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Biomedical subjects

S Jinno

Publications and source records attributed to S Jinno.

At least 19 recordsLinked to original sources

Delirium during intravenous sedation with midazolam alone and with propofol in dental treatment.

A 62-year-old man visited our clinic for dental implantation under intravenous sedation. He demonstrated increased psychomotor activity and incomprehensible verbal contact during intravenous sedation. Although delirium caused by midazolam or propofol in different patients has been reported, the present case represents a delirium that developed from both drugs in the same patient, possibly because of the patient's smaller tolerance to midazolam and propofol.

Alveolar Ridge Augmentation↗

Postsynaptic and extrasynaptic localization of Kv4.2 channels in the mouse hippocampal region, with special reference to targeted clustering at gabaergic synapses.

Voltage-dependent potassium (Kv) channels in the CNS are involved in regulation of subthreshold membrane potentials, and thus reception and integration of synaptic signals. Although such features are particularly important for induction of hippocampal synaptic plasticity, relatively little is known about their subcellular localization. Here we analyzed the detailed distribution of Kv4.2 potassium channels in the mouse hippocampal region using confocal and electron microscopy. At the light microscopic level, the Kv4.2 immunoreactivity occurred in a punctate fashion in the whole area of the hippocampal region. In the hippocampus proper, most of the Kv4.2-positive puncta were small, and they were abundant at the dendritic compartments of pyramidal neurons. High-resolution confocal microscopy revealed that there was no apparent association between Kv4.2-positive puncta with major synaptic markers, such as vesicular glutamate transporters and glutamic acid decarboxylase. In the subicular complex and dentate gyrus, we encountered large distinct Kv4.2-positive puncta at the perimeter of somata and proximal dendrites of principal cells. These puncta were often in contact with glutamic acid decarboxylase-positive boutons, but showed no apparent association with vesicular glutamate transporters. The glutamic acid decarboxylase-positive boutons apposing to Kv4.2-positive puncta were parvalbumin-positive. Quantitative image analysis showed that approximately half of Kv4.2-positive puncta were closely apposed to glutamic acid decarboxylase-positive boutons in the parasubiculum and dentate gyrus. Electron microscopic examination substantiated the presence of large Kv4.2-positive patches at postsynaptic sites of symmetric synapses and small patches at extrasynaptic sites. No presynaptic terminals were labeled. The present findings indicate targeted clustering of Kv4.2 potassium channels at postsynaptic sites of GABAergic synapses and extrasynaptic sites, and provide some key to understand their role in the hippocampal region.

Animals↗

Patterns of colocalization of neuronal nitric oxide synthase and somatostatin-like immunoreactivity in the mouse hippocampus: quantitative analysis with optical disector.

In some brain regions, previous studies reported the frequent coexistence between neuronal nitric oxide synthase (nNOS) and somatostatin (SOM). In the hippocampus, nNOS and SOM were mainly expressed in GABAergic nonprincipal neurons. Here we estimated the immunocytochemical colocalization of nNOS and SOM in the mouse hippocampus using the optical disector. Both in the Ammon's horn and dentate gyrus, we encountered only a few nNOS-immunoreactive (IR)/SOM-like immunoreactive (LIR) neurons. They were mainly located in the stratum oriens of the Ammon's horn and in the dentate hilus. The nNOS-IR/SOM-LIR neurons usually showed characteristic large somata with thick dendrites, whereas the majority of nNOS-IR/SOM-negative neurons showed small somata with thin dendrites. Quantitative data revealed that the double-labeled cells represented only 4% and 7% of nNOS-IR neurons and SOM-LIR neurons, respectively, in the whole area of the hippocampus. We also found the laminar and dorsoventral differences in the degree of colocalization between nNOS and SOM. The percentages of nNOS-IR neurons containing SOM-like immunoreactivity were relatively high in the stratum oriens of the ventral CA1 region (24%), stratum lucidum of the dorsal CA3 region (29%) and dorsal dentate hilus (32%), but they were quite low in the other layers. On the other hand, the percentages of SOM-LIR neurons containing nNOS immunoreactivity were somewhat high in the stratum lucidum of the dorsal CA3 region (19%) and dorsal dentate hilus (28%), whereas they were very low in the other layers. Immunofluorescent triple labeling of axon terminals for nNOS, SOM and glutamic acid decarboxylase indicated that some nNOS-IR/SOM-LIR neurons might be dendritic inhibitory cells. The present results show the infrequent colocalization of nNOS and SOM in the mouse hippocampus, and also suggest that the double-labeled cells may be a particular subpopulation of hippocampal GABAergic nonprincipal neurons.

