[A case presenting severe respiratory failure with high antibody titers to Chlamydia pneumoniae].

"HITAZYME C. pneumoniae" is a diagnostic reagent that has been recently developed by adopting an ELISA method for detection of anti-Chlamydia pneumoniae (C. pneumoniae) antibodies. A case presenting bilateral interstitial opacities and severe respiratory failure with high titers of "HITAZYME C. pneumoniae" was described. Sputum, blood, serological, and bronchoalveolar lavage examinations failed to reveal other etiology to explain his severe respiratory illness. Clinicians should be aware that C. pneumoniae may cause severe respiratory failure or ARDS. Further studies are needed to evaluate the role of C. pneumoniae infection in the development of severe pneumonia or ARDS.

[A case of bronchioloalveolar carcinoma with multiple cystic shadows on chest CT].

A 68-year-old woman was admitted to our hospital in 1998 with shortness of breath on exertion. On the first admission, chest radiography revealed multiple nodular shadows and areas of ground-glass appearance mainly in the basal lung fields, and chest CT scans showed multiple thin-walled cystic lesions in both lung fields. Bronchioloalveolar carcinoma was diagnosed by transbronchial lung biopsy. The CA 19-9 level in the serum was abnormally high. The disease progressed, and the patient died 7 months after diagnosis. We report this case because CT scans showed multiple cystic lesions, which is very rare. The mechanism of cystic formation in this case of lung cancer may have involved disruption of the alveolar structure and enlargement of disrupted spaces or of the check valve mechanism.

Saccharin activates cation conductance via inositol 1,4,5-trisphosphate production in a subset of isolated rod taste cells in the frog.

The transduction mechanism of the conductance activated by saccharin was analysed in isolated bullfrog taste cells under whole-cell voltage-clamp. Bath application of 30 mM saccharin induced an inward current of -34 +/- 12 pA (mean +/- SEM, n = 10) at a membrane potential of -50 mV in 10 (23%) of 44 rod cells. The concentration-response relationship for the saccharin-gated current was consistent with that of the gustatory neural response. The saccharin-induced current was accompanied with a conductance increase under internal low Cl- condition (E(Cl) = -56 mV), suggesting that saccharin activated a cation conductance. The reversal potential of the saccharin-induced current was -17 +/- 2 mV (n = 10). Intracellular dialysis of 0.5 mM guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) completely blocked the saccharin-induced response, suggesting the involvement of a G protein in the transduction. The dialysis of heparin (1 mg/mL) also inhibited the response almost completely, but the dialysis of 1 mM 8-Br-cAMP did not affect the response significantly. Intracellular 50 microM inositol 1,4,5-trisphosphate (1,4,5 InsP(3)) also induced the inward current in five (38%) of 13 rod cells, but intracellular Pasteurella multocida toxin (5 microg/mL, G alpha q-coupled PLC activator) did not elicit any response in the cells. The results suggest that saccharin mainly activates a cation conductance in frog taste cells through the mediation of IP3 production.

Differential transduction mechanisms underlying NaCl- and KCl-induced responses in mouse taste cells.

The transduction mechanism of salt-induced responses of mouse taste cells was investigated using the patch clamp and the local stimulation techniques under quasi-natural conditions. Apically applied NaCl induced a voltage-independent current, which was partially suppressed by amiloride and Cd2+. In contrast, apically applied 0.5 M KCl induced an inwardly rectifying current (KCl-induced Iir). The KCl-induced Iir was unaffected by amiloride. The Iir was suppressed not only by external Ba2+ and Cs+, but also by a Cl- channel blocker, niflumic acid. The Er of the KCl-induced response was independent of the apical ionic concentration, but rather was close to the equilibrium potential of Cl- (E(Cl)) at the basolateral membrane. The KCl-induced Iir displayed a fast run-down under the conditions of the conventional whole cell clamp method, but not under the perforated patch conditions. Immunohistochemical localization of an inwardly rectifying Cl- channel protein, ClC-2, was observed in taste bud cells of the fungiform papillae. It is concluded that the transduction mechanism of NaCl-induced responses is completely different from that of KCl-induced responses in mouse taste cells.

Non-synaptic transformation of gustatory receptor potential by stimulation of the parasympathetic fiber of the frog glossopharyngeal nerve.

