Expression of membrane-bound and soluble receptor activator of NF-kappaB ligand (RANKL) in human T cells

The receptor activator of NF-kappaB ligand (RANKL) and its receptor RANK are critical regulators for immune responses as well as bone remodeling. RANKL is a type II transmembrane protein that has two forms-a membrane-anchored protein and a secreted protein. In this report, we demonstrate for the first time the kinetical expression of two forms of RANKL in human T cells using two monoclonal antibodies (mAbs) against human RANKL, which we newly derived. Freshly isolated T cells rarely expressed mRANKL, while the activation of T cells induced a substantial but minimal level of mRANKL as well as the accumulation of considerable amounts of sRANKL. The addition of the metalloprotease inhibitor KB-R8301 efficiently suppressed the release of sRANKL from activated T cells or RANKL-transfectants, and reciprocally enhanced the mRANKL expression. The membrane form of RANKL was also expressed on the infiltrating T cells in the rheumatoid synovial fluid and in the gingival tissues of patients with periodontitis. Our results demonstrate that the expression of mRANKL on T cells is strictly limited, and the majority of RANKL protein produced by T cells may be active in the soluble form after shedding. The mAbs that were derived in this study may be useful for investigating the regulation and function of RANKL in immune responses and bone remodeling.     

Effect of histamine and substance P on the rabbit and human iris sphincter muscle

Background and methods: In an attempt to clarify the functional action of histamine and substance P on atropine-resistant miosis, we isolated rabbit and human iris sphincter muscles and investigated their mechanical properties using the isometric tension recording method. Results: Substance P dose-dependently contracted the rabbit iris sphincter, but had no effect on the human iris sphincter. In the rabbit iris sphincter, histamine reduced the amplitude of twitch contraction evoked by field stimulation but had no effect on carbachol-induced contraction. Thioperamide, but not mepyramine or cimetidine, partially antagonized the histamine-induced reduction in the amplitude of twitch contractions. In the human iris sphincter, on the other hand, histamine dose-dependently provoked contraction and the amplitude of histamine-induced contraction was affected neither by atropine nor by indomethacin. Conclusions: These results provide evidence that histamine has strong contractile effect on the human iris sphincter muscle; the rabbit iris sphincter muscle, however, apparently lacks functional histamine receptors. In rabbits, exogenously applied histamine only activates H₃ receptors located on the cholinergic nerve terminal, hence the excitatory neuro-effector transmission is suppressed. Thus, histamine may have an important roles in atropine-resistant miosis in humans, but not in rabbits.     

A case of ductal carcinoma in situ (DCIS; non-comedo type) detected by ultrasonography: Demonstration of occult multiple foci

We report a case of ductal carcinoma in situ (DCIS) of the breast detected by ultrasonographic mass screening in a 51-year-old woman. In a mass screening program for breast cancer, physical examination with inspection and palpation, and ultrasonography (US) were performed. A hypoechoic mass with a slightly irregular margin was detected by US in the lateral upper quadrant of the right breast, at a distance 2 cm from the edge of the nipple. The mass was not detected by physical examinations or by mammography (MMG). The mass, which measured 0.8 x 0.5 cm and was examined by fine needle aspiration biopsy (FNAB) under US guidance, was cytologically diagnosed as class X. Modified radical mastectomy (Auchincloss method) was performed with the patient's consent. Pathological examination of the resected specimen revealed DCIS (noncomedo type) and occult multiple foci of malignancy which was considered tracking centripetally underneath the nipple. This case suggests that US and FNAB performed under US guidance are useful in the detection and diagnosis, respectively, of a breast mass. We should take multifocality into consideration, particularly with tendency tracking to the nipple, in the treatment of small breast cancers such as DCIS.     

Effect of recombinant granulocyte colony-stimulating factor (rG-CSF) on chemotherapy-induced neutropenia in patients with urogenital cancer

Summary The effects of recombinant granulocyte colony-stimulating factor (rG-CSF) on the myelosuppression, especially neutropenia, induced by cancer chemotherapy in patients with urogenital cancer were investigated in a randomized, controlled clinical study. In this study, rG-CSF was given subcutaneously at a dose of 2 g/kg per day for 14 consecutive days. Changes in neutrophil counts were compared between the first (no rG-CSF) and second cycles (rG-CSF treatment period) of chemotherapy. rG-CSF administration was found to be effective in reducing the duration of neutropenia, in elevating the neutrophil nadir, and in reducing recovery time. Based on comparisons between the randomized rG-CSF treatment group (with rG-CSF) and the control group, treatment with rG-CSF resulted in the moderation or prevention of neutropenia and the acceleration of recovery. These results demonstrate that in chemotherapy of patients with urogenital cancer, in which neutropenia is a dose- or schedule-limiting factor, the concomitant use of rG-CSF may enable an increase in the dose (higher single dose or increased dose per unit of time) or shorten the chemotherapy period.     

