Angiotensinogen gene polymorphism as a risk factor for ischemic stroke.

While gene polymorphism for angiotensinogen (AGT) is reported to contribute to the regulation of blood pressure and salt sensitivity, its effect on the risk of ischemic stroke remains controversial. We hypothesized that polymorphism of the AGT gene could be a risk factor for ischemic stroke. Major clinical risk factors and the AGT gene M235T polymorphism were examined in 147 consecutive stroke patients and 133 healthy age-matched controls. All patients were categorized into four stroke types (single lacuna, multiple lacunae, large-artery atherosclerosis and branch atheromatous disease in brainstem) and two vascular groups (large and perforating arterial lesions). The AGT gene M allele significantly increased the risk of single lacuna, multiple lacunae and small arterial lesions, in male patients (p=0.029, 0.031 and 0.026, respectively). Synergistic effects of the AGT gene polymorphism and clinical risks were not observed. In conclusion, AGT M allele may present a risk of lacunar infarctions in Japanese men, independent of hypertension.     

Diagnosis and classification of mandibular osteomyelitis.

To establish a unified classification system for mandibular osteomyelitis, various diagnostic terms were critically assessed and clinicopathologic findings of the lesions were carefully reviewed. We recommend classifying mandibular osteomyelitis into bacterial osteomyelitis and osteomyelitis associated with the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Other diagnostic terms were excluded because they were not appropriate for classification. Diagnostic criteria for bacterial osteomyelitis are suppuration and osteolytic change. The lesions are easily cured by antibiotic treatments. Mandibular osteomyelitis in SAPHO syndrome is characterized by nonsuppuration and a mixed pattern on radiography, with solid type periosteal reaction, external bone resorption, and bone enlargement. The presence of osteomyelitis in other bones, arthritis, or skin diseases (palmoplantar pustulosis, pustular psoriasis, and acne) strongly suggests this syndrome. Antibiotic therapy is usually ineffective and the symptoms of SAPHO syndrome are often persistent.     

Mechanism of testicular atrophy induced by di-n-butyl phthalate in rats. Part 1

Repeated oral doses of di-n-butyl phthalate (DBP) to male rats caused a decrease in testicular fructose and glucose and a sloughing of the germ cells on the first day of treatment. On day 2, more severe sloughing was seen and was accompanied by decreases in testicular iron and zinc levels and increases in the level of inositol and cholesterols. The sloughing was followed by atrophy, accompanied by dissociation of the germ cells from the Sertoli cells and reduction of triglycerides, cholesterols and phospholipids containing choline and ethanolamine residues in the testis.     

Hypoxia‐inducible factor 1α may be a marker for vasculitic neuropathy

Neuromuscular biopsy is still an essential method for diagnosing vasculitic neuropathy, although its diagnostic sensitivity is at most 60%. Our objective was to examine the expression of hypoxia‐inducible factor 1α (HIF‐1α) in peripheral nerves and to evaluate its usefulness in diagnosing vasculitic neuropathy, especially for discrimination from other axonal neuropathies. Forty‐one patients with vasculitic neuropathy consisting of 20 definite, 14 probable and seven possible diagnoses, 15 patients with metabolic neuropathy, five with motor neuron disease and six with chronic inflammatory demyelinating polyneuropathy were included. Nerve biopsy specimens were immunohistochemically examined for HIF‐1α and various cell markers. Distinct immunoreactivity (IR) was observed in nuclei of endoneurial cells in 54% (22/41) of vasculitic patients, while specimens from metabolic neuropathies showed less nuclear IR and the difference of mean density of HIF‐1α‐positive nuclei was significant. Two patients with possible vasculitis who showed HIF‐1α‐positive nuclei in endoneurium, were later confirmed to have vasculitis by skin biopsies. Most of the cells expressing HIF were demonstrated to be Schwann cells. There was a trend in the vasculitic patients with early phase nerve damage to display higher endoneurial HIF‐1α‐IR. HIF‐1α may be an immunohistochemical marker for vasculitic neuropathy, especially when the observed section contains no vasculitic lesions.     

Excitatory mechanism of deflationary slowly adapting pulmonary stretch receptors in the rat lung.

The excitatory responses of deflationary slowly adapting pulmonary stretch receptor (SAR) activity to lung deflation ranging from approximately -15 to -25 cm of H(2)O for approximately 5 s were examined before and after administration of flecainide, a Na(+) channel blocker, and K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 microg/kg), an Na(+) channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na(+) channels on the nerve terminals of deflationary SARs.     

Time after excision and temperature alter ex vivo tissue relaxation time measurements

Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40°C, at room temperature (28°C), or in an ice bath (4°C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40°C (20-MHz spectrometer), the T1 of liver decreased from 280 msec ± 8 to 212 msec ± 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec ± 3 to 208 msec ± 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors.