Serum and plasma brain-derived neurotrophic factor concentration are elevated by systemic but not local passive heating.

Brain-derived neurotrophic factor (BDNF) plays a key role in neuronal adaptations. While previous studies suggest that whole-body heating can elevate circulating BDNF concentration, this is not known for local heating protocols. This study investigated the acute effects of whole-body versus local passive heating on serum and plasma BDNF concentration. Using a water-perfused suit, ten recreationally active males underwent three 90 min experimental protocols: heating of the legs with upper-body cooling (LBH), whole-body heating (WBH) and a control condition (CON). Blood samples were collected before, immediately after and 1 h post-heating for the determination of serum and plasma BDNF concentration, platelet count as well as the BDNF release per platelet. Rectal temperature, cardiac output and femoral artery shear rate were assessed at regular intervals. Serum and plasma BDNF concentration were elevated after WBH (serum: 19.1±5.0 to 25.9±11.3 ng/ml, plasma: 2.74±0.9 to 4.58±2.0; p<0.044), but not LBH (serum: 19.1±4.7 to 22.3±4.8 ng/ml, plasma: 3.25±1.13 to 3.39±0.90 ng/ml; p>0.126), when compared with CON (serum: 18.6±6.4 to 16.8±3.4 ng/ml, plasma: 2.49±0.69 to 2.82±0.89 ng/ml); accompanied by an increase in platelet count (p<0.001). However, there was no change in BDNF content per platelet after either condition (p = 0.392). All physiological measures were elevated to a larger extent after WBH compared with LBH (p<0.001), while shear rate and rectal temperature were higher during LBH than CON (p<0.038). In conclusion, WBH but not LBH acutely elevates circulating BDNF concentration. While these findings further support the use of passive heating to elevate BDNF concentration, a larger increase in shear rate, sympathetic activity and/or rectal temperature than found after LBH appears needed to induce an acute BDNF response by passive heating.

Hot water immersion induces an acute cytokine response in cervical spinal cord injury.

PURPOSE: The dysfunctional sympathetic nervous system in individuals with cervical spinal cord injury (CSCI) impairs adrenergic responses and may, therefore, contribute to the blunted post-exercise cytokine response. The purpose of this study was to investigate an alternative way to exercise to induce an acute cytokine response by passive core temperature elevation in CSCI. METHODS: Seven male participants with a motor complete CSCI and 8 male able-bodied controls were immersed for 60 min in water set at a temperature 2 °C above the individuals' resting oesophageal temperature. Blood was collected pre, post, and every hour up to 4 h post-immersion. RESULTS: Hot water immersion resulted in an IL-6 plasma concentration mean increase of 133 ± 144 % in both groups (P = 0.001). On a group level, IL-6 plasma concentrations were 68 ± 38 % higher in CSCI (P = 0.06). In both groups, IL-8 increased by 14 ± 11 % (P = 0.02) and IL-1ra by 18 ± 17 % (P = 0.05). Catecholamine plasma concentrations were significantly reduced in CSCI (P < 0.05) and did not increase following immersion. CONCLUSIONS: Passive elevation of core temperature acutely elevates IL-6, IL-8 and IL-1ra in CSCI despite a blunted adrenergic response, which is in contrast to earlier exercise interventions in CSCI. The present study lays the foundation for future studies to explore water immersion as an alternative to exercise to induce an acute cytokine response in CSCI.

Elevation of interleukin-6 and attenuation of tumor necrosis factor-α during wheelchair half marathon in athletes with cervical spinal cord injuries.

