14-3-3ζ-Mediated Stimulation of Oxidative Phosphorylation Exacerbates Oxidative Damage Under Hypothermic Oxygenated Conditions in Human Renal Tubular Cells (HK-2).

Cellular survival and death are at least partially regulated by the phosphorylation of proteins. A chaperon protein, 14-3-3ζ, regulates the activity of many proteins by covering the phosphorylation site within a 14-3-3 binding motif. Therefore, regulation of 14-3-3ζ activity may affect the fate of cells subjected to cold preservation and/or hypothermic oxygenated conditions. The present study assessed whether 14-3-3ζ protects cells from hypothermic oxygenation-induced injury and clarified its role in mitochondrial functions. Human renal tubular cell line HK-2 or 14-3-3ζ-overexpressed HK-2 (ζHK-2) cells were subjected to 72 hours of normoxic cold preservation in UW solution with or without antioxidants and hydroperoxides. Cellular death, adenosine triphosphate (ATP) content, and MTT catabolism were evaluated. Deferoxamine treatment reduced cellular death and augmented ATP content in both cell types. These indices were higher in ζHK-2, regardless of deferoxamine treatment. Exposure to hydroperoxides did not affect cellular death in either cell type, whereas hydroperoxide supplementation significantly reduced ATP content, except for low-dose hydrogen peroxide in HK-2 cells. MTT assay at normal state showed higher values in ζHK-2 cells, whereas it was impaired by hydroperoxides in both cell types. These results suggest that accumulation of hydroperoxides as a byproduct of the augmented oxidative phosphorylation by 14-3-3ζ overexpression causes mitochondrial dysfunction. In conclusion, despite possessing many potentially protective functions, 14-3-3ζ exacerbates cellular injury under hypothermic oxygenated conditions. 14-3-3ζ accelerates mitochondrial functions together with iron-dependent oxidative damage. Although further investigations are necessary, upregulation of 14-3-3ζ could be a method to maintain mitochondrial function under hypothermic oxygenated conditions, as shown in hypothermic machine preservation of renal grafts, when appropriate antioxidant treatment is administered.

Anti-influenza activity of Alchemilla mollis extract: possible virucidal activity against influenza virus particles.

Influenza virus infection is a major public health problem that leads to significant morbidity and mortality. The emergence of resistance to the currently available anti-influenza agents has necessitated the development of new drugs with novel targets. Studying known ethno-medicinal plants is a promising approach for the discovery of new antiviral compounds. Alchemilla mollis is used in traditional medicine in Europe for different indications, including minimizing the symptoms of a sore throat. In this study, we found that A. mollis extract has anti-influenza activity, and investigated the mechanism underlying its inhibition of influenza virus replication. Plaque assays demonstrated that treatment of cells with A. mollis extract prior to infection did not inhibit influenza virus infection. However, plaque formation was markedly reduced when infected cells were overlaid with an agarose gel containing A. mollis extract. In addition, exposure of the virus to A. mollis extract prior to infection and treatment of cells during virus infection significantly suppressed plaque formation. Influenza virus-induced hemagglutination of chicken red blood cells was inhibited by A. mollis extract treatment. The inhibitory effect was observed against influenza A virus subtypes H1N1, H3N2, and H5N2. These findings suggest that A. mollis extract has virucidal or neutralizing activity against influenza virus particles. Furthermore, inhibitory effect of zanamivir synergistically increased after combination with A. mollis extract. Our results suggest that A. mollis extract has the potential to be developed as an antiinfluenza agent.

Effectiveness of antiplatelet drugs against experimental non-alcoholic fatty liver disease.

