Exacerbation of rheumatoid arthritis following Helicobacter pylori eradication: disruption of established oral tolerance against heat shock protein?

A 62-year-old Japanese woman with RA received an eradication therapy against Helicobacter pylori in November 1999. Eight weeks later, successful eradication was confirmed by negative results for rapid urease test, pathologic findings, and a fall in anti-H. pylori IgG antibody titer. During the course, parameters for RA activity were exacerbated: C-reactive protein 1.1-4.2 mg/dL, rheumatoid arthritis precipitation antigen 2560-5120 dils., erythrocyte sedimentation rate 52-123 mm/h, and complements CH50 50 to over 60 U/mL. Lansbury index increased from 70% to 105%. Two more weeks later, the patient noticed right shoulder pain. She also complained of bilateral gonalgia two months later, and physical examination revealed increased fluid in the knee joints. Prednisolone was required to control the disease activity. The results of this case suggested that RA patients might experience a deleterious effect on the disease activity following H. pylori eradication possibly through disruption of the established oral tolerance against stress protein such as mycobacterial heat shock protein 65.     

FAMILIAL AMYLOID POLYNEUROPATHY WITH MARKED HYPERTROPHY OF THE PERIPHERAL NERVES

Autopsy findings in a 40-year-old male with heredofamilial amyloidosis and polyneuropathy are reported. He had been suffering from progressive autonomic as well as sensorimotor dysfunctions. Prominent amyloid deposit was found in the kidney, heart, thyroid, and testis, and less in the interstitium and small vessels of almost all organs. The peripheral nerves, some showing prominent hypertrophy, were most severely involved by amyloid deposit in a form of stellate mass, which ultrastructurally consisted of radially arranged amyloid filaments. In the hypertrophied nerves and ganglia, in addition to amyloid, massive accumulation of acid mucopolysaccharide (AMPS) was seen filling up the interstitial space, which was the cause of hypertrophy. Ultrastructurally, AMPS was seen as finely granular substance. An extracted amyloid from the kidney showed 8 nm filament on negative staining and was estimated of having a molecular weight of 14,000.     

Two cases of a renal epithelial tumour resembling immature nephron

Summary Two cases of renal epithelial tumours are reported in females aged 46 and 66 years respectively. In spite of the large size of the tumours, neither invasive growth nor metastasis was observed. Histologically, the tumours were composed of immature epithelial cells forming tubules with abortive glomeruloid structures. Electron microscopy of tumour cells revealed poorly developed polarity and intracytoplasmic organelles. They showed similar immunohistochemical reactions to those of developing nephrons, particularly to those of the S-shaped body. The nuclear DNA content of the tumour cells was almost euploid. We conclude that the lesions were epithelial tumours of the kidney histologically mimicking developing renal parenchyma.     

A common mutation in methylenetetrahydrofolate reductase gene among the Japanese population

Summary Hyperhomocysteinemia has been reported as an independent risk factor for atherosclerotic cerebrovascular and coronary heart diseases. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes responsible for hyperhomocysteinemia. The C to T transition of the MTHFR gene at nucleotide position 677 results in decreasing the enzymatic activity and increasing the plasma homocysteine level. We studied the distribution of the MTHFR gene mutation among the Japanese population. The subjects were 129 Japanese males (aged 40–59 years). The allele frequency of the mutation was 0.38. The frequencies of the three genotypes were as follows: +/+, 11%; +/–, 54%; –/–, 35% (+ and – indicate the presence and absence of the mutation, respectively). We also studied the frequency of the MTHFR gene mutation in the middle-aged Japanese males with hypertension to investigate the possibility that this mutation is related to essential hypertension. The normotensive and hypertensive subjects were identical in the distribution of the mutated allele and the frequencies of the three genotypes. Furthermore, the prevalence of hypertension in each genotype group was same, although the mean diastolic pressure of the group with homozygous mutation was significantly higher than that of other groups (p<0.05).     

Chromium-induced pulmonary cancer. Report of a case and a review of the literature

A 57-year-old man, whose occupational history was that of a chromate worker for about 35 years, suffered nasal perforation during and died due to pulmonary cancer. In the autopsy materials, the concentration of chromium in the lung tissues was very high, being about 90 times the amount found in normal lungs. The chromium particles in the lung tissues could not be detected by analytical electron microscope, but they could be found in the anthoracotic lesions of the lungs by means of an X-ray microanalyser. The present case was judged to be a case of chromium-induced pulmonary cancer since all the pathologic data obtained were similar to those found in similar cases reported in the literature.     

Timing mechanism and effective activation energy concerned with aging and lifespan in the long-lived and thermosensory mutants of Caenorhabditis elegans

The lifespans of many poikilothermic animals, including the nematode Caenorhabditis elegans, depend significantly on environmental temperature. Using long-living, thermosensory mutants of C. elegans, we tested whether the temperature dependency of the mean lifespan is compatible with the Arrhenius equation, which typically represents one of the chemical reaction rate theories. The temperature dependency of C. elegans was the Arrhenius type or normal, but daf-2(e1370) mutants were quite different from the others. However, taking into account the effect of the thermal denaturation of DAF-2 with the temperature, we showed that our analyzed results are compatible with previous ones. We investigated the timing mechanism of one parameter (the onset of biodemographic aging (t₀)) in the lifespan equation by applying the RNAi feeding method to daf-2 mutants in order to suppress daf-16 activity at different times during the life cycle. In summary, we further deepened the biological role of two elements, t₀ and z (the inverse of the aging rate), in the lifespan equation and mean lifespan formulated by our diffusion model z² = 4Dt₀, where z is composed of t₀ and D (the diffusion constant).     

