Efferent modulation of pre-neural and neural distortion products.

Distortion product otoacoustic emissions (DPOAEs) and distortion product frequency following responses (DPFFRs) are respectively pre-neural and neural measurements associated with cochlear nonlinearity. Because cochlear nonlinearity is putatively linked to outer hair cell electromotility, DPOAEs and DPFFRs may provide complementary measurements of the human medial olivocochlear (MOC) reflex, which directly modulates outer hair cell function. In this study, we first quantified MOC reflex-induced DPOAE inhibition at spectral fine structure peaks in 22 young human adults with normal hearing. The f1 and f2 tone pairs producing the largest DPOAE fine structure peak for each subject were then used to evoke DPFFRs with and without MOC reflex activation to provide a related neural measure of efferent inhibition. We observed significant positive relationships between DPOAE fine structure peak inhibition and inhibition of DPFFR components representing neural phase locking to f2 and 2f1-f2, but not f1. These findings may support previous observations that the MOC reflex inhibits DPOAE sources differentially. That these effects are maintained and represented in the auditory brainstem suggests that the MOC reflex may exert a potent influence on subsequent subcortical neural representation of sound.

[Effects of interferon on the cell cycle of human hepatoma HLF cells analyzed by flow cytometry].

Growth inhibition by interferon (IFN) was investigated in human hepatoma HLF cells by use of flow cytometry to study the cell cycle. INF-alpha or -beta inhibited growth more than IFN-gamma. Use of either IFN-alpha or -beta and IFN-gamma at the same time inhibited growth more than with any one kind of IFN, but use of IFN-alpha and -beta together did not cause much inhibition. IFN inhibited growth by causing cells to accumulate in the S phase instead of moving on to the G2 phase. Accumulation in the S phase was less with IFN-gamma than with -alpha or -beta. It increased with the combination of IFN-alpha or -beta with IFN-gamma, but not with the combination of IFN-alpha and -beta.

Caffeine-induced reorganization of DNA replicating system occurs on or near nuclear matrix in HeLa cells.

Since caffeine reorganizes the DNA replicating system, with several consequences, we studied the effect of caffeine on the DNA replication which normally occurs on or near the nuclear matrix in a variety of eukaryotic cells. When HeLa cells, treated with or without the DNA-damaging agent, neocarzinostatin, were postincubated in the presence or absence of caffeine and then pulse-labeled with [3H]thymidine, the DNA remaining tightly associated with the matrix was enriched in the newly synthesized DNA at the same level as that seen in untreated cells. The nuclear matrix-bound DNA polymerase alpha activity was also the same in these cells. Therefore, in the presence of caffeine, DNA replication, with or without DNA damage, also occurs on or near the nuclear matrix, as is the case in normal DNA replication.

[Non-Hodgkin's malignant lymphoma with central nervous involvement--report of 7 cases].

We encountered 7 non-Hodgkin's lymphomas involving the central nervous system (CNS) among 78 cases of lymphomas seen at the 3rd Dept. of Internal Med. between 1965 and 1980; 5 cases were diffuse histiocytic lymphomas (DH) and 2 were diffuse poorly differentiated lymphomas (DPDL). The age ranged from 27 to 66 years, there were 6 males and 1 female. In 4 cases, CNS involvement was the presenting symptom at the time of diagnosis of lymphoma. The diagnostic procedures in CNS lymphoma included complete neurological physical examination by a neurologist, spinal fluid cytology, surface marker study on lymphocytes of spinal fluid, if possible, computed tomography scan, and myelogram if spinal cord compression was suspected. The prognosis of patients with CNS involvement by lymphoma was poor even if early diagnosis was made. The conventional therapy for CNS lymphoma included cranial irradiation, systemic chemotherapy, and intrathecal instillation of methotrexate and/or cytosine arabinoside, or a combined modality; however, these treatments were only effective temporarily.

[The combination chemotherapy of vincristine, methotrexate, ACNU, and adriamycin for anaplastic carcinoma of the lung].

Recent advances in the chemotherapy of malignant diseases, particularly, in hematopoietic malignancies, has opened oncologists' eyes in wonder, whereas the chemotherapy of solid malignant diseases including the carcinoma of the lung is not satisfactory compared with the results of other modalities such as radiotherapy and surgery. The chemotherapy, however, gradually becomes a great importance because the majority of the cases of lung cancer is that of advanced one. Between June, 1974 and December 1980 we experienced 54 inoperable cases of lung cancers among which there were 11 cases diagnosed as an anaplastic carcinoma. The combination chemotherapy of vincristine (1 mg/body, iv, day 1), methotrexate (30 mg/body, iv, day 1 and 5), ACNU (100mg/body, iv, day 2) and adriamycin (40mg/m2, iv, day 2) was employed. Vincristine and methotrexate were given every 3 weeks and ACNU and adriamycin were repeated every 9 weeks. If the moderate degree of neuropathy due to vincristine occurred it was suspended and methotrexate was stopped if WBC was less than 2000/mm or if patients were suffered from stomatitis which disturbed their swallowing. According to the response criteria of Koyama-Saito 4, cases were responded and one of them survived 17 months after the initiation of above 4-drug combination chemotherapy, although she received another combination chemotherapy because of the relapse of disease. The combination chemotherapy of ACNU and adriamycin was tried to utilize the advantage of their time different effects on the bone marrow suppression and to cover heterogenous histopathological diagnosis of anaplastic carcinoma. The heterogeneity of anaplastic carcinoma included undifferentiated squamous cell carcinoma, adenocarcinoma, large cell carcinoma and even small cell carcinoma. In taking consideration of these points, the drug-combination was designed. Clinically, however, the long resting period made the tumor regrow in some cases due to severe delayed myelosuppression by the combination of ACNU and adriamycin. Thus, more cautiously-designed combination should be considered.

Phlebitis associated with the intravenous use of cephapirin and cephalothin in the combination therapy of antibiotics.

Phlebitis related to antibiotic infusion is one of the most frequent causes of morbidity in the debilitated patients with severe infection. There are a number of causes of infusion-induced phlebitis such as pH of intravenous fluid, needle used, and contamination of venipuncture site. Vein used to play an important role, particularly in patients with granulocytopenia receiving intravenous infusion. Cephalothin is an effective antibiotic in the treatment of granulocytopenic infection and is widely used currently. When cephalothin was introduced commercially, the frequency of phlebitis was as high as 50%. The main reason was thought to be acidity of the antibiotic solution. The cephalothin solution used currently is neutral in pH, but prevention of phlebitis is still not perfect. In contrast, cephapirin recently developed cephalosporin antibiotic, which resembles cephalothin in the antimicrobial activity and pharmacological properties caused less phlebitis than cephalothin in initial clinical studies. The patients receiving chemotherapy for malignant diseases frequently die of infections. A cephalosporin antibiotic is administered intravenously for a prolonged time in the presence of thrombocytopenia, and under such circumstances, other antibiotics such as carbenicillin (CBPC) and aminoglycoside are usually used in combination. The influence of these antibiotics injected through the same vein must be considered, but the possibility of phlebitis due to CBPC and aminoglycoside is negligible. In the present clinical study, 24 granulocytopenic patients were treated with the combination of antibiotics, cephapirin-carbenicillin-amikacin and cephalothin-carbenicillin-amikacin. Besides the clinical effect of the antibiotics, the incidence and severity of phlebitis were studied.