Ketotic hypoglycemia in patients with allergic diseases

BACKGROUND: Ketotic hypoglycemia is the most common cause of recurrent hypoglycemia in early childhood but its etiology is poorly understood. Elimination diets have been used for the prevention or treatment of some allergic diseases; however, these diets entail a risk to the normal nutrition and growth of children. The present study investigated whether elimination diets are related to the occurrence of ketotic hypoglycemia. METHODS: The prevalence of allergy treated with elimination diet therapy was retrospectively investigated in 18 patients with ketotic hypoglycemia seen in Yamaguchi University Hospital between January 1995 and September 1999. Data were gathered by reviewing the patients' medical charts. RESULTS: Ten (55.6%) of 18 patients with ketotic hypoglycemia had allergic diseases. Six (60%) of the patients had been treated with strict elimination diets and the others were on incomplete elimination diets for the prevention of allergy. The ketotic hypoglycemia patients with allergic diseases had experienced fewer pre-existing infectious diseases than those without allergic diseases. CONCLUSIONS: Patients with allergic diseases treated with elimination diets have a relatively high tendency towards developing ketotic hypoglycemia. They might have a lower capacity to tolerate fasting due to their excessive avoidance of many foods, even during periods when they are not undergoing strict elimination diets.     

More than 10 years of follow-up of two patients after total femur replacement for malignant bone tumor

One patient with osteosarcoma and one with Ewing’s sarcoma of the femur were in 1987 and 1988 treated with prosthetic replacement of the femur and chemotherapy. There has been no loosening of the prostheses and no recurrence of the tumor. The patients have maintained 60% and 63% limb function scores evaluated by ISOLS criteria.

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Résumé  Deux patients, l’un avec un ostéosarcome, l’autre avec un sarcome d’EWING, furent opérés en 1987–1988 avec remplacement prothétique du fémur, associéà une chimiothérapie. Ces patients ont été suivis sans qu’il soit noté de récidive. Il n’y a pas de descellement, ni de luxation de la prothèse. Un score fonctionnel évalué selon les critères de l’ISOLS, montre une conservation de 60% et 63% de la fonction du membre inférieur.

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Accepted: 17 March 2000     

Dimeric flavonol glycoside and galloylated C-glucosylchromones from Kunzea ambigua

A novel dimeric flavonol glycoside linked through a methylene group, kunzeagin A (1), and six new chromone C-glucosides, kunzeachromones A-F (2-7), were isolated along with seven known compounds from the leaf extract of Kunzea ambigua. The structures of these compounds were elucidated on the basis of spectroscopic analyses and chemical properties. Kunzeachromones A-F provided additional examples of galloylated C-glucosidic chromones occurring in the Myrtaceae. Kunzeagin A (1) and major constituents of this plant (6-C- and 8-C-glucosylchromones and their monogallates) exhibited potent inhibitory effects on activation of Epstein-Barr virus early antigen induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells.     

Pre-synaptic actions of noradrenaline on the dog ciliary muscle tissue

Effects of noradrenaline (NA) on the electrical and mechanical properties of the dog ciliary muscle were investigated using microelectrode- and isometric tension recording methods. Electrical-field stimulation to the tissue evoked excitatory junctional potentials (e.j.ps) followed by twitch contractions. Both responses were abolished by tetrodotoxin (TTX, 10(-7) M) or atropine (10(-6) M), thereby indicating that these responses are cholinergic-related. Exogenously applied NA (greater than 10(-8) M) suppressed the amplitude of e.j.ps and the following twitch contraction evoked by field stimulations, with no change in the resting tension, membrane potential and input membrane resistance of the smooth muscle cells. Exogenously applied carbachol dose-dependently contracted the ciliary muscle. However, NA (10(-5) M) did not affect the carbachol-induced contraction, thereby indicating that NA acts on the nerve terminals and reduces the amount of transmitter released from the terminals. Inhibitory effects of NA on the twitch contraction were antagonized by yohimbine (10(-6) M), but not by prazosin (10(-6) M) or timolol (10(-6) M). Guanethidine (5 X 10(-6) M) had no effect on the contraction evoked by field stimulation. These results provide evidence that exogenously applied NA activates the alpha 2-adrenoceptor located on cholinergic nerve terminal, hence the excitatory neuro-effector transmission is suppressed. These actions may explain the decrease in near point of accommodation observed with clinical application of adrenergic agents.     

Sensory Ataxic Guillain-Barré Syndrome with Dysgeusia after mRNA COVID-19 Vaccination

Guillain-Barré syndrome (GBS) has occasionally occurred in people who have received coronavirus disease 2019 (COVID-19) vaccines. Dysgeusia is rare symptom of GBS. We herein report a rare case of sensory ataxic GBS with dysgeusia just after the second dose of the Pfizer-BioNTech COVID-19 vaccine. Although autoantibodies against glycolipids were not detected, immunotherapy with intravenous immunoglobulin and methylprednisolone pulse therapy effectively ameliorated the symptoms. Our report suggests that the COVID-19 vaccine may induce various clinical subtypes of GBS, including a rare variant with sensory ataxia and dysgeusia.