OBJECTIVE: No effective drugs have been developed to date to prevent or treat non-alcoholic fatty liver disease (NAFLD), although diet modification and exercise to improve obesity have been attempted. Therefore, development of a novel drug/strategy to treat NAFLD is urgently needed. In the present study, a novel concept is proposed for the treatment of NAFLD. METHODS: Fisher 344 male rats were given a choline-deficient, l-amino acid-defined (CDAA) diet or a high-fat high-calorie (HF/HC) diet with or without the antiplatelet agents, aspirin, ticlopidine or cilostazol for 16 weeks. Liver steatosis, inflammation and fibrosis, and the possible mechanisms involved were investigated. RESULTS: All three antiplatelet drugs, namely aspirin, ticlopidine and cilostazol, significantly attenuated liver steatosis, inflammation and fibrosis in the CDAA diet group. Of the three agents, cilostazol was the most effective, and the drug also suppressed HF/HC diet-induced liver steatosis. Cilostazol appeared to exert its beneficial effect against NAFLD by suppressing mitogen-activated protein kinase activation induced by oxidative stress and platelet-derived growth factor via intercepting signal transduction from Akt to c-Raf. CONCLUSION: Antiplatelet agents, especially cilostazol, offer the promise of becoming key agents for the treatment of NAFLD.

Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats.

Acotiamide hydrochloride (Z-338) is a member of new class prokinetic agents currently being developed for the treatment of functional dyspepsia (FD). DNA microarray analysis showed that acotiamide altered the expressions of stress-related genes such as gamma-aminobutyric acid (GABA) receptors, GABA transporters and neuromedin U (NmU) in the medulla oblongata or hypothalamus after administration of acotiamide. Therefore, effects of acotiamide on stress-related symptoms, delayed gastric emptying and feeding inhibition, in rats were examined. Acotiamide significantly improved both delayed gastric emptying and feeding inhibition in restraint stress-induced model, but did not affect both basal gastric emptying and feeding in intact rats, indicating that acotiamide exerted effects only on gastric emptying and feeding impaired by the stress. On the other hand, mosapride showed significant acceleration of gastric emptying in intact and restraint stress-induced model, and itopride showed no effect on restraint stress-induced delayed gastric emptying. In addition, gene expression of NmU increased by restraint stress was suppressed by administration of acotiamide, while acotiamide had no effect on delayed gastric emptying induced by an intracerebroventricular administration of NmU, suggesting that the suppressive effect of acotiamide on gene expression of NmU might be important to restore delayed gastric emptying or feeding inhibition induced by restraint stress. These findings suggest that acotiamide might play an important role in regulation of stress response. As stress is considered to be a major contributing factor in the development of FD, the observed effects may be relevant for symptom improvement in FD.

Effect on partial pressure of oxygen in arterial blood in percutaneous vertebroplasty.

BACKGROUND AND PURPOSE: The purpose of this study is to estimate the change in partial pressure of oxygen (Pao(2)) during percutaneous vertebroplasty and also to examine the factors related to the change in Pao(2). MATERIALS AND METHODS: We retrospectively reviewed preprocedural and postprocedural Pao(2) of 59 consecutive patients who underwent percutaneous vertebroplasty between November 2003 and April 2005 (11 men and 48 women; age range, 50-93; mean age, 75 years). Fifty-four patients were treated for osteoporosis-related fractures and 5 had malignant disease. Percutaneous vertebroplasty was performed in a conventional manner under local anesthetics and conscious sedation. Preprocedural and postprocedural blood drawing was performed 5 days to 30 minutes before percutaneous vertebroplasty and also at 30 minutes after the injection of bone cement. The difference between preprocedural and postprocedural data of Pao(2) was correlated with patients' age, number of treated vertebral bodies, presence of cement leakage, and presence of malignant neoplasm for each patient. RESULTS: Mean pre-Pao(2) and post-Pao(2) were 80.9 +/- 1.4 and 70.6 +/- 1.3 mm Hg (mean +/- SE) respectively (P = .0001). Using analysis of variance, there was a significant difference according to the number of vertebral bodies. There was a positive trend of decrease in Pao(2) according to the number of vertebral bodies during percutaneous vertebroplasty. Using multiple linear regression and after adjusting by preprocedural Pao(2) and other variables, the number of vertebral bodies was still highly significant. CONCLUSION: Pao(2) decreases during percutaneous vertebroplasty, and there is a correlation between the number of treated vertebral bodies and decrease in Pao(2).

Viral infectious disease and natural products with antiviral activity.