STUDY DESIGN: Nonrandomized study. OBJECTIVES: The purpose of this study was to determine the effects of long and intensive exercise on interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in athletes with cervical spinal cord injuries (CSCI). SETTING: The 30th Oita International Wheelchair Marathon Race. METHODS: Blood samples from six athletes with CSCI and eight athletes with thoracic and lumber spinal cord injuries (SCI) participating in wheelchair half marathon race were collected before the race, immediately after the race and 2 h after the race. IL-6, TNF-α, adrenaline and blood cell counts were measured. RESULTS: Monocyte count remained stable throughout the study in the CSCI group but was significantly high at 2 h after the race in the SCI group. Plasma IL-6 concentrations were significantly elevated immediately after the race in both groups, although the levels in CSCI were significantly lower than in the SCI group. Plasma adrenaline was significantly elevated immediately after the race in the SCI group but recovered at 2 h after the race. In contrast, plasma adrenaline did not change in the CSCI group throughout the study and was significantly lower than in the SCI group. Plasma TNF-α did not change throughout the study in the SCI group compared with a significant decrease at 2 h after the race in the CSCI group. CONCLUSION: Long and intensive exercise increased IL-6 in the CSCI group despite the small muscle mass and lack of sympathetic nervous system. The post-race fall in plasma TNF-α in the CSCI group could be related to the inhibitory effect of rising IL-6 in the presence of normal monocyte count and stable adrenaline level.

Increase in interleukin-6 immediately after wheelchair basketball games in persons with spinal cord injury: preliminary report.

STUDY DESIGN: Case series. OBJECTIVES: To investigate the effects of wheelchair basketball game on plasma interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and blood cell counts in persons with spinal cord injury (SCI). SETTING: The 2009 Mei-shin League of Wheelchair Basketball Games held at Wakayama, Japan. PARTICIPANTS: Five wheelchair basketball players with SCI voluntarily participated in this study. INTERVENTIONS: Blood samples were taken approximately 1 h before the player warm-up for the game and immediately after the game. MAIN OUTCOME MEASURES: IL-6, TNF-α, CRP and blood cell count were measured. RESULTS: Plasma IL-6 level and number of monocytes were significantly increased after the game, compared with pre-game measurements (P<0.05). No changes were observed in other measurements. There was a significant relationship between increased IL-6 levels and accumulated play duration. CONCLUSION: The lack of change in TNF-α and CRP levels suggested that the exercise-induced rise in IL-6 was not related to exercise-induced inflammatory response. Furthermore, the associated increase in the number of monocytes did not correlate with exercise-induced IL-6 changes, negating monocytes as the source of IL-6.

Wheelchair half-marathon race increases natural killer cell activity in persons with cervical spinal cord injury.

STUDY DESIGN: Non-randomized study. OBJECTIVE: We reported that individuals with cervical spinal cord injury (CSCI) showed no increase in natural killer cell activity (NKCA) in response to 20-min arm exercise. It could be argued that this lack of response was owing to the short duration and intensity of the exercise. SETTING: The 29th Oita International wheelchair marathon race. METHODS: The present study compared the effects of wheelchair half-marathon race on natural killer (NK) cell count, NKCA and other hematological and hormonal parameters in six subjects with CSCI and seven control subjects with spinal cord injury between T4 and L1 (SCI), before, immediately after and 2 h after recovery. RESULTS: NK cell counts increased at both time points after the race in SCI, but not in CSCI, compared with before the race. NKCA increased immediately in both groups of subjects after the race, and then returned to the pre-race level at 2 h after the race. Plasma cortisol did not change in both groups throughout the study. Plasma adrenaline increased sharply in SCI after the race, then returned to the pre-race level at 2 h after the race, whereas no change was observed in CSCI throughout the study. CONCLUSION: The present study demonstrated that wheelchair half-marathon race increases NKCA despite the lack of increase in plasma adrenaline in CSCI, suggesting the activation of NKCA by mechanisms other than circulating adrenaline level.

Effect of age on bowel management in traumatic central cord syndrome.