When the glossopharyngeal nerve (GP) in the frog was strongly stimulated electrically, slow potentials were elicited from the tongue surface and taste cells in the fungiform papillae. Injection of atropine completely blocked these slow potentials. The present and previous data indicate that the slow potentials induced in the tongue surface and taste cells are due to a liquid junction potential between saliva secreted from the lingual glands due to parasympathetic fiber activity and an adapting solution on the tongue surface. Intracellularly recorded depolarizing receptor potentials in taste cells induced by 0.5 M NaCl and 3 mM acetic acid were enhanced by depolarizing slow potentials induced by GP nerve stimulation, but were depressed by the hyperpolarizing slow potentials. On average, the receptor potential of taste cells for 0.5 M NaCl was increased by 25% by the GP nerve-induced slow potential, but the receptor potential of taste cells for 3 mM acetic acid was decreased by 1% by the slow potential. These transformations of receptor potentials in frog taste cells were not due to a synaptic event initiated between taste cells and the efferent nerve fiber, but due to a non-synaptic event, a lingual junction potential generated in the dorsal lingual epithelium by GP nerve stimulation.

Serotonin inhibits voltage-gated sodium current by cyclic adenosine monophosphate-dependent mechanism in bullfrog taste receptor cells.

We have investigated the effect of 5-hydroxytryptamine (serotonin) (5-HT) on the membrane properties of bullfrog taste receptor cells (TRCs) using patch-clamp technique. External application of 5-HT reversibly suppressed the voltage-gated Na(+) current (I(Na)) in about half of the TRCs sampled. The magnitude of suppression of peak I(Na) was dependent on the holding potential of the cell. Forskolin and cyclic adenosine monophosphate (cAMP) mimicked the suppressive effect of 5-HT on I(Na), but an internal protein kinase A-inhibitor potentiated I(Na). These results suggest that 5-HT suppresses I(Na) of bullfrog TRCs via protein kinase A-dependent phosphorylation, resulting in suppression of the excitability of bullfrog TRCs.

The origin of slow potentials on the tongue surface induced by frog glossopharyngeal efferent fiber stimulation.

When the glossopharyngeal (GP) nerve of the frog was stimulated electrically, electropositive slow potentials were recorded from the tongue surface and depolarizing slow potentials from taste cells in the fungiform papillae. The amplitude of the slow potentials was stimulus strength- and the frequency-dependent. Generation of the slow potentials was not related to antidromic activity of myelinated afferent fibers in the GP nerve, but to orthodromic activity of autonomic post-ganglionic C fibers in the GP nerve. Intravenous injection of atropine abolished the positive and depolarizing slow potentials evoked by GP nerve stimulation, suggesting that the slow potentials were induced by the activity of parasympathetic post-ganglionic fibers. The amplitude and polarity of the slow potentials depended on the concentration of adapting NaCl solutions applied to the tongue surface. These results suggest that the slow potentials recorded from the tongue surface and taste cells are due to the liquid junction potential generated between saliva secreted from the lingual glands by GP nerve stimulation and the adapting solution on the tongue surface.

[Measles pneumonia presenting with multiple nodular opacities on chest radiographs].

A 22-year-old woman presented with fever, cough, and maculopapular erythematous rash on hands and feet. These symptoms developed 14 days after the onset of natural measles in the patient's daughter. Chest radiographs obtained on the first examination showed multiple nodular opacities and infiltrates in the left and right lung fields. Serological examinations disclosed elevated levels of the specific IgM antibody and a remarkably elevated hemagglutination inhibition (HI) titer, indicating a recent measles infection. The patient's symptoms, skin eruptions, and abnormal chest radiograph findings disappeared after several days. However, chest computed tomographic scans taken 8 months after the initial examination revealed small, residual nodular opacities. Other than the fact that the patient had received attenuated measles virus vaccine, these findings were typical of the clinical course for atypical pneumonia. We concluded that in the differential diagnosis of multiple nodular opacities on chest radiographs, adequate attention should be given to pulmonary involvement of measles infection.

Acid and salt responses in mouse taste cells.

Acid and salt responses of taste cells induced by natural stimulation have not been investigated with exception of early studies with conventional microelectrode method, due to the toxicity of high concentration of salt or low pH of acid stimuli applied to isolated taste cells. This indicates that the application of rapid and localized stimulation to the apical membrane of taste cells is necessary for recording of natural responses to salt or acid stimuli using patch clamp technique. Recently we have developed a procedure to accomplish the quasi-natural condition including rapid, localized stimuli to the apical receptive membrane and the maintenance of taste bud polarity. In this review, we present our recent results obtained under quasi-natural condition using patch clamp techniques, comparing with the previously proposed hypothesis. One of our major finding is the fact that the acid-induced responses of taste cells in the mouse fungiform papillae are never suppressed by amiloride but an apical proton-gated conductance and a basolateral Cl(-) conductance possibly contribute to sour transduction. On the other hand, salt-induced responses are suppressed by amiloride, although the salt-induced responses recorded from a single cell involve both amiloride-sensitive and -insensitive components. Furthermore, the amiloride-insensitive component of salt responses possibly consists of multiple subcomponents including an apical sodium-gated nonselective cation conductance and a basolateral Cl(-) conductance. Recent reports also support the hypothesis that both acid and salt responses require specific receptor mechanisms of inorganic cations such as H(+) and Na(+) at the apical receptive membrane.

