Exponential hyperbolic sine function fitting of heart rate response to constant load exercise.

We attempted to fit heart rate (HR) changes induced by constant exercise loads of different intensities to an exponential hyperbolic sine curve by the least-squares method, and we compared the results with the fitting of the changes to exponential curves. Seven healthy male volunteers performed three different intensities of constant-load exercise on a bicycle ergometer. The exponential hyperbolic sine function adequately fitted the HR responses induced by all three different intensities of loads: low (30 W: correlation coefficient, r = 0.68 +/- 0.13, mean +/- SD), moderate (75 W: r = 0.93 +/- 0.07) and high (125 W: r = 0.97 +/- 0.02). The first-order exponential curve fitted only the moderate load response. Although the second-order exponential equation fitted the HR response for both the moderate and high loads, the equation did not fit the low-load response (r = 0.43 +/- 0.26). In low-load exercise, the sum of the power of the residuals for the exponential hyperbolic sine curve fitting was significantly smaller than that for the first- or second-order exponential curve fitting. In conclusion, the exponential hyperbolic sine function is useful for quantitative analyses of the HR response to exercise loads of various intensities.

Effects of cilostazol on heart rate and its variation in patients with atrial fibrillation associated with bradycardia.

BACKGROUND: Heart-rate (HR) variability is an important predictor of mortality in patients with heart disease. We examined the effects of cilostazol, a quinolinone derivative, on HR and HR variability in patients with chronic atrial fibrillation associated with bradycardia episodes. PATIENTS AND METHODS: Thirteen patients with chronic atrial fibrillation associated with bradycardia episodes (minimal HR <40/min and/or pauses, ie, episodes with an RR interval > 2.5 sec) received cilostazol (100 or 200 mg/day) orally for at least 2 months and 24-hour Holter electrocardiography was performed before and after the start of cilostazol administration. RESULTS: Minimal HR was significantly increased, by an average of 14 beats/min (bpm), at 3.3 +/- 0.8 weeks (mean +/- SD) after the start of cilostazol treatment. The number of pauses was significantly decreased. As a consequence, mean HR was increased by an average of 18 bpm. Maximal HR was also increased by an average of 19 bpm. The circadian variation of the HR, determined by cosine fitting, was not changed by cilostazol treatment. The time-domain HR variabilities, ie, the SD of the mean RR interval and the SD of the 5-minute mean RR intervals, were also unchanged. New York Heart Association functional class was significantly improved and the plasma atrial natriuretic polypeptide level was significantly decreased after the initiation of cilostazol treatment. CONCLUSION: Cilostazol improves the slow HR episodes associated with chronic atrial fibrillation and maintains the HR circadian variation and time-domain variability, indicating that cilostazol has therapeutic utility for the treatment of the slow HR associated with chronic atrial fibrillation.

Morphological study of the regeneration mechanism of acetic acid-injured colon crypts in the rat.

The regeneration mechanism of injured rat colonic mucosa with 1% acetic acid was certified in this study. The injured colons were studied periodically on experimental days 1, 3, 5, 7, 15, and 20 with light and scanning electron microscopy. Specimens were examined in paraffin sections stained with hematoxylin and eosin; crypts were isolated with the HCl digestion method; and three-dimensional stromal collagen tissue was prepared with the NaOH cell maceration method. Damage to the mucosal and submucosal layers peaked between the 1st and 3rd days with edema, regeneration, necrosis, and inflammation. The edema and inflammation subsided, and mucosal atrophy and crypt reduction remained at around 1 week. At 2 weeks the mucosa became thick, and crypts showed many branches in their lower two-thirds; and by 3 weeks the mucosa had recovered to almost normal. The ratio of number of crypts at the base and surface was almost 1.5 on the 15th day and 1.0 on the 20th day, suggesting that each branch progresses upward to create an independent crypt. We believe that the fission mechanism plays an important role in crypt repair after acetic acid injury of the colonic mucosa. As the proliferative zone of the colonic crypt is localized at the crypt base, fission of the crypt starting at the base and progressing up to the surface is the most reasonable and efficient mechanism for repair by increasing the number of crypts.

Requirement of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced growth arrest and apoptosis.

Signaling events leading to B cell growth or apoptosis are beginning to be unravelled, but detailed information is still lacking. To identify signaling molecules involved in B cell antigen receptor (BCR)-initiated pathways, we used the immature B cell line, WEHI-231, to investigate protein tyrosine phosphatases (PTP) whose expression was modulated by BCR ligation. Among the PTP cloned by reverse transcription-PCR, mRNA expression of the proline-, glutamic acid-, serine- and threonine-rich (PEST) domain phosphatase (PEP) was selectively elevated 3.1-fold within 3 h after anti-IgM antibody stimulation. In contrast, expression of another PEST domain phosphatase, PTP-PEST, was unaffected. Western blot analysis revealed that 71% of PEP was located in the cytosolic fraction, while 29% was in the membrane fraction. To examine the direct contribution made by PEP to BCR-initiated signal transduction, we transfected an antisense PEP cDNA into WEHI-231 cells. Two stable clones were established in which PEP expression was reduced by 34% and 47%, respectively. Strikingly, BCR-mediated inhibition of DNA synthesis was significantly rescued in the clones, and G1 phase cell cycle arrest and apoptosis were almost completely ablated. Considered collectively, these results indicate that PEP is a positive, crucial regulator in determining B cell fate triggered by BCR engagement.

Design of and metrological results from a bent parabolic mirror.

This article describes the successful design and fabrication of, and metrological results from, an elastically bent parabolic mirror. The mirror is equipped with a bending structure that allows the mirror to be bent meridionally to a parabolic shape. This bent parabolic mirror is the key component of the extremely high-quality monochromators designed for the SPring-8 figure-8 soft X-ray undulator and the 2.0 GeV high-brilliance synchrotron radiation source (VSX).

Thermal and deformation analyses of side-cooled monochromator mirrors for the SPring-8/Figure-8 soft X-ray undulator.

The numerical results for a bent parabolic mirror monochromator designed for the SPring-8/Figure-8 soft X-ray undulator are described. A thermal and structural finite-element analysis is presented for side-cooled premirrors of the bent parabolic mirror monochromator. Using a ray-tracing code, the effect of the final induced figure errors on the performance of the premirror are discussed.

Comparison of monochromators with a bent parabolic mirror and a varied-spacing grating for the 2.0 GeV high-brilliance synchrotron radiation source (VSX).

A design study of monochromators for a 2.0 GeV electron/positron storage ring for high-brilliance synchrotron radiation in the vacuum ultraviolet (VUV) and the soft X-ray regions is described. Two types of VUV/soft X-ray grazing-incidence monochromators, one with a bent parabolic mirror and the other with a varied-spacing grating, are designed. Without any slope error, the expected resolving power of the former is much higher, but the latter is less affected by slope errors of the optical elements.

Decremental oscillation curve fitting of heart rate response following face immersion into cold water.

Using 18 healthy volunteers, we attempted to fit the heart rate response to a decremental oscillation curve by the least-squares method following facial immersion into cold water. The decremental oscillation equation was as follows: HR = alpha.e(-betat) sin omegat + gamma, where HR is the instantaneous heart rate at t s, alpha the maximum amplitude of the decremental oscillation, beta the decremental rate, omega the angular velocity and gamma the basal heart rate. Each subject immersed his/her face fully in a basin filled with ice-cold water (4 degrees C) for 30 s. The heart rate response to facial immersion was significantly fitted to the decremental oscillation curve with a correlation coefficient > 0.75 in all the trials. Double trials with a 15-min intertrial interval did not show any significant change in the coefficients. Atropine sulfate decreased the value of coefficient omega and increased that of gamma but did not change alpha or beta, indicating that omega is determined mainly by parasympathetic tone. There were no differences for any coefficient between men and women. The coefficients beta and gamma increased in association with age. Given the significant fitting to the decremental oscillation curve of the heart rate response, we propose that the corresponding electrical circuit consists of a resistance and an inductor connected in series, with a condenser in a parallel circuit with a direct current impulse. This method of fitting with the corresponding electric circuit may be useful for analysis of the heart rate response to physiological stimulus.

Malignant tumors of the nasal cavity: review of a 60-case series.