Animals↗

Heterogeneous expression of the cholecystokinin-like immunoreactivity in the mouse hippocampus, with special reference to the dorsoventral difference.

The neuropeptide cholecystokinin (CCK) is widely distributed in the CNS. We herein investigated the immunocytochemical localization of CCK in the glutamatergic excitatory pathways in the mouse hippocampus, with particular reference to the dorsoventral difference. The intense CCK-like immunoreactivity (CCK-LI) was found in the mossy fiber pathway (stratum lucidum and dentate hilus) and in the inner molecular layer of the dentate gyrus. In the mossy fiber pathway, the CCK-LI was more intense at the ventral level than at the dorsal level. On the other hand, the CCK-LI in the stratum lucidum was more intense in the distal portion than in the proximal portion, both at the dorsal and ventral levels. High-resolution three-dimensional image analysis revealed the coexpression of CCK and synaptoporin (SPO) in the single mossy terminal, where they were spatially segregated but adjacent to each other. Quantitative image analysis indicated the difference in the amount of CCK within the mossy terminals along the dorsoventral and transverse axes of the hippocampus. On the other hand, in the inner molecular layer, CCK- and SPO-positive elements appeared to have little relation to each other. We also examined the postnatal development of the CCK-LI in the mouse hippocampus. The CCK-LI was detected in the inner molecular layer of the ventral dentate gyrus at postnatal day (P) 7. In the mossy fiber pathway, the CCK-LI was first evident at P 14, but it was restricted to the distal portion of the stratum lucidum in the ventral hippocampus. Interestingly, the distributions of the SPO immunoreactivity at P 7 were already similar to those of adult mice. The patterns of expression of CCK-LI at P 28 were almost similar to those of adult mice. The present data demonstrate the heterogeneous expression of CCK-LI in the mouse hippocampus, and provide a baseline to understand the role of CCK in the mouse brain.

Animals↗

Presynaptic inhibition of GABAergic miniature currents by metabotropic glutamate receptor in the rat CNS.

The modulation of spontaneous miniature GABAergic inhibitory postsynaptic currents (mIPSC) by the metabotropic glutamate receptors was investigated in the mechanically dissociated rat nucleus basalis of Meynert neurons using the conventional whole-cell patch recording configuration. An application of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (tACPD) reversibly reduced the frequency of mIPSC without affecting the current amplitude distribution. The application of K+ channel blockers such as 4-aminopyridine, Cs+, Ba2+ or tetraethylammonium increased the mIPSC frequency, but failed to inhibit the tACPD action on mIPSC. Although the removal of Ca2+ from the extracellular solution reduced the mIPSC frequency, the inhibitory effect of tACPD on mIPSC was unaltered. These results suggested that neither voltage-dependent K+ or Ca2+ channels are involved in the inhibitory effect of tACPD on mIPSC frequency. Forskolin, an activator of adenylate cyclase, facilitated the mIPSC frequency in a concentration-dependent manner and inhibited the tACPD-induced suppression of mIPSC frequency. 8-Br-cAMP, a membrane permeable analog of cAMP, also prevented the inhibitory action of tACPD. However, Sp-cAMP, an activator of protein kinase A, could not prevent the inhibitory action of tACPD. L-CCG-I and (2R,4R)-APDC, group II mGluR agonists, mimicked the tACPD action on mIPSC frequency, but L-AP4, a group III mGluR agonist, had no such effect. MCCG, a group II mGluR antagonist, fully blocked the tACPD action. It was concluded that the activation of group II mGluR on the GABAergic presynaptic nerve terminals projecting to the rat nucleus basalis of Meynert neurons therefore inhibits the GABA release by reducing the activity of the cAMP-dependent pathway.

Adenylyl Cyclases↗

Immunocytochemical localization of neuronal calcium sensor-1 in the hippocampus and cerebellum of the mouse, with special reference to presynaptic terminals.