[Sjögren's syndrome with malignant lymphoma, interstitial pneumonia, and pulmonary hypertension].

A 62-year-old woman was admitted to our hospital for further examination of cough and dyspnea on exertion. She had suffered xerostomia and xerophthalmia for 7 years. Physical examinations showed purpura on the lower extremities, Raynaud's phenomenon, and swelling of the parotid glands. Laboratory data disclosed thrombocytopenia, hypergammaglobulinemia, and high titers of anti-nuclear antibody, anti SS-A, and anti SS-B antibodies. Sicca symptoms, a positive Schirmer's tear test, and laboratory findings together yielded a diagnosis of Sjögren's syndrome. Chest X-P and computed tomographic films demonstrated diffuse reticulonodular shadows and multiple nodules in the left lower lung. Echocardiography and right cardiac catheterization revealed enlargement of the right ventricle, tricuspid regurgitation, and elevated pulmonary arterial pressure. Histologic findings from an open-lung biopsy specimen revealed accumulation of inflammatory cells and fibrosis around broncho-vascular bundles, and diffuse large cell lymphoma. Despite a favorable response to chemotherapy, the patient died of right ventricular failure.

[A case of pulmonary Nocardia farcinica infection in a patient with non-tuberculous mycobacteriosis].

A 64 years old woman without systemic immunological disorders was admitted to our hospital because of a productive cough, low grade fever and bloody sputum. Chest X-ray revealed multiple nodules with calcification, infiltrates and bronchiectasis. Laboratory findings showed mild hypoproteinemia and elevated sedimentation rate. Both Nocardia farcinica and Mycobacterium intracellulare were isolated from the bronchial lavage fluid. Administration of sulfamethoxazole-trimethoprim improved her symptoms. In a recurrent study of bronchial lavage N. farcinica was not isolated, but M. intracellurale was still isolated. We believe that N. farcinica may cause infectious exacerbation of chronic lung disease: non-tuberculous mycobacteriosis and bronchiectasis.

Comparison of a Ca(2+)-gated conductance and a second-messenger-gated conductance in rat olfactory neurons.

The effect of a rise in intracellular Ca(2+) concentration was analyzed in isolated rat olfactory neurons using a whole-cell patch-clamp technique. Intracellular dialysis of 1 mmol l(-)(1) Ca(2+) in a standard-K(+), low-Cl(-) internal solution (E(Cl)=-69 mV) from the patch pipette into the olfactory neurons induced a sustained outward current of 49+/-5 pA (N=13) at -50 mV in all the cells examined. The outward currents were inhibited by external application of 100 micromol l(-)(1) 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB). External application of a Ca(2+) ionophore, 3 micromol l(-)(1) ionomycin, induced an inward current in three of eight cells whose voltages were clamped using the gramicidin-perforated technique, but ionomycin elicited an outward current in the other five cells, suggesting that natural intracellular Cl(-) concentration in the olfactory neurons was heterogeneous. While intracellular dialysis of 50 micromol l(-)(1) inositol 1,4,5-trisphosphate (1,4,5-InsP(3)) in the standard-K(+), low-Cl(-) internal solution induced the NPPB-sensitive outward current in 31 % of cells, and 500 micromol l(-)(1) cAMP induced it in 21 % of cells, a large proportion of the cells displayed an inward current in response to 1,4,5-InsP(3) and cAMP. The results suggest that 1,4,5-InsP(3) and cAMP can elicit Ca(2+)-dependent Cl(-) conductance and Ca(2+)-independent cation conductance in rat olfactory neurons.

[Pancreatic pleural effusion accompanied by bronchopleural fistula].

