PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients

Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.     

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor,BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol.
2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats, New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC₅₀ was 1.0 μM in SD rats. 2.1 μM in NZ white rabbits, and 0.3 μM in WHHL rabbits. With human SMC, the value was 0.02 μM in the presence of 10% FCS and 0.2 μM with a mixture of growth factors.
3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg⁻¹ day⁻¹. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P<0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P<0.05). By anti-α smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P<0.01).
4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

     

Solute Absorption from the Airways of the Isolated Rat Lung. IV. Mechanisms of Absorption of Fluorophore-Labeled Poly-α,β-[N(2-Hydroxyethyl)-DL-Aspartamide]

The pulmonary absorption kinetics of a single molecular weight distribution (MWD) of fluorophore-labeled poly-,-[N(2-hydroxyethyl)-DL-aspartamide] (F-PHEA), a hydrophilic and biocompatible synthetic polypeptide, were studied in the isolated, perfused rat lung (iprl) as functions of administered polymer concentration, dose, vehicle, and presence and absence of fluorophore. The MWD was characterized before and after absorption by measurement of weight- and number-averaged molecular weights (M _wand M _n, respectively) using high-performance gel-permeation chromatography. Values for M _w and M _n were 8.6 and 5.3 kD before, and 6.7 and 4.7 kD after, absorption into the perfusate; there was no significant metabolism and the MWD of the absorbed polymer was independent of both dose and sampling time over a 3-hr period. F-PHEA failed to show any evidence of aggregation in solution or changes in dose distribution within the airways as functions of increasing polymer concentration and dose. A concentration ranging study indicated the presence of a saturable, carrier-mediated transport process for F-PHEA with a maximum absorption rate, V _max, of approximately 180 µg or 0.027 µmol/hr. Coadministration of fluorophore-free PHEA was capable of depressing the absorption of F-PHEA. The transport process for F-PHEA appeared to have a molecular weight limit of about 7 kD for this hydrophilic polymer.     

Breast parenchymal activity on scintimammography: Comparison between bone-seeking agents and99mTc-sestamibi

The aim of this study was to evaluate breast parenchymal activity on scintimammography with bone-seeking agents and 99mTc-MIBI. Scintimammography was performed with bone-seeking agents in 61 patients and with 99mTc-MIBI in 33 patients. Activity in the breast parenchyma contralateral to the suspected lesion was visually assessed by two independent observers. Increased breast parenchymal activity was shown in 19 of 61 patients examined with bone-seeking agents, while it was demonstrated in only two of 33 patients examined with 99mTc-MIBI. Breast parenchymal activity of bone-seeking agents was higher in patients aged 50 years or younger than in those older than 50. Increased parenchymal activity of bone-seeking agents may disturb visualization of primary breast cancer especially in relatively young patients. Low parenchymal activity is suggested to be a favorable characteristic of 99mTc-MIBI as a scintimammographic agent.     

Primary anorectal malignant melanoma: Report of a case

(Received for publication on Aug. 18, 1997; accepted on May 15, 1998)     

Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging

The authors performed a serial study of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome (MELAS) who presented with diffusion-weighted MRI (DWI). DWI demonstrated a higher apparent diffusion coefficient in the lesion than in the control region during the acute stage of stroke. Vasogenic edema is present in stroke-like episodes in MELAS.     

The 301 to 314 amino acid residue of beta-tubulin is not a target epitope for serum IgM antibodies in chronic inflammatory demyelinating polyneuropathy

Connolly et al. [Neurology 48 (1997) 243] reported that IgM M-proteins from three patients selectively binds to an epitope on beta-tubulin that consists of amino acids 301 to 314. We therefore investigated whether these 14 amino acid residues beta301-314 are the target epitope for serum IgMs in sera from 67 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 50 with Guillain-Barré syndrome, 50 with motor neuron diseases, and 50 normal controls. IgM anti-beta301-314 antibodies were not restricted to nor were selectively associated with CIDP. We conclude that beta301-314 is not a target epitope for serum IgMs in CIDP.     

Origin of the "N10" stationary-field potential after median nerve stimulation.

The scalp far-field potentials after median nerve stimulation at the wrist consist of P9, P11, P13, and P14 positive components. Earlier, Emerson et al. (1984) identified the "N10" negative potential in-between the P9 and P11 and claimed that this was not merely a passive return to the baseline after the P9 positive deflection but a distinct component reflecting a proximal brachial plexus volley. They thought N10 was a far-field potential having widespread distribution with a fixed latency. In this study we found that N10 was of higher amplitude after median nerve stimulation at the elbow than after stimulation at the wrist. Indeed the N10 latency was fixed from the lower anterior neck to the scalp, and its amplitude was maximum at the anterior lower neck. The latency of N10 was about 0.3 milliseconds longer than the Erb's potential and 0.15 milliseconds longer than the potential recorded from the lateral neck on the side of stimulation. The N10 amplitude increased in parallel with increased stimulus intensity. In order to explore the origin of the N10 stationary field potential, we designed a paired stimuli paradigm applied to the wrist (S1) and to the elbow (S2). The interstimulus interval between S and S2 was adjusted so that the timing of S2 was immediately after the traveling impulse produced by the S1 stimulus as it passed through the S2 stimulus site. This technique allowed stimulation of the anterior interosseous nerve selectively at the elbow while the median nerve originating from the wrist was undergoing refractory period. The response of (S1 + S2) - S1 showed only the N10 with absence of cervical and cortical responses, implying that N10 was activated, predominantly by the interosseous nerve, i.e., an antidromic motor volley, when the median nerve was stimulated at the elbow.     

Influence of antigenic forms and adjuvants on the IgG subclass antibody response to Aujeszky's disease virus in mice.

The influence of antigenic forms of Aujeszky's disease virus (ADV) and adjuvant types on the production of IgG subclass antibodies in mice was investigated. Particulate antigen, inactivated ADV, alone induced IgG1 and lower IgG2a antibody production, while the antigen adsorbed onto aluminum phosphate gel (alum) enhanced IgG1 antibody production but suppressed IgG2a antibody production as well as solubilized ADV antigen adsorbed onto alum. QS21 saponin purified from Quillaja saponaria promoted the production of IgG1 and IgG2a antibodies in a large extent against the both particulate and soluble antigens, while this saponin has strong hemolytic activity. Lablaboside F saponin isolated from Dolichos lablab without hemolytic activity, also induced the production of large IgG1 and little IgG2a antibody against both antigens. Oil-based adjuvant, ISA70 of water-in-oil type and ISA25 of oil-in-water type, increased IgG1 and IgG2a antibodies against the both soluble and particulate antigens, whereas a combination of ISA25 and soluble antigen reduced IgG2a antibody response. These results indicate that IgG1 antibody production was not suppressed by a combination of antigenic form and adjuvant type, however, IgG2a antibody production was influenced.