Viral diseases, such as acquired immunodeficiency syndrome (AIDS), respiratory diseases, and hepatitis, are the leading causes of death in humans worldwide, despite the tremendous progress in human medicine. The lack of effective therapies and/or vaccines for several viral infections, and the rapid emergence of new drug-resistant viruses have urged a growing need for developing new and effective chemotherapeutic agents to treat viral diseases. Recent advances in the understanding of both the cellular and molecular mechanisms of virus replication have provided the basis for novel therapeutic strategies. Several hundred natural products have been isolated for screening and identifying antiviral activity, and some have been shown to have great medicinal value in preventing and/or ameliorating viral diseases in preclinical and clinical trials. There are innumerable potentially useful medicinal plants and herbs waiting to be evaluated and exploited for therapeutic applications against genetically and functionally diverse virus families. This review focuses on several selected pathogenic viruses, including the human immunodeficiency virus (HIV), influenza virus, hepatitis B and C viruses and herpes viruses, and antiviral natural compounds from medicinal plants (herbs), while paying particular attention to promising compounds in preclinical and clinical trials. We also focused our attention on the need to develop effective screening systems for antiviral activity.

Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats.

Phosphorus directly controls parathyroid hormone (PTH) synthesis and secretion. Serum levels of the novel phosphate-regulating hormone, fibroblast growth factor 23 (FGF23), are positively correlated with hyperphosphatemia in patients with chronic renal insufficiency (CRI). We proposed that changes in serum PTH and FGF23 levels might be associated with changes in serum phosphorus levels caused by the phosphate binder sevelamer hydrochloride (sevelamer, i.e. crosslinked poly[allylamine hydrochloride]). Rats were fed a diet containing adenine for 4 weeks to establish CRI. Animals were then offered either a normal diet or a diet containing 1 or 3% sevelamer for 8 weeks continuously, or intermittently with sevelamer diet or a normal diet offered for alternating 2-week periods. Changes in the serum levels of phosphorus, calcium, PTH, FGF23, and 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) were monitored over time. Adenine-treated rats developed severe CRI, with markedly elevated serum levels of phosphorus, PTH and FGF23, and reduced levels of serum 1,25(OH)(2)D(3). Continuous treatment with sevelamer suppressed these increases throughout the study period. Serum phosphorus, PTH, and FGF23 levels decreased rapidly when sevelamer treatments commenced and recovered rapidly once they were discontinued. However, the changes in serum FGF23 levels began after the onset of changes in serum phosphorus and PTH levels. In conclusion, circulating PTH, and FGF23 levels can be promptly manipulated through the control of serum phosphorus levels. Moreover, phosphate-binder treatment can effectively inhibit the elevation of serum FGF23 levels, as well as PTH levels, under conditions of CRI.

Sevelamer hydrochloride (Renagel), a non-calcaemic phosphate binder, arrests parathyroid gland hyperplasia in rats with progressive chronic renal insufficiency.

BACKGROUND: It has been demonstrated that dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI) independently of serum calcium and 1,25(OH)(2)D3 levels. This study was conducted to examine whether sevelamer hydrochloride (Renagel); hereafter referred to as sevelamer), a non-calcaemic phosphate binder could inhibit the parathyroid gland (PTG) hyperplasia in rats with progressive CRI. METHODS: Male Sprague-Dawley rats were injected twice with low doses of adriamycin (ADR). Two weeks after the last injection of ADR, rats were fed a diet containing 1 or 3% sevelamer for 84 days. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of study, serum 1,25(OH)(2)D3 levels were measured and the maximal two-dimension area of the PTG in paraffin section was calculated using an imaging analyser. RESULTS: Dietary sevelamer treatment inhibited the elevations of serum phosphorus, calciumxphosphorus product, and PTH levels that occurred as the study progressed. Sevelamer also suppressed maximal PTG area and there existed positive strong correlation between maximal PTG area and serum PTH levels at the end of the study. Serum phosphorus levels positively correlated well with serum PTH levels and maximal PTG area. In contrast, serum calcium or 1,25(OH)(2)D3 levels did not show any correlation with serum PTH levels and maximal PTG area. CONCLUSIONS: Sevelamer treatment arrested hyperphosphataemia and PTG hyperplasia accompanied by the elevation of serum PTH levels. The correlation analysis suggests that reduced serum phosphorus levels contributed to the suppression of PTG hyperplasia and resulted in the reduction of PTH levels in this animal model after the sevelamer treatment. The management of phosphorus control started from early stage of CRI could prevent PTG hyperplasia and facilitate later management of secondary hyperparathyroidism.