STUDY DESIGN: A retrospective multicenter study. OBJECTIVES: To investigate the characteristics of bowel dysfunction in elderly people with traumatic central cord syndrome (TCCS). SETTING: A total of 28 Rosai hospitals in Japan. METHODS: The Rosai Hospital registry included 3006 persons with spinal cord injury during 1997-2007. The study subjects were 186 patients with TCCS (160 men, 26 women; mean age, 61.7±11.6 years, ±s.d.). Patients were divided according to age into the young group (<50 years, n=30), the middle-age group (50-69 years, n=112) and the elderly group (≥70 years, n=44). We assessed the differences in bowel management techniques (spontaneous, rectal medications and manual emptying) and activity of daily living (ADL) with respect to bowel care at discharge among the three groups. RESULTS: Continent spontaneous defecation was the most common bowel management method (50%, 93/186). The percentage of elderly subjects on continent spontaneous defecation (36.4%) was significantly less than that of the young group (66.7%; P<0.05). Furthermore, the percentage of elderly patients who required no bowel care (18.2%) was significantly less than those of the young (53.3%) and middle-age groups (41.1%; P<0.01). However, few differences in bowel care-related ADL were recognized among the three groups in patients who required manual emptying. CONCLUSION: The results identified significantly fewer patients aged ≥70 years with 'continent spontaneous defecation' or 'independent for bowel care' compared with younger patients. The results also highlighted the clinical importance of bowel dysfunction associated with TCCS especially in elderly people.

Plasma IL-6 levels during arm exercise in persons with spinal cord injury.

STUDY DESIGN: Non-randomized study. OBJECTIVES: Previous studies indicated that at least 2-h leg exercise at more than 60% maximum oxygen consumption (VO(2)max) increased plasma interleukin (IL)-6 in able-bodied (AB) subjects. The purpose of the present study was to compare IL-6 response to arm exercise in AB subjects and persons with spinal cord injury (SCI). SETTING: Wakayama Medical University in Japan. METHODS: Six subjects with SCI between T6 and T10 and seven AB subjects performed 2-h arm crank ergometer exercise at 60%VO(2)max. Plasma catecholamines, IL-6, tumor necrosis factor (TNF)-α and high-sensitivity C-reactive protein (hsCRP) were measured before exercise, 60-min exercise, immediately and 2 h after the completion of exercise. RESULTS: Arm exercise increased myoglobin and plasma IL-6 levels in SCI and AB (P<0.01), but there were no differences in them between the two groups throughout the study. Plasma levels creatine kinase, lactate dehydrogenase, TNF-α and hsCRP did not change throughout the study in both groups. CONCLUSION: These findings suggest neither significant muscle damage nor inflammatory response during exercise. The increase in plasma IL-6 in SCI was not unexpected, confirming that moderate intensity and relatively long-arm exercise is safe and beneficial for SCI subjects with regard to IL-6 excretion, as in AB subjects.

Incidence of symptomatic autonomic dysreflexia varies according to the bowel and bladder management techniques in patients with spinal cord injury.

STUDY DESIGN: A retrospective, multicenter study. OBJECTIVES: To investigate the relationship between bowel and bladder management methods and symptomatic autonomic dysreflexia (AD) during hospitalization in patients with spinal cord injury (SCI). SETTING: Twenty-eight Rosai hospitals in Japan. METHODS: The study subjects were 571 patients with SCI who had been admitted to 28 Rosai hospitals between April 1997 and March 2007 for rehabilitation therapy and fulfilled the following criteria: (1) SCI at or above sixth thoracic level, (2) discharged from hospital after more than 4 months of admission for initial injury and (3) lack of pressure ulcers, deep venous thrombosis, ureteral and renal stones or heterotopic ossification throughout hospitalization to exclude possible influence of these complications on cardiovascular reflexes. The study subjects were examined for the incidence of symptomatic AD according to age, sex, ASIA Impairment Scale, injury level, bowel and bladder management techniques at discharge. RESULTS: The Rosai Hospital registry included 3006 persons with SCI during 1997-2007, and 571 patients fulfilled the above criteria. The highest incidence of symptomatic AD was diagnosed in subjects using reflex voiding and in those using manual removal of stool. By contrast, the lowest incidence of symptomatic AD was in those on continent spontaneous voiding and continent spontaneous defecation. CONCLUSION: Medical staff should evaluate the presence of AD in patients with SCI at or above the T6 level under bladder and bowel management such as reflex voiding and manual removal of stool.

Impaired immune response to voluntary arm-crank ergometer exercise in patients with cervical spinal cord injury.

