[The orodental status of a population of school children in the southeast of France in 1991].

An epidemiological survey was conducted in 1991 in the South-East of France in order to estimate the oral health conditions of a sample of 6-15 year old children. The caries prevalence of 457 subjects was presented as mean values of the dft, dfs, DMFT and DMFS indices. The dft and dfs indices decreased from the age of 6 years and the mean number of decayed surfaces of deciduous teeth was always lower than two. First carious lesions in permanent teeth were diagnosed at 6 years, but no filling was observed before 7 years. The fissure caries were the most frequent. Extractions for caries were very rare. The comparison of this study with a similar one made in 1987 showed a reduction in caries more important in the permanent teeth. A decrease in the number of decayed surfaces was also observed. This improvement in oral health seemed to be mainly related to better oral hygiene and an increase in the use of fluoridated dentifrices.


A simple stimulator for periodontal mechanoreceptors in human subjects.

Mechanoreceptors in the periodontal ligament are activated by tooth movements as little as 1-3 microns. It has been difficult in the past to move a tooth only over this small distance in order to activate the periodontal receptors without at the same time activating other receptors in related structures. This paper describes a simple solution to this problem based on the use of von Frey hairs (in the form of nylon filaments) rather than a rigid probe, to move the tooth. Filaments of different stiffness are mounted on the moving coil of a loudspeaker to apply different forces to the tooth. The timing of the contact of the filament with the tooth is measured precisely with a simple impact detector. The sensation elicited by this stimulator is abolished by local alveolar anaesthesia, indicating that the stimulation was localised to the periodontal area. The flexible probe is an important safety feature, as it limits the force applied to the tooth, and therefore the distance that the tooth can be displaced. The stimulator, suitable for psychophysical studies on the thresholds of periodontal receptors, on the reflex responses to stimulation of periodontal mechanoreceptors, and teaching applications, can be constructed from readily available components at minimal cost.


Cariogenic changes in dental enamel of boys and girls in relation to salivary properties. II. Radiological examination.

In earlier clinical studies of a group of children subjected to an intense fluoride treatment programme several salivary properties were related to cariogenic changes in the enamel surface, as assessed by mirror and probe. In this study the relationship between salivary parameters and cariogenic changes was investigated on bitewings taken from the same teeth. Inverse correlations were found between the acid producing capacity of the micro-organisms in the saliva (as determined in the Snyder test) and most cariogenic changes detected in bitewings particularly in boys. These radiologically detected changes in enamel were the reverse of those obtained clinically. These discrepancies were explained by differences in sensitivity between clinical and radiological techniques used to diagnose cariogenic changes. In contrast it was confirmed radiologically that for girls the P concentration in saliva and for boys the amount of resting saliva are important for preventing extension of caries into deeper layers of enamel.


Susceptibility of Candida albicans to peroxidase-catalyzed oxidation products of thiocyanate, iodide and bromide.

The susceptibility of Candida albicans (ATCC 10231 and wild strains) to hypo(pseudo)halous ions (OSCN-, OBr-, OI-) produced by the lactoperoxidase system was tested. Six strains of Candida albicans were isolated from swabs taken from the mouths of children with orthodontic appliances and selected on Sabouraud-Chloramphenicol-Actidione agar plates. The survival rate of Candida blastospores after a 30 min exposure to lactoperoxidase system ranged from 79 to 105% in the presence of 615 microM thiocyanate, from 56 to 88% in the presence of 345 microM bromide and from 0 to 4% in the presence of 250 microM iodide. Results showed that only OI- could exert a strong inhibiting effect in vitro on Candida albicans at physiological concentrations. Nevertheless, the activity of the hypoiodite generating system in saliva was found to be under the control of thiocyanate concentration.


Posterior reduction and stabilization of painful spondylolisthesis.

The authors reported 16 cases of first to third grade painful spondylolisthesis. The treatment was posterior reduction and stabilization in one stage operation by modified Vidal et al and Luque techniques. The operation consisted of stabilization of an above involved vertebra and another one below with a rectangular rod and sublaminar wirings. The pedicular screws were inserted through the Harrington hooks which levered upon the rectangular rod for reduction of the displaced vertebra. The posterolateral intertransverse arthrodesis of two spinal segments was also added. A 2-5-year follow-up study showed all patients were relieved from pain initially, and could ambulate early following the operation. The vertebral displacement did not increase postoperatively and solid posterolateral fusion was obtained.


Microneurovascular decompression: early experiences in Srinagarind Hospital.

These results support other studies that indicate that M.V.D. is the best procedure to treat these patients. There are some points to emphasize M.V.D. in order to achieve the best results and lowest complication rate. These include good preoperative patient preparation; more lateral suboccipital craniectomy to expose the cranial nerves with minimal retraction; adequate drainage of CSF from the cistern before attempting to identify the nerve; thorough inspection of the affected cranial nerve, especially in the root entry (exit) zone; adequate mobilization of blood vessels and stable interposition of teflon felt between the blood vessels and the affected nerve.


Computed tomography of spinal tuberculosis.

CT findings of 20 proven cases of tuberculous spondylitis were reported. Vertebral fragmentation and paravertebral abscesses were found to be important findings. CT should be performed in cases without characteristic plain radiographic features and in cases that the extent of the disease is to be evaluated.


Determination of hemoglobin Bart's in alpha thalassemia traits by two-site immunoradiometric assay. II. Detection of hemoglobin Bart's in alpha thalassemia traits.

A sensitive method for the determination of minute amounts of Hb Bart's in hemolysate of alpha thalassemia-1 and alpha thalassemia-2 was carried out by two-site immunoradiometric assay. This technique is very sensitive and is able to detect minute amounts of substances. When this method is used with specific anti-Hb Bart's derived from affinity column chromatography, then labelled with radioactive 125I, the two-site immunoradiometric assay will contain both the sensitivity and specificity for the determination of Hb Bart's. In this study, parents of fetus with Hb Bart's hydrops fetalis contained high levels of Hb Bart's 0.73-1.11 per cent (mean +/- S.D. = 0.86 +/- 0.12%). Parents of Hb H diseases had Hb Bart's in two groups. The first group contained high levels of Hb Bart's of 0.73-1.20 per cent (mean +/- S.D. = 0.88 +/- 0.14%), while the second group had levels of 0.39-0.45 per cent (mean +/- S.D. = 0.42 +/- 0.02%). Mothers of patients with Hb H disease contained Hb Bart's of 0.42 +/- 0.48 per cent (mean +/- S.D. = 0.45 +/- 0.02%). Eight out of ten normal subjects contained low levels of Hb Bart's of 0.17-0.26 per cent (mean +/- S.D. = 0.22 +/- 0.04%), while two contained high levels of Hb Bart's of 0.46 and 0.43 per cent respectively. The two-site immunoradiometric assay was able to differentiate the level of Hb Bart's among alpha thalassemia-1, alpha thalassemia-2 and normal subjects.


Vascular complications in noninsulin dependent diabetes mellitus (NIDDM) in Srinagarind Hospital, Khon Kaen.

We prospectively conducted a hospital based study to determine the prevalence of vascular complications in NIDDM and their risk factors. Using standard protocol for interviewing, physical examination and laboratory investigations, we studied 207 patients from the diabetic clinic and medical outpatient department (ratio 3.9:1) by systematic sampling. The prevalence of hypertension, coronary heart disease cerebrovascular disease, peripheral and large vessel disease was 22.2, 22.2, 8.2, 21.3 and 34.8 per cent respectively. We found that the prevalence of small vessel disease, retinopathy and nephropathy was 34.3, 25.1 and 12.5 per cent respectively. The complications were slightly higher in females and increased with duration of diabetes. By univariate and logistic regression analysis, we found that the risk factors of large vessel disease were body mass index, diastolic blood pressure, duration of diabetes and for small vessel disease were duration of diabetes and high uric acid.


Prediction of low birth weight outcome in Thailand: multiple regression analysis.

In the present study the risk approach using maternal risk factors for LBW newborns in Thailand is applied. The study may be considered as a managerial tool for developing local strategies and is particularly useful in maternal and child health care. The main objective is to develop a model to predict LBW outcome with an aim to screen those at risk at the level of health centres, district and provincial hospitals. Using MLR analysis, it is concluded that Model I and Model II (Table 3 and 4) can be used to predict which pregnant women are likely to deliver LBW newborns. The prediction can be made as early as the first trimester. If the prediction is shown to be accurate, the two models will be very helpful for use in Thai people. For general use, the investigators believe that Model I will be appropriate for application at the level of provincial and district hospitals, while Model II should be used at the health centre level peripheral to the health delivery system.


Outcomes of pregnancy in adult idiopathic thrombocytopenic purpura.

The outcomes of 39 pregnancies in 36 idiopathic thrombocytopenic purpura (ITP) patients were analysed. Among the 36 pregnant patients, 23 had active ITP (platelet count < 100,000 per mm3), 12 had inactive ITP, during pregnancies, while one patient had active and inactive ITP during each of her two pregnancies. Maternal bleeding during delivery occurred more commonly in thrombocytopenic patients and was more frequent by cesarean section than by vaginal delivery. There was a 56 per cent incidence of neonatal thrombocytopenia. Maternal platelet count had no predictive value for neonatal thrombocytopenia. There was no serious bleeding among neonates born from thrombocytopenic mothers. In our experience, vaginal delivery was a relatively safe procedure for delivering small neonates from multiparous ITP mothers. Cesarean section should be used to deliver relatively big neonates especially from primigravida ITP mothers and splenectomy should be done at the same time.


Carbamate insecticide and myocarditis.

The report of a 25-year-old Thai woman who came to the emergency room of Chulalongkorn Hospital dead on arrival. The gross and microscopic anatomic findings of lungs were compatible with carbamate poisoning which was confirmed by the analysis of the liver. Another important finding was profuse myocarditis which might be another cause of death. We found no relationship between myocarditis and carbamate poisoning in previous reports. (Computerized search by Medline).


True hermaphrodite, 46,XX/46,XY karyotype with surgical reconstruction of ambiguous genitalia: a case report and literature review.

A 17-year-old phenotypic female with ambiguous genitalia is presented. The patient complained of progressive dysmenorrhea, passing urine and menstrual blood through the same opening since menarche. Pelvic examination revealed and enlarged clitoris with prominent phallus, an enlarged right labio-scrotal fold with palpable gonad and a 3 mm diameter opening of both the urethral meatus and vaginal orifice at the vestibule. Chromosome analysis showed 46,XX/46XY karyotype. Laparotomy via right inguinal incision confirmed true hermaphroditism because of finding a right unilateral ovotestis. Factors leading to delay in presentation are discussed and the need for early diagnosis and management is emphasized. The clinical, cytogenetic features, gonadal histology and management are described and discussed.