Neuronal calcium sensor-1 (NCS-1) is a member of the EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. In this work, we first examined the distribution patterns of NCS-1 in the hippocampus and cerebellum. The intense NCS-1-immunoreactive (IR) elements in the hippocampus were restricted to dendritic layers, while those in the cerebellum occurred in both dendritic and cellular layers. Then, we examined the exact localization of NCS-1 using immunofluorescent double labeling for NCS-1 and synaptophysin, a marker of presynaptic terminals. In the hippocampus, the mossy fiber systems (terminals and bundles) exhibited intense NCS-1 immunoreactivity. On the other hand, the presumed principal cell dendrites were also NCS-1-IR in the stratum lacunosum-moleculare of Ammon's horn and molecular layer of the dentate gyrus, where NCS-1-IR elements and synaptophysin-IR presynaptic terminals showed characteristic complementary distribution patterns. In the cerebellum, some of the basket cell axon terminals surrounding the somata of Purkinje cells exhibited NCS-1 immunoreactivity, while the pinceau showed consistent labeling for NCS-1. Higher magnification observations revealed that the NCS-1-IR presumed granule cell dendrites and synaptophysin-IR mossy fiber terminals in the glomeruli of the cerebellum showed characteristic complementary distribution patterns. Furthermore, we estimated quantitatively the relative amount of NCS-1 in the presynaptic terminals in individual layers, and confirmed that the mossy fiber terminals in the hippocampus contained comparatively high amounts of NCS-1. These results showed the diverse localization of NCS-1 in pre- and/or postsynaptic elements of the hippocampus and cerebellum, and suggest potential roles in specific synaptic transmission.

Animals↗

Oncogenic cell cycle start control.

The ability to proliferate in the absence of anchorage is a fundamental attribute of cancer cells, yet how it is acquired is one central problem in cancer biology. By utilizing growth factor-transformable NRK cells and its insensitive mutants, we recently found that oncogenic stimulation invokes Cdk6 to participate in a critical step of the cell cycle start, but not via the regulation of its catalytic activity and that Cdk6 participation closely correlates with the anchorage-independent growth ability. Since many hematopoietic cells employ predominantly Cdk6 for the cell cycle start and perform anchorage-independent growth by nature, this finding raises the possibility that the mechanism by which oncogenic stimulation invokes anchorage-independent growth of NRK cells is similar to the one used for hematopoietic cell proliferation. We discuss this novel mechanism and its implication.

Animals↗

Morphometric multivariate analysis of GABAergic neurons containing calretinin and neuronal nitric oxide synthase in the mouse hippocampus.

Several studies reported the morphology of calretinin-positive (CR+) neurons and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) labeled or neuronal nitric oxide synthase-positive (nNOS+) neurons in the rodent hippocampus, where these neurons showed similar morphological features. In addition, a previous study reported the frequent colocalization of CR and NADPH-d in the rat hippocampus. In this study, we aimed to examine whether CR+ neurons and nNOS+ neurons belong to a same morphological subpopulation of GABAergic neurons in the mouse hippocampus. Neurons were immunocytochemically classified into three groups, i.e., CR+/nNOS-, CR-/nNOS+ and CR+/nNOS+ groups. The present morphometric analysis was performed in the mouse Ammon's horn, because CR+/nNOS+ neurons were rarely found in the mouse dentate gyrus. We selected three morphometric parameters, i.e., soma area, soma form factor (FF) and number of primary dendrites. Dunnett's post-hoc analysis revealed that soma area, soma FF and number of primary dendrites were significantly larger in CR-/nNOS+ group than in CR+/nNOS- and CR+/nNOS+ groups. The morphometric data of CR+/nNOS+ group were quite similar to those of CR+/nNOS- group. The morphometric multivariate logistic regression analysis revealed that these three morphometric parameters were independent significant variables to discriminate between CR+/nNOS- and CR-/nNOS+ groups, and the majority of CR+/nNOS- and CR-/nNOS+ groups were correctly classified from the morphometric features. The present results clearly indicate that CR+/nNOS- neurons and CR-/nNOS+ neurons belong to different morphological subpopulations, and lead us to speculate that they might play different functional roles in the hippocampal circuit. The further application of morphometric multivariate analysis would be valuable to understand the functional roles of chemically defined neurons in the various brain regions.

