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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 721 records · Page 40Linked to original sources

In vitro colony inhibition of carboplatin against stomach and lung cancer cell lines in comparison with cisplatin.

The effects of carboplatin and cisplatin on colony formation in stomach and lung cancer cell lines were examined and compared. The colony-inhibitory activity of carboplatin against stomach and lung cancer cell lines was similar to that of cisplatin when one-tenth of the peak plasma concentration of each drug was used (r = 0.80). One of the four stomach cancer cell lines was sensitive to carboplatin although all the stomach cancer cell lines were resistant to cisplatin. Of the three small cell lung cancer cell lines tested, two were sensitive to both carboplatin and cisplatin, and only one cell line (N857) was resistant to cisplatin; all the non-small cell cancer cell lines tested were resistant to both drugs. On the basis of these preliminary results, we suggest that carboplatin has potential therapeutic activity against stomach cancer and should be evaluated carefully from this aspect.

Carboplatin↗

Prognostic factors in non-small cell lung cancer: multiregression analysis in the National Cancer Center Hospital (Japan).

A total of 190 patients with unresectable non-small cell lung cancer (NSCLC) were analyzed retrospectively using eight pretreatment and three treatment-related prognostic factors in terms of influence on survival. All the patients received chemotherapy with or without chest irradiation, according to the protocol of phase II or phase III trials of the National Cancer Center Hospital Tokyo between April 1980 and December 1985. The eight pretreatment factors selected were performance status, sex, stage, age, histology, and metastasis to brain, bone or, liver. Three treatment-related factors were radiation therapy to the primary site, response to chemotherapy, and treatment period, before or after clinical administration of cis-diamminedichloroplatinum (II) (CDDP). Of the 190 patients, 71 (37.4%) were alive for more than 1 year, but only 17 patients (8.9%) survived 2 years after the initiation of chemotherapy. By univariate analysis, performance status 0-1, female, no metastasis to bone or liver, response to chemotherapy, and treatment period after CDDP were considered to be favorable prognostic factors. By multiregression analysis, performance status, sex, and treatment period after CDDP proved to be important factors for long-term survival. Consideration of these prognostic factors could enable the results of chemotherapy to be more accurately evaluated, and stratification of patients with advanced NSCLC based on performance status and sex before entry into a randomized controlled trial is recommended.

Adenocarcinoma↗

Chromosome studies of hematopoietic colonies for distinct diagnosis of megakaryoblastic crisis of chronic myelogenous leukemia: a case report.

Chromosome studies of cells from megakaryocytic colonies (CFU-Meg) as evidenced by a megakaryocyte-specific monoclonal antibody, TP80, from a patient with chronic myelogenous leukemia (CML) in the blast crisis (BC) revealed the same aberrant karyotype, 52,XY,+9,+9,+18,+19,+21,+22,t(9;22)(q34;q11),t(9;22), as that having newly appeared in the peripheral blood. Cells from erythroid bursts (BFU-E) showed only the standard 46,XY,t(9;22) karyotype, and cells from granulocyte/macrophage colonies (CFU-GM) had either of these karyotypes. These results demonstrated that the whole megakaryocytic line and part of the granulocyte/macrophage line had been involved in the BC while the erythroid line totally belonged to the original clone. Chromosome analysis coupled with immunophenotyping of hemopoietic colonies was useful for a definite diagnosis of megakaryoblastic crisis of CML in this patient.

Adult↗

Ph1-positive CML-derived myeloid-monocytoid precursor cell line producing substance(s) that stimulates normal CFU-C.

A new Ph1-chromosome positive cell line, KOPM-28. was established from a patient with chronic myelogenous leukemia (CML) in blast crisis. KOPM-28 cells were phenotypically immature: without azurophilic granules; negative for myeloperoxidase and positive for specific and nonspecific esterases. The nonspecific esterase reaction was intensified by TPA, and retinoic acid reinforced the specific esterase reaction without inducing morphological changes. KOPM-28 cells were not phagocytic. The cells expressed complement receptors, myeloid-monocytoid antigens, an Ia-like antigen and T4 antigen. CALLA, T-lymphocyte specific antigens, B-lymphocyte related antigen and platelet-megakaryocyte-megakaryoblast specific antigen were not detected. KOPM-28 cells formed colonies in semi-solid medium; this ability was augmented by GM-CSA. The addition of culture medium conditioned by KOPM-28 cells to normal bone marrow cells resulted in the increase of the CFU-C colonies. These findings indicate that KOPM-28 cells have features of myeloid and monocytoid precursor cells and that they are producing substance(s) which stimulates normal CFU-C.

Antigens, Surface↗

Differentiation of blasts from patients in myeloid crisis of chronic myelogenous leukemia by in-vivo and in-vitro plicamycin treatment.