Intracerebral hematoma caused by sparganum: a case report.

Cerebral sparganosis is caused by migrating larvae of Spirometra mansonoides. This condition is rare. The presenting symptoms include headache, seizures and focal neurological deficit, which are due to a parasitic granulomatous space-occupying lesion. The authors report a case of intracerebral hematoma, which has never been reported as a presenting symptom of cerebral sparganosis. The surgical treatment of this complicated condition yielded poor results when compared to previous reports of the uncomplicated condition.


Severe head injury in a paediatric population.

Forty eight, patients under fourteen years of age, with severe head injury, who were admitted to the Children's Hospital, over a a period of 4 years were studied. During the same period 2500 children with head injury admitted, an incidence 2% approx. The low mortality and the good prognosis of these children is pointed out. The literature is also reviewed and a few conceptions regarding treatment, age of the patients in various series and intracranial haematomas were reconsidered. Extradural and subdural haematomas are excluded from this particular study.


Cavernous sinus tumors: neuroradiologic and neurosurgical considerations on 150 operated cases.

We reviewed the neuroimaging studies of 150 patients with cavernous sinus tumors operated on during an 8-year period. Meningiomas (66 cases), chordomas (18 cases), trigeminal neurolemmomas (12 cases), and chondrosarcomas (11 cases) were the most common diagnosed neoplasms. Neuroradiological findings are briefly described for each different kind of tumor encountered. The surgical impact of these findings is discussed.


The changing panorama of shunt complications. Twenty-five years' experience.

The distribution of shunt complications is analyzed in a series of 226 children and infants out of a total of 978 shunt operations performed between the years 1965 and 1989. The rate of shunt infections and obstructions has decreased significantly during the last ten years while the rate of CSF overdrainage complications has increased. A policy of active, elective shunt revisions has led to a reduction in the total rate of shunt revisions required. As only minor changes in the shunts available and used have taken place during the period converted, it is concluded that the main reason for the changing panorama of shunt revisions lies in improved neuroimaging and a better knowledge of complying with shunt complications.


Hydrocephalus, lumbar canal stenosis and Maroteaux-Lamy syndrome (mucopolysaccharidosis type 6). Case report.

A case of communicating hydrocephalus and lumbar canal stenosis in a child with mucopolysaccharidosis type 6 is reported. We review the literature and discuss the aetiology of communicating hydrocephalus in this condition.


The role of CSF ventricular drainage in controlling intracranial hypertension in patients with brain lesions. Comparison of three methods. Preliminary results.

Results obtained with three different CSF ventricular drainage methods (intermittent with no outflow resistance, continuous against a positive pressure, continuous with pre-arranged positive pressure), were evaluated in fifty nine cases of traumatic cerebral lesions and spontaneous intracerebral hematomas with intracranial hypertension. Continuous CSF withdrawal gives better clinical results and is more effective in controlling intracranial pressure than intermittent drainage (50% vs 13% successes respectively). Results obtained with continuous drainage against a steady positive pressure and with a pre-arranged pressure ("tidal drainage") are almost similar. However an outflow resistance 3-5 mmHg higher than diastolic level of ICP represents a rational approach to the problem.


[Genetic background of bronchial asthma].

Familial aggregations and genes for atopy, airway hyperresponsiveness, and serum IgE were studied in 69 members of five atopic asthmatic families spanning three generations. Atopy was found in 68%, bronchial asthma in 26%, airway hyperresponsiveness in 45%, and positive mite allergen in 59%. Both atopy and airway hyperresponsiveness were inherited in an autosomal dominant fashion, but were not related to each other. No linkage was found of HLA with atopy and mite positivity. T cell gamma receptor gene (7p15), IL-3, IL-4, and IL-5 genes (5q23), and postulated atopic gene (11q13) were all not linked to atopy. However, alle 2.5 kb of 11q13 showed an association with serum IgE level. The beta 2 adrenergic receptor gene (5q31-32) was linked to airway responsiveness to inhaled beta 2 adrenergic agonist, and was associated with the occurrence of bronchial asthma.


[Involvement of cholinergic mechanism in respiratory chemosensitivity to CO2 in humans].

In an attempt to elucidate the role of cholinergic mechanism in respiratory chemosensitivity to CO2 in humans, we examined 17 healthy male volunteers for ventilatory responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia on three separate days in a randomized, double-blind fashion. Pirenzepine, a M1 muscarinic antagonist which does not cross the blood-brain barrier, biperiden, another M1 muscarinic antagonist which is expected to penetrate into the central nervous system, or placebo was intravenously preinjected before the measurement of ventilatory responses. There were no significant differences in the mean magnitude of ventilatory responses among the three experimental days. However, despite the poor correlation between the magnitude of ventilatory response to hypercapnia in the placebo and pirenzepine studies, there was a significant correlation between them when the value in the pirenzepine study was expressed as % of control, value i.e., subjects with greater hypercapnic ventilatory response in the placebo study showed greater declines with biperiden. Since these relations were seen only for the ventilatory response to hypercapnia with biperiden, we suggest that a cholinergic mechanism, particularly the M1 muscarinic receptor, may be involved in chemoreception to CO2 in the central nervous system and constitute the neurochemical background for the interindividual variation in hypercapnic ventilatory response in humans.


Schwannoma of the cavernous sinus. Case report and review of the literature.

A patient operated on for a schwannoma entirely developed into the cavernous sinus is described. Abducens nerve is supposed to be the origin of the tumor, although it could not be identified during the operation. Schwannomas of the cavernous sinus are exceedingly rare lesions. Only four reports exist in the literature. In three cases the tumor arose from the abducens nerve, in one case probably from the trochlear nerve. Direct approach to the cavernous sinus has become possible in recent years, but preoperatively impaired cranial nerve function shows a slim chance of postoperative recovery.


Chondroma of the cervical spinal canal. Case report.

The authors report a case of cervical spinal canal chondroma in a 28 year-old man. The tumor was removed completely. Only about 10 similar cases are reported up to now.


Primary choroid plexus carcinoma in an infant. Report of a case evaluated by MRI.

Primary carcinoma of the choroid plexus is a very rare neoplasm. We report a 17-month old female patient who was evaluated by MRI. The tumor was gross totally removed and radiotherapy was given subsequently. CT and MR correlation and histopathological differential diagnosis criteria of such tumors are discussed with an emphasis on total tumor removal. New chemotherapy regimens are needed for better survival especially in cases of recurrences.


[Hypoxic ventilatory response and hypoxic depression].

We investigated whether or not the adaptation of peripheral chemoreceptor (PCR) activity can contribute to hypoxic ventilatory depression (HVD) during sustained hypoxia for 20 min in both healthy subjects and patients with sleep apnea. Effects of HVD on diaphragm (DIA) and genioglossal muscle (GG) were also assessed. Withdrawal test, which is well established to solely represent the function of PCR, was repeatedly conducted at 5 and 20 min during sustained hypoxic condition. The results suggested that PCR did not play an important role in the development of HVD. When HVD ensued during sustained hypoxia, minute ventilation and EMGDIA were suppressed to the same extent in both groups. On the other hand, EMGGG was strongly and consistently attenuated in OSAS, whereas it was not always the case in healthy subjects. We speculate that treatment for hypoxic conditions can induce improvement of impaired regulation of breathing via central mechanisms, and it can be an important factor reducing the incidence and the severity of upper airway occlusion or collapse.


[Respiratory control in diffuse interstitial lung disease].

Whether the change of lung volume affect ventilatory responsiveness to chemical stimuli has not been studied in patients with interstitial lung disease (ILD). We measured the responses of minute ventilation (VE), tidal volume (VT), and occlusion pressure (P0.1) to hypercapnia (HCVR) and hypoxia (HVR) in these patients. Breathing efficiency (delta VE/delta P0.1) and effective compliance (delta VT/delta P0.1) were also measured under the same stimuli. 1) HCVR and HVR were measured in one female patient with hypersensitivity pneumonitis. VE responses during low VC phase (VC; 71% of predicted value) were similar to that during increased VC phase (VC; normal level) in both HCVR and HVR. However, VT responses of low VC phase were lower than those of increased phase, and P0.1 responses of low VC phase were higher than those of increased VC phase. Both breathing efficiency and effective compliance of low VC phase were lower than those of increased VC phase. 2) Thirty one patients with ILD were divided into two groups: low VC group; VC < 80% of predicted value, and normal VC group; VC > 80% of predicted value. HCVR and HVR were compared between two groups. Mean values of VE response to hypercapnia and hypoxia in low VC group were lower than those of in normal group, although they were not significantly different. VT response to hypercapnia and hypoxia were significantly lower of low VC group than those of normal VC group. Mean values of P0.1 responses to hypercapnia and hypoxia of low VC group were higher than those of normal VC group, although they were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)


Benign solitary nerve sheath tumors of the spinal accessory nerve in the posterior triangle of the neck. Report of two cases.

A case of solitary schwannoma and one of solitary neurofibroma originating from the spinal accessory nerve in the posterior triangle of the neck are described. Location of such neoplasms in this region is exceptional. The authors emphasize the importance of accurately enucleating the mass; when it is impossible to preserve the continuity of the neural pathway, nerve repair should be considered.


[Hypercapnic and hypoxic ventilatory responses in patients with chronic obstructive pulmonary disease].

In patients with chronic obstructive pulmonary disease (COPD), we examined ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR). HVR was with normal limits, although HCVR was decreased in half of the patients. The patients with COPD often developed oxygen desaturation during sleep. Also, they had severe hypoxemia during exercise. High responders both to HCVR and HVR had no hypoxic episode during sleep or exercise. We conclude that hypoxemia during sleep or exercise may be related to both HCVR and HVR.


[Bronchial asthma].