Combination effect of lignin F and natural products.

We investigated the effect of lignin F, isolated from the alkaline extract of the cone of Pinus parviflora Sieb. et Zucc, on the cytotoxic activity and radical intensity (measured by ESR spectroscopy) of various natural products. Lignin F slightly inhibited the proliferation of human oral tumor cell lines (human squamous cell carcinoma HSC-2, human salivary gland tumor HSG), but not that of human gingival fibroblast HGF, suggesting its tumor specific cytotoxic action. Lignin F enhanced the cytotoxic activity of vitamin K2, vitamin K3, sodium ascorbate (vitamin C), epigallocatechin gallate (EGCG) (a major component of green tea), gallic acid (structural unit of tannin), chlorogenic acid, and 6 tea extracts (Japanese green tea, Japanese barley tea, black tea, Chinese green tea, Chinese Jasmin tea, Chinese Oolong tea), to various extents. On the other hand, lignin inhibited the cytotoxic activity of curcumin and dopamine. ESR spectroscopy demonstrated that combination of lignin and vitamin K3, EGCG or gallic acid synergistically augmented the radical intensity. Lignin F enhanced the bactericidal activity of EGCG against E. coli. These data suggest the beneficial effect of the combination of lignin F and natural products.

Suppression of allergic reactions by royal jelly in association with the restoration of macrophage function and the improvement of Th1/Th2 cell responses.

We studied the immunomodulatory effects of royal jelly (RJ), the principal food source of the queen honeybee. In this study, suppression of allergic reactions by RJ was investigated in DNP-KLH immunized mice (DNP-KLH mice). Oral administration of RJ (1 g/kg) to DNP-KLH mice significantly decreased the serum levels of antigen-specific Ig E and significantly inhibited DNP-KLH mediated-histamine release from mast cells, resulting in the suppression of immediate hypersensitivity reactions of ear skin. In DNP-KLH mice, IFN-gamma (Th1 cytokine) production from CD4+ T cells was suppressed and IL-4 (Th2 cytokine) production from CD4+ T cells was increased as compared to normal mice. On the other hand, RJ improved the balance of Th1/Th2 cell responses from Th2-dominant to Th1-dominant. RJ significantly increased GSH levels in macrophages from DNP-KLH mice. In addition, the administration of RJ to DNP-KLH mice increased IL-12 p40 mRNA expression and NO production, and decreased PG E2 production from macrophages as compared to untreated DNP-KLH mice. These results suggested that RJ suppressed antigen-specific Ig E production and histamine release from mast cells in association with the restoration of macrophage function and improvement of Th1/Th2 cell responses in DNP-KLH mice.

Diverse biological activities of healthy foods.

Diverse biological activities of 7 healthy foods [powdered pine needle, citrate-fermented sesame, powdered coffee, royal jelly, propolis, pollen and white sesame oil (extracted by super critical state (40 degrees C, 350 atmospheric pressure))] were investigated. The pine needle, sesame and powdered coffee was also extracted successively by ethanol and hot water, and lyophilized. The pine needle and coffee extracts, and propolis showed higher in vitro cytotoxic, bactericidal and oxidation activity, as compared with other 4 lipophilic healthy foods. However, propolis showed slightly lower, but significant cytotoxic and bactericidal activity with much reduced oxidation potential. ESR spectroscopy demonstrated that the cytotoxic activity of these extracts was closely related to their radical generation and O2- scavenging activities. Healthy food components may have both pro-oxidant and anti-oxidant properties. Pre-treatment of mice with pine needle, sesame or powdered coffee extract significantly reduced the lethality of bacterial infection, possibly due to their host-mediated action. These extracts failed to reduce the cytophatic effect of HIV-1 (human immunodeficiency virus) infection in MT-4 cells. No apparent acute toxicity was detected in mice by oral administration of 10 g/kg of these extracts. This data suggest the medicinal efficacy of healthy foods.