STUDY DESIGN: Non-randomized study. OBJECTIVE: The mechanism underlying exercise-induced argumentation of natural killer cell cytotoxic activity (NKCA) in humans remains unclear. To address this, NKCA responses were studied during and after exercise in persons with cervical spinal cord injury (CSCI) and dysfunctional sympathetic nervous system. SETTING: Kibikogen Rehabilitation Center for Employment Injuries. METHODS: We examined the NKCA responses to 20-min arm-crank ergometer exercise at 60% of maximum oxygen consumption in eight persons with CSCI (between C6 and C7) and six able-bodied subjects. NKCA, adrenaline, and cortisol were measured before, immediately after exercise, 1 h after exercise, and 2 h after exercise. RESULTS: In able-bodied subjects, NKCA increased immediately after exercise (P<0.01) and then decreased to below the pre-exercise level 1 h after exercise, before recovering to the baseline level at 2 h after exercise. Plasma adrenaline concentrations increased significantly immediately after exercise (P<0.01) and returned to the baseline level 1 h after exercise. The plasma cortisol level did not change throughout the study. In contrast, NKCA, plasma concentrations of adrenaline, and cortisol did not change throughout the study in subjects with CSCI. CONCLUSION: In subjects with CSCI, the lack of response in NKCA throughout the experiment is probably mainly due to a dysfunctional sympathetic nervous system.

Topical anesthesia blunts the pressor response induced by bowel manipulation in subjects with cervical spinal cord injury.

DESIGN: Prospective double-blind study. OBJECTIVE: Manual emptying of rectal contents is necessary for patients with spinal cord injury to prevent bowel obstruction; however, this maneuver induces a rise in blood pressure (BP) and autonomic dysreflexia (AD). The purpose of this prospective double-blind study was to investigate whether topical anorectal anesthesia attenuates the BP rise and AD during bowel manipulation in patients with cervical spinal cord injury (CSCI). SETTING: Kibikogen Rehabilitation Center for Employment Injuries. METHODS: The study subjects were 25 consecutive clinically stable patients with CSCI. Each subject received a complete bowel program involving manual removal of stool in lateral recumbency, after topical application of lidocaine or placebo jelly to the anorectal area. Systolic and diastolic BP, heart rate and symptoms of AD were recorded before, during and after bowel manipulation. RESULTS: Systolic BP was significantly lower during the lidocaine arm of the study compared with placebo at insertion of rectal medication, digital stimulation, beginning of stool flow, manual removal of stool, end of stool flow and at 5-min after emptying. The mean maximal increase in systolic BP during lidocaine treatment (33.2+/-14.6 mm Hg) was less than during placebo (50.2+/-19.5 mm Hg, P<0.001). CONCLUSION: On the basis of our findings, we recommend induction of lidocaine jelly immediately before rectal manipulation in patients with CSCI to minimize the incidence and severity of AD.

Low-echoic lesions underneath the skin in subjects with spinal-cord injury.

STUDY DESIGN: Criterion standard and survey cases. OBJECTIVES: To assess the utility of ultrasonography for detecting deep tissue injury or incipient pressure ulcers and to determine the patterns of development of pressure ulcers in subjects with chronic spinal-cord injury (SCI). SETTING: Ambulatory setting at public hospital. METHODS: The subjects were 43 men with SCI between C5 and L1 (age: 42.6+/-11.6 years, mean+/-s.d.). A total of 129 areas (sacral region and bilateral ischial regions in each subject) were examined by inspection, palpation and ultrasonography. RESULTS: Of the 129 areas, 112 were normal by inspection, palpation and ultrasound imaging. Nine areas were abnormal on ultrasonography alone and six were lesion positive by palpation and ultrasonography. Only two areas were abnormal by all three methods. Ultrasonography always detected a heterogeneous pattern and low-echoic areas directly adjacent to the bone. CONCLUSIONS: Our results indicated that low-echoic lesions, signaling deep tissue injuries or early pressure ulcers, originated in areas near the bone and extended toward the epidermis. The results suggest that ultrasonography is a useful tool for the early detection of deep tissue injuries or pressure ulcers.

Attenuation of natural killer cell activity during 2-h exercise in individuals with spinal cord injuries.

