1±14.3%). At Day 7, NK activity of CD16^– cells increased up to 21.4±14.9%, accompanied by an increase in CD3^–-cell activity (54.5±20.6%). LAK activities of both subsets were also enhanced, with activity at Day 7 of 6.5±5.6 and 9.4±6.6% in CD16^– and CD3^– cells, respectively. These increased activities were maintained at the same level during the induction. Phorbol myristate acetate-induced polymorphonuclear leukocyte (PMNL) O ₂ ^– generation was significantly increased, from the original 81.1±28.1 to 95.6±34.9 pmol/min/10⁴ cells, after 1 week of treatment. Protein kinase C activity in the cytosol decreased, and the activity in the membrane fraction conversely increased. No remarkable adverse effects except for mild fever were observed. Together with LAK induction ability and PMNL enhancement, with scarce toxicity, a combination of low-dose rIL-2 and rIFN- is thought to be useful in cancer treatments.     

The therapeutic effects of aspoxicillin on various infectious diseases in children

Clinical application to ascertain the effects of aspoxicillin (ASPC), a new semisynthetic penicillin antibiotic, upon several infectious diseases of children was performed in 7 cases with pneumonia, 5 cases with acute bronchitis, each case with tonsillitis, enterocolitis, urinary tract infection and suspected sepsis. ASPC was injected by drip infusion and the dosage was 63-117 mg/kg/day in 3 and 4 times a day. Clinical efficacy obtained as "excellent" was in 7 cases, "good" in 8 cases "poor" in 1 case, and efficacy rate was 93.8%. From the bacteriological point of view, eliminated in each of H. influenzae, H. parainfluenzae, group A beta-Streptococcus and unchanged in a case of E. coli. There were transient thrombocytopenia in 2 cases and eosinophilia in 3 cases.     

Change of Alkaloid Distribution in the Regenerated Plants of Duboisia myoporoides During Development

The alkaloid composition of regenerated plants from DUBOISIA MYOPOROIDES R. Br. (Solanaceae) callus was determined at various stages of development. Anabasine, nornicotine, scopolamine and hyoscyamine, which are main alkaloids in leaves of the mother plant, were analysed. The main alkaloids were not detected in the leaves of regenerated plantlets at the early stage of development, but eventually the alkaloid spectrum approached that of the mother plant at the later stage; on the way, various alkaloid spectra were found. Qualitative and quantitative differences between regenerated plantlets and seedlings with respect to alkaloid distribution were discussed.