Mg2+-dependent unwinding of DNA by nonhistone chromosomal protein HMG(1 + 2) from pig thymus as determined by DNA melting temperature analysis.

In the previous studies with endonucleases specific for single-stranded DNA, we have indicated that the nonhistone chromosomal protein HMG(1 + 2) prepared from pig thymus has an activity to unwind DNA partially at low protein-to-DNA weight ratios (Yoshida, M. & Shimura, K. (1984) J. Biochem. 95, 117-124). In the present work, we have pursued the unwinding reaction by HMG(1 + 2) by thermal melting temperature analysis of DNA, and by investigating the effect of Mg2+ on the reaction. The melting temperature of DNA in the presence of HMG(1 + 2) at low protein weight ratios decreased in 2 mM Tris-HCl, pH 7.8, whereas it increased at higher ratios. The depressions of melting temperature by HMG(1 + 2) at low ratios were not observed either in the system of 2 mM Tris-HCl, pH 7.8, containing EDTA or in the system containing samples treated in advance with EDTA. An addition of Mg2+ to the system reproduced the depression of melting temperature at low protein-to-DNA ratios as well as the increase at higher ratios. Analysis by Mg2+-equilibrated gel filtration revealed that HMG(1 + 2) is a Mg2+-binding protein. However, the depression of melting temperature at low protein-to-DNA ratios was not due to removal of Mg2+ from DNA by HMG(1 + 2). From these results, it is concluded that HMG(1 + 2) causes a partial DNA unwinding detectable by thermal melting temperature analysis of DNA, and that Mg2+ is necessary for the unwinding reaction.

Total removal of a falcotentorial junction meningioma by biparietooccipital craniotomy in the sea lion position: a case report.

The successful total removal of a huge falcotentorial junction meningioma in a 59-year-old woman by biparietooccipital craniotomy with the patient in the sea lion position (prone with a hyperextended neck and with 20 degrees elevation of the upper and lower halves of the body) is reported, with some comments on the advantages of this approach and position. Taking advantage of the exposure of the dural sinus, the confluens sinuum pressure was measured by direct catheterization with the patient in various positions. The pressure was 3.6 cm H2O in the sea lion position, 2.4 cm H2O in the reverse jackknife position (supine with 20 degrees elevation of the upper and lower halves of the body), and -12 cm H2O in the sitting position.

Long-term effects of steroid treatment on nephrotic syndrome associated with Kimura's disease and a review of the literature.

A 68-year-old Japanese male (Case 1) and a 59-year-old Japanese male immigrant to Brazil (Case 2) who suffered from subcutaneous eosinophilic lymphoid granuloma (Kimura's disease) of several years duration, developed nephrotic syndrome. Renal biopsy demonstrated membranous nephropathy in Case 1 and minimal-change lesion in Case 2. Both patients were treated with prednisolone for several months. There was complete remission of nephrotic syndrome in eight years in Case 1 and in three months in Case 2. Proteinuria did not reappear after remission of nephrotic syndrome in either case. In contrast subcutaneous tumors subsided in both cases during steroid treatment but again became active immediately following discontinuation of the drug. These clinical observations suggest that, though some common factor(s) might mediate the development of both skin and renal lesions, the mechanism of action on these two target organs may differ, perhaps serving only as a "trigger" for the initiating mechanism of renal disease.

[Interleukin-2 (IL-2) in active pulmonary tuberculosis].

To clarify the precise of cellular immunity mechanism in pulmonary tuberculosis, we investigated the amount of IL-2 in patients with untreated active pulmonary tuberculosis. When serum adenosine deaminase (ADA) activity was examined using enzyme assay, an abnormally high level was observed in all patients (29.0 + 11.6 IU/ml, mean + SD; 4.5-17.8, normal range). Likewise, the level of serum-soluble interleukin-2 receptor (IL-2R) measured by ELISA showed abnormal high level in all patients (844.3 + 584.8 IU/ml; 80-300, normal range). When stimulated using PHA, the peripheral lymphocyte's ability to produce IL-2 revealed no difference between control subjects and patients. It was, however, noted that the lymphocytes of the patients significantly suppressed IL-2 responsiveness when compared to the control subjects (P less than 0.05). The serum IL-2 concentration measured using RIA could not be detected in any of the patients as was the same for control subject. All of the above mentioned results suggest that T-cell activation which caused increment in serum ADA activity and soluble IL-2R occurred in active pulmonary tuberculosis. The suppressed IL-2 responsiveness in the peripheral lymphocytes of patients proposes the possibility of soluble IL-2R reduction by the negative feedback mechanism in IL-2-sensitive lymphocytes.

