Indoleamine 2,3-dioxygenase: distribution and function in the developing human placenta

Studies in mice have suggested that the placenta is protected from immune rejection by maternal T cells by means of localised indoleamine 2,3-dioxygenase dependent depletion of tryptophan. To determine whether such mechanisms might operate in the human placenta, we have studied the physiological importance of human placental indoleamine 2,3-dioxygenase immunohistochemically and functionally. Indoleamine 2,3-dioxygenase is detectable immunohistochemically from day 6 human blastocysts and thereafter throughout pregnancy in syncytiotrophoblasts, extravillous cytotrophoblasts and macrophages in the villous stroma and in the fetal membranes. Interferon-gamma added to villous explants markedly stimulates indoleamine 2,3-dioxygenase protein expression in macrophages. Indoleamine 2,3-dioxygenase-mediated tryptophan degradation in the first trimester villous and decidual tissue explants is stimulated by interferon-gamma and inhibited by 1-methyl-tryptophan (an inhibitor of indoleamine 2,3-dioxygenase). Peripheral blood mononuclear cell proliferation is controlled by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. These results suggest the cellular basis of a mechanism present at the human maternal-fetal interface involved in regulating the maternal immune response to conceptus.     

Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative diseases that are characterized by intracytoplasmic aggregates of hyperphosphorylated tau with four microtubule-binding repeats. Although PSP and CBD have distinctive pathological features, no biochemical difference in aggregated tau has been identified. In this study, we examined the brains of eight patients with PSP, six patients with CBD, and one atypical case with pathological features of both CBD and PSP. On immunoblots of sarkosyl-insoluble brain extracts, a 33kDa band predominated in the low molecular weight tau fragments in PSP, whereas two closely related bands of approximately 37kDa predominated in CBD. Immunoblots of the atypical case showed both the 33kDa band and the 37kDa doublet. Protein sequencing and immunochemical analyses showed that the 33kDa band and the 37kDa doublet consisted of the carboxyl half of tau with different amino termini. These results suggest that, despite the identical composition of tau isoforms, different proteolytic processing of abnormal tau takes place in these two diseases. Such a biochemical divergence may be related to the neuropathological features of these diseases.     

Corticobasal degeneration with primary progressive aphasia and accentuated cortical lesion in superior temporal gyrus: case report and review

A 57-year-old woman showed progressive sensory aphasia as an initial symptom, and then developed total aphasia within 6 years and, finally, severe dementia. Neuropathologically, the cerebral cortex was most severely affected in the superior and transverse temporal gyri, and subsequently in the inferior frontal gyrus, especially in the pars opercularis. The degeneration in the subcortical grey matter was most severe in the substantia nigra, and it was moderate to mild in the ventral part of thalamus, globus pallidus and striatum. Cytopathologically, in addition to achromatic ballooned neurons, massive tau-positive types of cytosekeletal abnormalities were observed both in neurons and glia, mainly in the degenerating region. This cytoskeletal pathology coincided with that reported in corticobasal degeneration (CBD). On Bodian staining, only a few neurofibrillary tangles were found in the entorhinal pre-alpha layer and substantia nigra. Pick’s bodies and senile plaques could not be found. This case is thought to represent a type of CBD, but with its cortical lesion focus located in the speech area instead of the frontoparietal region. A survey of 28 pathologically evaluated cases of CBD revealed two similar cases, both of which began with progressive aphasia and presented cortical degeneration in the superior temporal gyrus. An overview of CBD cases clarified the features in another group of cases, in which the cerebral accentuated focus was shifted forward from the central region, clinically resembling Pick’s disease. The clinical manifestations in CBD seem to be the expression of these diverse cortical lesions. Primary progressive aphasia may include cases of CBD with involvement of the language center. Received: 5 February 1996 / Revised, accepted: 13 May 1996     

Evaluation of OPC-17116 against important pathogens that cause respiratory tract infections.

The antibacterial activity of OPC-17116, a new fluoroquinolone antibacterial agent, against important pathogens that cause respiratory tract infections was evaluated in vitro and in vivo and compared with those of ciprofloxacin, ofloxacin, and norfloxacin. The pharmacokinetic profiles of OPC-17116 were studied in both mice and rats given the drug orally at doses of 50 and 40 mg/kg of body weight, respectively. OPC-17116 showed a high degree of distribution in the lung tissues of both species, with maximum concentrations of 29.6 and 32.0 micrograms/g, respectively. Furthermore, the drug concentrations in lung tissue were about 10 to 15 times greater than the concentrations in plasma. OPC-17116 showed potent antibacterial activity against such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, and Moraxella catarrhalis. The MICs of this compound for 90% of these organisms except methicillin-resistant S. aureus and P. aeruginosa ranged from < or = 0.006 to 0.78 microgram/ml. The in vitro antibacterial activity of OPC-17116 was reflected by the efficacy of a single oral dose against systemic bacterial infections in mice. OPC-17116 showed a superior effect against gram-positive bacteria, H. influenzae, and M. catarrhalis. In comparison with the other reference compounds, the efficacy of OPC-17116 was less than that of ciprofloxacin against K. pneumoniae and P. aeruginosa. OPC-17116 showed a greater therapeutic effect than the other drugs against experimental acute pneumonia caused by these organisms in mice or rats. This excellent therapeutic effect against respiratory tract infections may be a result of its high level of distribution in lung tissue.     