In the first study, to clarify whether increased vagal afferent activity contributes to the increase in ventilatory response to CO2 in patients with asthma, we examined the effects of prostaglandin E2 (PGE2) inhalation on the respiratory response to CO2 in seven normal subjects. After PGE2 inhalation, the ventilatory and occlusion pressure responses to CO2 increased significantly compared with those after saline inhalation, with no increase in respiratory resistance. These results suggest that increase in vagal afferent activity may play a role in the increased hypercapnic response during acute exacerbations of asthma. In the second study, to clarify the reduced respiratory chemosensitivity associated with asthma-related deaths, we examined the hypercapnic and hypoxic ventilatory responses in five patients with near-fatal asthma who were given artificial ventilation and/or became unconsciousness during an acute exacerbation of asthma. Hypoxic ventilatory response was significantly lower in these subjects than in patients with uncomplicated asthma and normal subjects, suggesting that lowered hypoxic ventilatory response may be related to death from asthma.


[Effect of diaphragmatic fatigue on ventilatory response to carbon dioxide].

To clarify the effect of respiratory muscle fatigue on ventilatory response to carbon dioxide, we performed CO2 rebreathing study before and after diaphragmatic fatigue in nine healthy males. Diaphragmatic fatigue was induced by inspiratory resistor loading and confirmed by the increase in Tension Time Index and the decrease in Pdi max at FRC. The effects of diaphragmatic fatigue were as follows: 1) S and B value of VE-CO2 curve did not change. 2) P1-CO2 curve shifted to the left but the slope of the curve did not change. 3) delta Ppl response to CO2 decreased, but delta Pdi response to CO2 did not change. 4) The increase in respiratory accessory muscle EMG was more prominent, compared to diaphragmatic EMG. 5) Rib cage movement became more marked. In conclusion, diaphragmatic fatigue (with 60 percent decrease in Pdi max at FRC) does not affect on ventilatory response to carbon dioxide. To maintain the homeostasis of the chemical ventilatory feedback system, diaphragmatic dysfunction is compensated by the increased activity of respiratory accessory muscles with possible increase in neural drive.


[Exposure to high altitude: ventilatory control in relation to syndromes of high altitude].

To investigate the role of hypoxic ventilatory response (HVR) in the pathogenesis of acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE), we performed two studies. In the first study, nine healthy male lowlanders were exposed to a simulated altitude of 3,700 m (485 Torr) for 24 h in a hypobaric chamber. Subjects (n = 4) with lower alveolar ventilation on arrival at 3,700 m subsequently developed more severe AMS 24 h after the exposure. The relative hypoventilation was related to the lower HVR measured at low altitude, suggesting a possible role of low HVR in AMS. In the second study nine lowlanders with a previous history of HAPE (HAPE-S) and six control subjects were exposed to a simulated altitude of 3,200 m (515 Torr). At low altitude, HVR (delta VE/delta SaO2) in HAPE-S was significantly lower than that of controls (-0.40 +/- 0.20 vs. -0.85 +/- 0.21 L/min/%, p < 0.01). At high altitude HAPE-S showed lower PaO2, higher PaCO2 and lower PAO2, compared with controls, i.e., relative hypoventilation. In one of the HAPE-S, who showed the lowest PaO2 at the simulated altitude, oxygen breathing resulted in a paradoxical increase in ventilation, suggesting hypoxic ventilatory depression. These two studies suggest that low HVR may a contributing rather than a critical factor in the pathogenesis of AMS and HAPE.


[Hyperventilation syndrome].

Of 16 patients with hyperventilation syndrome (HVS), 11 experienced hypoxemic episodes (defined as PaO2 < or = 60 Torr or SaO2 < or = 90%). To investigate the relationship between hypoxemia in HVS patients and their hypoxic ventilatory response (HVR), we examined 9 of 11 HVS patients who experienced hypoxemic episodes after acute hyperventilation attacks. In order to investigate the genesis of hypoxemia after hyperventilation, we also examined minute ventilation and visual analog scale (VAS) scores representing the sensation of dyspnea at the start and at 70% arterial O2 saturation (SaO2) during HVR in 9 normal subjects under isocapnia and hypocapnia following voluntary hyperventilation (VHV). The HVR of 9 HVS patients who experienced hypoxemic episodes was normal. In 9 normal subjects, minute ventilation and VAS scores representing the sensation of dyspnea at 70% SaO2 during HVR were higher under isocapnia than under hypocapnia following VHV (p < 0.01). VAS scores taken during the HVR immediately following VHV and at 70% SaO2 were not significantly different. HVR and VAS scores representing the sensation of dyspnea were decreased under hypocapnia following VHV. These reductions were thought to be the main factors responsible for the genesis of hypoxemia following acute hyperventilation attacks in HVS patients. We conclude that hypoxemia is an important clinical sign in HVS patients, and it is important to investigate the breathing and chemical drive under hypocapnia, in order to understand the chemical regulation of breathing in HVS patients.


[Oxygen-conserving delivery system].

Three methods for improving oxygen delivery efficiency--transtracheal oxygen therapy (TTO), reservoir cannula, and demand-pulse oxygen delivery--are currently available. We discuss our experiences of TTO and its characteristics compared with the other two methods. Since 1988, we have tried to apply TTO to the candidates for home oxygen therapy (HOT) fulfilling the following criteria: 1) good activity and enthusiasm to daily life, 2) high oxygen flow rate with nasal cannula, 3) complicating nasal disorders such as chronic sinusitis, or 4) suffering complications from nasal cannula therapy. We used a disposable 8-Fr feeding tube for a trnastracheal catheter. Patients were taught to change their catheters themselves every day by simply removing the old and reinserting the new catheter. We have experienced nine patients on HOT with TTO. A half to a third of the flow rate of nasal cannular was required with TTO to achieve an equivalent PaO2 level. In cases with hypercapnea, a persistent significant increase of PaCO2 was not found. We measured arterial blood gases, changing the distance from the tract opening to the catheter tip, and it was suggested that in each case there may be an optimum distance to achieve the highest PaO2 level. Seven cases received TTO for more than 18 months, a mean of 30.2 months (range 19.3-48.9) and HOT for a mean of 26.6 months. They all maintained a high degree of enthusiasm for TTO. Two cases could return to work. Five cases enjoyed active daily lives, such as shopping, going out for recreation, travelling, and attending concerts.(ABSTRACT TRUNCATED AT 250 WORDS)


[Home oxygen therapy using liquid oxygen system].

Home oxygen therapy (HOT) for patients with chronic respiratory failure has been believed to increase the quality of life and to improve the prognosis of such patients. In Japan, HOT for chronic respiratory failure has been supported by health insurance since March 1985. Since then, patients with HOT have increased progressively, and it has been reported that there are now over 20,000 patients with HOT. The oxygen concentrator which extracts oxygen from atmospheric air has been commonly used as the oxygen delivery system. Recently the liquid oxygen system has provided an attractive, convenient source of oxygen. Since April 1990, HOT using liquid oxygen system has been supported by health insurance, and its use will become widespread in Japan. A major characteristic of this system is that oxygen condensed into a liquid form allows storage of a larger supply. This system consists of two parts: stationary type which stores the liquid oxygen, and a portable type which can easily be refilled with oxygen a larger source. In the present study, we examined the efficacy of portable liquid oxygen in 50 patients with chronic pulmonary diseases including patients with chronic respiratory failure who had PaO2 < 55 mmHg during air breathing. We measured changes of ten minutes walking distance (10 MD) and blood gas analysis with and without portable liquid oxygen. We also performed on estimation of efficacy of liquid oxygen by questionnaires in patients receiving liquid oxygen for HOT. We did not find a significant improvement of 10 MD with portable liquid oxygen, but found a significant improvement of arterial oxygen tension at the end of walking.(ABSTRACT TRUNCATED AT 250 WORDS)


[The introduction of home mechanical ventilation in Japan].

In the same context as home oxygen therapy in Japan, there is an urgent need to establish a home mechanical ventilation (HMV) support system for clinically stable patients dependent on long-term mechanical ventilation who wish to spend their lives outside institutions; at home in the community. We have cared for 3 HMV cases as long as 8, 5 and 2 years. All patients suffer from respiratory muscle paralysis with chronic neuromuscular diseases and require CMV mode mechanical ventilation for 18 to 24 hours/day using electrically drived portable ventilators connected to a tracheostomy tube. They need no oxygen supplementation. All patients clearly expressed a desire for the life style with HMV. Their families as the main caregivers willingly received the necessary training and mastered the techniques quickly, including AMBU-bag manual ventilation for occasional ventilator troubles, and bronchial hygiene. Our experiences of three HMV cases may be local and limited, but reveal the potential significance and technological possibility for home application of the care techniques that have been developed on or in-patient basis. The nationwide surveys of the status of patients requiring long-term mechanical ventilation for more than 3 months of duration by Suetsugu et al. (supported by Respiratory Failure Research Council of Health and Welfare Ministry) (1987, 1988 and 1989) listed 53 HMV cases in 1989 and revealed a slowly increasing trend from the 17 cases in 1987. However, it is important to recognize that the true medicosocial establishment of HMV in Japan is still behind and should be an urgent goal of respiratory care programs.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of home oxygen therapy on prognosis of patients with chronic pulmonary disease associated with pulmonary hypertension].

We prospectively elucidated the effect of home oxygen therapy (HOT) on the prognosis of patients with chronic pulmonary disease associated with pulmonary hypertension. One hundred and twenty-seven patients with pulmonary hypertension (mean pulmonary arterial pressure > or = 20 Torr) participated in this study. Fifty-four patients had chronic pulmonary emphysema, 5 chronic bronchitis, 19 diffuse panbronchiolitis, 29 old tuberculosis, 8 pulmonary fibrosis, and 12 other diseases. Fifty-one patients died of respiratory failure. The survival curve of patients who received HOT was not different from that of patients who did not receive HOT, although FEV1 and PaO2, both prognostic factors, were significantly worse in the patients who received HOT than in the patients who did not receive HOT. In the patients with COPD, the survival rate of patients who received HOT was significantly higher than that of those who did not receive HOT. The mean survival time of the patients who received HOT was significantly longer than that of the patients who did not received HOT (1971 +/- 217 SEM days and 978 +/- 156 days, respectively). From these data, we conclude that HOT improves the survival of patients with chronic pulmonary disease, especially COPD, associated with pulmonary hypertension.


[Psychosocial features of the patients with home oxygen therapy].

