Uncommon Type of Meningiomas with Conspicuous Plasmo-lymphocytic Infiltration: An Immunohistochemical and Histochemical Study

Two cases of meningioma revealing conspicuous plasmo lymphocytic tissue and hyalinized fibrous tissue components are reported. Histopathological examination of the plasmo lymphocytic infiltration was performed. Both lesions showed polyclonality of plasma cells as revealed by positive reactions for 1gG and paraimmunoglobulin χ- and λ light chains, and amyloid infiltration into the fibrous stroma and blood vessel walls. The histochemical and immunohistochemical characteristics of the lesion in relation to its etiology are briefly discussed. Acta Pathol. Jpn. 32: 190∼194, 1989.     

Expression of cyclin D1, retinoblastoma gene protein, and p16 MTS1 protein in atypical adenomatous hyperplasia and adenocarcinoma of the lung

 To clarify the events leading to the disruption of cell growth control that occurs during the development of pulmonary adenocarcinoma (AC), we used immunohistochemistry to evaluate the expression of G1 cycle regulators, cyclin D1, Rb protein (pRb), and p16 MTS1 protein and the tumour proliferation marker, Ki 67, both in AC of the lung and in its precursor lesion, atypical adenomatous hyperplasia (AAH). The frequency of lesions with cyclin D1 overexpression was relatively high in AAH (47–89%), but was decreased in early AC (28%) and overt AC (35%). The loss of pRb expression was rare in both AAH (0–18%) and early AC (0%), and was infrequent even in overt AC (13%). The loss of p16 expression was also relatively infrequent in both the premalignant and the malignant lesions (11–25%). Our results suggest that overexpression of cyclin D1 is an early event and plays an important part in tumorigenesis in the case of lung AC. However, cyclin D1 overexpression is not required for the development and maintenance of a malignant phenotype. It is likely that some cyclin D1-independent pathways other than Rb and p16 abnormalities have an important role in the malignant transformation from AAH to early AC. Received: 8 July 1997 / 26 September 1997     

Immunohistochemical analysis of 14-3-3 sigma and related proteins in hyperplastic and neoplastic breast lesions, with particular reference to early carcinogenesis

In order to confirm the role of 14-3-3 sigma (sigma) as a tumor suppressor in breast carcinogenesis, we have studied the expression of 14-3-3sigma immunohistochemically in usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) breast lesions. Immunostaining for estrogen receptor alpha (ERalpha), p53 and estrogen-responsive RING finger protein (Efp) was also carried out. Immunohistochemically, expression of 14-3-3sigma was seen in 92% UDH lesions and gradually decreased from 65% in DCIS to 23% in IDC. The expression of ERalpha decreased gradually from UDH to DCIS to IDC, while p53 showed an inverse staining pattern to that of ERalpha. The expression of Efp showed no significant difference among the three breast lesions. Hence, the present immunohistochemical study confirmed 14-3-3sigma as a tumor suppressor in breast carcinogenesis. A similar immunohistochemical analysis was then carried out on columnar cell hyperplasia with atypia (CCHA), in which the expression pattern of tumor suppressor 14-3-3sigma, ERalpha and p53 suggested that it might be possible that CCHA is a precancerous lesion.     

gamma-Aminobutyric acid-induced response in rat dissociated paratracheal ganglion cells.

1. The pharmacologic properties of gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) were studied in the paratracheal ganglion cells freshly dissociated from 7- to 10-day-old rat trachea in a whole-cell recording mode by the use of a conventional patch-clamp technique. 2. GABA- and muscimol-induced currents increased sigmoidally in a concentration-dependent manner, and both currents reversed at approximately -3 mV, which was close to the Cl- equilibrium potential (ECl). 3. Strychnine (STR) at low concentration and bicuculline (BIC) inhibited GABA response competitively, whereas STR at the higher concentrations, benzylpenicillin (PCG), or picrotoxin (PTX) inhibited noncompetitively. Inhibition of GABA response by PCG but not other antagonists was voltage dependent, indicating that PCG acts as a Cl- channel blocker. 4. The concentration-response curve of pentobarbital sodium (PB)-induced ICl was bell shaped. At concentrations higher than 10(-3) M, both the peak and plateau currents decreased, and a transient "hump" current appeared immediately after washing out PB. In the presence of PB, the concentration-response curve of GABA shifted toward left without changing the maximum response. 5. Although diazepam (DZP) at concentration used did not induce a response, it potentiated the GABA response in a concentration-dependent manner between 10(-8) and 10(-6) M. DZP also caused a parallel shift toward left in the concentration-response curve of GABA. 6. PB or DZP further enhanced the GABA response in the presence of the other agent. 7. It is concluded that the properties of GABAA receptors in the paratracheal ganglion cells are essentially similar to those reported in other preparations.     