Sound-induced laryngeal and respiratory reflexes originate from vestibular afferents.

To determine whether the auditory or vestibular system causes the sound-induced laryngeal reflex, which has been considered to participate in the auditory feedback control of vocalization, click-induced laryngeal responses were compared before and after sectioning of the cochlear and/or vestibular nerves in cats. The sound-induced reflex modulation of respiratory muscle activity was also investigated, because respiratory movement is important for vocal control. Sectioning of the cochlear nerves had little influence on these responses. In contrast, sectioning of the vestibular nerves abolished these responses. It was concluded that the sound-induced laryngeal and respiratory reflexes are attributed to the vestibular system.

(-)-Epigallocatechin gallate inhibits mos activation-mediated xenopus oocyte maturation induced by progesterone.

(-)-Epigallocatechin gallate (EGCG), one of the constituents of green tea known to have a tumor preventing effect, inhibited maturation of Xenopus laevis oocytes induced by progesterone when this polyphenol was microinjected into oocytes at a final concentration of about 1 mM. Western blot and activity measurement analyses showed that Mos translation and the subsequent activations of mitogen-activated protein kinase and p90(rsk), probably by protein phosphorylation, seemed to have been inhibited by the microinjection of EGCG. These results suggest that EGCG may have the ability to control Xenopus oocyte maturation at least during the stage of Mos activation.

Preoperative chemotherapy for advanced esophageal cancer and relation with histological effect.

The results of surgical treatment for advanced esophageal cancer remain extremely poor. Irradiation and chemotherapy are not superior to surgery. Perioperative morbidity and the influence on long-term survival of a combination of surgery and preoperative chemotherapy were investigated in patients with advanced esophageal cancer. Forty-nine patients with advanced esophageal squamous cell carcinoma were subjected to preoperative chemotherapy of cisplatin-5-fluorouracil. Fifty-seven patients were chosen as a historical control group who had not undergone chemotherapy before surgery but had the same histological stages as the chemotherapy group. The response to chemotherapy was assessed by histological studies of surgical specimens. The survival rates noted no significant difference between preoperative chemotherapy plus surgery and a resection alone. However, subclassification according to the grading of chemotherapeutic effectiveness showed that, compared with control, preoperative chemotherapy was beneficial to high responders (P = 0.01), ineffective in low responders (P = 0.61), and detrimental to nonresponders (P = 0.03). Postoperative morbidity was significantly higher in the chemotherapy group than in the control group (P = 0.02). These findings suggest that preoperative chemotherapy is necessary only for high responders and we therefore need to reliably identify non-, low, and high responders before chemotherapy to improve the survival and quality of life of patients with advanced esophageal cancer.

Effects of infusion of L-arginine on exercise-induced myocardial ischemic ST-segment changes and capacity to exercise of patients with stable angina pectoris.

BACKGROUND: Results of recent studies show that intracoronary administration of L-arginine, the precursor of nitric oxide, restores endothelial function in subjects with coronary risk factors and minimal coronary artery lesions. However, few investigators have examined the clinical feasibility of using L-arginine for treatment of myocardial ischemia due to coronary artery disease. OBJECTIVE: To examine the effect of supplementary L-arginine on exercise-induced myocardial ischemia and capacity to exercise of patients with stable effort angina pectoris. METHODS: Twelve patients confirmed to have a single epicardial coronary artery stenosis underwent two treadmill exercise tests after infusion of 10% L-arginine solution or placebo (5% dextrose) according to a randomized single-blind crossover design on two days separated by an interval of less than 1 week. Respiratory gas exchange kinetics were measured and myocardial ischemia was estimated by electrocardiography before and during exercise. RESULTS: Infusion of L-arginine did not alter exercise-induced changes in heart rate and blood pressure, and objective parameters of capacity to exercise. Exercise-induced maximum ST-segment depression (by 2.1 +/- 0.9 mm; with L-arginine; by 1.9 +/- 0.9 mm with placebo, NS) and onset of 1 mm ST-segment depression after exercise (after 261 +/- 131 s with L-arginine; after 247 +/- 136 s with placebo, NS) also remained unchanged. However, ST-segment depression was restored to baseline after exercise significantly more quickly after infusion of L-arginine than it did with placebo (after 331 +/- 167 s with L-arginine; after 400 +/- 165 s with placebo: P < 0.01). CONCLUSION: Intravenous administration of L-arginine did not alter capacity to exercise or the threshold for exercise-induced myocardial ischemia. However, it did reduce the time taken for recovery after ST-segment depression, suggesting that an earlier resolution of exercise-induced myocardial ischemia occurred.