Home oxygen therapy (HOT) has released patients with chronic respiratory failure (CRF) from hospitalization for the rest of their lives, and has brought some relief from their physical restriction due to CRF. However, some new psychosocial problems have arisen from this home care treatment. Research has been performed on 85 patients in our hospital by: (1) comprehensive psychosomatic questionnaire for patients with long-term oxygen therapy, (2) CMI, (3) SRQ-D (depression), (4) MAS and Questionnaire C of JMHW-CRF research group. The results of (1) indicated some problems in the majority of patients. Also in SRQ-D, about half of the patients showed a depressive state. In MAS, more than a few patients revealed a high anxiety level concretely, recognized psychosocial problems with loss of desire for treatment pessimism recording their prognosis, in addition to loss of QOL. All the above and an understanding by the staff of the psychosocial situation of patients and a grasp of their mental state are extremely important in the long-term care of HOT patients.


[Nursing care of long-term oxygen individuals in the home].

The system and experience of home care for patients with chronic lung disease in Urasoe Sougou hospital was reviewed from nursing points of view. Home oxygen care was started in October, 1984. The Health Care Department (HCD) was established in July, 1988 to provide both various home cares and daycare services for the aged. The number of personnel (public health nurses, registered nurses) were increased year by year to 15, include one physician as a medical director. They worked on a full-time basis in home care. The roles of the HCD in home oxygen care are 1) direct nursing services, medical and psychological assessment, consultation, education for patients in the home. 2) exchange informations, coordination and scheduling among physicians, in-hospital care team and durable medical equipment companies. Quality of care on 65 patients between before and after the establishment of the HCD were compared to assess the efficacy of system. Quality of care were measured by several items; 1, frequency of home visit. 2, medical, psychological assessment. 3, patient's ability to understand and accept the disease state and home care, to do self-responsible procedures (bronchial hygiene, medication, bathing, etc.), and to handle the equipment. 4, assessment on patient's daily activities and environments. After the establishment of the HCD, quality of care has been improved. On 10 patients in the remote locations or islands, the HCD exchanged informations and coordinated with the community public health nurses and local practitioners. These experience suggests full-time home care team like the HCD contribute to improve both quality of care and quality of life of patients.(ABSTRACT TRUNCATED AT 250 WORDS)


[Mechanisms of clearance of foreign bodies by macrophages].

Macrophages have specific functions related to the sites where they are found. Pulmonary alveolar macrophages (PAM) may play an important role the clearance of invading and degenerative substances from the alveolar spaces. To clarify the mechanisms of the clearance by macrophages, we studied the role of scavenger receptors (SR) and Fc receptors (FcR) of PAM. 1) SR: Expression and localization of SR in human PAM. Type I and II SRs were expressed in human PAM, and the two SRs were confirmed in the same cells by double staining method using polyclonal antibodies to the SRs. These SRs were localized on the cell membrane and the endosome in part. The expression of SR in PAM from normal nonsmokers, smokers and patients with pneumoconiosis was studied, but there were no differences among these groups. Kinetics of SR and acetylated low density lipoprotein (acLDL) in PAM. SR recognized acLDL, and SR and acLDL-Au conjugates were concentrated in a coated pit 2 min after incubation. The conjugates were then internalized in the endosome 5 min after incubation. A few acLDL-Au conjugates were present in the endosome near the nucleus, but most of them were found in the lysosome 10 min after incubation. SR was found in the Golgi apparatus 15 min after incubation. These results suggest that SR in PAM may play an important role in the removal of alveolar surfactant. 2) FcR: Effects of FcR mediated phagocytosis on O2-release and phagosome-lysosome fusion in the phagosome of PAM.(ABSTRACT TRUNCATED AT 250 WORDS)


[Induction of tumor cell killing by human alveolar macrophages and its regulation by IL-4].

The present study was undertaken to examine the effects of IL-4 on induction of cytotoxic killer activity and on production of antitumor mediators by human monocytes and alveolar macrophages (AM). The spontaneous tumoricidal activity of AM was slightly suppressed by IL-4. Addition of IL-4 to cultures of AM or monocytes with endotoxin resulted in dose-dependent suppression of their cytotoxic activity against A375 and its variant cells resistant to IL-1 and TNF-alpha. IL-4 inhibited the production of IL-1 and TNF-alpha by AM at the protein and mRNA levels. Oxygen radical production was also suppressed by treating AM with IL-4. IL-1 receptor antagonist (IL-1ra) was also produced by monocytes stimulated with LPS, but not with IL-4. Marked up-regulation by IL-4 of IL-1ra production in LPS-stimulated monocytes was observed at both the mRNA and protein levels. These findings suggest that IL-4 may be important in down-regulation of antitumor activation of human monocyte-macrophages, not only directly through inhibition of production of antitumor effector molecules, but also indirectly through up-regulation of production of IL-1ra.


[Expression of angiotensin II receptor on BALF macrophages from patients with sarcoidosis and healthy individuals].

We previously reported that angiotensin II (A-II) enhanced the accessory function of BALF macrophages in some patients with sarcoidosis. We hypothesized that this finding was mediated by the A-II receptor on BALF macrophages. From this viewpoint, we investigated the expression of A-II receptor on BALF macrophages. The binding of 125I-A-II to BALF macrophages was specifically inhibited by unlabeled A-II when incubated for 1 hour at 37 degrees C. However, the uptake of 3H-inulin to BALF macrophages was not inhibited by unlabeled inulin under the same conditions. These findings indicate that the binding of 125I-A-II to BALF macrophages was mediated by the putative A-II receptor, and was not due to pinocytosis.


[Coronet status of digital radiography in chest medicine].

It has been ten years since Computed Radiography (CR) was introduced to evaluate its efficacy on the diagnosis of chest diseases in Japan. Over 600 CR systems are in their daily clinical use. CR images improve the quality of chest X-ray diagnosis with its enhancement parameters, that is, the digital image's contrast and edge enhancement. In daily clinical work, however, some abnormalities on the images, such as infiltrative shadows and fine miliary shadows, have shown CR imaging to have no superiority in visualization compared to conventional X-ray films. The quality of CR images greatly depends on the reconstruction algorithm. The diagnostic system of CR images using CRT monitor and workstations will be warranted in order to make the CR system the optimal and most useful modality in chest medicine. The CR system is potentially applicable in Picture Archiving and Communication System (PACS).


[CT diagnosis of diffuse lung disease].

The first HRCT of the lung was obtained in 1979 in Japan. Since then, CT-pathologic correlations have been performed in the major diffuse lung diseases. For this purpose, lung specimens were fixed in the inflated condition, which enables precise stereomicroscopic observations to be performed on sliced lung specimens. The first successful correlation was performed in diffuse panbronchiolitis (DPB), where nodular densities in HRCT were proven to correspond to chronic inflammation in the respiratory bronchioles and their neighboring structures. However, further investigation of the correlations are required in diffuse lung diseases showing ground glass-like densities in CT, since this finding is nonspecific and may occur in both airspace and interstitial lung disease.


[Evaluation of mediastinal lymph nodes by computed tomography in lung cancer].

It is important to evaluate hilar and mediastinal lymph node metastasis accurately, since the findings are used to determine the indications for therapies and to estimate the patient's prognosis. Computed tomography (CT) is a useful method for this purpose, but it is known that healthy people may also have lymphadenopathy up to 10 to 15 mm, and metastasis is sometimes observed in lymph nodes less than 10 mm in cases of adenocarcinoma. For this reason, it is necessary to establish an optimal criteria for measured values of lymph nodes on CT images. In this study, we compared the size of mediastinal lymph nodes on CT images and histological findings in 425 lymph nodes of 153 primary lung cancer patients resected in our hospital from 1984 to 1991. Criteria were expressed as possible criteria which can be obtained from ROC analysis with compatibility of sensitivity and specificity, and definite criteria which offer highest efficiency. We analyzed these two criteria by minor axis, major axis, their sum, and their product. As a result, minor axis offered the best criteria. The value of possible criteria was 8.7 mm (sensitivity: 73%, specificity: 70%) and definite criteria was 13 mm (efficiency: 88%) in 425 lymph nodes. Analyzed by histological type, the criteria of epidermoid carcinoma (possible criteria: 9.5 mm, definite criteria: 13 mm) were larger than those of adenocarcinoma (possible criteria: 8.3 mm, definite criteria: 11 mm). Analysed by anatomical region and histological type, the criteria of epidermoid carcinoma varied by with the location of lymph nodes, but those of adenocarcinoma were almost constant.(ABSTRACT TRUNCATED AT 250 WORDS)


[Pulmonary arteriography and bronchial arteriography in pulmonary embolism].

Pulmonary arteriography is the most reliable technique for evaluation of pulmonary embolism and other vascular abnormalities. A definitive diagnosis of pulmonary embolism is made on the basis of direct angiographic signs of emboli of intravascular filling defect and vessel cut-off sign. To obtain these findings, pulmonary arteriography needs to be performed as soon as possible, and in acutely ill patients who are in shock and under consideration for thrombolytic therapy or emergency embolectomy, the study should be performed on an emergency basis. Digital subtraction pulmonary angiography may be an useful technique for massive pulmonary embolism, but it cannot exclude clinically important peripheral pulmonary embolism. Wedged pulmonary arteriography can demonstrate the direct signs of distal emboli, which are difficult to obtain by main pulmonary artery injection angiogram. In the chronic stage of pulmonary embolism, bronchial arteriogram shows collaterals to pulmonary arteries. This study may be useful in patients with chronic pulmonary embolism, especially when thromboembolectomy is planned.


[Diagnosis of respiratory system diseases using radio isotopes].

Common respiratory diagnostic imaging techniques using radioisotopes are ventilation-perfusion, perfusion, aerosol inhalation and tumor scintigraphy. The special features of respiratory imaging diagnostic techniques using radioisotopes are the possibility of early detection of disease and the non-invasiveness of the procedure. Also, no patient effort is required. The kinds of isotopes used are as follows: ventilation-perfusion (133Xe, 13N, 99mTc-pseudogas), perfusion (131I, 99mTc), aerosol inhalation (99mTc), tumor (67Ga, 201Tl). The advantages of these procedures are expected to lead to further developments in respiratory examinations using radio isotopes.


[Studies on the regulation of normal bronchial epithelial cell proliferation and proto-oncogene expression].