Animals↗

Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence.

Mammalian cells require a cyclin D-dependent kinase for the cell cycle start, yet many mesenchymal cells express three seemingly redundant D cyclins and similarly, seemingly redundant Cdk4 and Cdk6 as their kinase partners. We have found that the Cdk6-cyclin D3 complex is unique among the D cyclin and kinase combinations in the ability to promote the cell cycle start. In an anchorage-minus G(1)-arrested rat fibroblast, only Cdk6-D3 retains kinase activity due mainly to its ability to evade inhibition by p27(KIP1) and p21(CIP1) with a resemblance to viral cyclin-bound Cdk6. Rodent fibroblasts engineered to overexpress both Cdk6 and cyclin D3 highly resist serum starvation- or cell-cell contact-imposed G(1)-arrest. In BALB/c 3T3 cells, D3 is constitutively expressed, but Cdk6 is markedly induced with concomitant activation upon stimulation with a growth-promoting factor. These results suggest a role for the Cdk6-D3 complex in regulating cell's proliferation ability in response to external stimuli.

3T3 Cells↗

Colocalization of parvalbumin and somatostatin-like immunoreactivity in the mouse hippocampus: quantitative analysis with optical dissector.

The colocalization of parvalbumin (PV) and somatostatin (SS)-like immunoreactivity was studied quantitatively in the mouse hippocampus, with particular reference to their areal and dorsoventral differences. The optical disector method was applied by using a confocal laser scanning microscope with immunofluorescent double-labeling. In the present study, we found a particular subpopulation of hippocampal nonprincipal neurons that contained both PV and SS-like immunoreactivity, i.e., PV-immunoreactive (IR)/SS-like immunoreactive (LIR) neurons. In the CA1 region, PV-IR/SS-LIR neurons were restricted to the stratum oriens (SO). In the CA3 region, they were scattered in the SO, stratum pyramidale (SP), and stratum radiatum (SR). However, they were rarely seen in the dentate gyrus (DG). The proportion of PV-IR/SS-LIR neurons in the PV-IR neurons or SS-LIR neurons was about 10% in the CA1 region, 15-30% in the CA3 region, 0-5% in the DG, and 10-20% in total. Laminar analysis revealed that the proportions of PV-IR/SS-LIR neurons in the PV-IR neurons were high in the SO (about 25%) of the CA1 region, and in the SO (about 50%) and SR (30-45%) of the CA3 region. The proportion of PV-IR/SS-LIR neurons in the SS-LIR neurons was low in the SO of the CA1 region (about 10%), but high in the SO (35-65%) and SR (35-45%) of the CA3 region. Morphologically, medium-sized horizontal fusiform and multipolar PV-IR/SS-LIR neurons were frequently observed, and they showed weak immunoreactivity for PV. Large-sized vertical bitufted and triangular PV-IR neurons lacked SS-like immunoreactivity, and most of them showed moderate to intense immunoreactivity for PV. In addition, we provide direct evidence that some PV-IR/SS-LIR neurons projected to the medial septum by using retrograde labeling with Fluoro-Gold injection. These observations indicate that PV-IR/SS-LIR neurons constitute a particular subpopulation of hippocampal nonprincipal neurons.

Animals↗

Oncogenic stimulation recruits cyclin-dependent kinase in the cell cycle start in rat fibroblast.

The rat fibroblast NRK cells are transformed reversibly by a combination of growth factors. When stimulated with serum, NRK cells rely on cyclin-dependent kinase 4 (Cdk4) for their S phase entry. However, when stimulated with serum containing oncogenic growth factors, they come to rely on either Cdk4 or Cdk6, and their S phase entry cannot be blocked unless both Cdk4 and Cdk6 are immunodepleted. Such change of dependence does not occur in the NRK cell mutants defective in an oncogenic signal pathway and, therefore, deficient in anchorage-independent cell cycle start ability, correlating Cdk6 dependence with this remarkable, cancer-associated phenotype. However, both Cdk4 and Cdk6 are activated upon serum stimulation, and neither the amounts of Cdk6, Cdk4, cyclin D1, and cyclin-dependent kinase inhibitors nor the activities or subcellular localization of Cdk6 and Cdk4 are significantly influenced by oncogenic stimulation. Thus, oncogenic stimulation invokes Cdk6 to participate in a critical step of the cell cycle start in a rat fibroblast, but by a mechanism seemingly unrelated to the regulation of the kinase. Given that many hematopoietic cells employ predominantly Cdk6 for the cell cycle start and perform anchorage-independent growth by nature, our results raise the possibility that the oncogenic stimulation-induced anchorage-independent cell cycle start of NRK is elicited by a mechanism similar to the one used for hematopoietic cell proliferation.

