Effects of recombinant human granulocyte colony-stimulating factor on neutrophil functions in aged animals

We have studied the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on granulopoiesis and neutrophil functions in aged rats and aged mice. We subcutaneously injected rG-CSF or control vehicle into aged rats (22 months old and 25 months old) for 7 consecutive days, counted the peripheral neutrophils and evaluated the functions of neutrophils isolated from venous blood. The peripheral neutrophil count in aged rats tended to be increased as compared with that in young rats (11 weeks old). However, the neutrophils in aged rats exhibited a decline of superoxide anion (O2-) release and phagocytic activity as compared with young rats. The peripheral neutrophil count in aged rats was significantly increased 5-6-fold as many as the control value by rG-CSF treatment, which was accompanied by a significant enhancement of O2- release and of phagocytic activity being restored to normal levels or better. In another series of experiments, we subcutaneously injected rG-CSF or control vehicle into aged mice (24-28 months old) or young mice (8 weeks old) for 7 consecutive days, and evaluated the functions of neutrophils isolated from peritoneal cavity. The peritoneal exudate neutrophils from the aged mice exhibited a decline of phagocytic and chemotactic activity as compared with the young mice. These functions in both young and aged mice were significantly enhanced by rG-CSF-treatment, and these functions in rG-CSF-treated aged mice were restored to a level higher than the level in control young mice. These findings demonstrate that rG-CSF is capable of enhancing granulopoiesis and restoring the age-related decline of neutrophil functions.     

Immunoglobulin class switch from IgG to IgA in a patient with smoldering multiple myeloma

Serum of a 67-year-old male patient with smoldering multiple myeloma was shown to contain two monoclonal immunoglobulins, IgG and IgA. For the initial seven months, monoclonal IgG was predominantly elevated. During the next one year and eight months, however, serum concentration of the monoclonal IgA increased, with a concomitant decrease of IgG. N-terminal amino acid sequences of heavy and light chains separated from monoclonal IgG and IgA were analyzed. Both light chains were lambda-type and showed identical amino acid sequences of variable regions. The heavy chains also had the same N-terminal amino acid sequence between IgG and IgA. These results strongly suggest that two monoclonal proteins, IgG and IgA, in this patient were produced by B lymphocytes within a clone and that class switch from IgG to IgA in immunoglobulin production during B cell differentiation has taken place in the clinical course of this case.     

Triiodothyronine(T3) autoantibodies in a woman with nonthyroidal disorder: a study on preparation of serum IgG fraction employing protein A column chromatography

A 48-year-old non-goitrous woman, who had undergone cardiac surgery for mitral stenosis under the extracorporeal circulation, showed high levels of serum T3 and free T3 in a recent follow-up study, employing antibody coated-bead RIA for T3 and -Amerlex M particle RIA for free T3. However, other thyroid function tests (T4, free T4, TSH and TBG) were normal. We suspected that thyroid hormone autoantibodies (THAA) in her serum interfered with T3 and free T3 analyses. The presence of THAA was demonstrated by the use of various procedures as follows. Firstly, the patient's serum was directly incubated with 125I-T3 or -T4 analog which did not bind to TBG, followed by B/F separation with polyethyleneglycol, counting the precipitates. Secondly, after the serum was treated with an acid-charcoal solution to remove circulating thyroid hormone, the measurement of THAA was made as stated above. Normal sera were used as controls. Both the non- and acid-charcoal-treated sera showed much higher percentages of 125I-T3 analog precipitation as compared with controls. In the case of 125I-T4 analog, there was no difference between them. In the third study, the presence of IgG antibodies that bound T3 but not T4 was investigated. The IgG fraction of the patient's serum was separated employing a Protein A-Sepharose CL-4B column chromatography. Then, the prepared IgG fraction was purified by a technique of gel filtration chromatography (Sephacryl S 200). Non-purified and purified-IgG fractions both revealed higher binding percentages of 125I-T3 analog than the control IgG fraction and non-IgG fraction of the patient. Furthermore, a good dose response was observed between the binding percentage of 125I-T3 analog and each dose of the patient's serum or IgG fraction. From these observations, it was clarified that this woman had anti-T3 IgG autoantibodies using a Protein A column chromatography with confirmation of gel filtration chromatography.     

Institutional indications for islet transplantation after total pancreatectomy

Background/Purpose

This study was designed to establish institutional indications for pancreatic islet transplantation by examining patients with total pancreatectomy as candidates for islet allotransplantation.

Methods

In 12 patients who underwent total pancreatectomy, we compared pre-and postoperative plasma glucose level, body mass index, HbA1c, and daily insulin use; we examined candidacy for islet allotransplantation based on the guidelines of Japan’s islet transplantation registry.

Results

Eight of the 12 patients with total pancreatectomy were operated for intraductal papillary mucinous neoplasm. At our institution, the 5-year survival of patients with intraductal papillary mucinous neoplasm was far better (76.3%) than that of patients with pancreatic cancer. Postoperatively, plasma glucose level, HbA1c, and daily insulin use were increased in all patients with total pancreatectomy. Of the 12 patients treated with total pancreatectomy, 4 (intraductal papillary mucinous neoplasm, n = 2; islet cell tumor, n = 1; and acute pancreatitis due to arteriovenous malformation, n = 1) showed deteriorated diabetic control and therefore were considered to be candidates for islet allotransplantation according to the guidelines.

Conclusions

Islet allotransplantation could be indicated for patients with favorable postoperative survival who have had a total pancreatectomy for either benign or neoplastic disease.     

Reconstruction of the external auditory canal using full-thickness rolled-up skin graft after lateral temporal bone resection for T1 and T2 external auditory canal cancer

ObjectiveTo present our results of the external auditory canal (EAC) reconstruction procedure using rolled-up full-thickness skin graft with tympanoplasty after lateral temporal bone resection (LTBR) for early-stage EAC carcinoma.Patients and MethodsA retrospective review of 15 patients who had undergone LTBR with reconstruction of the EAC for T1 and T2 EAC cancer between 2016 and 2020.ResultsPostoperative mean air-bone gap was 30.7 decibel hearing level. Although a few patients experienced chronic granulation, persistent otorrhea, and/or laterization of the tympanic membrane, most patients showed no serious complications related to the EAC reconstruction.ConclusionEAC reconstruction using a full-thickness skin graft in combination with tympanoplasty is useful for minimizing the hearing loss, maintaining the cosmetic appearance, and facilitating the observation into the ear cavity.