Hepatocyte attachment onto thermosensitive poly(N-isopropylacrylamide-co-N-p-vinylbenzyl-O-beta-D-galactopyranosyl-(1 --> 4)-D-gluconamide)

Temperature sensitive poly(N-isopropylacrylamide) (PIPAAM) was incorporated into hepatocyte-recognizable poly[N-p-vinylbenzyl-O-beta-D-galactopyranosyl-(1 --> 4)-D-gluconamide] (PVLA) for thermal modulating of hepatocyte attachment. The copolymer, poly(N-isopropylacrylamide-co-N-p-vinylbenzyl-O-beta-D-galactopyranosyl-(1 --> 4)-D-gluconamide) (abbreviated as [P(IPAAM-co-VLA)] (PIPAAM/PVLA = 9/1 in mol%) exhibited lower critical solution temperature (LCST) at 34 degrees C and also showed very good hepatocytes-recognizablility through the specific interaction between asialoglycoprotein receptors on the cell surfaces and galactose moiety of the copolymer. The cells attached on this copolymer were easily detached by lowering the temperature below the LCST of the copolymer. Morphological damage of the detached cell was not observed.     

Adenosine A1 receptor-mediated presynaptic inhibition of GABAergic transmission in immature rat hippocampal CA1 neurons

In the mechanically dissociated rat hippocampal CA1 neurons with native presynaptic nerve endings, namely "synaptic bouton" preparation, the purinergic modulation of spontaneous GABAergic miniature inhibitory postsynaptic currents (mIPSCs) was investigated using whole-cell recording mode under the voltage-clamp conditions. In immature neurons, adenosine (10 microM) reversibly decreased GABAergic mIPSC frequency without affecting the mean current amplitude. The inhibitory effect of adenosine transmission was completely blocked by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM), a selective Alpha(1) receptor antagonist, and was mimicked by N(6)-cyclopentyladenosine (CPA, 1 microM), a selective Alpha(1) receptor agonist. However, CPA had no effect on GABAergic mIPSC frequency in postnatal 30 day neurons. N-ethylmaleimide (10 microM), a guanosine 5'-triphosphate binding protein uncoupler, and Ca(2+)-free external solution removed the CPA-induced inhibition of mIPSC frequency. K(+) channel blockers, 4-aminopyridine (100 microM) and Ba(2+) (1 mM), had no effect on the inhibitory effect of CPA on GABAergic mIPSC frequency. Stimulation of adenylyl cyclase with forskolin (10 microM) prevented the CPA action on GABAergic mIPSC frequency. Rp-cAMPS (100 microM), a selective PKA inhibitor, also blocked the CPA action. It was concluded that the activation of presynaptic Alpha(1) receptors modulates the probability of spontaneous GABA release via cAMP- and protein kinase A dependent pathway. This Alpha(1) receptor-mediated modulation of GABAergic transmission may play an important role in the regulation of excitability of immature hippocampal CA1 neurons.     

Immunoexpression of the α subunit of a guanine nucleotide-binding protein (Go) in pulmonary neuroendocrine cells and neoplasms

The α subunit of a GTP-blndlng protein, Go, was investigated in pulmonary neuroendocrine neoplasms and fetal tissues of the lung by an immunohistochemlcal method. Positive immunostaining for the α subunit of Go (Goα) was found predominantly on the cell membrane and found occasionally in the cytoplasm. Typical carcinoids were all positively stained (9/9), and small cell carcinoma showed weaker and less frequent staining (5 positive cases in 10). Atypical carcinoids were variously stained (3/4). The tendency for obvious neuroendocrine differentiation to be immunohistochemically determined in typical carcinoids and not in small cell carcinoma is also true of staining for neuron specific enolase (NSE), chromogranin A (CG-A) and synaptophysin. In the lung, Goα-immunostaining was positive not only in nerve tissues but also in the airway epithelium. In the fetal lung, serial sections immunostained for NSE, CG-A and Goα confirmed that Goα-immunoreactive cells belong to the neuroendocrine cell population. The biological significance of Goα is unclear in normal and neoplastic lung tissues, but Goα is a useful marker of neuroendocrine cells and neoplasms of the lung.     

