Immuno-chemotherapy of malignant lymphoma using OK-432, a streptococcal agent

Clinical trials of immuno-chemotherapy were conducted on malignant lymphoma patients. Patients during the period from 1972 through 1977 were allocated to two groups retrospectively according to the mode of treatment, i.e., chemotherapy alone (historical control group, 35 patients) and chemotherapy with OK-432 (treated group, 15 patients). Comparisons were made of the two groups, which were homogeneous with regard to induction chemotherapy, maintenance chemotherapy, stage and histologic type of disease. The treated group had a higher remission rate, and a longer remission duration and survival than the control groups, especially in patients with Hodgkin's disease but the difference was not statistically significant owing to the limited number of cases.</p

Potential oxygen consumption and community composition of sediment bacteria in a seasonally hypoxic enclosed bay

The dynamics of potential oxygen consumption at the sediment surface in a seasonally hypoxic bay were monitored monthly by applying a tetrazolium dye (2-(4-iodophenyl)-3-(4-nitrophenyl)-5-phenyl-2H-tetrazolium chloride [INT]) reduction assay to intact sediment core samples for two consecutive years (2012–2013). Based on the empirically determined correlation between INT reduction (INT-formazan formation) and actual oxygen consumption of sediment samples, we inferred the relative contribution of biological and non-biological (chemical) processes to the potential whole oxygen consumption in the collected sediment samples. It was demonstrated that both potentials consistently increased and reached a maximum during summer hypoxia in each year. For samples collected in 2012, amplicon sequence variants (ASVs) of the bacterial 16S rRNA genes derived from the sediment surface revealed a sharp increase in the relative abundance of sulfate reducing bacteria toward hypoxia. In addition, a notable shift in other bacterial compositions was observed before and after the INT assay incubation. It was Arcobacter (Arcobacteraceae, Campylobacteria), a putative sulfur-oxidizing bacterial genus, that increased markedly during the assay period in the summer samples. These findings have implications not only for members of Delta- and Gammaproteobacteria that are consistently responsible for the consumption of dissolved oxygen (DO) year-round in the sediment, but also for those that might grow rapidly in response to episodic DO supply on the sediment surface during midst of seasonal hypoxia

8-14 translocation in a Japanese Burkitt's lymphoma.

Chromosome analysis was performed on cells obtained from the pleural effusion of a Japanese patient with Burkitt's lymphoma. Two modal chromosomal numbers were found: 45 and 46. Five different karyotypes were present, all having a t (8q-;14q+) translocation. This case illustrates that Burkitt's lymphomas of Japanese are no exception to the frequent association of this chromosomal abnormality with Burkitt's lymphomas.</p

Increased IP-10 production by blood–nerve barrier in multifocal acquired demyelinating sensory and motor neuropathy and multifocal motor neuropathy

Objective Dysfunction of the blood–nerve barrier (BNB) plays important roles in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). The aim of the present study was to identify the candidate cytokines/chemokines that cause the breakdown of the BNB using sera from patients with CIDP and MMN. Methods We determined the levels of 27 cytokines and chemokines in human peripheral nerve microvascular endothelial cells (PnMECs) after exposure to sera obtained from patients with CIDP variants (typical CIDP and multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]), MMN and amyotrophic lateral sclerosis (ALS), and healthy controls (HC), using a multiplexed fluorescent bead-based immunoassay system. Results The induced protein (IP)10 level in the cells in both the MADSAM and MMN groups was markedly increased in comparison with the typical CIDP, ALS and HC groups. The other cytokines, including granulocyte colony-stimulating factor, vascular endothelial growth factor (VEGF) and interleukin-7, were also significantly upregulated in the MADSAM group. The increase of IP-10 produced by PnMECs was correlated with the presence of conduction block in both the MADSAM and MMN groups. Conclusion The autocrine secretion of IP-10 induced by patient sera in PnMECs was markedly upregulated in both the MADSAM and MMN groups. The overproduction of IP-10 by PnMECs leads to the focal breakdown of the BNB and may help to mediate the transfer of pathogenic T cells across the BNB, thereby resulting in the appearance of conduction block in electrophysiological studies of patients with MADSAM and MMN

Combination chemotherapy of advanced non-Hodgkin's lymphoma with adriamycin, vincristine, ifosfamide and prednisolone (AVIP): a preliminary report

Eighteen patients with advanced non-Hodgkin's lymphoma other than the diffuse histiocytic type were treated with a combination of adriamycin, vincristine, ifosfamide and prednisolone (AVIP). The objective response rate was 83% (15/18); 61% (11/18) achieved complete remission. The median duration of complete remission was 11 months ranging from 2 to 39+ months. Eleven of the 18 patients are still alive during the median follow-up time of 13 months. The median survival was 14+ months for complete responders, and 9.5 months for partial and nonresponders. A myelosuppressive toxicity was well tolerated. AVIP offers some hope as treatment of advanced non-Hodgkin's lymphoma.</p

Chromosome 14q+ in a Japanese patient with Burkitt's lymphoma.