Sixty cases of primary malignant tumor of the nasal cavity treated in our hospital between 1962 and 1993 were reviewed. Males were affected 2.8 times more frequently than females. The age at the first consultation ranged from 11 to 92 years, with a mean of 55.1 years. The peak distribution was seen in the 6th decade. Twenty-six cases were epithelial malignancies (squamous cell carcinoma 15; adenocarcinoma 3; adenoid cystic carcinoma 3; undifferentiated carcinoma 3; mucoepidermoid carcinoma 1; malignant mixed tumor 1), while 34 cases were non-epithelial malignancies (malignant melanoma 14; malignant lymphoma 14; plasmacytoma 3; olfactory neuroblastoma 2; rhabdomyosarcoma 1). The most common symptom on presentation was nasal obstruction (66.7%), followed by epistaxis (55.0%). The first recurrence was local in 19 patients, whereas cervical lymph node metastasis occurred in three patients, bone metastasis in two, intraperitoneal metastasis in two, and brain metastasis in one. The overall five-year cumulative survival rate was 48.0%. The five-year survival rates for squamous cell carcinoma, malignant melanoma, and malignant lymphoma were 57.0%, 31.0%, and 40.0%, respectively.

Adhesion-inducible DNA synthesis regulated by tyrosine phosphorylation/dephosphorylation.

Non-malignant rat liver epithelial cell line BRL was reported to adhere to a substrate by fibronectin. DNA synthesis of these cells was induced by adhesion to a substrate by fibronectin, while DNA synthesis in non-adhered cells was not observed. These results indicated that DNA synthesis in BRL cells is inducible by the cell adhesion signaling. Adhesion-inducible DNA synthesis was strongly inhibited by Herbimycin A. In contrast, vanadate showed the tendency to promote adhesion-inducible DNA synthesis. These results suggest that DNA synthesis caused by the cell adhesion in these cells was regulated by both phosphorylation and dephosphorylation at tyrosine residue.

Antigen receptor-initiated growth inhibition is blocked in CD45-loss variants of a mature B lymphoma, with limited effects on apoptosis.

Role of CD45 in B cell antigen receptor (BcR)-mediated signaling events in mature B cells was examined using BAL-17 and its CD45-negative clones. In the CD45-negative clones, BcR stimulation induced tyrosine phosphorylation almost identical to the parental cells, with a few exceptions of reduced phosphorylation, especially of a protein of about 60 kDa. BcR-induced calcium responses were reduced in the CD45-negative clones, but the kinetics were similar to the parent. BcR stimulation led to growth inhibition in the parental cells, but signals for growth inhibition were completely blocked in the CD45-negative clones. Interestingly, the same stimulation induced low, but significant levels of apoptosis both in the parent and in the CD45-negative clones. Thus, in mature BAL-17 cells, CD45 subtly mediate early signaling events (tyrosine phosphorylation and Ca2+ mobilization), and is absolutely required for the signaling pathway leading to growth regulation, but has limited effects on apoptosis.

[Fourteen cases of malignant melanoma of the nasal cavity].

Fourteen cases of malignant melanoma of the nasal cavity were treated in our department during 31 years from 1962 to 1993. Ten were males and 4 were females. The ages ranged from 48 to 92 years old, with an average of 64.6 years. The chief complaints were epistaxis in 10 cases, nasal obstruction in 7, nasal cavity tumor in 1, and dull headache in 1. Histologically, 3 cases were amelanotic type, 3 oligomelanotic and 8 melanotic. The cellular types were classified as follows: 5 spindle and 9 large epitheloid cell types. Palliative treatment was performed in 1 patient, and 13 patients were treated radically. Local recurrences were seen in 8 patients, 9 regions; 3 near the posterior margin, 1 near the upper margin, 1 cheek, 2 ethmoid sinus, 1 maxillary sinus, and 1 uncertain. The cumulative survival rate among the 14 patients was 54.2% after 2 years and 31.0% after 5 years. One patient had local recurrence 13 years after surgical treatment.

Negative regulation of apoptotic death in immature B cells by CD45.

