Acrania: an autopsy case and review of the literature

ABSTRACT We report an autopsy case of acrania with a review of the literature. A 31-year-old woman was admitted in poor genaral condition and diagnosed as pregnant at the 26th week of gestation. The fetus was suspected to be anencephalic or hydrocephalic by ultrasonography. She delivered a stillbirth male baby at the 28th week of gestation. Autopsy showed the cranium lacked the cranial vault The scalp directly covered the hydrocephalic brain without calvaria. No cerebellum was found macroscopically. On histological examination, the thinned cerebral layer was composed of white matter-like brain tissue with glial and ependymal cells. In the cerebral layer near the base of the skull, a few NSE-positive neurons among many GFAP-positive glial cells and oligodendrocyte-like cells were observed. The choroid plexuses were observed inside the ependymal layers. The brain stem and the spinal cord were normally preserved with clusters of NSE-positive neurons. Agnethia and horseshoe kidney were combined as malformations other than the brain. We reviewed 42 cases of acrania from the literature.     

Ataxic mutant mice with defects in Ca2+ channel α1A subunit gene: morphological and functional abnormalities in cerebellar cortical neurons

ABSTRACT This review summarizes recent studies in the morphological and functional abnormalities of cerebella in three ataxic mutant mice, i.e. tottering mouse, leaner mouse, and rolling mouse Nagoya (RMN). These mutants carry mutations in the Ca²⁺ channel α_1A subunit gene, and become useful models for human neurological diseases such as episodic ataxia type-2, familial hemiplegic migraine, and spinocerebellar ataxia type-6. All three mutants exhibited altered morphology of the Purkinje cells, ectopic synaptic contacts between granule cell axons (parallel fibers) and Purkinje cell dendritic spines and abnormal expression of tyrosine hydroxylase in Purkinje cells. In leaner mice, Purkinje cell loss was observed in alternating sagittal compartments of the cerebellar cortex corresponding to the Zebrin II-negative zones. The mutated Ca²⁺ channel α_1A subunit was highly expressed in granule and Purkinje cells, and the P-type Ca²⁺ currents in Purkinje cells were selectively reduced in the mutant mice. Therefore, we concluded that altered Ca²⁺ currents through the mutated Ca²⁺ channel α_1A subunit might be involved in the functional and morphological abnormalities in granule and Purkinje cells, and might result in expressions of behavioral phenotypes including ataxia. Increased levels of corticotropin-releasing factor and cholecystokinin in some climbing and mossy fibers were observed in RMN. These neuropeptides modulated the excitability of granule and Purkinje cells, indicating the possible expression of ataxic symptoms.     

TGF-beta3-dependent SMAD2 phosphorylation and inhibition of MEE proliferation during palatal fusion.

Transforming growth factor (TGF) -beta3 is known to selectively regulate the disappearance of murine medial edge epithelium (MEE) during palatal fusion. Previous studies suggested that the selective function of TGF-beta3 in MEE was conducted by TGF-beta receptors. Further studies were needed to demonstrate that the TGF-beta signaling mediators were indeed expressed and phosphorylated in the MEE cells. SMAD2 and SMAD3 were both present in the MEE, whereas SMAD2 was the only one phosphorylated during palatal fusion. SMAD2 phosphorylation was temporospatially restricted to the MEE and correlated with the disappearance of the MEE. No phosphorylated SMAD2 was found in MEE in TGF-beta3(-/-) mice, although nonphosphorylated SMAD2 was present. The results suggest that TGF-beta3 is required for initiating and maintaining SMAD2 phosphorylation in MEE. Phospho-SMAD3 was not detectable in palate during normal palatal fusion. Previous results suggested TGF-beta-induced cessation of DNA synthesis in MEE cells during palatal fusion in vitro. The present results provide evidence that inhibition of MEE proliferation in vivo was controlled by endogenous TGF-beta3. The number of 5-bromo-2'-deoxyuridine (BrdU) -labeled MEE cells was significantly reduced in TGF-beta3(+/+) compared with TGF-beta3(-/-) mice when the MEE seam formed (t-test, P < 0.05). This finding suggests that TGF-beta3 is required for inhibiting MEE proliferation during palatal fusion. The inhibition of MEE proliferation may be mediated by TGF-beta3-dependent phosphorylation of SMAD2.     

Characterization of TROY/TNFRSF19/TAJ-expressing cells in the adult mouse forebrain

A member of the tumor necrosis factor receptor superfamily (TNFRSF), TROY/TNFRSF19/TAJ, is highly expressed in the brain of adult mice. Northern blot analysis using mRNA taken from regions of the adult CNS showed the expression of TROY in all regions examined, including the olfactory bulb, cerebral cortex, striatum, and hippocampus. In situ hybridization and immunohistochemistry revealed that TROY mRNA and protein were strongly expressed in the rostral migratory stream (RMS) and subventricular zone (SVZ) of adult mice. In the adult SVZ, some glial fibrillary acidic protein (GFAP)-positive cells (type B cells) are thought to be multipotent neural stem cells. These type B cells divide slowly and generate epidermal growth factor receptor (EGFR)-positive transit-amplifying precursor cells (type C cells) in the presence of epidermal growth factor (EGF). Type C cells give rise to neuron-specific class III beta-tubulin (TuJ1)-positive neuroblasts (type A cells) that migrate to the olfactory bulb along the RMS. TROY-expressing cells were GFAP-positive, EGFR-positive, and TuJ1-negative in the adult SVZ. From these findings, TROY appears to be expressed in type B and type C cells, but not in type A cells, which was supported by immunoelectron microscopy. In addition, TROY was expressed in GFAP-positive astrocytes of the various regions, such as the cerebral cortex, striatum, and hippocampus. Thus, TROY was expressed in uncommitted precursor cells and astroglial lineage cells, suggesting that TROY plays some roles in the regulation of gliogenesis in the adult CNS.     

Intravenous immunoglobulin for acute exacerbation of fibrotic idiopathic interstitial pneumonias

Background and aim:Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition with no established treatment. Intravenous immunoglobulin (IVIG) is a unique therapy with both anti-inflammatory and anti-infective effects. Therefore, we hypothesized that IVIG may have a positive effect on AE of interstitial pneumonia. This study aimed to determine the effect of IVIG in patients with AE of fibrotic idiopathic interstitial pneumonias (IIPs), including IPF.Methods:We retrospectively analyzed consecutive patients who were diagnosed with AE of fibrotic IIPs and treated with pulse corticosteroid therapy (methylprednisolone 500–1000 mg/day for 3 days) between April 2018 and May 2021 at Kagawa Rosai Hospital and KKR Takamatsu Hospital.Results:This study included 52 patients with AE of fibrotic IIPs (IPF,41; fibrotic IIPs other than IPF,11). Thirteen patients received IVIG (5 g/day for 3–5 days) concurrently with pulse corticosteroid therapy. The remaining 39 patients were assigned to the control group. The survival rate on day 90 was significantly higher in the IVIG group than that in the control group (76.9% vs. 38.5%, p = 0.02). IVIG administration (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.02–0.69; p = 0.02) and C- reactive protein (OR, 1.19; 95% CI, 1.06–1.33, p < 0.01) were independently associated with 90-day mortality.Conclusions:The results indicate that administration of IVIG may improve the survival of patients with AE of fibrotic IIPs. We are now conducting a prospective study to confirm the effect of IVIG on AE of IPF since May 2022 (jRCT1061220010).     