Distinct isoforms of tau aggregated in neurons and glial cells in brains of patients with Pick's disease, corticobasal degeneration and progressive supranuclear palsy

We investigated isoform composition of aggregated tau protein in brains with Pick's disease (PiD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) by immunoblot analysis of sarkosyl-insoluble fractions of brain homogenates. We also examined the adjacent brain tissues immunohistochemically with a rabbit antibody, Ex10, which specifically recognizes exon 10 of tau. The Ex10 recognizes tau isoforms with four microtubule-binding repeats (4Rtau) but not those with three microtubule-binding repeats (3Rtau). Sarkosyl-insoluble tau from the brains of patients with CBD and PSP consisted of 4Rtau. Insoluble tau from the PiD brains contained both 3Rtau and 4Rtau, where 3Rtau predominated over 4Rtau. In brain tissues of CBD and PSP, Ex10 immunostained all neuronal and glial tau-positive structures. They included pre-tangles, astrocytic plaques, tuft-shaped astrocytes, and oligodendroglial coiled bodies. In PiD brains, astrocytic inclusions were also positive for 4Rtau. However, the majority of, if not all, Pick bodies and oligodendroglial tau inclusions were negative for 4Rtau. Such results suggest that, in neurons and oligodendroglia, tau isoforms involved in the pathological processes differ between CBD/PSP and PiD, and are thus disease specific. This contrasts with the astrocytic tau isoforms that accumulate similarly in all three disorders.     

Audiometry with nasally presented masking noise: novel diagnostic method for patulous eustachian tube.

OBJECTIVE: Nasal-noise masking audiometry was developed to assess the acoustic transfer function from the nasopharyngeal cavity to the middle ear via patulous eustachian tube (ET). STUDY DESIGN: Prospective. SETTING: Tertiary referral center. PATIENTS: Twenty-seven ears of 18 patients with patulous ET and 20 ears of 10 healthy subjects with no history of ear disease or complaints of aural symptoms. MAIN OUTCOME MEASURES: Audiometric measurement was conducted with and without masking noise presented in the nasal cavity. RESULTS: The masking effect of nasally presented noise caused elevation of the threshold for the tone presented in the external auditory canal. This threshold elevation was significantly greater, particularly in the lower-frequency region, in ears with patulous ET and was decreased to the normal range after obstructive treatment of the patulous ET. CONCLUSION: Nasal-noise masking audiometry is a simple and effective way to identify patulous ET.     

Pulsatile tinnitus caused by pneumocephalus after Janneta surgery

Pulsatile tinnitus of nonvascular origin is rare. We herein present a case of pulsatile tinnitus complicated with Jannetta surgery due to a communication created between the drilled mastoid cells and epidural space. She was successfully cured by otological surgery where the mastoid tip was packed with bone cement. A 68–year-old woman was referred to the previous hospital with complaints of right autophony, aural fullness, hyperacusis to her footsteps, and pulsatile tinnitus for the past three years. She had received Jannetta surgery for right hemifacial spasm seven years before. The computed tomography (CT) of the right temporal bone showed bony dehiscence between the mastoid cells and posterior cranial fossa. She underwent otological surgery to obliterate the tip of the mastoid cavity with artificial bone cement (BIOPEX^?) under general anesthesia. Her annoying aural symptoms were immediately abolished and she has been free from symptoms at ten months after surgery. It is critical to ensure the closure of any communication created between the middle ear and epidural space during surgeries in order to prevent the occurrence of pulsatile tinnitus.     

Usefulness of preoperative simulation with patient-specific hollow vascular models for high-flow renal arteriovenous fistula embolization using a preloading coil-in-plug technique

The development of three-dimensional printers has facilitated the creation of patient-specific hollow vessel models. Preoperative simulations using these types of models have improved our ability to select appropriate devices and embolic materials before performing complex endovascular procedures. This report describes 2 cases of high-flow renal arteriovenous fistulas (r-AVFs) that were successfully treated via short-segment embolization using the preloading coil-in-plug (p-CIP) technique. To our knowledge, this is the first report of r-AVF being treated using the p-CIP technique. Our findings demonstrate that preoperative simulation has the potential to improve the safety and reliability of complex vascular embolization procedures.