[Serum adenosine deaminase (ADA) activity in patients with active pulmonary tuberculosis].

To clarify the immunological aspect of tuberculosis, we investigated serum adenosine deaminase (ADA) activity, T and B cell percentile in total peripheral mononuclear cells, peripheral T cell subpopulation and their relationship with other inflammatory parameters in 20 patients with active pulmonary tuberculosis. Serum ADA activity showed abnormal high level in all patients in nontreated phase with significant regression after three months treatment by anti-tuberculous drugs (P less than 0.05). In addition, significant positive correlation was observed between serum ADA activity and erythrocyte sedimentation rate at 1 hour (r = 0.56). Concerning about peripheral T cell subpopulation studied by two colour flow cytometry with FITC-conjugated anti-CD4 and phycoerythrin-conjugated anti-HLA-DR antibody, there was positive correlation between CD4(-) HLA-DR(+) T cell and serum ADA activity (r = 0.59) without any abnormal frequency of each T cell subpopulation. Additionally, after the treatment of pulmonary tuberculosis, significant increase of T cell percentile in total peripheral mononuclear cells were observed (P less than 0.005). In conclusion, these results may suggest serum ADA activity could be a parameter of activity of pulmonary tuberculosis and reflect the function of activated suppressor/cytotoxic T cell.

[A case of systemic lupus erythematosus associated with cryptococcal meningitis which was successfully cured by the administration of massive dose of amphotericin B].

A case of SLE with moderately deteriorated renal function due to lupus nephritis developed cryptococcal meningitis. Long term administration of amphotericin B (cumulative dose 5 g) combined with 5-flucytosine eradicated this fungal infection. Throughout amphotericin B administration urinary excretions of Na and K, as well as plasma HCO3 concentration were monitored, and, Na, K and HCO3 were supplemented orally and intravenously so much as to replace their urinary losses. Neither prominent water-electrolyte disturbance nor severe azotemia, which are the most serious side effects of amphotericin B, did not ensue. This case study indicates that sufficient water.electrolytes supplementation is important to prevent the nephrotoxicity of amphotericin B.

Unwinding of DNA by nonhistone protein HMG1 and HMG2.

The enzyme kinetic studies with endonucleases specific for single-stranded DNA and the thermal denaturation analyses of DNA showed that a high mobility group (HMG) nonhistone protein fraction HMG (1 + 2), composed of HMG1 and HMG2, has an activity to unwind DNA partially at low protein-to-DNA weight ratio. Isolated HMG1 and HMG2 have the same activity. Divalent cations such as Mg++ or Ca++ were necessary for the unwinding reaction. A peptide containing high glutamic and aspartic (HGA) region, isolated from the tryptic digest of HMG (1 + 2), unwound DNA depending on the presence of Mg++ or Ca++, suggesting that the HMA region in HMG protein is the active site for the DNA unwinding reaction. Poly-L-glutamic acid, employed as a model peptide of the HGA region, showed the activity. Finally, mechanisms of the DNA unwinding reaction by the HMG protein and possible role of the divalent cations are discussed.

Neuroleptic malignant syndrome-like state following a withdrawal of antiparkinsonian drugs.

A 63-year-old woman with diagnosis of Parkinson's disease developed an unusual symptom complex which consisted of extrapyramidal symptoms, disturbances of consciousness, diaphoresis, fever, and increased serum creatine phosphokinase following the discontinuation of large doses of combined antiparkinsonian drugs. After the patient's condition did not improve with the first 14 days of treatment consisting of intravenous fluids and antibiotics, a trial administration of L-dopa and carbidopa brought about definite clinical improvement. The symptoms strongly resembled neuroleptic malignant syndrome which is often a serious complication of antipsychotic drugs. The symptoms and the treatment of the present case suggest that dopaminergic hypoactivity in the brain may be an important factor in antiparkinsonian drug withdrawal syndrome and that similar neurochemical mechanisms may exist in neuroleptic malignant syndrome.