Hormone replacement therapy causes a decrease in hepatocyte growth factor in hypertensive women

OBJECTIVE: Serum hepatocyte growth factor (HGF) is associated with blood pressure. We investigated whether the serum HGF level differs between hypertensive and normotensive postmenopausal women (PMW) and whether hormone replacement therapy (HRT) alters the serum HGF level and blood pressure in hypertensive and normotensive PMW. DESIGN: Prospective observational study. METHODS: A total of 33 PMW with mild to moderate essential hypertension controlled by antihypertensive treatment (mean age, 57 +/- 6 years) and 23 normotensive PMW (mean age, 57 +/- 7 years) received continuous HRT (0.625 mg of conjugated equine estrogen combined with 2.5 mg of medroxyprogesterone acetate) once a day orally for 12 months, and we measured serum HGF levels and blood pressure before and 12 months after the start of HRT. RESULTS: The baseline serum HGF level was significantly higher in hypertensive PMW than in normotensive PMW. HRT significantly decreased the serum HGF level in hypertensive subjects, from 2.85 +/- 0.64 pmol/l to 2.49 +/- 0.65 pmol/l (P < 0.001), but not in normotensive subjects. HRT did not change blood pressure in either group. CONCLUSIONS: Serum HGF level before the start of HRT was higher in the hypertensive PMW than in the normotensive PMW. Furthermore, HRT decreases serum HGF without decreasing blood pressure in hypertensive PMW. The HRT-induced decrease in serum HGF was greater in hypertensive PMW than in normotensive PMW, and the decrease was independent of blood pressure changes.     

Effects of intravenous atrial natriuretic peptide on cardiac sympathetic nerve activity and left ventricular remodeling in patients with first anterior acute myocardial infarction.

OBJECTIVES: We sought to evaluate the effects of atrial natriuretic peptide (ANP) on cardiac sympathetic nerve activity (CSNA) and left ventricular (LV) remodeling in patients with first anterior acute myocardial infarction (AMI) after primary coronary angioplasty. BACKGROUND: The activation of the renin-angiotensin-aldosterone system (RAAS) prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide, a circulating hormone of cardiac origin, has vasodilatory and diuretic properties, and can inhibit the RAAS. METHODS: We studied 50 patients with first anterior AMI who were randomly assigned to receive ANP (group A) or isosorbide dinitrate (group B) before and after primary coronary angioplasty. The ANP or ISDN was continuously infused >48 h. The extent score (ES) was determined from 99mTc-pyrophosphate scintigraphy to evaluate the area of initial myocardial damage 3 to 5 days after primary angioplasty. The LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine scintigraphy after 3 weeks. RESULTS: After primary angioplasty, age, gender, risk factors, peak serum creatine phosphokinase concentration, recanalization time, and ES were similar in the 2 groups. However, in group A (n = 25), the TDS was significantly lower (34 +/- 8 vs. 41 +/- 8; p < 0.05), the H/M ratio was significantly higher (1.96 +/- 0.18 vs. 1.74 +/- 0.23; p < 0.05), and the WR was significantly lower (35 +/- 8% vs. 44 +/- 12%; p < 0.005) than in group B (n = 25). Moreover, the LVEDV and LVEF in group A were better than in group B (LVEDV: 85.5 +/- 28.5 ml vs. 106.3 +/- 39.4 ml [p < 0.05]; LVEF: 47.9 +/- 10.2% vs. 41.5 +/- 11.8% [p < 0.05]). CONCLUSIONS: Intravenous ANP improves CSNA and prevents LV remodeling in patients with first anterior AMI.     

Angiotensin II plays an important role in maintaining blood pressure in postmenopausal women receiving hormone replacement therapy

BACKGROUND: We investigated the role of angiotensin (Ang) II in maintaining blood pressure (BP) by administering a small dose of candesartan, an Ang II type 1 receptor antagonist, in postmenopausal women receiving long-term hormone replacement therapy (HRT). METHODS: A single dose of 2 mg of candesartan was administered orally to 13 normotensive postmenopausal women receiving HRT (continuous combined conjugated estrogen and medroxyprogesterone acetate orally; HRT group) and 13 normotensive postmenopausal women not receiving HRT (control group). Both BP and heart rate (HR) were measured at baseline and at 1, 2, 3, 4, 5, and 6 h after administration. Plasma renin activity (PRA) and Ang I, Ang II, and bradykinin concentrations were measured at baseline and 4 h after the administration of candesartan. RESULTS: Candesartan lowered the BP and raised the HR in both groups. However, the decrease in BP was significantly greater in the HRT group than in the control group (P < .05), whereas no significant difference in the change in HR was observed between the two groups. In the HRT group, significant increases were found in PRA, Ang I, and Ang II (all P < .05) and a significant decrease in bradykinin (P < .01) with candesartan treatment. In the control group, candesartan as associated with an increase in PRA (P < .05) but not in Ang I, Ang II, or bradykinin. CONCLUSIONS: Based on our study results, Ang II plays an important role in maintaining BP in normotensive postmenopausal women receiving HRT. Maintenance of BP may be dependent on the balance between the hypertensive effect of Ang II and the hypotensive effect of bradykinin.