The regulatory mechanisms of proliferation and differentiation of normal airway epithelial cells seem important for the better understanding of lung carcinogenesis. We isolated bovine and human bronchial epithelial cells by enzymatic digestion of bronchi, and cultured them in serum-free growth factor-supplemented medium. To determine the role of growth factors in the proliferation of bovine bronchial epithelial cells, the effect of each of these additives was evaluated. Of these, fetal calf serum (FCS), bovine pituitary extract (BPE), insulin and insulin-like growth factor-1 (IGF-1) showed a significant stimulatory effect on cell growth. These four additives induced transient increases in c-fos, c-jun and c-myc proto-oncogene mRNA levels. Transforming growth factor beta (TGF beta) inhibited growth factor-induced cell proliferation, and also showed selective inhibition of c-myc induction. We also studied the effect of interleukin 6 (IL-6) on human bronchial epithelial cell proliferation. IL-6 showed a significant inhibitory effect on cell growth. These cells were capable of expressing and releasing IL-6 and had specific receptors for IL-6, suggesting an autocrine mechanism. These results suggest that TGF beta and IL-6 may play roles in the regulation of airway epithelial cell growth as inhibitory growth factors.


[MRI of the thorax; clinical application and efficacy in 100 thoracic diseases].

We carried out a retrospective analysis of about 100 surgical cases of mediastinal, pleural, chest wall and pulmonary disorders in order to determine the clinical application and efficacy of MRI (magnetic resonance imaging) of the thorax. Coronal and/or axial image of T1-weighted images were obtained in all cases, and T2-weighted or gadolinium-DTPA contrast-enhanced T1-weighted images were additionally obtained in several selected cases. All MR images were compared with findings of chest X-ray, CT and IVDSA (intravenous digital subtraction angiography) as appropriate. As a result, MR images were considered to provide additional information to that obtained by conventional techniques of chest X-ray and CT, in demonstrating chest wall invasion of pulmonary carcinoma, detecting hilar masses, which were difficult to distinguish from vessels, and in defining mediastinal masses. The anterior segment of the diaphragm is clearly depicted, aiding the differentiation of Morgagni hernia from other entities. Tuberculoma showed peripheral enhancement in Gd-enhanced T1 WI, which was distinctly different from the enhancing pattern of carcinomas. With the use of surface coil, the pleura and chest wall anatomy were clearly demonstrated. It is hoped that the wide application of this technique will increase the diagnostic accuracy of chest wall tumor invasion.


[Application of ultrasonography in chest diseases--usefulness of ultrasonography and physiologic evaluation of low pressure vascular system].

Air and bones, which limit echo penetration to the lesion, are the major components of the thorax. Recently, however, there have been many reports concerning the valid application of ultrasonography for evaluation of chest diseases. In this paper, we report the usefulness of ultrasonography to analyze thoracic lesions based on our experience. Generally, ultrasonography is a method providing high resolution and real-time images. Using these characteristics, we tried to obtain physiological information concerning the hemodynamics of the right heart system. We addressed the results of our studies using ultrasonography as follows; 1) relationship between ventilatory change of IVC and central venous pressure, 2) estimation of pulmonary arterial pressure by measuring the size of the pulmonary artery, 3) dynamic changes of SVC configuration.


[Cytogenetic analysis of lung tumors by in situ hybridization with chromosome-specific DNA probes].

Fluorescent in situ hybridization (FISH) with biotinated chromosome-specific repetitive DNA probes was used for the cytogenetic study of lung tumors and three cell lines of human lung cancer. The authors utilized a set of satellite DNA probes, specific for chromosomes 7, 17, X, Y in order to detect numerical chromosome aberrations in tumor cell nuclei. Normal diploid human lymphocyte nuclei, which served as the control, have have two signal spots in 95% of nuclei in response to 7, 17 chromosome probes. However, lung cancer cells have numerical heterogeneity, and copy numbers as determined by FISH were not definite with each probe. Discrepancies between cytogenetic and flow cytometric studies in the detection of aneuploidy in some tumors were shown. The number of FISH spots showed a correlation only with the Ki-67 labeling index expressed in proliferating cells. Loss of the Y chromosome in a high percentage of cells was seen by FISH in some tumors from male patients. These data indicate that FISH with chromosome-specific repetitive DNA probes can serve as a cytogenetic tool for the analysis of interphase nuclei of lung tumors with respect to the detection of numerical chromosome abnormalities.


[Analysis of oncogenes and suppressor genes in lung cancer and bronchial lesions from high risk group].

The authors investigated methods for analysis of oncogenes and tumor suppressor genes in lung cancers and bronchial lesions from high risk patients (retired poison gas factory workers). Amplifications of C-, L-, N-myc, length of terminal repeat array (TRA), mutations of p53 gene, p53 mRNA and K-ras genes were analysed in frozen specimens of surgically resected lung cancers. Various lesions including dysplasia, squamous metaplasia, goblet cell metaplasia, and basal cell hyperplasia were detected in the bronchial epithelium of biopsied specimens from retired poison gas factory workers. Analysis of p53 gene and k-ras gene mutations was performed on these formalin fixed, paraffin embedded samples, but no evidence of mutation has been found to date.


[Induction of tumor immunity by cytokine cDNA transfected Lewis lung carcinoma].

It is difficult to induce anti-tumor immunity in tumors with low antigenicity. In order to develop a more effective method of immunotherapy, we transfected interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6) genes into Lewis lung carcinoma (LLC) cells. Then, 1 x 10(6) LLC-IL-2, LLC-IL-4 or LLC-IL-6 cells were transplanted into C57BL/6 mice subcutaneously. All mice transplanted with LLC-IL2 and half those with LLC-IL-4 rejected the tumor cells. Survival time of LLC-IL-6 transplanted mice was significantly shorter than that of LLC transplanted mice, with no difference in tumor growth. These data suggest that transplantation of IL-2 or IL-4 gene transfected cells could effectively induce immunity against LLC. IL-6 transfection did not induce immunity, but induced cachexia.


[Biochemical and clinical aspects of pulmonary surfactant proteins].

Pulmonary surfactant is a complex mixture of phospholipids and proteins which is synthesized and secreted by alveolar type II cells. Its presence is essential to prevent the collapse of alveoli at the end of expiration. Recently, it has been demonstrated that in addition to its reduction of surface tension of alveolar surfaces, pulmonary surfactant exhibits several other functions in the alveolar lining layer, and surfactant proteins are definitely involved in the expression of these functions. The present study first focused on the recent advances in basic research of hydrophilic surfactant apoproteins, SP-A and SP-D. Both are glycoproteins with C-type lectin structure at the C-terminal region and collagenous structure at the N-terminal half of the proteins. We revealed that SP-A binds specifically to dipalmitoylphosphatidylcholine and galactose-ceramide and asialo GM2, while SP-D binds specifically to phosphatidylinositol and glucose-ceramide. We discuss the physiologic and metabolic roles of the specific lipid binding with surfactant proteins of the surfactant system. We next studied changes in pulmonary surfactant in respiratory diseases using anti-human SP-A monoclonal antibodies. We demonstrated SP-A immunoglobulin complex in the sera of patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis.


[The role of muscarinic receptor subtypes in feline tracheal submucosal gland secretion].

To determine what muscarinic receptor subtype regulates the rise of intracellular calcium concentration ([Ca2+]i) and resultant airway submucosal gland secretion on muscarinic receptor stimulation, we examined the effects of atropine (ART), pirenzepine (PZ), 11([2-(diethylamino) methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pirido (2,3-b)(1,4)-benzodiazepine-6-one (AF-DX116) and 4-diphenylacetoxy-N-methylpiperidine methiodode (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, mucus glycoprotein (MGP) secretion and electrolyte secretion from submucosal glands isolated from feline tracheae. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura2. We determined MGP secretion by measuring trichloroacetic acid (TCA)-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP and ATR against MCh (10(-5) M)-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M and 6 x 10(-9) M, respectively. IC50 values of these antagonists against MCh (10(-5) M)-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na-efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M ATR (p < 0.01, respectively), but the inhibitory effect of PZ (10(-7) M) was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)


[Characterization of a receptor for interleukin-5 on pulmonary eosinophils with eosinophilic pneumonia].

Interleukin-5 (IL-5) acts on eosinophil differentiation and activation, suggesting the existence of a membrane receptor for IL-5 on eosinophils. Here, we report that 125I-labeled recombinant human IL-5 bound to high affinity receptors on human eosinophils, especially pulmonary eosinophils in eosinophilic pneumonia obtained bronchoalveolar lavage (BAL). No specific binding occurred on neutrophils, nor on the undifferentiated eosinophilic cell line. EoL-3, in the absence of stimulation. The specific binding of IL-5 was induced by incubation at 37 degrees C of human eosinophils and EoL-3 cells with GM-CSF and with the supernatants of BAL cells from patients with eosinophilic pneumonia. These results indicate the existence of a specific binding site for IL-5 on human eosinophils with variable affinity in eosinophil hypodense or normodense subpopulations, as previously reported for other membrane receptors. Furthermore, lung cells (BAL cells) in patients with eosinophilic pneumonia may be involved in the production certain eosinophilopoietic growth cytokines such as IL-3, GM-CSF and IL-5.


[Interleukin 6 receptors on human bronchial epithelial cells].

It has been suggested that a variety of cytokines may play important roles in the regulation of immune and inflammatory responses in the lung. The purpose of this study was to determine whether interleukin 6 (IL-6) could affect the cell growth of human bronchial epithelial cells via a specific receptor for IL-6. Human recombinant IL-6 inhibited the cell proliferation in a dose-dependent manner. Binding assay with radiolabelled IL-6 demonstrated that human bronchial epithelial cells had specific receptors for IL-6. Moreover, Northern blot analysis using digoxigenin-labelled IL-6R mRNA expression in these cells. Interestingly, proinflammatory cytokines IL-1 alpha and IL-6 upregulated IL-6R mRNA levels. These results suggest that IL-6 may affect the functions of bronchial epithelial cells via a specific receptor, and that its activity on cells may be regulated at the level of receptor-cytokine binding.


[Functional evaluation of possible cytokine receptors on airway smooth muscle: modification of airway smooth muscle responses by cytokines].

Recently, the role of activated T-cell derived cytokines in the pathophysiology of asthma has been recognized. In this study, we evaluated the effects of interleukin-2 (IL-2) and gamma interferon (IFN-gamma) on contractile and relaxing responses of guinea-pig tracheal strips in isometric tension measurement system. IL-2 enhanced carbachol (Carb)- and KCl-induced contraction, and attenuated isoproterenol (Iso)-induced relaxation. IFN-gamma had little effect on Carb and KCl contraction, but enhanced Iso relaxation. These effects of cytokines were abolished by denuding epithelium from tracheal strips. These results suggest that IL-2 and IFN-gamma are able to affect functions of non-immune cells in the airway, and that the airway epithelium has some role in the effects of cytokines on airway responses.


[Diversity of T-cell antigen receptor response in individuals with sarcoidosis].

T-lymphocytes recognize specific antigen(s) through T-cell antigen receptors (TCRs). There are two classes of TCRs: those composed of alpha beta chain dimers and those formed by gamma delta dimers. Although the pathogenesis of sarcoidosis is still unclear, participation of exogenous antigen(s) is highly suggested. To investigate the mechanism of activation and accumulation of T-lymphocytes at the sites of disease, the bias of TCRs in individuals with sarcoidosis was evaluated with respect to several points. Eighteen of 51 cases of sarcoidosis showed increase of gamma delta-TCR positive T-lymphocytes in the blood. In contrast to the blood, a low number of gamma delta T-cells and evidence of T-cell stimulation through alpha beta-TCR were observed in the lung. The TCR junctional regions of V gamma 9, V delta 2 and V beta 8 gene segments were sequenced from blood and lung T-cells of individuals with sarcoidosis and normal subjects, using RT-PCR. In normals, a huge diversity of the junctional region sequences was observed in V gamma 9, V delta 2 and V beta 8 transcripts in the blood and lung. In contrast to normal subjects, a subgroup of sarcoidosis showed an increase of V gamma 9 transcripts sharing identical sequences. Although less marked than for V gamma 9, an increase in identical junctional region sequences was also observed in V delta 2 transcripts. All junctional region sequences of V beta 8 transcripts in the blood and lung were unique, indicating polyclonal activation of T-cells through TCR beta-chain.(ABSTRACT TRUNCATED AT 250 WORDS)


[67kDa-laminin receptor in human lung cancer].

Complimentary DNA for the 67kDa-laminin receptor was cloned from the cDNA library derived from a human lung cancer cell line, and the nucleotide sequence was determined. Expression of the gene was estimated by Northern analysis in various types of human lung cancer. As a result, increased expression of the laminin receptor was demonstrated especially in the cell types of small cell cancer and bronchioloalveolar cell cancer, which are aggressive biologically. Antibody raised against a partial sequence of the polypeptide was prepared for immunodetection of 67kDa-laminin receptor. It was shown that immunohistochemistry with the antibody could be applied to diagnostic use in lung cancer. The results also suggest that the laminin receptor polypeptide is not necessarily a membrane-associated protein and may function without further processing to the receptor.


Substance abuse in head injury rehabilitation.

The desire for relief of discomfort appears to be universal, and the fact that certain chemicals can provide relief from physical/emotional discomforts may understandably result in recourse to them. Various factors may result in these chemicals having deleterious effects, either because of toxicity, addiction, or adverse sociocultural consequences. The widespread use of these chemicals and their manifold effects warrant increasing study and familiarity with patterns of abuse, etiology, and management on the part of all who are involved in the delivery of human services.


[The use of the pupillometric gauge by the nurses' aide].

To test the use of the "pupillometer tongue depressor" by auxiliary nursing was the goal of this study. The same evaluation used by nurses was performed in this group. After explaining the use of the device, each auxiliary nursing registered on a "Card-test" the value of the two circles, which diameters were equal or unequal. Afterward, a pair of the auxiliary nursing evaluates the pupil diameter of one patient. The accuracy of the millimeter circles was very high but not the effectiveness of the pupil diameter measurement. Nearly 1/3 of the auxiliary nursing referred difficulties in performing this evaluation.


[The use of new dressing resources in the nursing consultation].

The author performed the treatment of infected or non-infected wounds with the association of papain and 2 types of synthetic dressings: activated charcoal cloth dressing and hydrocolloid dressing. Eighteen (18) patients, mean age 58.4 years, were followed during 20 dressings. The treatment period was 2 1/2 months-3 months. The infected wounds were treated with the activated charcoal cloth dressing and the non-infected wounds with the hydrocolloid dressing. The evolution of wound healing until the tenth dressing, (about 1 month of treatment) showed that area initially affected was reduced between 48.6% and 89.7% until the twentieth dressing.


[Pain: its occurrence and evolution in the postoperative period of heart and abdominal surgery].

The high incidence and low resolution of the pain after surgery are shown in international literature. During the five days after the cardiac and abdominal surgery, these patients were asked once a day about their pain. Nearly 50% of the patients answers showed pain complaints. At the cardiac patients 47% did not take treatment during the last four hours, although the medicine was prescribed by the doctor to be used in eventual necessity. Similar occurrences happened with abdominal patients where no medicine was given in 68.2% events of their pain complaints. So, we find that the under-identification and undertreatment of the pain are like the other studies.


Expression of Mn-superoxide dismutase in carcinogenesis.

Human liver manganese superoxide dismutase (Mn-SOD) was highly purified by a simple procedure and crystallized. A monoclonal antibody against Mn-SOD, whose antigen-binding epitope is a C-terminus peptide was developed. Using this antibody, an enzyme-linked immunosorbent assay (ELISA) was developed. We found that Mn-SOD is highly expressed in human ovarian cancer and the serum level of the enzyme is a useful marker for the diagnosis and monitoring of the epithelial type of ovarian cancer. Tumor necrosis factor-alpha (TNF), lipopolysaccharide, IL-1 and phorbol ester induced the m-RNA of Mn-SOD as well as protein levels in TNF-resistant cells. No such induction was observed in Cu, Zn-SOD. Studies on the induction mechanisms indicated that at least two separate signal-transducing pathways are involved in expression of the Mn-SOD gene. One is triggered by protein kinase C activation itself in the absence of new protein synthesis. The other can be activated by stimulations with various cytokines in which a protein factor that can be induced by phorbol ester treatments is involved.


Role of intestinal microflora in metabolism of glutathione conjugates of 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide.

DNA adduct formation in the liver of B6C3F1 mice after administration of 1-nitropyrene (1-NP) was shown by the 32P-postlabeling technique. The major adduct was not N-(deoxyguanosin-8-yl)-1-aminopyrene, which was easily formed in in vitro nitroreduction of 1-NP in the presence of DNA, but the major spots migrated to the same position as the in vitro DNA adduct spots of K-region epoxides of 1-NP (1-NP 4,5- and 9,10-oxide). 1-NP oxides formed by the oxidative activation of 1-NP in the liver were excreted into the bile as detoxified glutathione conjugates which were changed to cysteine conjugates in the upper intestinal tract. The cysteine conjugates were degraded by cysteine conjugate beta-lyase (beta-lyase) of intestinal microflora in the lower intestinal tract. The mutagenicity of cysteine conjugates of 1-NP oxides for Salmonella typhimurium was enhanced by addition of beta-lyase and was decreased by addition of aminooxyacetic acid, a beta-lyase inhibitor. The in vitro binding of the cysteine conjugates to calf thymus DNA was increased by addition of beta-lyase and xanthine oxidase. We administered glutathione conjugates of 1-NP oxides to two groups of mice that had been treated with antibiotics or saline by gavage and analyzed the DNA adducts in the lower intestinal mucosa. The specific DNA adducts were detected in the saline-treated group but not in the antibiotics-treated group. These results suggest that intestinal microflora play an important role in activation of glutathione conjugates of 1-NP oxides.


DNA repair pathways in mammalian cells analyzed by isolation of ACNU-sensitive Chinese hamster ovary cells.

1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) causes chloroethylation of DNA strand followed by cross linking through an ethylene bridge. We recently isolated two ACNU sensitive mutants from mutagenized Chinese hamster ovary cells, and found them to be new drug sensitive recessive mutants (Hata et al. 1991). The O6-methyl guanine DNA methyl transferase (MT) activities of these cells were undetectable as the parental cell line, indicating that the sensitivity of the mutant cell lines to ACNU was not due to the decreased cellular level of this enzyme. By complementation analysis with the 7 established UV-sensitive CHO cell lines, one of the mutants, UVS1, turned out to complement their UV-sensitivity and, therefore, build a new complementation group among all the CHO cell lines ever reported. The other mutant, CNU1 showed hypersensitivity only to chlorethylating agents (ACNU, CCNU) and exhibited a slightly reduced unscheduled DNA synthesis (UDS) induced by UV. It is, therefore, suggestive that this mutant is defective in a specific step of DNA repair systems, which is important for the processing of DNA damages produced by ACNU. Only cell lines from the complementation group 1 and 4 out of 7 established complementation groups of UV-sensitive CHO mutants were more sensitive to ACNU than UVS1 and CNU1, indicating some steps of excision repair pathways as well as specific repair system play important roles in repairing ACNU-induced DNA damages.


[The systematization of nursing care for the colostomy-ileostomy patient in a private hospital].

A Systematic Nursing care to ostomized patients at Oswaldo Cruz German Hospital (São Paulo Brazil) has been used in order to care for these patients through a nursing process approach since December 1988. Until June 1991 the group gave orientation to 115 patients. This systematic nursing care has three steps: pre-operative period, pos-operative period and discharge. These steps improved self care without complications and guided the patients to work with ostomy associations which helped them im their whole reintegration.


Mass screening for neuroblastoma in Miyagi Prefecture.

In Japan, aiming at early and preclinical detection of neuroblastoma in infancy a mass screening program for the tumor has been implemented nationwide using urinary tests for catecholamine metabolites, vanillylmandelic acid (VMA) and homovanillic acid (HVA) (Sawada 1990; Sawada et al. 1991). In this report, the results obtained from the screening program in Miyagi Prefecture for the last 6 years are described. The detection rate of neuroblastoma by mass screening was 1:8,377 among 125,652 infants tested in Miyagi Prefecture. All but one patients survived after removal of the primary tumor and none or minimal chemotherapy.


Phosphorylation of the anti-oncogene products and control of the cell cycle.

To investigate the function of the RB protein, we have studied cellular RB binding proteins and protein kinases responsible for phosphorylation of the RB protein. (1) We purified a cellular RB-associated protein p56 which competes with SV40 large T antigen for binding to the RB protein. (2) In another experiment, we screened expression libraries of U937 monocytic leukemia cell line by West-Western method and obtained two cDNA clones that encode RB binding proteins. (3) The RB protein was found to be phosphorylated by cdk2 and MAP kinase in vitro. Most of the sites phosphorylated in vitro are the same as those phosphorylated in vivo and the time course of activation of cdk2 in the cell cycle were similar to that of phosphorylation of the RB protein.


Mutations of the p53 gene and other genes involving in human colorectal carcinogenesis.

In this study, structural changes of the p53 gene in primary specimens of human colorectal carcinomas were analyzed by polymerase chain reaction mediated-DNA sequencing method. Point mutations of p53 gene, including an intronic mutation case, were detected in 8 of 14 carcinomas (57%). Point mutations of the gene were also observed in 2 of 2 adenomas, suggesting that mutations occur prior to the carcinoma stage. These results support that p53 gene plays an important role in the development of colorectal cancer. The frequency of Ki-ras oncogene mutations was also studied by polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP). This resulted in the rate of 42% (10/24), a quite similar value obtained by other methods. As PCR-SSCP analysis is a convenient method to detect point mutation, we have now examined 24 colorectal cancers for the p53 gene by this method, and detected the mutations. Furthermore, expression of the DCC gene, a candidate of tumor suppressor gene involved in colorectal carcinogenesis, was examined by reverse transcriptase-mediated PCR (RT-PCR) assay, resulting in significant reduction on the DCC expression in 8 of 14 carcinoma cases (57%).


[The telephone interview: the methodological strategy for collecting population data].

The interview by telephone is not an ordinary procedure to obtain investigation data. By knowing that is rarely used in Brazil, the study was planned aiming to: identify the individuals' characteristics who answer the sampled telephones; raise the interviews' statements about the operational technique and evaluate the telephone used as data collection procedure. The data indicate that most of the people who were interviewed, were females, between 30 and 40 years old and housewives. The interviewers considered between 30 and 40 years old and housewives. The interviewers considered the experience interesting, in despite of the difficulty to maintain people talking on the phone. The authors state that the interview by telephone is an efficient and fast way of bringing up data for investigation which aims to raise opinions about certain matters.


A novel general strategy for cloning tumor suppressor genes using radiation-reduced chromosomal superfragments.

To identify the tumor suppressor gene on human chromosome 11p15, we generated mouse microcell hybrids containing small transferable chromosome 11p15 fragments, which we have termed "DNA superfragments". These hybrids will be used to identify which fragments contain a tumor suppressor gene by direct transfer of the fragments to tumor cells via microcell fusion.


[Simulation in the teaching of the cardiorespiratory system: a report of innovative experience].

The nurse teachers in charge of the Auxiliary Nursing Course at the Heart Institute (InCor-FMUSP) propose simulation as an innovative teaching strategy and describe its application to the Cardiorespiratory System. By doing this, they make their students participate actively in their classes, thus improving the teaching-learning process.


Fos and Jun: oncogenic transcription factors.

The fos and jun proto-oncogenes are members of the set of genes known as cellular immediate-early genes. Their expression is induced transiently by a great variety of extracellular stimuli associated with mitogenesis, differentiation processes or depolarization of neurons. They encode DNA binding proteins that form dimeric complexes through a leucine zipper structure that function as transcription factors. Continuous overexpression of fos or jun causes transformation of fibroblasts. Because of their ubiquitous expression it is believed that the target genes regulated by Fos and Jun are different in the many circumstances in which they are expressed. Thus, their functional specificity is likely to be regulated at several levels. We have uncovered several potential mechanisms that could contribute to their regulation. These include formation of a large number of heterodimeric complexes, post-translational modification by phosphorylation and a novel reduction/oxidation (redox) mechanism, presence of both positive and negative transcriptional domains and the ability of Fos and Jun to induce distinct bends in DNA structure.


Complex regulation of a tumor marker expression. Enhancer and silencer of the GST-P gene.

Glutathione transferase P (GST-P) is expressed at high levels in precancerous lesions and hepatocellular carcinomas from a very early stage of chemically-induced hepatocarcinogenesis in the rat. To explore the molecular mechanisms of its specific activation, we are investigating the regulation mechanisms of the GST-P gene expression. By using gene technology, we have identified a strong enhancer, GPEI, at 2.5 Kb and a silencer region at about 400 bp upstream from the transcription start site. GPEI has a palindromic structure composed of two TPA-responsive element (TRE)-like sequences and binds at least three proteins including AP-1 (c-jun/c-fos). The silencer is composed of several sequences resembling each other and binds at least three proteins including SF-B/LAP/LIP. To determine whether the GST-P gene is activated together with a putative hepato-oncogene because they are located close to each other (cis-mechanism), or because they share a trans-acting factor that can activate both genes simultaneously (trans-mechanism), transgenic rats were produced with GST-P control region connected to the CAT reporter. The results unequivocally demonstrate that GST-P gene is activated position-independently by a trans-mechanism.


[The profile of nursing teachers in undergraduate courses in greater São Paulo].

This paper searches to identify some aspects of the profile of the undergraduate nursing faculty members and to detect the differences and similarities among the group of teachers of public and private schools. A sample of 120 faculty members of five schools was studied in August of 1990 using a questionnaire. The data was analysed according to the following categories: demographic data, social economical status, university stand, professional development and perspectives. The results showed that there are more similarities than differences within this faculty members, once they belong to the an homogeneous social, economical and cultural class with a few exceptions.


Transcriptional control by myb oncogene product.

Structure and function of two domains of c-Myb were analyzed. We show that a leucine zipper structure is a component of the negative regulatory domain, because its disruption markedly increases both the transactivating and transforming capacities of c-Myb. Our results suggest that an inhibitor which suppresses transactivation binds to c-Myb through the leucine zipper, and that c-Myb can be oncogenically activated by mis-sense mutation. We also proposed a model, the "tryptophan cluster", for the structure of the Myb DNA-binding domain, in which the three tryptophans form a cluster in the hydrophobic core in each repeat. The results of NMR analysis of repeat 3 revealed that the conserved tryptophans play a key role to make the hydrophobic core.


Regulation of Myc: Max complex formation and its potential role in cell proliferation.

The myc family of proto-oncogenes encodes short-lived nuclear phosphoproteins (Myc) involved in the control of cell proliferation and differentiation. Here we discuss the evidence for Myc's involvement in normal and abnormal cell proliferation and review recent information on Max, a novel protein that forms a sequence-specific DNA-binding complex with Myc. The properties of the Myc: Max heterodimeric complex suggest a model for how Myc may function in the cell.


Role of c-Myc on erythroid differentiation.

In the early event of the induction of mouse erythroleukemia (MEL) cell differentiation, c-myc mRNA levels show a biphasic change. The elevated expression of a transfected c-myc gene inhibits the commitment and differentiation of MEL cell transformants. In the present work, we have introduced human c-myc mutants into MEL cells under the inducible promoter to define the functional domains of c-Myc involved in erythroid differentiation. The c-Myc domains necessary for commitment and differentiation are not colocalized; almost entire regions are required for inhibition of commitment, whereas domains II and IV that are essential for co-transforming activity with ras are required for inhibition of differentiation. Interestingly, mutants that delete domains for c-Myc dimerization motifs enhanced differentiation. Thus, c-Myc interferes with MEL cell differentiation by interacting with c-Myc partners and the induced protein(s) through dimerization domains. These results suggest that c-Myc may regulate commitment and differentiation by interacting with proteins through different domains.


Functional role of glycosphingolipids in tumor progression.

Molecular modeling of glycosphingolipids (GSLs), and their organization in membranes, suggest that GSL "patches" provide binding sites for interaction with ligands and adjacent cells, and that GSLs or their catabolites modulate transmembrane signaling. Aberrant GSL expression is a ubiquitous phenotype common to essentially all types of tumors, and leads to (i) formation of tumor-associated antigens defined by a large variety of monoclonal anti-bodies; (ii) aberrant adhesion favoring metastasis and invasiveness of tumor cells; and (iii) aberrant catabolism leading to altered transmembrane signaling and loss of growth control. Classical immunotherapy is based on (i). New approaches termed "antiadhesion" and "anti-signaling" therapy, based on (ii) and (iii), are hereby proposed.


Multiple forms of mammalian sialidase: altered expression in carcinogenesis.

We have demonstrated that rat liver contains at least four types of sialidase differing in subcellular location, in catalytic property and immunologically. They are intralysosomal, cytosolic and membrane-associated sialidases I and II. Membrane sialidase I locates mainly in plasma membrane and sialidase II in lysosomal membrane. Immunological study reveals that the same types of sialidase exist in various tissues of rat and of other mammalian species. Based on these results, we examined the sialidases in rat hepatomas and in transformed cells of JB6 mouse epidermal cell. Hepatomas were found to possess four types of sialidase and the three of them altered quantitatively. Intralysosomal sialidase activity was higher but cytosolic and lysosomal membrane sialidase activities were lower in hepatomas than in control liver. When the sialidases of transformants of JB6 cells were compared with those of control cells, the activities of two lysosomal sialidases were decreased and contrarily plasma membrane sialidase was increased. We discussed a possible significance of the sialidase alterations in carcinogenesis.


The IL-2/IL-2 receptor system: involvement of a novel receptor subunit, gamma chain, in growth signal transduction.

We previously demonstrated the existence of a third component, p64, of IL-2 receptor (IL-2R), tentatively named the gamma chain of IL-2R. Our recent studies provided evidence suggesting that the gamma chain endows the beta chain of IL-2R with IL-2 binding ability. The gamma chain was detected in lymphoid transfectants of IL-2R beta cDNA, which showed the intermediate-affinity IL-2R, but not in nonlymphoid transfectants of IL-2R beta cDNA, which showed no IL-2 binding activity. The comparative study between two subclones of lymphoid MOLT4 transfectant of IL-2R beta cDNA demonstrated that the amount of the gamma chain coprecipitated with IL-2R beta was proportional to numbers of the IL-2 binding sites. These results suggest the possibility that the gamma chain associates with IL-2R beta and has an important role in formation of the intermediate-affinity IL-2R complex. On the other hand, we have also demonstrated the association of IL-2R beta with a certain tyrosine kinase, of which activation by IL-2 could be indispensable process at the initial pathway of signal transduction.


The molecular biology of lung cancer.

Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. The morphological changes progress from hyperplasia, to metaplasia, to dysplasia, to carcinoma in situ, to invasive cancer and finally to metastatic cancer. Multiple molecular changes have been documented in lung cancers, both small cell (SCLC) and non-small cell (NSCLC) types. The number of changes has been estimated to be in double digits. These changes include activation of dominant oncogenes myc family, (K-ras and neu genes), as well as loss of recessive growth regulatory genes or anti-oncogenes (p53, and RB as well as unidentified gene or genes on chromosome 3). However, cytogenetic and molecular genetic studies indicate that multiple other specific sites of actual or potential DNA loss may be present in lung cancers. Other changes may include development of drug resistance, and production of growth factors and their receptors. It is tempting to associate specific molecular changes with specific morphological changes, as has been attempted in the colon. However, because of the difficulties in serially sampling the respiratory tract, such studies have not been performed to date. Documentation of molecular changes in premalignant lesions and prospective studies of their prognostic effects will be necessary for the design of rational chemoprevention trials.


Development of the human colonic adenocarcinoma from adenoma as a histopathologically continuous process.

The adenocarcinoma sequence of the human colon is usually divided into three separate steps according to the grade of epithelial dysplasia, i.e., adenomas with mild, moderate and severe dysplasia. In an attempt to re-examine whether or not this sequence can be morphologically separable as usually assumed, a total of 192 epithelial lesions including adenomas with various grades of dysplasia were analyzed, relying on morphometrical and multivariate-statistical techniques. Histologic features of epithelial lesions were characterized by 10 quantitative parameters and subjected to 10-variate cluster analysis. In the result of computations, separation of neoplastic lesions into different groups proved to be rather ambiguous, not justifying the classification into three groups as generally expected. It was concluded that adenocarcinoma can develop from adenoma as a seemingly continuous process which may involve more steps than usually assumed.


Overexpression and amplification of alpha-PDGF receptor gene lacking exons coding for a portion of the extracellular region in a malignant glioma.

Overexpression of the alpha-Platelet Derived Growth Factor Receptor (alpha-PDGF) gene was detected in a case of malignant glioma. This overexpression was accompanied with amplification of rearranged alpha-PDGF receptor gene. We have isolated a cDNA for the transcript derived from the amplified receptor gene. Characterization of the cDNA revealed a deletion of 243 nucleotides coding for 81 amino acids in the extracellular region of the receptor. This in-frame deletion removed a part of the immunoglobulin-like domains in the extracellular region of the receptor. Analysis of the amplified alpha-PDGF receptor gene in the glioma indicated that exons coding for the 81 amino acids were lost by a gene deletion. The gene amplification was also detected in macroscopically normal cortex adjacent to the glioma from the same patient. However, the amplified gene in the macroscopically normal cortex had no major gene rearrangement. These data suggest that the overproduction of structurally altered alpha-PDGF receptor may take part in the onset and the development of malignant glioma.


A Ca(2+)-independent protein kinase C, nPKC eta: its structure, distribution and possible function.

Protein kinase C consists of a protein family which can be classified into two major groups: Ca(2+)-dependent conventional protein kinase C and Ca(2+)-independent novel protein kinase C (nPKC). Among eight known members of protein kinase C family, we found that nPKC eta (eta) isolated from cDNA library of mouse skin, is most abundant in epithelial tissues including skin and epithelia of digestive and respiratory tracts. These data suggest potential role of this isoform in growth, differentiation and carcinogenesis of epithelial tissues.


A novel steroidogenic role of suramin-blocked luteal cell growth factors.

Growth factors synthesized in the ovarian corpus luteum (CL) have been implicated in the development of the CL. One of these growth factors is basic fibroblast growth factor which acts on luteal cells in an autocrine manner (Tamura et al. 1991; Asakai et al. 1992). To elucidate effects of these growth factors in the development of the CL, we cultured immature luteal cells with defined medium for a week in the presence or absence of a growth factor inhibitor, and measured progesterone in the medium as an indicator of cell differentiation. Culture of luteal cells showed an increased amount of progesterone for three days and continued to synthesize progesterone for at least another four days without serum and pituitary hormones. The addition of suramin, previously reported to inhibit autocrine growth stimulation, accelerate the daily progesterone production of luteal cells apparently by switching on the early onset of differentiation. Suramin also induced apoptosis of the cells after the 3rd day of culture. These data suggest that an autostimulation mechanism by growth factors plays a physiological role on normal cell differentiation, and it is not limited to neoplastic transformation.


Flow cytometric DNA analysis of lung cancer cell lines.

Tumor DNA content (ploidy) was analyzed by use of flow cytometry (FCM) in 17 lung cancer cell lines which were subcultured in our laboratory. The study included 6 adenocarcinomas, 2 squamous cell carcinomas, 1 adenosquamous cell carcinoma, 5 large cell carcinomas, and 3 small cell carcinomas. Of the 17 lung carcinoma cell lines, 15 revealed aneuploid patterns with DNA index above 1.1, whereas one had diploid. The mean DNA index (DI) in adenocarcinoma, was 1.34 +/- 0.09, DI 1.6, in squamous cell carcinoma, DI 1.0 in adenosquamous cell carcinoma, DI 1.70 +/- 0.66 in large cell carcinoma, and DI 1.29 in small cell carcinoma. Of the 17 cell lines, three lines showed multiploid patterns with clinically poor prognosis and indicated heterogeneity. Flow cytometric DNA analysis using lung cancer cell lines could provide further basic study of lung cancer cells and give a useful information on the degree of the malignancy clinically.


Cell kinetic study of murine jejunal crypts during multiple doses per day.

We studied cell kinetics of mouse jejunal crypts during multiple fractionation using double labeling methods. Mice were irradiated to the total body once a day or twice a day. Fraction size was 2 Gy. Overall time was 1, 3 and 5 days. Labeling index (LI), duration of S phase (Ts) and potential doubling time (Tpot) were assessed next morning following the irradiation schedule. Mice were administered both bromo-deoxyuridine (BrdUrd) and 3H-Thymidine ([3H]dT) with a constant interval. Removed jejunum were stained with immuno-histochemistry and, then, processed for autoradiography. BrdUrd and [3H]dT LIs were the same and were increased up to 5 days despite the fractionation schedule. After 1 day following 2 fx/day, both Ts and Tpot decreased significantly. For 1 fx/day treatment, neither Tpot nor Ts changed. After 5 day following 1 and 2 fx/day, both Ts and Tpots were the same and Tpots were significantly shorter than that obtained from control. It seems that proliferative responses between 1 and 2 fx/day were different.


N-(F-18)-fluoroacetyl-D-glucosamine: a new positron labeled pharmaceutical for cancer study.

In order to evaluate the role of hexosamine metabolism in tumor tissue, we studied the biodistribution of N-(F-18)-fluoroacetyl-D-glucosamine (FAGlu) in male Donryu rats bearing poorly differentiated hepatomas (AH109A and AH272). Compare with the former result of the high tumor uptake of FAGlu in C3H/He mice bearing well differentiated spontaneous hepatoma, the tumor uptakes of FAGlu in these tumors showed the lower values. This suggested that spontaneous hepatoma maintained a high activity of glucosamine metabolism, while poorly differentiated hepatoma had little activity. Metabolism of glucosamine in tumor tissue may be another marker for characterizing tumors. We also discuss the tissue distribution of new F-18 labeled hexosamines, N-(F-18)-fluoroacetyl-D-mannosamine and N-(F-18)-fluoroacetyl-D-galactosamine in tumor bearing rats.


New strategies to establish human monoclonal antibodies.

In order to establish human monoclonal antibodies to any sort of antigens efficiently, we have made following two approaches. Our first approach is to improve cell fusion frequency. By improving our previous method for production of human hybridomas, we obtained higher frequency (1/700 vs. 1/5500) compared with our previous method by adding irradiated myeloma cells to culture of fusion cells and modifying the selective medium. Our second approach is to use a SCID-hu mouse for immunization. Since the injection of human PBL can result in the stable long-term reconstitution of a human immune system in SCID mouse, we tried to immune SCID-hu mouse with KLH. In the serum of immunized SCID-hu mouse, we obtained human IgG antibodies to KLH. Additionally, we succeeded in establishing human B lymphoblastoid cell lines which produced antibodies specific to KLH. These methods will open new prospects for the detection and therapy of cancer.


Diagnostic use of anti-modified nucleoside monoclonal antibody.

By use of monoclonal antibodies (MoAbs) termed APU-6 and AMA-2, we determined the usefulness of urinary modified nucleosides, pseudouridine and 1-methyladenosine, as markers for malignancy. In patients with leukemia and other forms of cancer, these nucleosides elevated significantly and reflected the disease status of patients. The immunohistochemical analysis showed that cancer cells were specifically stained with the MoAbs. Chemical identification of the cellular components reactive with the MoAbs revealed that APU-6-associated antigens were mainly rRNA and AMA-2-associated antigens were mainly tRNA. These results suggest that APU-6 and AMA-2 would be useful tools for clinical and biological studies of cancer.


Marrow transplantation in cancer therapy.

Issues in bone marrow transplantation were addressed. Reconstitution of hematopoietic function is achieved by autologous, syngeneic, or allogeneic bone marrow transplant. Problems related to transplants from HLA mismatched family members, and HLA matched unrelated donors were also delineated.


Selective anti-gene therapy for cancer: principles and prospects.

Oligodeoxynucleotides can act as antisense complements to target sense sequences of natural mRNAs to selectively regulate gene expression by translation arrest. This is a form of interventional gene therapy. Chemically modified analogs that are nuclease-resistant enable this strategy to be utilized in practice. Of the chemically modified backbone analogs of oligodeoxynucleotides we have used the phosphorothioate (PS) analog, in which a non-bridging phosphate oxygen atom is substituted with a sulfur atom. We have shown that these oligodeoxynucleotide analogs inhibit beta-globin expression in cell free systems, and that they are taken up by cells. Specific sequences have been shown to selectively regulate viral and cellular gene expression, for example the bcl-2 oncogene that is found in ca. 90% of lymphomas. However, the PS analog has certain disadvantages, notably reduced hybridization and non-selective inhibition of translation. We have therefore synthesized a series of (PS-PO) co-polymers and characterized their properties. Other related approaches include catalytic ribozymes, and formation of triplexes by direct interaction of oligomers in the major groove of DNA. In general, a chemically modified oligodeoxynucleotide analog can be regarded as a novel form of informational drug.


Basic approach to application of liposomes for cancer chemotherapy.

The method for augmentation of systemic in vivo anticancer effect of liposomes (Lip) containing adriamycin (ADM) and endocytosis activity of cancer cells to liposomal preparations have been studied. Encapsulation of ADM in liposomes increases its maximal tolerated dose and pretreatment of animals bearing tumor with tumor necrosis factor alpha (TNF) resulted in effective targeting of ADM-Lip to tumor, leading to its augmented therapeutic effect, but only when TNF and ADM-Lip were administered with an appropriate interval. All human tumor cell lines tested showed endocytosis activity to liposomes but the activity was differed among different tumor cell lines.