Biomedical subjects

M Munakata

Publications and source records attributed to M Munakata.

At least 181 records · Page 10Linked to original sources

PubMed1990

Pharmacological differentiation of epithelium-derived relaxing factor from nitric oxide.

We examined the possibility that nitric oxide is one of the epithelium-derived relaxing factors in guinea pig airways. First we studied whether nitric oxide could relax isolated tracheal strips, and then we examined the effects of known inhibitors of endothelium-dependent relaxation (EDR) in the vascular system [hemoglobin, methylene blue, and NG-monomethyl-L-arginine (L-NMMA)] on epithelium-dependent relaxation (EpDR) induced by hyperosmotic stimuli in perfused whole tracheal preparations. Mannitol (160 mM in Krebs-Henseleit solution) applied to the epithelial surface was used as an osmotic stimulus to induce EpDR after carbachol-induced contraction (2 microM, serosal side). Nitric oxide produced concentration-dependent and complete relaxation of epithelium-denuded tracheal strips. Preincubation of the whole trachea with hemoglobin significantly inhibited osmotic-induced EpDR (P less than 0.05), but preincubation with methylene blue and L-NMMA did not. Hemoglobin introduced into the epithelial side after EpDR induced by hyperosmotic stimuli reversed relaxation, but methylene blue and L-NMMA did not. These results suggest that, although EpDR and vascular EDR have some pharmacological similarities and nitric oxide can relax airway smooth muscle, nitric oxide is not responsible for osmotic-induced EpDR.

Animals↗

PubMed1990

Cardiovascular depression and stabilization by central vasopressin in rats.

The role of endogenous vasopressin in cardiovascular homeostasis was examined using vasopressin-deficient rats (Brattleboro) (n = 194) and their parent strain, Long-Evans rats (n = 181). Mean arterial pressure (blood pressure) and heart rate were measured every 4 seconds with or without infusion of drug solution for 21 hours, and mean values and their standard deviations (lability) were calculated. Blood pressure in Brattleboro rats (116 +/- 1.1 mm Hg, mean +/- SEM) was significantly higher than that in Long-Evans rats (96 +/- 0.7 mm Hg, p less than 0.001), whereas heart rates (381 +/- 3.3 and 375 +/- 2.9 beats/min, respectively) were similar. The lability of blood pressure and heart rate in Brattleboro rats (9.2 +/- 0.1 mm Hg and 42.3 +/- 0.7 beats/min) was also greater than that in Long-Evans rats (6.7 +/- 0.1 mm Hg, p less than 0.001 and 38.4 +/- 0.8 beats/min, p less than 0.01, respectively). In Brattleboro rats, intravenous vasopressin (0.1 ng/kg/min or 0.6 ng/kg/min) did not affect blood pressure, although it did reduce heart rate and decreased lability of blood pressure and heart rate. Intracerebroventricular (central) infusion of vasopressin (2 pg/kg/min) in Brattleboro rats induced initial hypertension and tachycardia followed by long-lasting hypotension and bradycardia, whereas in Long-Evans rats it induced only hypertension and tachycardia. In both strains, central vasopressin dramatically decreased the lability of blood pressure and heart rate. Neither intravenous (0.2 ng/kg/min) nor central desmopressin (2 pg/kg/min or 0.2 ng/kg/min), a V2 renal receptor agonist, changed any of these parameters in Brattleboro rats, although both diminished urinary volume. Neither intravenous (50 ng/kg/min) nor central (3.3 pg/kg/min) d(CH2)5-Tyr(Me)-arginine vasopressin, a vasopressin V1 receptor antagonist, modulated any of these parameters in Long-Evans rats. These results suggest that endogenous as well as exogenous vasopressin acts centrally as a cardiovascular inhibitor and stabilizer through a receptor mechanism other than V1 or V2 receptor mechanisms.

Animals↗

PubMed1990

Cosinor analysis of changes in circadian blood pressure rhythm with aging in spontaneously hypertensive rats.