Long‐term observation of a Japanese mucolipidosis IV patient with a novel homozygous p.F313del variant of MCOLN1

Mucolipidosis type IV (MLIV) is an autosomal recessively inherited lysosomal storage disorder characterized by progressive psychomotor delay and retinal degeneration that is associated with biallelic variants in the MCOLN1 gene. The gene, which is expressed in late endosomes and lysosomes of various tissue cells, encodes the transient receptor potential channel mucolipin 1 consisting of six transmembrane domains. Here, we described 14‐year follow‐up observation of a 4‐year‐old Japanese male MLIV patient with a novel homozygous in‐frame deletion variant p.(F313del), which was identified by whole‐exome sequencing analysis. Neurological examination revealed progressive psychomotor delay, and atrophy of the corpus callosum and cerebellum was observed on brain magnetic resonance images. Ophthalmologically, corneal clouding has remained unchanged during the follow‐up period, whereas optic nerve pallor and retinal degenerative changes exhibited progressive disease courses. Light‐adapted electroretinography was non‐recordable. Transmission electron microscopy of granulocytes revealed characteristic concentric multiple lamellar structures and an electron‐dense inclusion in lysosomes. The in‐frame deletion variant was located within the second transmembrane domain, which is of putative functional importance for channel properties.     

cAMP-dependent presynaptic regulation of spontaneous glycinergic IPSCs in mechanically dissociated rat spinal cord neurons

Spontaneous miniature glycinergic inhibitory postsynaptic currents (mIPSCs) in mechanically dissociated rat sacral dorsal commissural nucleus (SDCN) neurons attached with intact glycinergic presynaptic nerve terminals and evoked IPSCs (eIPSCs) in the slice preparation were investigated using nystatin-perforated patch and conventional whole cell recording modes under the voltage-clamp conditions. Trans-ACPD (tACPD) reversibly reduced the mIPSC frequency without affecting the mean amplitude. The effect was mimicked by a specific metabotropic glutamate receptor (mGluR) II subtype agonist, (2S, 1'S, 2'S)-2-(carboxycyclo propyl) glycine (L-CCG-I), and a specific mGluRIII subtype agonist, 2-amino-4-phosphonobutyrate (L-AP4). These inhibitory effects on mIPSC frequency were blocked by the specific antagonists for mGluRII, alpha-methyl-1-(2S, 1'S, 2'S)-2-(carboxycyclo propyl) glycine and (RS)-alpha-cyclopropyl-4-phosphonophenylglycine. In the slice preparation, eIPSC amplitude and mIPSC frequency were decreased reversibly by L-CCG-I (10(-6) M) and L-AP4 (10(-6) M). In K(+)-free or K(+)-free external solution with Ba(2+) and Cs(+), Ca(2+)-free or Cd(2+) external solution, the inhibitory effect of tACPD on mIPSC frequency was unaltered. Forskolin and 8-Br-cAMP significantly increased presynaptic glycine release, and prevented the inhibitory action of tACPD on mIPSC frequency. Sp-cAMP, however, did not prevent the inhibitory action of tACPD on mIPSC frequency. It was concluded that the activation of mGluRs inhibits glycine release by reducing the action of cAMP/PKA pathway.     

Regional variation of excitatory and inhibitory amino acid-induced responses in rat dissociated CNS neurons.

Regional differences in glutamate (Glu), aspartate (Asp), gamma-aminobutyric acid (GABA) and glycine (Gly) responses in CNS neurons were investigated by means of the whole-cell mode of the patch-clamp technique. The neurons were freshly dissociated from rat cortex, limbic system (hippocampal CA1 region), diencephalon (ventromedial hypothalamus), medulla (nucleus paragigantocellularis lateralis) and spinal cord (spinal dorsal horn). The current amplitudes induced by Glu and GABA did not show any regional differences whereas those of Asp- and Gly-induced responses were significantly different among CNS regions. The enhancement of Asp response by Gly was observed in all regions, and the facilitatory ratio did not differ among these regions. Even though the NMDA response in cortical neurons was significantly greater than that in spinal neurons, the ratios of NMDA response facilitation by Gly were also the same in both regions. When the current amplitudes induced by individual amino acids were estimated for the unit surface area of respective neurons (current density), the Glu, Asp and Gly responses showed regional heterogeneity whereas the GABA response did not.