Two cases in myeloid blast phase of chronic myelogenous leukemia (CML) responded to treatment with plicamycin alone. Their total white blood cell (WBC) count and immature myeloid cells fell in one case rapidly and in the other gradually. Approximately two to three weeks after initiation of plicamycin their total WBC count began to rise again, whereas the mature myeloid cells remained constant throughout the treatment. These results suggest that plicamycin may be effective in suppressing proliferation of blasts and promoting their maturation in the myeloid blast phase of CML, but that plicamycin alone may not be effective enough to sustain duration of response.

Adult↗

Nonrandom additional chromosome changes in acute nonlymphocytic leukemia with inv(16)(p13q22).

Five patients with acute nonlymphocytic leukemia and inv(16)(p13q22), all with additional chromosome changes, are reported. Three were diagnosed as having acute myelomonocytic leukemia (FAB-M4), and the other two as having acute monocytic leukemia (FAB-M5b). All five patients had abnormal eosinophils in the bone marrow at diagnosis. Two had a deletion of the long arm of chromosome #7, del(7)(q31), and a trisomy of chromosome #22. These changes have been reported frequently in acute nonlymphocytic leukemia with inv(16), but are extremely rare in leukemias with other specific rearrangements including t(9;22), t(8;21), and t(15;17). Our findings and review of the literature indicate that inv(16) is observed not only in acute myelomonocytic leukemia but also in acute monocytic leukemia, and that del(7q) and +22 are nonrandomly associated with inv(16) as additional abnormalities. No significant differences in the clinical features seem to exist between the patients with only inv(16) and those with inv(16) and additional chromosome changes, except for the lower white blood cell count in the latter group.

Adolescent↗

Cross-resistance to ouabain in a murine leukemia cell variant selected for cis-dichlorodiammineplatinum(II) resistance.

A murine leukemic cell line (R1.1) variant (R1.1/CDDPR-E8) resistant to cis-dichlorodiammineplatinum(II)(CDDP) was also found to be resistant to ouabain, a postulated specific inhibitor of sodium-potassium ATPase. The variant established by the culture of parental cells in step by step increasing concentrations of CDDP, exhibited 11-fold higher resistance to CDDP than the parental R1.1 cells. The present study suggests that a mutational change leading to an alteration in cell membrane characteristics associated with ouabain has also changed the sensitivity of cells against CDDP. Alternatively, the present data may indicate that the cytotoxicity of CDDP is closely linked to its effects on cell membrane.

Animals↗

Renal arteriovenous fistula associated with a huge renal vein dilatation.

We report a case of an aneurysmal type of renal arteriovenous fistula with a huge spherically dilated renal vein. Although the findings on routine computerized tomography made us strongly suspect renal cell carcinoma associated with a hilar lymph node metastasis, we were able to diagnose the arteriovenous fistula by means of a dynamic computerized tomography scan. On the basis of the roentgenographic findings, partial nephrectomy was performed successfully.

Adult↗

Synaptic modification of parallel fibre-Purkinje cell transmission in in vitro guinea-pig cerebellar slices.

1. Synaptic transmission from parallel fibres to Purkinje cells and its modification by paired stimulation of parallel fibres and climbing fibres were studied in in vitro slices of the cerebellum obtained from guinea-pigs. 2. Intracellular recordings were made from Purkinje cells, mainly from dendrites in the middle third of the molecular layer, but also, in a few cases, from somata. Climbing fibres were activated by stimulation of the white matter, while parallel fibres were stimulated with an electrode placed near the pial surface of the molecular layer. 3. Stimulation of the white matter elicited antidromic spikes, all-or-none climbing fibre responses, disynaptic responses through mossy fibres and parallel fibres, and trisynaptic responses through inhibitory interneurones. Climbing fibre responses were often followed by a small plateau potential, usually less than 2-3 mV in amplitude and less than 100 ms in duration, followed by a slow hyperpolarization which reached its peak in several seconds. Inhibitory inputs to Purkinje cells were blocked with picrotoxin for the experiments described below. 4. Stimulation of the superficial molecular layer with currents less than 50 microA produced graded parallel fibre-mediated excitatory postsynaptic potentials (e.p.s.p.s) ranging from 4 to 8 mV in peak amplitude. 5. Conjunctive stimulation of climbing fibres and parallel fibres at 4 Hz for 25 s induced depression of parallel fibre-mediated e.p.s.p.s in Purkinje cells, both in the peak amplitudes and in the slopes. The depression was about 30% on average and lasted for more than 50 min. 6. No such depression occurred when the intensity of the white matter stimulation was set just subthreshold for the climbing fibre innervating the Purkinje cell under study. Instead, the parallel fibre-mediated e.p.s.p.s were moderately potentiated for a period ranging from 10 to 50 min. Repetitive stimulation of the climbing fibre alone did not affect parallel fibre-mediated e.p.s.p.s. 7. Immediately after the conjunctive stimulation or the repetitive stimulation of climbing fibres alone, a transient hyperpolarization which lasted for several minutes was seen. Its time course was similar to that of the hyperpolarization following a climbing fibre response. Except for this, there were no associated changes in the membrane potential, the input resistance, or the magnitudes of climbing fibre responses in any of the cases mentioned in 5 and 6 above.