Evolution of circadian rhythm of blood pressure with age in male spontaneously hypertensive rats (SHR) was compared with that in male Wistar Kyoto rats (WKY). Three different age groups (5-6 week old, 19-22 week old, 29-31 week old) were provided for each strain. Chronogram and cosinor method were used for time series analyses. In all age groups of WKY, a diurnal fall and a nocturnal rise in blood pressure (BP) as well as in heart rate (HR) were observed. There was no significant difference in acrophase between BP and HR in each age group of WKY. Regarding SHR, however, each age group demonstrated a different relation between circadian BP rhythm and HR rhythm. In 5-6 week old SHR, a difference in acrophase between BP and HR (about 6.9 hr, p less than 0.1) was observed, which became more conspicuous with the increase in age, eventually presenting an inverted relation between BP and HR in 19-22 week old SHR. The relation between circadian BP rhythm and circadian HR rhythm in 29-31 week old SHR was almost identical with that in 19-22 week old SHR. In other words, a phase lag of acrophase of BP from that of HR already observed in young SHR increased with aging. The results indicate that parasympathetic periodicity remained unchanged even in SHR since circadian HR rhythm was similar in all groups, while the periodicity of sympathetic neural tone relating to the regulation of circadian BP rhythm seems to be disturbed. The mechanism responsible for development and maintenance of high BP in SHR may be linked to a disturbance in the sympathetic mechanism which regulates BP periodicity.

Aging↗

PubMed1990

Influence of age on the nocturnal fall of blood pressure and its modulation by long-acting calcium antagonists.

The clinical significance of the nocturnal fall of blood pressure (BP) was examined. BP was monitored every 5 min for 24 hrs by means of a finger volume oscillometric device. The nocturnal fall was observed in all age groups (young: less than 40, n = 49; adult: 40 less than or equal to less than 60, n = 110; old: 60 less than or equal to, n = 33). The amplitude of nocturnal fall of BP (averaged daytime blood pressure--averaged nighttime blood pressure) in old patients (systolic = 13 +/- 11, diastolic = 10 +/- 8 mmHg, mean +/- SD) was similar to that in the young patients (systolic = 11 +/- 8, diastolic = 10 +/- 8 mmHg). These 192 subjects were also classified according to mean BP level (MBP) averaged for daytime in the ambulatory blood pressure monitoring records [MBP less than 85 (mmHg), n = 31; 85 less than or equal to MBP less than 100, n = 72; 100 less than or equal to MBP less than 115, n = 49; 115 less than or equal to MBP, n = 25]. BP level did not affect the pattern of circadian variation in the normal subjects or in the essential hypertensive patients at WHO stage I or II. The amplitude of the nocturnal fall in systolic BP increased with the increase in BP level, but this was not the case with diastolic BP (mean daytime BP less than 85 mmHg: systolic = 11 +/- 8, diastolic = 8 +/- 6 mmHg; 85 less than or equal to less than 100: systolic = 14 +/- 8, diastolic = 11 +/- 6 mmHg; 100 less than or equal to less than 115: systolic = 17 +/- 9, diastolic = 11 +/- 8; 115 less than or equal to: systolic 17 +/- 8, diastolic = 11 +/- 6 mmHg). Nitrendipine (8.6 +/- 5.6 mg, 22.5 +/- 11.4 days, n = 14) and nisoldipine (9.3 +/- 6.2 mg, 21.5 +/- 11.4 days, n = 15) administered once daily in the morning or nifedipine slow release tablet, 20 mg twice daily (n = 15, 17.7 +/- 5.2 days) induced a significant downward shift in the circadian BP pattern, in other words, the hypotensive effect was also observed during the night when the BP had already been low. Taken together, the information on the nocturnal behavior of BP would be valuable, especially in treating aged patients with essential hypertension with a long-acting antihypertensive drug.

Aging↗

PubMed1990

A cross-sectional survey of home blood pressure in a rural community in northern Japan.

A cross-sectional survey was performed on home blood pressure recordings (home BP) in a rural community in northern Japan. In total, 1190 participants (495 men and 695 women which consist 61.5% of the greater than or equal to 15 year-old regional population, n = 1933) were asked to measure home BP every morning for a month, using a semiautomatic BP measuring device. The actual measurements were done 16.8 +/- 10.2 times (mean +/- SD) for men and 19.0 +/- 9.4 times for women. Home systolic (SBP) and diastolic BP (DBP) was elevated gradually with age in both sexes, although DBP tended to fall after reaching 70 years old in men. SBP and DBP thus measured were significantly lower than those of casual BP of ordinary Japanese people reported by the Ministry of Health and Welfare, Japan, by 11.4 +/- 4.3 mmHg SBP (mean +/- SD) and 5.9 +/- 1.6 mmHg DBP in men, and 12.7 +/- 5.1 mmHg SBP and 8.1 +/- 2.5 mmHg DBP in women. When WHO criteria were applied to the home BP, 2.8% of men and 0.6% of women were considered to be definitely hypertensive, and 7.9% of men and 6.4% of women as of borderline cases, indicating the underestimation of hypertensive population by means of home BP. Based on these data, we demonstrated the values equal to 1SD or 2SDs above the mean in each age group to tentatively determine biological normalcy. It is necessary to define the relationship between home BP and target organ disease or hypertensive complications. A long-term prospective study is also necessary to define the relationship between home BP and long-term morbidity or mortality.

Adolescent↗

PubMed1990

Failure to visualize bilateral adrenal glands in a patient with primary aldosteronism.

Failure to visualize either adrenal gland by adrenal imaging was experienced in a patient with biochemical evidence of primary aldosteronism. Visualization of the adrenal glands was not possible after the administration of ACTH-Z (1 mg/day) for 3 days. The administration of ACTH and dexamethasone elicited an increase in blood pressure. Although the reason for this failure to visualize the adrenal glands by scanning and for the rise in blood pressure brought on by ACTH and dexamethasone remain unclear, we think that the case herein reported is a rare type of primary aldosteronism.

Adosterol↗

PubMed1990

Serotonin induces constriction and relaxation of the guinea pig airway.

The response of guinea pig trachea to 5-hydroxytryptamine (serotonin; 5-HT) was investigated by studying tracheal strips suspended in organ chambers for isometric tension measurements. Serotonin concentrations of 0.1 to 10 microM produced concentration-dependent contractions, whereas at higher concentrations (10-300 microM) the agonist caused concentration-dependent relaxations. The 5-HT2 antagonist ketanserin shifted the bimodal 5-HT response-curve to the right (pA2 for ketanserin was 8.98). The 5-HT1A agonist, (+)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide and 5-HT3 antagonist, ICS 205930 (3-tropanyl-indole-3-carboxylate) had no effect on the 5-HT-response curve. Incubation with atropine resulted in a depression of the maximal contractility and an increase in the EC50 without changing the bimodal nature of the concentration-response curve. Hexamethonium was able to block the atropine effect without significantly affecting the 5-HT concentration-response curve. Neither the constriction nor the relaxation was altered by propranolol, chlorpheniramine or capsaicin pretreatment. Histamine and carbachol preconstricted airways were also relaxed by 5-HT in a concentration-dependent fashion and this relaxation was antagonized by ketanserin (pKb for ketanserin in histamine preconstricted airways was 9.4). Epithelial denudation did not inhibit the 5-HT-induced relaxation. 5-HT stimulated inositol-monophosphate production which also exhibited a bimodal response and correlated well with the functional response. The above findings suggest that 5-HT causes both constriction and relaxation of the guinea pig airway, and that both responses are antagonized by a 5-HT2 receptor blocker. In addition, part of the constrictor response of 5-HT is mediated through a cholinergic preganglionic pathway. Finally, inositol-monophosphate production induced by 5-HT correlates with the functional response.

Acetylcholine↗

PubMed1990

Does ambulatory blood pressure monitoring improve the diagnosis of secondary hypertension?

Ambulatory blood pressure monitoring can determine the average blood pressure level and the short- and long-term blood pressure variability (circadian rhythm). The circadian blood pressure rhythm appears to be mediated mainly by the circadian rhythm of the sympathetic tone which is linked to changes in physical and mental activity, e.g. the waking-sleeping cycle. A statistically significant circadian blood pressure rhythm was observed in approximately 80% of mild to moderate essential hypertensive patients as well as in normal subjects. However, in patients with Cushing's syndrome, under glucocorticoid treatment, or with hyperthyroidism, central and/or peripheral autonomic dysfunction (Shy-Drager syndrome, spinal cord injury, brainstem lesions, diabetic neuropathy, uremic neuropathy, etc), chronic renal failure, eclampsia, malignant hypertension, sleep apnea syndrome or systemic atherosclerosis, the normal circadian blood pressure rhythm appears to be eliminated or reversed, while in those with primary aldosteronism, renovascular hypertension, pheochromocytoma without paroxysmal hypertension, diabetes insipidus, acromegaly, hyperparathyroidism or hyperprolactinemia, the nocturnal blood pressure fall has been observed as in normal subjects. The alteration in the circadian blood pressure rhythm was observed with different pathophysiological conditions, although no specific pattern was observed for any condition. A disturbance in any part of the hierarchy of factors that regulate the circadian rhythm of sympathetic neural tone seems to disturb the circadian blood pressure rhythm. We conclude that ambulatory blood pressure monitoring is not critically important in the diagnosis of secondary hypertension although it does help in screening for secondary hypertension.

Autonomic Nervous System Diseases↗

PubMed1990

Circadian blood pressure variations under different pathophysiological conditions.

The daily variation in blood pressure (circadian blood pressure rhythm) is characterized by a nocturnal fall and a diurnal rise. The circadian blood pressure rhythm seems to be mediated mainly by the circadian rhythm of sympathetic tone, linked to changes in physical and mental activities, e.g. the waking-sleeping cycle. Statistically significant circadian blood pressure rhythms have been confirmed in approximately 80% of mild to moderate essential hypertensive patients as well as in normal subjects. However, the normal pattern of circadian blood pressure rhythm is reversed in elderly people and in those with Cushing's syndrome, those undergoing glucocorticoid treatment, and those with hyperthyroidism, central and/or peripheral autonomic dysfunction (Shy-Drager syndrome, tetraplegia, diabetic or uremic neuropathy, etc), chronic renal failure, renal or cardiac transplantation, congestive heart failure, eclampsia, sleep apnea syndrome, malignant hypertension, systemic atherosclerosis and accelerated hypertensive organ damage. However, in those with primary aldosteronism, renovascular hypertension, pheochromocytoma without paroxysmal hypertension, or those with cardiac pacing, a nocturnal blood pressure fall is ordinarily observed. It may be that a fall in cardiac output rather than in peripheral resistance may be mainly responsible for the nocturnal fall in blood pressure. It also seems that a nocturnal heart rate fall is not responsible for it, since the nocturnal blood pressure fall remained unchanged in patients undergoing cardiac pacing and was disturbed in patients with Cushing's syndrome or hyperthyroidism in whom the circadian heart rate rhythm remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System Diseases↗

PubMed1990

[A prospective study of idiopathic interstitial pneumonia and collagen vascular disease preceded by interstitial pneumonia].

The incidence and latency period of collagen vascular disease (CVD) were surveyed prospectively in patients originally diagnosed as idiopathic interstitial pneumonia (IIP). We also examined whether there were differences between IIP and CVD preceded by interstitial pneumonia. Background information, extrapulmonary symptoms, smoking history, laboratory findings, prognosis (Kaplan-Meier estimates), respiratory functions, and radiological findings were compared. The subjects consisted of 68 patients of whom 13 (19%) developed CVD (RA; 5 cases, DMPM; 5 cases, SLE; 1 case, Sjoegren syndrome; 1 case, Overlap syndrome; 1 case). The latency period for development of CVD was 24.9 +/- 39.2 (mean +/- SD) months. IIP patients who developed CVD were predominantly female and were younger than those without CVD (p less than 0.05). These patients also had faster ESR, higher CPK values, and a higher incidence of arthralgia, joint deformity and clubbed fingers (p less than 0.05). Abnormal shadows around costo-phrenic angles were seen more frequently in patients with CVD (p less than 0.05). These results suggest that quite a number of patients with IIP develop CVD. The clinical course of these patients should be followed by keeping these clinical findings in mind.

Aged↗

PubMed1990

[A case of elderly (83-year-old) woman with possible left atrial myxoma].

A 78-year-old woman with exertional dyspnea (Hugh-Jones Grade III) and dry cough was admitted to our hospital in April, 1983. She had marked cardiac cachexia and a loss of body weight due to long term heart failure. On physical examination a systolic ejection murmur and a diastolic rumbling murmur were heard without the opening snap sound. Chest radiography revealed pleural effusion and cardiomegaly. M-mode and two dimensional echocardiography demonstrated abnormal echoes in the left atrium, the density being 22.7 Hounsfield Unit. Radionuclide angiography and magnetic resonance imaging (MRI) provided similar findings. No other mass lesion existed in the other chambers. Based on these findings, the mass was diagnosed as a left atrial myxoma. She has been well except for periodic congestive heart failure, for about five years since her discharge. The course of her ailment is interesting because her treatment is mainly symptomatic.

Aged↗

PubMed1990

[A case of pulmonary sarcoidosis which exacerbated bronchial asthma in remission].

A 34-year-old woman had history of bronchial asthma in childhood, was admitted complaining of coughs and wheezes. Chest X-ray examinations showed bilateral hilar lymphadenopathy. A diagnosis of bronchial asthma was made because of her past history, reversible airflow limitation and moderate bronchial hyperreactivity. In addition, findings of chest X-ray films and TBLB specimens were indicative of pulmonary sarcoidosis. When bilateral hilar lymphadenopathy disappeared, her wheezes and bronchial hyperreactivity also improved. In this case, it was suggested that pulmonary sarcoidosis was a factor which worsened bronchial hyperreactivity and bronchial asthma which had been in remission.

Adult↗

PubMed1989

Clinical evaluation of semiautomatic and automatic devices for home blood pressure measurement: comparison between cuff-oscillometric and microphone methods.

The accuracy and reliability of blood pressure (BP) values were evaluated by comparing values obtained with eight automatic or semiautomatic devices designed for home BP measurement (four microphone devices based on the Korotkoff-sound technique and four cuff-oscillometric devices) with those obtained by the auscultatory method, using a standard mercury sphygmomanometer. Systolic blood pressure (SBP) values obtained using the microphone devices coincided well with those obtained by the auscultatory method. However, these devices produced a certain proportion of errors in the measurement of diastolic blood pressure (DBP), sometimes resulting in recordings at least 25 mmHg higher than those obtained by the standard method. The most frequent causes of this phenomenon were an auscultatory (silent) gap and a weak Korotkoff sound after phase IV. A microphone device using a condenser microphone built into the manometer displayed comparatively good acoustic characteristics for determining DBP. All cuff-oscillometric devices demonstrated minimal mean differences and a constant s.d. of mean difference for DBP, with no great differences from the auscultatory method. However, mean differences and s.d.s in SBP measurements using cuff-oscillometric devices were relatively greater than those obtained using some of the microphone devices. Furthermore, the direction of the mean differences in measurements from those obtained with the auscultatory method differed. The error in relation to the auscultatory method tended to be reproducible in the same subjects with both the microphone and the cuff-oscillometric devices.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗

PubMed1989

Age-related changes in blood pressure, heart rate and baroreflex sensitivity in SHR.

1. The age-related changes in mean arterial pressure (MAP), heart rate (HR), and baroreflex sensitivity (BRS) were studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats from 4 to 20 weeks of age. 2. Intra-arterial blood pressure (BP) was continuously recorded for 24 h in conscious, freely moving rats. Twenty-four hour MAP and HR were calculated by an online computer. Baroreflex sensitivity was measured by phenylephrine infusion. 3. In SHR, BRS was significantly lower than in WKY as early as 4-5 weeks, at which time MAP in SHR was only slightly raised. During subsequent weeks, rapid increase in MAP occurred in SHR, in association with progressive bradycardia. 4. It was concluded that a reduced BRS may be detected in young prehypertensive SHR and this impairment of BRS may be central in origin.

Aging↗

PubMed1989

Protective role of epithelium in the guinea pig airway.

We developed an in vitro system to assess the role of the epithelium in regulating airway tone using the intact guinea pig trachea (J. Appl. Physiol. 64: 466-471, 1988). This method allows us to study the response of the airway when its inner epithelial surface or its outer serosal surface is stimulated independently. Using this system we evaluated how the presence of intact epithelium can affect pharmacological responsiveness. We first examined responses of tracheae with intact epithelium to histamine, acetylcholine, and hypertonic KCl when stimulated from the epithelial or serosal side. We then examined the effect of epithelial denudation on the responses to these agonists. With an intact epithelium, stimulation of the inner epithelial side always caused significantly smaller changes in diameter than stimulation of the outer serosal side. After mechanical denudation of the epithelium, these differences were almost completely abolished. In the absence of intact epithelium, the trachea was 35-fold more sensitive to histamine and 115-fold more sensitive to acetylcholine when these agents were applied to the inner epithelial side. In addition, the presence of an intact epithelium almost completely inhibited any response to epithelial side challenge with hypertonic KCl. These results indicate that the airway epithelial layer has a potent protective role in airway responses to luminal side stimuli, leading us to speculate that changes in airway reactivity measured in various conditions including asthma may result in part from changes in epithelial function.