Cross-linking of membrane IgM receptor on B cells induces tyrosine phosphorylation within 1 min. This biochemical alteration triggers a cascade of signaling events which ultimately leads to activation in mature B cells but growth arrest and cell death by apoptosis in immature B cells. To study the mechanisms underlying the bifurcation of signals, we chose to examine the role of receptor-type protein tyrosine phosphatase (PTP) CD45 using CD45- clones isolated from an immature B cell line WEHI-231. Here we report that in CD45- clones, tyrosine phosphorylation was constitutively induced but not enhanced by anti-IgM stimulation and anti-IgM-induced Ca2+ flux was slightly delayed but evidently prolonged. Further, the degree of growth arrest and DNA fragmentation induced by anti-IgM antibody was more evident in CD45- clones than the parental cells. These results indicate that initial alterations in signaling are effectively transduced into effector signals and that IgM receptor-mediated growth arrest and apoptosis in immature B cells are negatively regulated by CD45.

Mediastinal tracheostomy during esophagectomy for cervicothoracic esophageal carcinoma invading the proximal trachea.

A total of 16 patients with carcinoma in the cervicothoracic esophagus underwent pharyngolaryngoesophagectomy with construction of a mediastinal tracheostoma. Among them, seven patients underwent transhiatal esophagectomy without thoracotomy, four proximal esophagectomy by cervicotomy and sternal split, and five cervical and thoracic esophagectomy and lymphadenectomy by cervicotomy and right thoracotomy. Free jejunal transfer was performed to reconstruct the esophagus in five patients, and the stomachs were used in ten. One patient died of pneumonia 27 days after surgery, and two of arterial blowout. Plastic and reconstructive surgery techniques were introduced to protect large vessels and cover the wound. The postoperative 30-day mortality was 6.3% and the total operative mortality was 18.8%. Median survival was 327 days. Mediastinal tracheostomy is safely applicable today for patients with esophageal carcinoma invading the proximal trachea, allowing them to achieve safe respiration and to enjoy meals.

Alteration in protein-tyrosine phosphatase of rat epithelial cells by RSV-transformation: application of phospho-tyrosyl glutamine synthetase to the study of protein-tyrosine phosphatase.

We prepared phospho-tyrosyl glutamine synthetase (P-GS) with suppressed activity from a highly adenylylated glutamine synthetase and applied it to the assay of protein-tyrosine phosphatase (PTPase) present in non-malignant rat liver cells (BRL) by RSV-transformation. The maximum PTPase activity toward P-GS was observed at neutral pH (pH 7.5-8.0) in the soluble and particulate fractions prepared from both BRL and RSV-transformed (RSV-BRL) cells. At low activity levels (< about 0.3 U), the PTPase activity in each fraction was proportional to the sample protein concentration (A280) and the specific activity of PTPase in the soluble fraction of BRL cells was about twofold higher than that in the soluble fraction of BRL cells, while those in particulate fractions of BRL and RSV-BRL cells were almost the same as each other. Soluble fractions of BRL and RSV-BRL were subjected to molecular-sieve and anion-exchange chromatographies. One major PTPase activity, with an M(r) of about 40,000 (40k), was detected in the BRL soluble fraction, and two were detected in the RSV-BRL soluble fraction with M(r)s of about 40k and 60k. The 40k PTPases in BRL and RSV-BRL had the same profiles on anion-exchange chromatography, but the 60k PTPase in RSV-BRL cells showed a different profile. We suggest that the RSV-transformation of BRL cells induced the appearance of the 60k PTPase in the soluble fraction.

Laryngeal metastasis from a pulmonary papillary adenocarcinoma: a case report.

Metastases to the larynx from distant primaries are very rare. The present article reports a case of metastatic papillary adenocarcinoma of the larynx of lung origin. The patient was a 59-year-old female non-smoker, who had a history of adenocarcinoma of the right lung. For the laryngeal tumor, we performed a partial laryngectomy following biopsy. The tumor of the larynx was a papillary adenocarcinoma resembling the lung tumor, both demonstrating positive immunohistochemical staining for pulmonary surfactant apoprotein. The findings emphatically indicated the laryngeal tumor to be metastasis from the primary papillary adenocarcinoma of the lung. The present case report presents the clinical findings, course of disease and histopathological findings with brief reviews of the literature.

Lymphoscintigraphy of head-and-neck cancer.