DESIGN: Non-randomized study. OBJECTIVE: To determine natural killer cell cytotoxic activity (NKCA) to 2-h arm ergometer exercise in persons with spinal cord injuries (SCI) and the underlying mechanism of such response. SETTING: University of Occupational and Environmental Health, Japan. METHODS: We examined NKCA response to 2-h arm crank ergometer exercise at 60% of maximum oxygen consumption (VO(2max)) in SCI and able-bodied persons. NKCA and plasma concentrations of prostaglandin E(2) (PGE(2)), adrenaline and cortisol were measured before, during and immediately after the exercise. The study included seven subjects with SCI between Th11 and L4 and six able-bodied persons. RESULTS: NKCA in able-bodied subjects increased (P<0.05) at 60 min of exercise and immediately after the exercise, and remained elevated up to 2 h after exercise. However, NKCA in SCI decreased (P<0.05) immediately after exercise but recovered at 2 h after exercise. Plasma adrenaline in both groups increased significantly (P<0.05) immediately after exercise and returned to baseline level 2 h after the exercise. Plasma cortisol in both groups remained constant throughout the study. In SCI, PGE(2) significantly increased immediately after 2 h exercise and returned to the baseline level 2 h after exercise; however, it remained unchanged during the test in able-bodied subjects. CONCLUSION: Our results suggested that increase of PGE(2) in SCI partially contributes to NKCA.

The incidence of post-race symptoms of upper respiratory tract infection in wheelchair marathon racers.

STUDY DESIGN: Prospective analysis. OBJECTIVES: To investigate the influence of exercise and major competition on infectious episodes in athletes with spinal cord injuries (SCI). SETTING: Japan. METHODS: We examined the self-reported infectious episodes of upper respiratory tract infection (URTI) in athletes with SCI during a 1-month period before the race and 2 weeks after the race. The study included 21 persons with SCI who participated in the 18th Oita International Wheelchair Marathon. Thirteen persons with SCI who did not participate in the race were studied as control subjects. RESULTS: The number of URTI episodes in marathoners was 0.086+/-0.036/week during the 1-month period before the race and 0.089+/-0.040/week during the 2-week post-race period, whereas that of the controls was 0.139+/-0.046/week during the 1-month period before the race and 0.072+/-0.047/week during the 2-week post-race period. There were no significant differences between before and after the race in marathoners, or between marathoners and controls during each period. However, the number of URTI episodes 2 weeks after the race was significantly higher in subjects who trained more than 65 km/week compared to those who trained less than 65 km/week. CONCLUSIONS: In subjects with SCI who completed a wheelchair full marathon race, the incidence of URTI after the race was not high compared to control subjects who did not participate in the race. According to the number of URTI episodes and the training data, it is recommended that wheelchair marathoners should consider their risk for URTI during excessive practice.

Muscle endurance and power spectrum of the triceps brachii in wheelchair marathon racers with paraplegia.

OBJECTIVE: To investigate differences in triceps brachii endurance and electrical activity between elite marathon and recreational wheelchair athletes with paraplegia. DESIGN AND METHODS: Nine male elite wheelchair athletes between 20 and 46 years of age (average 29.0 +/- 8.2 years) with complete (ASIA-A) T4-L1 paraplegia were compared to a group of six male height- and weight-matched recreational wheelchair athletes with similar ages and injuries. Right triceps brachii maximum voluntary contraction (MVC), as well as the duration of the ability to maintain a 50% MVC were determined for all subjects. Median frequency (MF) and mean power frequency (MPF) were evaluated with fast Fourier transform spectrum analysis. MF and MPF rates of change were calculated and compared with the Student's t-test. SETTING: : Department of Rehabilitation Medicine, University of Occupational and Environmental Health, Japan. RESULTS: Right triceps brachii MVCs of the marathoners (42.4 +/- 8.8 N m (range 33-55 N m)) and recreational athletes (41.6 +/- 9.3 N m (range 32-56 N m)) did not differ significantly (P = 0.63). Endurance, however, did. All of the athletes, but none of the control subjects, were able to maintain a 50% MVC contraction of the right triceps brachii for 2 min (the average contraction duration in the latter group was 75.5+/-16.2 s). MF and MPF of the triceps brachii decreased linearly in both groups, but the slopes in the marathoners (-8.9 +/- 4.6 (-3.8 to -16.4) and -9.7 +/- 4.6 (-4.0 to -17.2)%/min, respectively) were statistically less steep than those in the recreational athletes (-22.3 +/- 8.2 (-9.6 to -31.4) and -21.2 +/- 6.4 (-11.4 to -28.6)%/min, respectively). CONCLUSION: Elite marathoners and active wheelchair users have similar triceps brachii strength. The marathoner's triceps brachii, however, display a significantly improved endurance and a slower decline of MF and MPF with time than do those of their recreational athlete control group.