Acetylcholine↗

PubMed1989

Role of vasopressin in cardiovascular response to central cholinergic stimulation in rats.

The cardiovascular effects of centrally administered cholinomimetics were examined in conscious Long-Evans and Brattleboro rats. Carbachol (1 microgram/kg) or physostigmine (50 micrograms/kg) induced a long-lasting increase in blood pressure and a decrease in heart rate in Long-Evans rats whereas no bradycardia was observed in Brattleboro rats, and the pressor response was significantly less than that in Long-Evans rats. The cardiovascular responses to nicotine (30 micrograms/kg) in Brattleboro rats were not different from those in Long-Evans rats. Intravenous vasopressin antagonist, d(CH2)5Tyr(Me) arginine vasopressin, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol in Long-Evans rats. However, the pressor response to carbachol in Brattleboro rats was still significantly less than that in Long-Evans rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in Long-Evans rats and completely eliminated it in Brattleboro rats. Combined intravenous treatment with phentolamine and vasopressin antagonist completely eliminated the pressor response to carbachol in Long-Evans rats. Centrally administered methylatropine eliminated either the hypertensive or bradycardic response to carbachol in Long-Evans rats. These results indicate that the pressor and bradycardic response to carbachol or physostigmine is mediated by the central muscarinic receptor mechanism. Hypertensive response to intracerebroventricularly administered carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by vasopressin.

Animals↗

PubMed1989

Dry air-induced bronchoconstriction--a role for voltage-sensitive calcium channels?

We examined the role played by voltage-sensitive calcium channels (VSCC) in airflow-induced bronchoconstriction (AIB). Collateral resistance (Rcs) in anesthetized male mongrel dogs was measured before and after periods of elevated airflow, or before and after hypocapnic challenge, using a wedged bronchoscope technique. A dihydropyridine calcium channel antagonist (nifedipine) was ineffective in preventing or even attenuating AIB in the canine lung periphery. Treatment with nifedipine did not affect the response of peripheral airways to aerosolized acetylcholine, indicating that receptor-operated calcium channels (ROCC) and/or release of calcium from intracellular stores were unaffected by this drug. Despite the ability of a calcium agonist (BAY K8644) to enhance responses to a hypocapnic challenge, it did not alter peripheral airway responses to dry air. Neither nifedipine nor BAY K8644 affected airway wall temperature at any time during the dry air experiments. We conclude that dihydropyridine receptors do not play a significant role in initiating AIB in the canine lung periphery.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1989

Five-year follow-up of Micropolyspora faeni antibody in smoking and nonsmoking farmers.

To examine factors that influence changes in Micropolyspora faeni (MF) antibody titer in farmer's lung disease (FLD), we followed for 5 yr the prevalence of serum MF antibody and the epidemiologic factors (years on farm, hours in barn, and hay-handling time) among 92 dairy farmers in Hokkaido, Japan. The prevalence of MF antibody among nonsmokers was significantly higher than that among smokers: 27.1% versus 7.7% in 1979, 31.3% versus 2.9% in 1984. There was no remarkable change in overall prevalences of MF antibody between 1979 and 1984 (18.5 and 19.6%, respectively). However, out of 17 seropositive farmers, six (35%) became seronegative, and out of 75 seronegative farmers, seven (9.3%) became seropositive after 5 yr. The nonsmoking farmers who remained seronegative throughout the follow-up period were older and had worked longer on farms than the farmers with seroconversion. These results suggest that in addition to smoking habits, age and exposure time to MF influence the immune response to MF in dairy farmers. Out of 11 farmers who remained seropositive throughout the 5-yr period, two (18.2%) developed FLD. Therefore, continuously positive MF antibody is one of the risk factors in the development of FLD.

Adult↗