Animals↗

Quantitative analysis of neuronal nitric oxide synthase-immunoreactive neurons in the mouse hippocampus with optical disector.

A detailed quantitative analysis of immunocytochemically identified nonprincipal neurons containing neuronal nitric oxide synthase (nNOS) was performed on the mouse hippocampus, with particular reference to the dorsoventral gradient. The present study applied two variations of a stereologic technique, the optical disector--one that used confocal laser-scanning microscope optical sections to examine colocalization of nNOS and glutamic acid decarboxylase 67 (GAD67), and the other that used conventional thick sections to examine numerical densities (NDs) and cell sizes of nNOS-immunoreactive (IR) neurons. Colocalization analysis indicated that practically all nNOS-IR neurons (97.6%) were GAD67-IR, whereas a part of the GAD67-IR neurons (about 30%) were nNOS-IR in the whole hippocampus at both dorsal and ventral levels. The percentages of GAD67-IR neurons containing nNOS were higher in the dentate gyrus (DG, about 50%), and lower in the Ammon's horn (about 20%). Laminar analysis revealed that the majority of GAD67-IR neurons contained nNOS in the stratum lacunosum-moleculare of the CA3 region (about 60%) and in the molecular layer of the DG (about 80%). The NDs of nNOS-IR neurons in the whole hippocampus showed a dorsoventral gradient, which increased from dorsal (1.6 x 10(3)/mm3) to ventral (2.2 x 10(3)/mm3) levels. The NDs were relatively higher in the principal cell layers, where about 40% of nNOS-IR neurons were situated both in the Ammon's horn and DG. The mean cell sizes of nNOS-IR neurons showed no remarkable laminar differences or dorsoventral gradient in the Ammon's horn, but they were extensively larger in the hilus of the DG than in other layers. These results indicate that nNOS-IR neurons in the mouse hippocampus represent a subpopulation of gamma-aminobutyric acid (GABA)ergic neurons and suggest that the laminar distributions of nNOS-IR neurons related to possible functional heterogeneity of GABAergic neurons in each hippocampal layer.

Animals↗

Total synthesis of an antioxidant isolated from yeast via palladium-catalyzed coupling and its application for related compounds.

A total synthesis of an antioxidant (1) having a benzofuran skeleton was achieved in four steps via the palladium(0)-catalyzed cross-coupling reaction. We also prepared several related compounds bearing a variety of aromatic or heterocyclic rings. Some of these compounds demonstrate more potent than 1 for antioxidative activity using guinea pig liver microsomes.

Animals↗

Cell cycle start from quiescence controlled by tyrosine phosphorylation of Cdk4.

In mammals Cdk4 (or Cdk6 in some cell types) is required for starting the cell cycle. Recently we showed that Cdk4 is regulated by tyrosine phosphorylation and dephosphorylation, and that this regulation is required for a DNA damage-induced G1 arrest. We report here that a generic anti-phosphotyrosine antibody can detect tyrosine-phosphorylated Cdk4 and that as revealed by immunoblot detection and kinase assay, this regulation is employed for DNA damage-responsive checkpoint control during cell cycle start from quiescence. In rat fibroblasts traversing G1 or arrested in G1 by deprivation of anchorage, Cdk4 does not undergo tyrosine phosphorylation. Tyrosine phosphorylation occurs only during cell's arrest in quiescence and dephosphorylation during their cell cycle start. Ultraviolet irradiation blocks dephosphorylation and concomitant activation of Cdk4, thereby preventing the start of cell cycling. Thus, unlike tyrosine phosphorylation of Cdc2, which controls phase transition in the regular cell cycle, tyrosine phosphorylation of Cdk4 is employed for controlling cell cycle start from quiescence in a rat fibroblast.