A standardized protocol for assessing regulators of pigmentation.

Varied effects of chemical or biological compounds on mammalian pigmentation have been reported by many groups, but to date, no standardized method has established necessary and/or optimal parameters for testing such agents. A standardized method has been developed to screen compounds with potential effects on pigmentation. The protocol comprises basic parameters to analyze melanogenic effects and allows for further characterization of candidate compounds, providing important insights into their mechanism of action. In this protocol (termed STOPR, for standardized testing of pigmentation regulators), compounds are initially screened using purified tyrosinase and are then tested on melanocytes in culture. After treatment of melanocytes with potentially bioactive compounds, cell proliferation and viability, total melanin accumulated, and melanogenic potential are measured. This protocol is an important first step in characterizing chemical regulation of effects on melanogenesis. When bioactive candidate compounds are identified, testing may proceed for pharmacological or otherwise commercial applications in coculture and/or organ culture models followed by in vivo testing. As an application of this method, results for compounds known to stimulate and/or inhibit melanogenesis (including arbutin, hydroquinone, kojic acid, melanocyte-stimulating hormone, and thymidine dimers) as well as some commercial skin whiteners are reported.

Effects of L-arginine on lower limb vasodilator reserve and exercise capacity in patients with chronic heart failure.

OBJECTIVE: To determine whether the reactive hyperaemic response of the lower limb increases with improved exercise capacity after acute supplementation with L-arginine, the precursor of nitric oxide, in patients with chronic heart failure. METHODS: 19 patients with chronic heart failure were enrolled in the study. Rest calf blood flow and femoral occlusion induced calf blood flow changes were measured by venous occlusion plethysmography before and after intravenous infusion of 10% L-arginine solution (5 ml/kg for 30 minutes) or placebo. Postexercise calf blood flow was also measured after the experimental infusion. During both postinfusion periods, several exercise capacity indices were determined by a symptom limited cardiopulmonary exercise test using a bicycle ergometer. RESULTS: Baseline calf blood flow, systemic blood pressure, and heart rate showed no significant changes in either of the two experimental conditions. However, the occlusion induced blood flow response was significantly enhanced by L-arginine infusion (mean (SEM) peak flow, 19.6 (1.5) v 28.9 (3.1) ml/min/dl calf tissue; p < 0.01), but not by placebo (peak flow, 19.1 (1.4) v 20.9 (1.8) ml/min/dl calf tissue; NS). Calf blood flow response after exercise was also higher after L-arginine infusion than after placebo (peak flow, 4.8 (0.4) v 6.0 (0.8) ml/min/dl calf tissue; p < 0.05). L-arginine infusion had no significant effect compared with placebo on exercise capacity indices such as peak oxygen uptake (17.1 (1.0) v 15.8 (1.1) ml/min/kg; NS), anaerobic threshold (10.5 (0.6) v 10.4 (0.7) ml/min/kg; NS), and exercise time (296 (23) v 283 (22) s; NS). CONCLUSIONS: Acute supplementation with the nitric oxide precursor L-arginine increased lower limb reactive hyperaemia but did not lead to any significant improvement in exercise capacity in patients with chronic heart failure.

[Supervised cardiac rehabilitation for the patients with the disturbance of the motor function after cardiac surgery: the significance of physical therapists' participation].