Incidence of hepatitis virus infection and severe liver dysfunction in patients receiving chemotherapy for hematologic malignancies.

Hepatitis virus infection through virus reactivation has a high risk of mortality in patients with hematological malignancies receiving chemotherapy. We examined the incidence of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and severe liver dysfunction (alanine aminotransferase >ten times the normal upper limit and total bilirubin >5 mg/dl) during chemotherapy in 268 patients with hematological malignancies. Eight patients (3.0%) were infected with HBV and 22 patients (8.2%) were infected with HCV. One patient (0.4%) was infected with both HBV and HCV. HBV- or HCV-infected patients showed severe liver dysfunction at a significantly higher incidence than non-infected patients (11/31 (35.5%) vs. 0/237 (0%), p<0.0001). Furthermore, the incidence of severe liver dysfunction in HBV-infected patients was significantly higher than in HCV-infected patients (6/8 (75.0%) vs. 4/22 (18.2%), p<0.01). Three of eight HBV-infected patients were initially negative for hepatitis B surface antigen (HBsAg) by latex agglutination and became positive for HBsAg during chemotherapy. Furthermore, all three patients developed severe liver dysfunction and two developed fatal fulminant hepatitis. From an examination of the original stock of serum samples before chemotherapy, two patients were found to be positive for HBV-DNA by polymerase chain reaction (PCR). Although post-transfusion HBV infection was suspected in the one remaining patient, the cause of HBV infection could not be clarified due to the impossibility of examination in blood donors. Since HBV-infected patients develop severe liver dysfunction at a higher incidence than either patients not infected with virus or HCV-infected patients before chemotherapy for hematological malignancies, it is recommended that HBV-DNA should be tested by PCR to detect HBV marker-negative carriers and liver function tests should be carefully monitored.

CD34 expression by murine hematopoietic stem cells. Developmental changes and kinetic alterations.

For more than a decade it was believed that hematopoietic stem cells express CD34. However, this dogma was recently challenged by the observation that stem cells of normal adult mice are CD34-. In order to clarify the controversy, we carried out systematic examination of stem cells by using C57BL/6 mice that are congenic for Ly-5. As reported previously, stem cells in the normal adult mice were CD34-. However, stem cells stimulated in vivo by 5-fluorouracil injection or in vitro by a combination of interleukin-11 and steel factor were CD34+. The activated CD34+ stem cells reverted to CD34- when the recipients' marrow achieved steady state. The majority of G-CSF-mobilized stem cells also were CD34+ and reverted to CD34- under steady-state conditions. Most recently, we examined the developmental changes of stem cell CD34 expression. In order to gain information on the total population of stem cells we prepared CD34+ and CD34- populations of mononuclear cells without prior enrichment and studied their engrafting potentials. All stem cells from perinatal to 5-week-old mice were CD34+. In 7-week-old mice CD34- stem cells began to emerge, and the majority of the stem cells were CD34- in the 10- and 20-week-old mice. An estimated 20% of the adult stem cells expressed CD34. These observations provide insight into the current controversy regarding CD34 expression by adult hematopoietic stem cells.

Fulminant hepatitis type B after chemotherapy in a serologically negative hepatitis B virus carrier with acute myelogenous leukemia.