3T3 Cells↗

Isolation of a mammalian homologue of a fission yeast differentiation regulator.

In the fission yeast Schizosaccharomyces pombe the nrd1(+) gene encoding an RNA binding protein negatively regulates the onset of differentiation. Its biological role is to block differentiation by repressing a subset of the Ste11-regulated genes essential for conjugation and meiosis until the cells reach a critical level of nutrient starvation. By using the phenotypic suppression of the S. pombe temperature-sensitive pat1 mutant that commits lethal haploid meiosis at the restrictive temperature, we have cloned ROD1, a functional homologue of nrd1(+), from rat and human cDNA libraries. Like nrd1(+), ROD1 encodes a protein with four repeats of typical RNA binding domains, though its amino acid homology to Nrd1 is limited. When expressed in the fission yeast, ROD1 behaves in a way that is functionally similar to nrd1(+), being able to repress Ste11-regulated genes and to inhibit conjugation upon overexpression. ROD1 is predominantly expressed in hematopoietic cells or organs of adult and embryonic rat. Like nrd1(+) for fission yeast differentiation, overexpressed ROD1 effectively blocks both 12-O-tetradecanoyl phorbol-13-acetate-induced megakaryocytic and sodium butyrate-induced erythroid differentiation of the K562 human leukemia cells without affecting their proliferative ability. These results suggest a role for ROD1 in differentiation control in mammalian cells. We discuss the possibility that a differentiation control system found in the fission yeast might well be conserved in more complex organisms, including mammals.

Amino Acid Sequence↗

Total synthesis of a natural antioxidant and structure-activity relationships of related compounds.

A total synthesis of benzodioxole derivative 1 was achieved via a palladium(0)-catalyzed cross-coupling reaction in a 68% overall yield (4 steps). A novel series of benzodioxoles bearing a variety of aromatic and heterocyclic rings was also prepared and the antioxidative activity evaluated using in vitro model systems. Structure-activity studies revealed that i) intramolecular hydrogen-bonding in the phenol moiety reduced activity, ii) introduction of disubstituents at the ortho location relative to the phenol increased activity, and iii) the methylenedioxy function contributed to stabilization of the phenoxy radical. Among of these compounds, 5,7-di-(4-methoxyphenyl)-4-methoxy-6-hydroxy-1,3-benzodioxole (7p) was the most favorable agent and more potent than n-propyl gallate.

Animals↗

[Large cell carcinoma of the lung with metastasis of the gastric submucosa].

A 66-year-old man was admitted with dyspnea on exertion and an abnormal shadow on chest roentgenogram. Transbronchial biopsy yielded a diagnosis of large cell carcinoma of the lung. His dyspnea improved following irradiation and corticosteroid treatment and one month later, he was admitted again for chemotherapy. Because occult blood in stool was detected, upper gastrointestinal endoscopy was performed. Gastric submucosal large cell carcinoma was diagnosed, and this was considered to be metastatic from the lung. Such cases diagnosed prior to death are rare.

Aged↗

[Interstitial pneumonitis associated with Sweet's syndrome in the elderly].

Sweet's syndrome occurring during the course of interstitial pneumonitis in a 70-year-old woman was encountered. She was admitted because of dyspnea on exercise, dry cough and interstitial shadow on chest x-ray. Lung biopsy, together with other findings confirmed interstitial pneumonitis. Five days after admission, genital ulcer and aphtha on the oral mucosa were detected and exudative erythema appeared on her right shoulder, chest and back. Histological examination of the skin lesions demonstrated numerous nutrophilic infiltration in the upper dermis, indicating Sweet's syndrome. The skin eruption rapidly disappeared on treatment with colchicine. Although six months after admission interstitial pneumonitis caused respiratory failure, treatment with prednisolone and cyclophosphamide was effective. Serological and immunological tests demonstrated hyper-gammaglobulinemia and positive reaction for anti SS-A antibody. Pathological examination of the lip revealed numerous lymphocyte infiltrates around the duct of the minor salivary gland, suggesting Sjögren's syndrome as the background disease of Sweet's syndrome and interstitial pneumonitis. This evidence indicating that even in elderly patients, skin lesions of Sweet's syndrome may reveal the background disease.

Aged↗