To achieve the visualization of regional lymph nodes by lymphoscintigraphy, 21 patients with head-and-neck cancer were studied with the aid of 99mTc-labeled rhenium sulfur colloid (99mTc Re). Four injection sites were selected; the injections were given into the subcutaneous tissue of the parietal area of 11 patients, into the submucosa of the retromolar area of 6 patients, into the subcutaneous tissue of the postauricular area of 2 patients, and into the thyroid glands of 2 patients. Lymphoscintigraphy was done three hours after the injection. The cervical regions were visible in 85.7% of the patients on the affected side and in 90.5% on the healthy side. The visualization comprised the following regions: submental, submandibular, deep cervical, accessory, and supraclavicular regions. In total, 102 nodes were visualized on the affected side (average 4.8 per patient) and 110 nodes in the healthy side (average 5.5). Histologically, 15 of 21 patients had lymph nodes metastases and 6 did not. Of these 21 patients, 66.7% (14/21) had confirmed lymph node metastases in the visualized regions. This technique appears to be a relatively easy and efficient method of imaging the regional lymph nodes in head-and-neck cancer both before treatment and after neck surgery.

Changes in cell attachment by RSV transformation in rat liver epithelial cells.

BRL, a non-malignant rat liver epithelial-like cell line, possessed the ability to adhere through fibronectin to a solid substrate. Oncogenical transformation of these BRL cells with RSV induced a significant decrease in the fibronectin molecules in the extracellular matrix and reduction in its ability to adhere to fibronectin. The alpha 5 and beta 1 subunits of integrin (fibronectin receptor) were quantitatively diminished during RSV transformation in BRL cells. These results suggest that adhesive reduction of BRL cells to a substrate by RSV transformation may be caused by a decrease in cell surface fibronectin and fibronectin receptor molecules.

Purification and properties of growth inhibitor from normal rabbit serum.

It was previously found that rabbit serum contains a growth-inhibitory substance for a tumorigenic rat liver cell line RSV-BRL. In the present study, the growth inhibitor was purified from normal rabbit serum to show a homogeneous protein band with a molecular weight (Mr) of 56 k on SDS-polyacrylamide gel electrophoresis under non-reducing conditions. The purified growth inhibitor, tentatively named rabbit serum-derived growth inhibitor (RSGI), potently inhibited the growth of RSV-BRL and nine kinds of other cell lines including three human tumor cell lines at a concentration of 20 ng/ml or higher. The growth-inhibitory effect of RSGI was reversible and appeared to be cytostatic rather than cytotoxic. RSGI was stable to heating at 56 degrees C for 30 min or treatment with 0.1 M 2-mercaptoethanol, but labile to heating at 100 degrees C for 3 min or treatment with 1 M acetic acid (pH 2.3), 6 M urea, 50% (v/v) 1-propanol, or 0.1% (w/v) trypsin. These properties of RSGI suggested that it was different from type beta transforming growth factors, tumor necrosis factor-alpha, and other known growth-regulatory factors.

A study on the toxicity of antineoplastic drugs (bleomycin, peplomycin and cis-diamminedichloroplatinum) by simultaneous administration (Part 1).

In order to clarify the toxicity of the antineoplastic drugs, bleomycin (BLM), peplomycin (PEP) and cis-diamminedichloroplatinum (CDDP), which are commonly used to treat head and neck cancer by simultaneous administration, the semiacute toxicity of each of these drugs in rats was studied as an initial step. Body-weight change, general behavior, red blood cell count (RBC), white blood cell count (WBC), serum biochemistry (s-GOT, s-GPT, BUN, GLU, ALB, TP), A/G ratio, relative organ weight and histopathological features were determined. BLM and PEP given by ip administration once a week produced severe diarrhea, decreased diet consumption, emaciation, piloerection and loss of hair, enhancements of RBC and WBC, several changes in serum biochemistry, proliferation and mitosis of epithelial cells in the forestomach and occasional granular and vacuolar degeneration in the liver. CDDP administered in the same manner produced a significant decrease of WBC, several changes in serum biochemistry parameters especially BUN, an increased focal-segmental mesangial matrix in the glomeruli and vacuolar degeneration of epithelial cells of the convoluted tubule of the kidney.