In recent years, chronic massive pleural effusions have been increasingly recognized as a serious complication of pancreatitis. We describe the third reported case of a pancreatic pleural effusion accompanied by bronchopleural fistula. A 49-year-old man suffering from chronic alcohol-related pancreatitis was admitted to our hospital complaining of cough and shortness of breath. A chest x-ray film disclosed a large right pleural effusion with an air-fluid level. Ultrasonography and computed tomography of the upper abdomen demonstrated a giant pancreatic pseudocyst in the pancreatic tail and a fistulous tract reaching into the posterior mediastinum via the esophageal hiatus. Thoracentesis revealed sterile hemorrhagic fluid with markedly elevated amylase activity of 20,955 IU/l (pancreatic isozyme, 100%) and no malignant cells. A diagnosis of pancreatic pleural effusion was made. The therapy for pancreatic internal fistula is somewhat controversial. We employed conservative therapy, including hyperalimentation and chest tube drainage that successfully decreased the pleural effusion and closed the fistulous tract. Nonetheless, we were still troubled by a continuous air-leak via the drainage tube. Pleurodesis confirmed the tentative diagnosis of bronchopleural fistula and successfully stopped the air-leak. No re-accumulation of pleural effusion has been seen for 2 years. We concluded that pancreatic enzyme-rich effusions, if long-standing, may be complicated by bronchopleural fistula, thus underscoring the need for urgent drainage and initially conservative management.

Distributions of sensory spots in the hand and two-point discrimination thresholds in the hand, face and mouth in dental students.

Densities of pressure, pain and temperature spots in the back of the hand in 551 students and two-point discrimination thresholds in the hand, the face and the mouth in 684 students were measured. The mean numbers of pressure, pain, warm and cold spots in the back of the hand were 24.7/cm2, 130.5/cm2, 3.4/cm2 and 9.1/cm2, respectively. The mean thresholds of two-point discrimination were 1.7 mm in the tip of the tongue, 2.4 mm in the upper lip, 5.5 mm in the lower jaw, 7.5 mm in the palm, 8.8 mm in the forehead, and 11.8 mm in the back of the hand. There were mostly no differences between males and females in the values of sensory spots and two-point discrimination thresholds.

Strain difference in amiloride-sensitivity of salt-induced responses in mouse non-dissociated taste cells.

The chorda tympani nerve responses to NaCl in a mouse strain, C57BL/6 are known to be much more sensitive than those in BALB/c. We compared the NaCl-induced responses obtained from taste cells of the fungiform papillae in these two strains of mice. Amiloride inhibited, in the same degree, the responses induced by a bath-application of normal extracellular solution (NES) containing 140 mM NaCl in either taste cells of C57BL/6 and BALB/c mice. In contrast, amiloride inhibited 62% of responses induced by an apically applied 0.5 M NaCl in the C57BL/6 strain, but only 33% of responses in the BALB/c strain. These results suggest that the difference in amiloride-sensitivity between taste cells in both strains mainly derives from the difference in density of functional amiloride sensitive Na+ channels at the apical receptive membrane but not at the basolateral membrane.

[An autopsy case of interstitial pneumonia probably induced by Sho-saiko-to].

A 66-year-old woman had been treated for 3 years by her local physician with Sho-saiko-to for chronic hepatitis C virus (HCV) infection and liver cirrhosis. She was admitted to our hospital because of cough, fever, and infiltrative shadows on chest x-ray films. Sho-saiko-to-induced pneumonitis was diagnosed and steroid therapy started. Though a temporary improvement was observed, interstitial pneumonitis relapsed and the patient died of respiratory failure and liver dysfunction. Autopsy findings showed diffuse alveolar damage and honeycombing. Furthermore, reverse-transcriptase polymerase chain reaction techniques detected HCV-RNA in specimens of fibrotic lung tissue. For comparison, HCV-RNA was not histologically detected in lung tissue specimens from 4 control subjects who were positive for HCV antibodies but who did not have interstitial lung disease. It was speculated that the progression of interstitial pneumonia in the present case may have been caused by HCV in combination with Sho-saiko-to-induced lung injury.

Sour transduction involves activation of NPPB-sensitive conductance in mouse taste cells.

