The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis

Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD).

Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n?=?93, Study 2: n?=?99) were retrospectively analyzed.

Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p?r²: 0.088, p?=?.02). While average sCa of the patients was 9.2?mg/dL before treatment, it increased time-dependently to 9.6?mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3?mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3?mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3?mg/dL (0.8%, p?=?.038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed.

Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD.     

Suppression by adrenoceptor beta-agonists of vascular permeability increase and edema formation induced by arachidonate metabolites, platelet-activating factor, and tumor-promoting phorbol ester TPA

Air-pouch-type inflammation was induced by injecting sodium carboxymethyl cellulose solution containing leukotriene C4 (LTC4, 3.20 x 10(-7) M, 0.2 micrograms/ml) and prostaglandin E2 (PGE2, 5.68 x 10(-6) M, 2.0 micrograms/ml), platelet-activating factor (PAF, 1 x 10(-6) M, 0.52 micrograms/ml), or 12-O-tetradecanoyl phorbol 13-acetate (TPA, 1.62 x 10(-6) M, 1.0 micrograms/ml) into an air pouch made on the dorsum of rats. Vascular permeability and tissue edema formation were significantly increased by injecting the phlogogen solution. The histamine level in the pouch fluid was dramatically increased by injecting TPA but not by LTC4 and PGE2, or PAF. Injection of isoproterenol or procaterol with the phlogogen solution produced dose-dependent suppression of both vascular permeability increase and tissue edema formation. However, the TPA-induced increase in the histamine level was not suppressed in parallel with the decrease of vascular permeability or tissue edema formation. These results indicate that beta-agonists suppress vascular permeability response and local tissue edema formation not by inhibiting mast cell degranulation, but by inhibiting the reactivity of the local vasculature to chemical mediators such as arachidonate metabolites, PAF, and histamine and serotonin released from mast cells.     

Off-pump resection of a coronary arterial fistula using the Harmonic Scalpel

Off-pump surgery was performed in a patient with post-infarction angina complicated with aneurysmal coronary-pulmonary arterial fistula. Epicardial echocardiography localized the artery feeding the fistula in the myocardium, which had not been revealed by visual inspection, palpation, or transesophageal echocardiography. The patient underwent off-pump coronary artery bypass grafting concomitant with aneurysmectomy. The feeding arteries were dissected easily using a Harmonic Scalpel and ligated. The flow in the aneurysm disappeared immediately and aneurysmectomy was performed without bleeding.     

Effects of nitric oxide synthase inhibitors on gastric alkaline secretion in rats.

The effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on gastric HCO3- secretion were examined in anesthetized rats. Intravenous administration of L-NAME (1, 2.5, 5 mg/kg) increased HCO3- secretion in a dose-related manner. This effect of L-NAME was mimicked by NG-mono-methyl-L-arginine (50 mg/kg, i.v.) and was antagonized significantly by concurrent administration of L-arginine but not D-arginine (200 mg/kg, i.v.). These results indicate that gastric HCO3- secretion is stimulated by inhibition of NO biosynthesis.     

Surgical treatment of myasthenia gravis associated with Graves's disease]

During past 30 years, we experienced 253 patients who underwent surgery for myasthenia gravis. Among these patients, 9 were associated with Graves' disease. No patients had thymoma. Five patients underwent thymectomy after they had become euthyroid by medical treatment, though four patients required subtotal thyroidectomy before thymectomy. One patient developed myasthenic crisis following thyroidectomy and was treated with respirator for 5 days. But thymectomy was performed without myasthenic crisis in these four patients between 25 days and 60 days after thyroidectomy. They have been doing well and no see-saw phenomenon was presented. Thymectomy is safe and effective even in the patients with Graves's disease, and we recommend to perform it after they become euthyroid by medical or surgical treatment.     

Deconjugating activity for sulfoconjugated dopamine in homogenates of organs from dogs.

To clarify the possibility that sulfoconjugated dopamine (DA) may play a physiological role by being converted to active free DA, we examined the deconjugating activity in homogenates of organs from dogs. Each tissue homogenate was incubated with sulfoconjugated DA, and the deconjugating activity of the organs was compared. The kidney and liver exhibited the highest deconjugating activities. In contrast, the intestine and heart showed lower arylsulfatase activities, and almost no activity was found in the brain or skeletal muscle. Moreover, in the heart, the deconjugating activity for sulfoconjugated DA was higher in the atrium than the ventricle. These results indicate that sulfoconjugated DA is converted to active free DA in homogenates of organs from dogs and that the deconjugating activity varies between different parts of an organ. Sulfoconjugated DA must be looked upon as a possible precursor or reservoir for the production of active free DA.     

Cell culture of clonal ginbuna crucian carp hematopoietic cells: differentiation of cultured cells into erythrocytes in vivo

We cultivated kidney hematopoietic cells from clonal triploid ginbuna crucian carp, Carassius auratus langsdorfii. Proliferating cells from hematopoietic cell cultures were harvested and injected into tetraploid hybrids (clonal triploid ginbuna and goldfish hybrid) which possess three sets of chromosomes from a triploid clone and a haploid set of chromosomes from goldfish (Carassius auratus). After injection of cultured triploid cells (donor cells), blood samples were obtained from tetraploid hybrids (recipients) every other week. Blood cells stained with acridine orange were measured by flow cytometry to trace the injected donor cells by means of differences in DNA content. Although erythrocytes were not produced in donor cell cultures, such cultures maintained precursor cells capable of differentiation into erythrocytes in vivo. After 4-12 weeks of transplantation, mature erythrocytes derived from the donors were observed in the blood circulation of the recipient fish. These results indicated that the ginbuna hematopoietic cell culture system is an in vivo situation suitable for the study of hematopoietic control mechanisms.     

Protective Role of Nitric Oxide in Staphylococcus aureus Infection in Mice

This study was carried out to determine the role of nitric oxide (NO) in Staphylococcus aureus infection in mice. NO production in spleen cell cultures was induced by heat-killed S. aureus. Expression of mRNA of the inducible isoform of NO synthase (iNOS) was induced in the spleens and kidneys of S. aureus-infected mice. When mice were treated with monoclonal antibodies (MAbs) against tumor necrosis factor alpha (TNF-α) or gamma interferon (IFN-γ) before S. aureus infection, the induction of iNOS mRNA expression in the kidneys was inhibited. These MAbs also inhibited NO production in spleen cell cultures stimulated with heat-killed S. aureus. NO production in the spleen cell cultures and levels of urinary nitrate plus nitrite were suppressed by treatment with aminoguanidine (AG), a selective inhibitor of iNOS. The survival rates of AG-treated mice were significantly decreased by either lethal or sublethal S. aureus infections. However, an effect of AG administration on bacterial growth was not observed in the spleens and kidneys of mice during either type of infection. Production of TNF-α and IFN-γ was not affected by AG treatment in vitro and in vivo. These results suggest that NO plays an important role in protection from lethality by the infection, but the protective role of NO in host resistance against S. aureus infection was not proved. Moreover, our results show that TNF-α and IFN-γ regulate NO production while NO may not be involved in the regulation of the production of these cytokines during S. aureus infection.     

Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.     

Induction of histidine decarboxylase in type 2 T helper lymphocytes treated with anti-CD3 antibody

Inflammation Research -