There are sporadic instances of patients with the motor function disturbance of non-cardiac origin after cardiac surgery, and these patients may need prolonged post-operative cardiac rehabilitation. We established our cardiac rehabilitation program for post-operative patients and a total of 124 patients underwent the post-operative cardiac rehabilitation program (male 73, female 51, average age 60). Among them, 12 patients (9.7%) received the physical therapy for the disturbance of motor function post-operatively. These 12 patients were retrospectively studied. Physical therapies performed were the exercise therapy to improve the range of motion to prevent contracture in 3 patients with peroneal nerve palsy and drop foot, the exercise therapy for pre-operative or post-operative hemiplegia in 6 patients, the instruction of exercise for lumbago in 1 patient with spinal cord disease, respiratory physical therapy in 1 patient, and myotherapy for arthritis in 1 patient. Treatment with physical therapy was very useful in rehabilitating these patients. Active participation of physical therapists in cardiac rehabilitation for patients with the disturbance of motor function after cardiac surgery is possible. It is expected that their participation may improve the quality of life in this subset of patients.

[Reinfection tuberculosis at a day-laborers' facility equipped with a sauna].

Restriction-fragment-length polymorphism (RFLP) analysis was used to study one outbreak of reinfection pulmonary tuberculosis at a day-laborers' facility equipped with a sauna. The results were interpreted in conjunction with clinical and epidemiologic data. The DNA prove was derived from the insertion sequence IS 6110. A 63-year-old man who stayed at a day-laborers' facility for eight months was found to have advanced cavitary lung disease with sputum smears strongly positive for acid-fast bacilli. One year later a 46-year-old man staying at the same facility for 24 months was also found to have sputum-positive tuberculosis. The 46-year-old man had undergone treatment for tuberculosis 16 years previously and showed radiographic evidence of previous lung damage from tuberculosis. The second man had no tubercule bacilli in sputum when the 63-year-old man was found to have sputum-positive tuberculosis. The organisms isolated from these two men were both drug sensitive and had a similar RFLP pattern which suggests that 63-year-old man was the source of this outbreak and that pulmonary tuberculosis in the 46-year-old man was caused by exogenous reinfection. We conclude that exogenous reinfection may have been one pattern of tuberculosis transmission in this high-risk environment.

Effect of restricted feed intake of dams and heat stress on mineral status of newborn calves.

To clarify the effects of restricted feed intake, heat stress, and parity on the mineral status of cows and heifers around parturition and on the mineral status of their calves during 1 wk of age, data were collected from 66 Holstein cows and heifers and their calves. In Experiment 1, 36 heifers and mature cows that calved during hot or cool weather were fed to meet requirements for total digestible nutrients (TDN), protein, and minerals. In Experiment 2, 15 mature cows that calved during hot or cool weather were fed to meet maintenance requirements for TDN plus requirements for TDN for the last 2 mo of gestation, and 15 heifers were fed to meet TDN requirements. Heat stress increased rectal temperatures of newborn calves. Blood hematocrit and hemoglobin of heifers around parturition were higher than those of mature cows, but blood hematocrit and hemoglobin of calves born from heifers were lower. The restricted feed intake of dams decreased blood hematocrit and hemoglobin as well as plasma Fe of calves in hot and cool weather. Plasma Ca, inorganic P, and alkaline phosphatase as well as colostral Ca, P, Mg, and Zn of heifers were higher than those of mature cows, but plasma Mg of heifers was lower. Plasma Mg of calves and their dams was lower in hot weather than in cool weather, and restricted feed intake accelerated the reduction in plasma Mg of calves and their dams during hot weather. Plasma Na of calves and their dams was higher in hot weather than in cool weather. Heat stress increased plasma K of heifers and their calves. Heat stress increased Ca concentration in meconium of calves born from cows, and the restricted feed intake increased P concentrations in meconium. These results suggest that the maintenance of optimum erythropoiesis and mineral status in heatstressed periparturient cows and heifers and their calves must be met by dietary energy and minerals that are fed at maintenance concentrations plus excess requirements necessary during the gestation period.