Specificity of physiological adaptation to endurance training in distance runners and competitive walkers.

The present study was designed to evaluate the specificity of physiological adaptation to extra endurance training in five female competitive walkers and six female distance runners. The mean velocity (v) during training, corresponding to 4 mM blood lactate [onset of blood lactate accumulation (OBLA)] during treadmill incremental exercise (training v was 2.86 m.s-1, SD 0.21 in walkers and 4.02 m.s-1, SD 0.11 in runners) was added to their normal training programme and was performed for 20 min, 6 days a week for 8 weeks, and was called extra training. An additional six female distance runners performed only their normal training programme every day for about 120 min at an exercise intensity equivalent to their lactate threshold (LT) (i.e. a running v of about 3.33 m.s-1). After the extra training, there were statistically significant increases in blood lactate variables (i.e. oxygen uptake (VO2) at LT, v at LT, VO2 at OBLA, v at OBLA; P less than 0.05), and running v for 3,000 m (P less than 0.01) in the running training group. In the walking training group, there were significant increases in blood lactate variables (i.e., v at LT, v at OBLA; P less than 0.05), and walking economy. In contrast, there were no significant changes in lactate variables, running v and economy in the group of runners which carried out only the normal training programme. It is suggested that the changes in blood lactate variables such as LT and OBLA played a role in improving v of both the distance runners and the competitive walkers.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilatory response and arterial potassium concentration during incremental exercise in patients with chronic airways obstruction.

The relationship of ventilation response (VE) to arterial potassium concentration (K+) during ramp incremental exercise was assessed in nine patients with chronic obstructive pulmonary disease (COPD), and in 10 healthy subjects. For COPD patients the maximum oxygen uptake (VOmax) was 19.6 +/- 3.8 ml kg-1 min-1 (+/- SD), and percentage of forced expired volume at 1 s (% FEV1) was 47.8 +/- 10.4%. In healthy subjects, VO2max was 44.4 +/- 7.0 ml kg-1 min-1 and FEV1 was 89.7 +/- 7.4%. Breath-by-breath determinations for VE, oxygen uptake (VO2) and carbon dioxide output (VCO2), as well as determinations for K+, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), pH and lactate in arterial blood were performed during a workout on an exercise bicycle at a ramp function work rate of 20 W min-1, preceded by a 40 min warm-up period. The major findings in the present study are: (1) that there is a linear relation between ventilation and arterial K+ concentration during ramp exercise in both healthy subjects and COPD patients; (2) that the slope of the VE-K+ relationship is significantly lower in COPD patients (16.2 +/- 7.3 l min-1 mM-1) than in normal subjects (37.4 +/- 6.9 l min-1 mM-1, P less than 0.01); and, (3) that the slope of the VE-K+ relationship is significantly related to the ability to ventilate during maximal exercise in both healthy subjects and COPD patients (P less than 0.05). It is thought that the significantly reduced slope of the VE-K+ relationship in the COPD patients could be interpreted as a reduced sensitivity to the stimulus and/or as a mechanical impairment of the ventilation.

Relationship between ventilation and arterial potassium concentration during incremental exercise and recovery.

The purpose of this study was to compare the relationship of ventilation (VE) with pH, arterial concentrations of potassium [( K+]a), bicarbonate [( HCO3-]a), lactate [( la]a), and acid-base parameters which would affect hyperpnoea during exercise and recovery. To assess this relationship, ten healthy male subjects exercised with intensity increasing as a ramp function of 20 W.min-1 until voluntary exhaustion and they were then allowed a 5-min recovery period. Breath-by-breath gas exchange data, [HCO3-]a, pH, [la]a, [K+]a and blood gases were determined during both exercise and recovery. Using a linear regression method, the VE/[K+]a relationship was analysed during both exercise and recovery. Several interesting results were obtained: a significant relationship between [K+]a and VE was observed during recovery as well as during exercise; the VE at any given values of [K+]a was significantly higher during recovery than during exercise and out of those factors affecting exercise hyperpnoea, only [K+]a had a similar time-course to VE during recovery. Changes in [K+]a during recovery were shown to occur significantly faster than VE with an [K+]a time constant of 70.0 s, SD 16.2 as opposed to 105.5 s, SD 10.0 for VE (P less than 0.01). These results provided further evidence that [K+]a might play an important role as a substance which can stimulate exercise hyperpnoea as has been suggested by other workers. The present study also showed that during recovery [K+]a contributed significantly to the control of VE.

