Studies of CD4+ (helper/inducer) T lymphocytes in autoimmune thyroid disease: demonstration of specific induction in response to thyroid peroxidase (TPO) in vitro and its relationship with thyroid status in vivo.

We have studied by flow cytometric analysis the antigen specific activation of CD4+ (helper/inducer) T lymphocytes by purified human thyroid peroxidase (TPO). Peripheral blood mononuclear cells were obtained from 26 patients with Graves' disease (GD), 16 with Hashimoto's thyroiditis (HT), 7 with nontoxic nodular goiter (NG), and 14 normal subjects (N). Cells were cultured for 7 days in the presence or absence of TPO at final concentrations of 3, 30, and 300 ng/mL. When harvested, cells were reacted with an FITC-conjugated anti-CD4 and a PE-conjugated anti-HLA-DR murine monoclonal antibodies. The percentage of HLA-DR+ CD4+ cells (activated CD4+ cells) was determined by a flow cytometer. In the absence of TPO, CD4+ cells had been activated without any specific stimulant. This is known as the autologous mixed lymphocyte reaction (AMLR). In the AMLR, CD4+ cells from GD and HT were less activated compared to those from NG and N. Results of TPO-specific activation were expressed as an incremental increase of activated CD4+ cells (II) (percentage of activated CD4+ cells cultured with TPO minus percentage of activated CD4+ cells cultured without TPO). II of N, GD, HT, and NG were 0.37 +/- 0.21, 2.20 +/- 0.45,** 2.0 +/- 0.66,* and 0.35 +/- 0.27 (mean +/- SEM), respectively (**p less than 0.01; *p less than 0.05 vs N). When patients were further subdivided, the highest mean II was found in patients with hyperthyroid GD (p less than 0.01), followed by euthyroid HT (p less than 0.05) and euthyroid GD (p less than 0.05), however there was no significant difference between hypothyroid HT and N. In conclusion (1) AMLR reactivity of CD4+ cells from GD and HT was impaired, (2) however, CD4+ cells from both GD and HT were significantly more induced by TPO compared to N, and (3) this induction depends, in part, on the in vivo thyroid status.     

Ob/ob mice as a model of delayed gastric emptying

Diabetic gastroparesis is a well-recognized delay of gastric emptying in diabetic patients. We assessed the gastric emptying rate in ob/ob mice, a genetic model of obesity and diabetes. The basal gastric emptying rate in 22- to 27-week-old ob/ob mice was significantly lower than that in 10- to 11-week-old ob/ob mice (P<.01). Our results indicate that the ob/ob mice are a useful model not only of glucose intolerance but also of delayed gastric emptying as a diabetic complication.     

Smoking and health: a review prepared by the Smoking and Health Subcommittee of the Tobacco Industries Council, a council formed by the Minister of Finance of Japan

Any definition of health is inevitably broad and contains various elements that may differ from one individual to another. Recent studies on the effects of smoking on physical and mental health have progressed remarkably and have great value in the fields of epidemiology, pathology, clinical medicine, and psychiatry. This report concludes that while smoking may have beneficial psychological effects on smokers, it may pose a risk to physical health.     

A case of septicemia type Vibrio vulnificus infection with necrotizing fasciitis rescued by lower extremity amputation]

We report a case of septicemia type Vibrio vulnificus infection. The patient was a 74-year-old man who had liver cirrhosis and hepatocelluler carcinoma. He felt a pain in the right femoral lesion after eating raw shellfish (Japanese "Umitake") two days ago. He was admitted to our emergency center due to his shock status and thrombocytopenia two days after the onset. We diagnosed necrotizing fasciitis due to Vibrio vulnificus infection, his life was saved by emergency amputation of the right lower extremity. The culture of the blood and vesicle fluid showed Vibrio vulnificus. There are some reports that the debridement was effective to necrotizing fasciitis due to Vibrio vulnificus infection, but these reports are all about single upper extremity lesion. As far as we know, this is the second report of lower extremity necrotiaong fasciitis due to septicemia type Vibrio vulnificus infection rescued by extremity amputation in Japan. The mortality of septicemia type Vibrio vulnificus infection with necrotizing fasciitis is very high, this is quite a valuable report in making a decision for therapy of septicemia type Vibrio vulnificus infection.     

Brain peptide YY receptors: highly conserved characteristics throughout vertebrate evolution.

We have shown previously that peptide YY (PYY) receptors are uniquely distributed in various mammalian brains and also have identified the receptor from porcine hippocampal membranes as a protein of 50,000 mol wt. To extend these observations, both the characteristics of PYY-receptor interaction and the structure of the receptor have been examined and compared with those of its sister peptide, neuropeptide Y (NPY), in the brains of various vertebrates including mammals (human, dog, guinea pig, rat, and mouse), birds (chicken), reptiles (snapping turtle), amphibians (bullfrog), and fish (yellowtail fish). The affinities and relative potencies of PYY as well as NPY receptors for pancreatic polypeptide (PP) family peptides were about the same in all species examined except for chickens. PYY and NPY bound to both the PYY and NPY receptors with high affinities, but porcine and avian PPs did not. In chicken brain, however, PYY, NPY, porcine PP, and avian PP all bound to the receptors with high affinity. Analysis of the equilibrium binding data for PYY receptors produced curvilinear Scatchard plots in all of the species, suggesting the existence of high and low affinity binding sites. Affinity cross-linking using disuccinimidyl suberate followed by electrophoretic analysis of ligand-receptor complexes characterized the molecular size of PYY and NPY receptors. [125I]PYY was cross-linked to a protein of 50,000 mol wt without sulfhydryl-bonded subunits on mammalian hippocampal membranes. A receptor protein with the same mol wt was identified in other brain areas, including hypothalamus and pituitary, PYY receptors in other vertebrate brains were similar in size to those of mammalian species except in chicken brain, where a receptor protein of 67,000 mol wt was observed. In addition, we also have demonstrated that the NPY receptor is a monomeric 50,000 and 55,000 mol wt protein in mammalian and fish brains, respectively. These findings indicate that brain PYY and NPY receptors in most vertebrate species from fish to man are pharmacologically and structurally similar and have been well conserved over a period of evolution of 400 million yr. The divergence of the receptors observed in chicken brain may reflect some change in their function.