Cytogenetic studies were performed on a biopsy specimen of a jaw tumor and on a bone marrow aspirate from a Japanese patient with Epstein-Barr virus-negative Burkitt's lymphoma. A 14q + chromosome was found in cells from either source, although each contained a different clone. Other karyotypic abnormalities present in common included 2dir dup (1q) (q21 leads to q32), 3q+, 6p--, +12, +mar.</p

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Studies on combination chemotherapy for malignant lymphomaPart II. Combination chemotherapy in malignant lymphoma: Results of a long-term follow-up

Results of combination chemotherapy for malignant lymphoma between 1973 and 1982 were analysed. In this series there were 17 patients with Hodgkin's disease (HD) and 109 patients with non-Hodgkin's lymphoma (NHL). None of the patients had prior chemotherapy. The two basic treatment programs in this series were BVCP or BCOP (combination of bleomycin, vincristine, cyclophosphafamide and prednisolone) and AVIP(combination of adriamycin, vincristine, ifosfamide and prednisolone). Of the 17 HD patients, 14 (82%) were effectively treated and achieved complete remission(CR). Six of the 14 patients relapsed between 15 and 65 months, while the remaining 8 patients have been disease-free between 8 and 126 months. The projected median CR duration was 65 months. No recurrent disease has occurred among 5 patients who were given AVIP as intensification therapy, suggesting the usefulness of adriamycin in the treatment of HD. Complete responders survived significantly longer than partial responders: 83% of the former survived 5 years, but none of the latter survived that long. Of the 109 patients with NHL, 25 patients had diffuse medium cell type histology(DM) and 43 patients had diffuse large cell type histology(DL). For DM, the CR rate was 64%, and the median response duration was 10 months. Of the 16 CRs, 9 have relapsed so far; however, the remaining 7 have been disease free for 12 to 95 months. For DL, the CR rate was 63% and the median remission duration was 43 months. Of the 27 CRs, 13 have relapsed so far, but the remaining 14 have been disease free for 13 to 115 months. The median survival time was 75 months for DM, and 23 months for DL. Complete responders lived significantly longer than partial or none-responders in DL. Prognostic factors were analysed in DM and DL patients. Among the chemotherapy effect, stage, constitutional symptoms, serum LDH, C-reactive protein (CRP), lymphocyte count of peripheral blood, and erythrocyte sedimentation rate(ESR), a CRP over 3+ and ESR over 30mm/hr were defined as poor prognostic factors for DM. Remission induction failure and CRP over 3+ were defined as poor prognostic factors for DL. Sixteen (6 HD and 10 NHL) of 72 complete responders (14 HD and 58 NHL) were disease free for at least 2 years after cessation of all treatment, suggesting that HD as well as NHL is curable by intensive combination chemotherapy

Studies on combination chemotherapy for malignant lymphomaPart I. Drug screening and combination chemotherapy usinga murine lymphosarcoma, LS-1, as a model of malignant lymphoma in man.

A murine lymphosarcoma (LS-1) which originated spontaneously in a DBA/2 mouse, was evaluated as a model of malignant lymphoma for drug screening and combination chemotherapy. Antitumor activity was distinct in the order of L-asparaginase (LASP), mitoxantrone, a new anthraquinone analogue (MIT), ifosfamide (IFO), cyclophosphamide (CPA), adriamycin (ADM), and aclarubicin, a new ADM analogue (ACR), when measured as increased life span of mice intravenously implanted with LS-1 and intraperitoneously treated with antitumor agents at an optimal dose. Methotrexate (MTX), vincristine (VCR), and vindesine (VDS) were marginally active against LS-1. Nitrosourea compounds, such as BCNU and ACNU, and bleomycin were inactive against the tumor. The murine lymphosarcoma, LS-1, appeared to provide a drug activity spectrum closely analogous to malignant lymphoma in man except for LASP. The combination of IFO and MIT was the most effective among six 2-drug combinations. CPA and MIT, IFO and ADM, and CPA and ADM were also effective combination. ACR, however, appeared antagonistic to IFO and CPA, since in combination with these agents, ACR did not prolong the life-span at any dose, as compared to the optimal dose of IFO or CPA alone. The murine experimental system using LS-1 should be usefull as a chemotherapy model of malignant lymphoma in man