Microsatellite instability in patients with gastric remnant cancer

Background. About 2% of patients who undergo partial distal gastrectomy for gastroduodenal diseases develop gastric remnant cancer 10 to 30 years after the gastrectomy. It is important in clinical practice to determine a molecular marker to identify patients susceptible to gastric remnant cancer. Methods. We investigated nine gastric remnant cancers (from nine individuals who had gastrectomies for primary gastric cancer or gastroduodenal ulcer) for microsatellite instability (MSI) at six loci, using the polymerase chain reaction (PCR). A control group of ten patients with sporadic gastric cancers in the upper third of the stomach was also similarly analyzed. Results. MSI was demonstrated in eight of nine cancers from the individuals who had had primary gastric cancer or gastroduodenal ulcer (88.9%) compared with two of ten cancers from the individuals with sporadic gastric cancer in the upper third of the stomach (20%). Conclusion. These results suggest that one or more MSI is associated with remnant gastric cancer after gastrectomy. Received on Sept. 6, 1999; accepted on Dec. 20, 1999     

A novel support system for patient immobilization and transportation for daily computed tomographic localization of target prior to radiation therapy

PURPOSE: To develop a method for quick and smooth transportation of patients from a computed tomography (CT) table to a linear accelerator (linac) table for confirming tumor center before radiation therapy. MATERIALS AND METHODS: We developed a system using a subtable for patient immobilization that is transported via a customized stretcher. The patient lies on the subtable and is immobilized by a vacuum cushion and thermoplastic body cast. The subtable stretcher is used to carry the subtable from the CT table to the linac table. During transportation, the subtable is kept flat and shock to the subtable is carefully avoided. Between August 2001 and September 2002, a total of 9 patients with solitary upper lung tumors (superior to carina) were treated using this system. RESULTS: Intrafractional tumor motion along the x (left-right), y (anterior-posterior), and z axis (superior-inferior) ranged from -2 mm to 2 mm, -2 mm to 2 mm, and -5 mm to 3 mm, respectively. The standard deviation of intrafractional tumor motion along the x, y, and z axis ranged from 0.5 mm to 1.5 mm, 0 mm to 1.7 mm, and 0.6 mm to 3.5 mm, respectively. Interfractional setup errors along the x, y, and z axis ranged from -5 mm to 4 mm, -6 mm to 8 mm, and -6 mm to 6 mm, respectively, and we could reduce interfractional setup errors in the majority of treatment sessions. CONCLUSIONS: We developed a system that allows patients to be immobilized and transported to verify tumor location on a daily basis. This system is highly useful for reducing setup errors.     

Connexin26-mediated gap junctional communication reverses the malignant phenotype of MCF-7 breast cancer cells

A growing body of evidence indicates that the gap junction (GJ) plays a pivotal role in tumor suppression by exerting cell-cell communication. It has, however, been reported that expression of connexin26 (Cx26) protein is induced in human ductal carcinomas of the breast and that its amount increases in proportion to the grade of malignancy. We thus examined the effects of over-expressed Cx26 on growth characteristics in GJ-deficient human MCF-7 breast cancer cells that maintain the phenotype of early-stage cancers. MCF-7 cells were transfected with Cx26 cDNA, and several clones of stable transformants exhibiting a high level of cell-cell communication were established. When they were examined in terms of various growth characteristics in vitro , the proliferation rate and the saturation density were drastically reduced in Cx26-transfected clones compared with the mock-transfectant. The anchorage-independent growth capacity was also decreased by 50–75% after transfection of Cx26. Furthermore, the cell migration toward growth factors and cell invasion into Matrigel in a Boyden chamber were suppressed to 5–10% and 20–60%, respectively, of the control in Cx26-transfected clones. When implanted into the mammary fat pads of nude mice in the presence of an excess of 17β-estradiol, Cx26-transfected clones tended to show slower tumor growth than the mock-transfectant, although the difference was not statistically significant. Our results strongly suggest that the induction of Cx26 protein observed in human breast cancers, reported previously, may not be very relevant to the development of breast cancers, and that Cx26 can function as a tumor suppressor in breast cancer cells.