We examined the sour taste transduction mechanism in the mouse by applying whole cell patch-clamp technique to nondissociated taste cells from the fungiform papillae. Localized stimulation with 0.5 M NaCl and 25 mM citric acid (pH 3.0) of the apical membrane enabled us to obtain responses from single taste cells under a quasi-natural condition. Of 28 taste cells examined, 11 cells (39%) responded to 0. 5 M NaCl alone and 2 cells (7%) responded to 25 mM citric acid alone, indicating the presence of salty- and sour-specific taste cells. Ten cells (36%) responded to both NaCl and citric acid and 5 cells (18%) responded to neither salt nor citric acid. Amiloride reversibly suppressed NaCl-induced responses in mouse taste cells but not citric acid-induced responses. On the other hand, a Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), reversibly suppressed all the citric-acid-induced responses. Most of the NaCl-induced current responses displayed an inwardly rectifying property, whereas all the citric-acid-induced responses displayed an outwardly rectifying property. The reversal potential for NPPB-sensitive component in citric-acid-induced current responses was -2 +/- 7 mV (mean +/- SE, n = 4), which was close to the equilibrium potential of Cl- (ECl), whereas the reversal potential for NPPB-insensitive component was 34 +/- 8 mV (n = 4). The reversal potential of citric-acid-induced current responses (19 +/- 8 mV, n = 4) was mostly present at the middle point between reversal potentials of NPPB-sensitive and -insensitive current components. In some taste cells, an inorganic cation channel blocker, Cd2+, suppressed citric-acid-induced responses, but an inorganic stretch-activated cation channel blocker, Gd3+, did not affect these responses. These results suggest that salt- and acid-induced responses were mediated by differential transduction mechanisms in mouse taste cells and that NPPB-sensitive Cl- channels play a more important role to sour taste transduction rather than amiloride-sensitive Na+ channels. However, the fact that the reversal potentials of citric-acid-induced responses had more positive than ECl suggests that Ca2+ or H+ permeable and poorly selective cation channels, which should be amiloride insensitive, may be activated by citric acid.

Inositol 1,4,5-trisphosphate activates non-selective cation conductance via intracellular Ca2+ increase in isolated frog taste cells.

The effect of intracellular Ca2+ increase was analysed in isolated frog taste cells under the whole-cell patch clamp. External application of a Ca2+-ionophore, ionomycin (3 microM) induced the sustained inward current of -200+/-17 pA (mean +/- SE, n = 23) at -50 mV in taste cells. The ionomycin-induced response was observed in most of the cells exposed in the drug, but not when 10 mM BAPTA (1,2-bis (O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) was included in the pipette (eight cells). Steady-state I-V relationships of ionomycin-induced currents were almost linear and reversed at -8+/-1 mV (n = 23). The simultaneous removal of Na+ and Ca2+ from the external solution eliminated the response completely (three cells). Intracellular dialysis with 1 mM Ca2+ or 50 microM inositol 1,4,5-trisphosphate (IP3) in K+-internal solution also induced an inward current in the taste cells. The Ca2+-induced and IP3-induced responses were observed in 82% and 36% of the cells dialysed with the drugs, respectively. The Ca2+-induced and IP3-induced currents were inhibited by external Cd2+ (1-2 mM). The reversal potentials of the inward currents were -15+/-3 mV (n = 9) in Ca2+ dialysis and -11+/-3 mV (n = 13) in IP3 dialysis. The half-maximal Ca2+ concentration in the pipette to induce the inward current was approximately 170 microM. The results suggest that IP3 can depolarize the taste cell with mediation by intracellular Ca2+.

Intracellular free calcium concentration in human taste bud cells increases in response to taste stimuli.

We examined changes of intracellular free calcium concentration [Ca2+]i elicited by taste stimuli of sucrose, denatonium and NaCl in the taste buds of seven human fungiform papillae. In one taste bud we observed an increase in [Ca2+]i induced by only NaCl. In another bud an increase of [Ca2+]i in response to both NaCl and sucrose was found. The Ca2+ responses to NaCl and sucrose occurred in differential areas within the one taste bud. In the other five fungiform papillae [Ca2+]i was not changed by the taste stimuli. These results suggest that an increase of [Ca2+]i participates in taste transduction mechanisms for sucrose and NaCl, and that taste cells in one taste bud may respond to differential stimuli.

Salty and sour transduction. Multiple mechanisms and strain differences.

The amiloride-sensitive and -insensitive components of salt- and acid-induced responses in C57BL/6 and BALB/c mouse nondissociated taste cells were examined using the whole-cell clamp technique and localized taste stimulation method. Both amiloride-sensitive and -insensitive components were involved in a salt-induced depolarizing response. The taste cells of both mouse strains exhibited an amiloride-insensitive salt-induced response, which consisted of multiple components. In C57BL/6 mice, an amiloride-sensitive strain, more than 60% of salt-induced responses were amiloride-sensitive at the apical membrane, whereas in BALB/c mice, an amiloride-insensitive strain, less than 40% of responses were amiloride-sensitive. All the acid-induced responses in taste cells examined were insensitive to amiloride, and were markedly suppressed by the Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB). These results suggest that multiple, different transduction mechanisms are involved in, and contribute to salty and sour transductions. In addition, we found that strain differences exist in salty transduction.