Effect of hypoxia on arterial and venous blood levels of oxygen, carbon dioxide, hydrogen ions and lactate during incremental forearm exercise.

The purpose of the present study was to investigate whether, in humans, hypoxia results in an elevated lactate production from exercising skeletal muscle. Under conditions of both hypoxia [inspired oxygen fraction (F1O2): 11.10%] and normoxia (F1O2: 20.94%), incremental exercise of a forearm was performed. The exercise intensity was increased every minute by 1.6 kg.m.min-1 until exhaustion. During the incremental exercise the partial pressure of oxygen (PO2) and carbon dioxide (PCO2), oxygen saturation (SO2), pH and lactate concentration [HLa] of five subjects, were measured repeatedly in blood from the brachial artery and deep veins from muscles in the forearm of both the active and inactive sides. The hypoxia (arterial SO2 approximately 70%) resulted in (1) the difference in [HLa] in venous blood from active muscle (values during exercise-resting value) often being more than twice that for normoxia, (2) a significantly greater difference in venous-arterial (v-a) [HLa] for the exercising muscle compared to normoxia, and (3) a difference in v-a [HLa] for non-exercising muscle that was slightly negative during normoxia and more so with hypoxia. These studies suggest that lower O2 availability to the exercising muscle results in increased lactate production.

Arterial blood gases, acid-base balance, and lactate and gas exchange variables during hypoxic exercise.

To determine the effect of hypoxia on lactate threshold (LT), onset of blood lactate accumulation (OBLA), and gas exchange threshold (GET), the lactate level together with VO2, VCO2, VE, and acid-base status in arterial blood from 12 female distance runners performing a progressive incremental treadmill test under the condition of hypoxic gas inhalation (HC: FIO2 is 16.0% in N2) compared with normoxic conditions (NC: FIO2 is 20.9%; i.e., air) were examined. During exercise, HC shifted LT, GET, and OBLA to a lower VO2 by 12.5%, 12.9%, and 9.3%, respectively. The GET during hypoxic exercise was well correlated with LT (GET = 0.973LT + 0.04; expressed in VO2 l.min-1). The close reciprocal changes in arterial blood lactate and bicarbonate (HCO3-) were observed during hypoxic as well as normoxic exercise. These findings provide evidence for the cause and effect relationship between LT and GET, even in hypoxic exercise. During submaximal exercise below the LT, PaCO2 and HCO3- slightly increased both in NC and HC with pH remaining unchanged. However, during exercise above the LT, the PaCO2, HCO3-, and pH all decreased with pH decreasing more markedly during hypoxia. In conclusion, this study demonstrated a clear increase in arterial lactate during hypoxic exercise above the LT. Both the LT and GET are shifted to a lower work rate by hypoxia in the same manner with the correlation between them remaining high, supporting the cause and effect relationship of these two parameters.

[Diffuse panbronchiolitis in two brothers with different clinical courses].

Diffuse panbronchiolitis in two brothers is reported. The elder brother aged 46, was admitted in May 1983 due to severe dyspnea and productive cough, which had gradually worsened over several years. He had severe hypoxemia and hypercapnia. He died at age 47 of respiratory failure due to pseudomonas infection despite antibiotic therapy. The younger brother, at age 41, was admitted in March 1983 due to fever, productive cough, and abnormal shadows on chest X-ray films. He showed mild hypoxemia and his symptoms improved with antibiotic treatment. Since then he has been followed as an outpatient for over 7 years while taking 400 mg of Erythromycin per day, and he has had no exacerbation. These two cases had different clinical courses despite the facts that both had similar conditions of chronic sinusitis and appeared to be exposed to no special environmental or occupational hazards. These facts suggest that not only intrinsic factors, such as defenselessness of airways, but extrinsic factors such as viral, mycoplasmal, or bacterial infection may act together on the mechanisms of the onset and progression of diffuse panbronchiolitis.