An increase in peripheral blood progenitor cells in primates by coadministration of recombinant human interleukin 6 and recombinant human granulocyte colony-stimulating factor.

BACKGROUND: We recently demonstrated that coadministration of recombinant human interleukin 6 (rhIL-6) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in mice synergistically increases peripheral blood stem cells (PBSC), which can rescue lethally irradiated recipient mice. However, there is little information about the effect of coadministration of rhIL-6 and rhG-CSF on PBSC in a primate system. METHODS: In cynomolgus monkeys, rhG-CSF (5 microg/kg day) alone was administered for 5 days (first cycle). After the wash-out period, rhIL-6 (0, 10, or 20 microg/kg/day) and rhG-CSF were coadministered for 5 days (second cycle). RESULTS: Total peripheral colony-forming cells levels were increased earlier by coadministration of rhIL-6 and rhG-CSF than by the administration of rhG-CSF alone. The maximum level in the coadministration cycle was obtained on day 5, and a high level was obtained for a further 3 days after cessation. The maximum number of peripheral total colony-forming cells in the coadministration cycle was a mean of 2.12-fold (range 1.38 to 3.35) higher than that in the rhG-CSF alone cycle. Coadministration also increased the peripheral mixed colony-forming units by a mean of 3.62-fold (range 1.02 to 5.52). Interestingly, monkeys that showed a low response to the administration of rhG-CSF alone also had a higher response to the coadministration. No significant difference was observed between the two cycles of administration of rhG-CSF alone. CONCLUSIONS: These findings suggest that coadministration of rhIL-6 and rhG-CSF may be useful for clinical PBSC collection.

Synthesis and antibacterial activity of 6- and 7-[2-(5-carboxyimidazole-4-carboxamido)phenylacetamido]-penicillins and cephalosporins.

The synthesis and antibacterial activity of a series of beta-lactam antibiotics having a 5-carboxyimidazole-4-carbonyl group attached through an amide linkage to ampicillin, cephaloglycin or their analogs are described. Some compounds of this series were found to possess high activity against Pseudomonas and other Gram-negative bacteria.

Skin blood flow responses during sleep by laser Doppler flowmetry.

Skin surface blood flow at the fingertips was measured in a 21-year-old woman during sleep using laser Doppler flowmetry. Skin blood flow responses (SBFR) are transient reductions in skin blood flow of about 25s in duration. In our subject, SBFR showed a delay time of 8-9s from the onset of skin potential responses (SPR) and appeared more consistently than SPR. The frequency of SBFR decreased during non-rapid eye movement sleep, especially when the sleep stage became deep. These findings indicate the validity of SBFR as a discrete index of autonomic function during sleep.

Individual differences in physiological responses and type A behavior pattern.

The relationships between individual differences in psychophysiological responses and tendency of Type A behavior pattern (TABP) were investigated during mental arithmetic (MA) at a steady rhythm, challenging calculation (Uchida-Kraepelin serial addition test: UK test), music listening, and exposure to an 80 dB SPL of white noise. Each mental task was sustained for 5 minutes. Sixteen healthy Japanese adults, (10 males and 6 females) with an age from 18 to 36 years old volunteered for this study. The KG's Daily Life Questionnaire (KG Questionnaire) was used to investigate the tendency toward TABP, which included three sub-factors: aggression-hostility, hard-driving and time urgency, and speed-power items. Recorded physiological variables were respiratory rate (RR), skin resistance response (SRR), eyeblinks, and heart rate (HR) calculated using frequency analysis to render high frequency power (HF) and the ratio of low/high frequencies (L/H ratio). During the MA and UK tests, significant increases in HR, L/H ratio, RR occurred, while significant decreases in HF were observed. Eyeblinks significantly increased during the MA test and significantly decreased during the UK test. During music and white noise, no significant changes occurred except for SRR, which decreased significantly. The coefficient of variances in each response was over 20% for almost all variables, indicating that individual differences in the magnitude of each response were large, even if the direction (increase or decrease) of the change was the same in almost all subjects. The highest correlation coefficients (r) between the mean values of relative magnitude for each variable and TABP scores during the MA and UK tests were obtained for the L/H ratio (MA: r = 0.591, UK test: r = 0.577) and the RR (MA: r = -0.576, UK test: r = -0.511). These values were statistically significant (p < 0.05). Similar results were obtained for TABP sub-factors. Though other investigations have reported relationships between HF and TABP, we found no significant relationship. It was suggested that sympathetic nerve activity became greater for TABP individuals than for Type B individuals under stress conditions.

Evaluation of sleep using ambulatory skin potential recording: differences between morning and evening type.

In order to validate the evaluation of sleep using cassette type ambulatory skin potential measurement system (C-SPA), sleep duration variables extracted from 24 h recordings were compared between two groups (16 of the intermediate type and 16 of the evening type) with different sleep-wake habits rated by Morningness and Eveningness Questionnaires (MEQ). Compared with the intermediate type, the evening type subjects go to bed and get up later, have difficulty in falling asleep and more frequently awaken during sleep. Thus, the sleep variables by C-SPA provide valuable information about duration of sleep and differentiate the sleep-wake habits.