Action Potentials↗

Ventilatory effectiveness of high-frequency oscillation applied to the body surface.

To determine the ventilatory effectiveness of high-frequency oscillation (HFO) at different sites on the body surface, we applied HFO separately to the abdomen, the rib cage, or the whole body in eight anesthetized and paralyzed dogs. Test frequencies were 5, 7, 9, and 11 Hz with tidal volume kept constant at 2.5 ml/kg. During HFO application to the abdomen, we observed significantly higher arterial O2 partial pressure (P less than 0.05) at 5, 7, and 9 Hz and lower arterial CO2 partial pressure (P less than 0.05) at 7, 9, and 11 Hz than with rib cage or whole-body HFO. There was no significant difference in blood gases between rib cage and whole-body HFO. Thus, using blood gases as an index of ventilatory effectiveness, the present study showed that HFO applied at the abdomen was the most effective of the three kinds of body surface HFO. In comparison to rib cage or whole-body application, abdominal HFO was accompanied by substantial paradoxical movement of the diaphragm and rib cage. The associated lung distortion may result in pendelluft, which in turn may be the mechanism for increased ventilatory effectiveness with abdominal application of HFO.

Abdomen↗

Effect of digitalis on the diaphragm in anesthetized dogs.

We examined the effect of digitalis on diaphragmatic contractility and fatigability in 19 anesthetized mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. In a first group of five dogs, Pdi-stimulus frequency relationships were compared before and after administration of ouabain in doses of 0.01, 0.02, and 0.04 mg/kg. In a second group, diaphragmatic fatigue was produced by bilateral phrenic nerve stimulation at 30 Hz. Ten seconds of stimulation and 15 s of mechanical ventilation were repeated for 30 min. The rates of decrease in Pdi were compared between two groups, one of 0.05 mg/kg deslanoside-treated dogs (n = 7) and one of nontreated dogs (n = 7). After ouabain administration Pdi was significantly greater at each frequency in a dose-dependent manner. On the other hand, the rate of decrease in Pdi in the deslanoside group was significantly smaller than that in the nontreated group, whereas deslanoside did not greatly change the Pdi-frequency curves in fresh diaphragm. We conclude that ouabain improves contractility of the fresh diaphragm and that deslanoside has a protective effect against fatigability.

Animals↗

Urethral metastasis from prostatic carcinoma as diagnosed by immunoperoxidase technique using prostate-specific antigen and prostate-specific acid phosphatase.

A rare case of urethral metastasis from prostatic adenocarcinoma is reported. Ordinary histological examination by hematoxylin and eosin staining could not determine whether the primary site was the prostate or the urethra. However, with an immunoperoxidase technique using prostate-specific acid phosphatase and prostate-specific antigen as markers for prostatic cells, we obtained a precise diagnosis of the primary sites. As a result, the patient could be successfully treated with hormonal therapy.

Acid Phosphatase↗

Monitoring of dopamine metabolism by in vivo voltammetry and high performance liquid chromatography in L-dopa-treated rats.

Following L-DOPA administration, DA metabolites were measured by both in vivo voltammetry and HPLC-ECD. In vivo, the amplitudes of the catechol oxidation currents in both the striatum and frontal cortex increased and reached a plateau from 60 min to 240 min after L-DOPA treatment. L-DOPA, DA, DOPAC and HVA levels measured by HPLC-ECD after L-DOPA treatment were increased in both regions, and the occurrence of the peak of each compound was dependent on its order in the metabolic pathway, i.e., 15 min for DA, 45 min for DOPAC and 60-180 min for HVA. However, NE remained unchanged. No indication of a rapid DA increase was apparent in the catechol oxidation current at 15 min; and thus, DA is unlikely to be a main contributor to the catechol oxidation current in the brain of rats treated with L-DOPA.

3,4-Dihydroxyphenylacetic Acid↗

Characterized dispersive wave-form of evoked compound muscle action potential in the localized ulnar nerve neuropathy.

Disorder of the ulnar nerve with continuity around the elbow is known to be a neuropathy produced by long lasting compression, friction or traction. Forty-four patients with clinical diagnosis of ulnar nerve neuropathy were examined by means of motor nerve conduction study and induced electromyography. Compound muscle action potentials (CMAPs) from hand muscle were evoked by stimulating many points proximal and distal to the elbow and analysis of CMAP was performed. In mild grade of nerve lesion, dispersive wave-form with the extension of its duration was elicited by only stimulating proximal points to the elbow. It was also found that conduction velocity is delayed only over the short distance across the elbow. Thus an initial stage of nerve lesion has a tendency of dysfunctioning of conductivity restricted in only affected portion. CMAP patterns are classified into four groups in comparison with the progress of clinical signs of the disease. This classification can be utilized for the evaluation of the progress of ulnar nerve lesion.

Adolescent↗