We report a case of a 41-year-old man with acute myelogenous leukemia who developed fulminant hepatitis from reactivation of trace hepatitis B virus (HBV) 2 months after complete remission. Although he became positive for HB surface antigen at the onset of fulminant hepatitis, he had been negative for HBV serum markers, and only HBV DNA was detected by polymerase chain reaction (PCR) amplification on admission. The original stocks of serum samples from all blood donors were tested again for HBV DNA by PCR, and all samples were negative. This case demonstrates that testing for HBV DNA by PCR is necessary before chemotherapy, because silent HBV carriers are rare and fulminant hepatitis may be induced by chemotherapy in patients with hematologic malignancies.

Reciprocal expression of CD38 and CD34 by adult murine hematopoietic stem cells.

The effects of activation of adult murine stem cells on their expression of CD38 were studied using a murine transplantation model. First, the published finding that the majority of long-term engrafting cells from normal adult steady-state marrow are CD38(+) was confirmed. Next, it was determined that the majority of stem cells activated in vivo by injection of 5-fluorouracil (5-FU) or mobilized by granulocyte colony-stimulating factor are CD38(-). Stem cells that were activated in culture with interleukin-11 and steel factor were also CD38(-). Previous studies have shown that expression of CD34 by adult stem cells is also modulated by in vivo or in vitro activation. To determine whether there is reciprocal expression of CD38 and CD34, 4 populations of post-5-FU marrow cells were analyzed. The majority of the stem cells were in the CD38(-)CD34(+) fraction. However, secondary transplantation experiments indicated that when the bone marrow reaches steady state, the majority of the stem cells become CD38(+)CD34(-). In addition, the minority populations of CD34(+) stem cells that occur in steady-state bone marrow are CD38(-). This reversible and reciprocal expression of CD38 and CD34 by murine stem cells may have implications for the phenotypes of human stem cells.

Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats.

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170 male Wistar rats were housed in a chamber at the equivalent of the 5500-m altitude level for 1-12 weeks. After 1 week of HHE, pulmonary arterial pressure was significantly raised, and the ratio of left ventricle plus septum over right ventricle of the heart showed a significant decrease (compared with those of ground-level control rats). In both ventricular tissues, the expression of ANP messenger (m)RNA and BNP mRNA increased after exposure to HHE. The amounts of ANP and BNP had decreased significantly in right atrial tissue at 12 weeks of HHE (compared with those of the controls), whereas in ventricular tissues at the same time point, both levels had increased significantly. In in situ hybridization and immunohistochemical studies, the staining of the mRNAs for ANP and BNP and of ANP and BNP themselves was more intense in both ventricular tissues after exposure to HHE than before (i.e., in the controls). The results suggest that, in response to HHE, the changes in ventricular synthesis are similar for ANP and BNP. These changes may play a role in modulating pulmonary hypertension in HHE. However, under our conditions, pulmonary hypertension increased progressively throughout the HHE period.

Effect of Interferon-α on Patients with Previously Untreated Chronic Myelogenous Leukemia in the Early Chronic Phase: Comparison between Interferon-α Continued Patients and Interferon-α Discontinued Patients.

In order to confirm the effect of interferon-α (IFN-α) in inducing a prolonged duration of the chronic phase (CP) on patients with chronic myelogenous leukemia (CML), we retrospectively compared the duration of CP between patients who continued on IFN-α and the patients in whom IFN-α was discontinued before the blast phase. Of the 32 patients not pretreated for CML in the early CP who received IFN-α therapy, 25 continued on IFN-α while seven discontinued the therapy (side effects, 5; resistance, 1; patient's refusal, 1). Only four of the 25 patients in whom IFN-α was continued (16.0%) progressed to the blast phase or accelerated phase, but six of the seven patients who discontinued IFN-α (85.7%) progressed to the blast phase or accelerated phase. Fourteen of the 25 patients who continued on IFN-α therapy showed cytogenetic response (complete cytogenetic response, 3; minimal cytogenetic response, 11) whereas 11 patients showed no cytogenetic response. However, non-responders showed a longer duration of CP than the patients whom IFN-α was discontinued. Although elderly patients showed a high incidence of side effects, and some patients progressed early after the beginning of IFN-α therapy, our data clearly demonstrated that in accordance with previous large multi-centric randomized studies the continuation of IFN-α, even in low doses, prevents disease progression.