Polyandry increases reproductive performance but does not decrease survival in female Brontispa longissima.

The costs and benefits of polyandry are still not well understood. We studied the effects of multiple mating on the reproductive performance of female Brontispa longissima (Coleoptera: Chrysomelidae), one of the most serious pests of the coconut palm, by using three experimental treatments: (1) singly-mated females (single treatment); (2) females that mated 10 times with the same male (repetition treatment); and (3) females that mated once with each of 10 different males (polyandry treatment). Both multiple mating treatments resulted in significantly greater total egg production and the proportion of eggs that successfully hatched (hatching success) than with the single mating treatment. Furthermore, the polyandry treatment resulted in greater total egg production and hatching success than with the repetition treatment. Thus, mate diversity may affect the direct and indirect benefits of multiple mating. Female longevity, the length of the preoviposition period, the length of the period from emergence to termination of oviposition, and the length of the ovipositing period did not differ among treatments. The pronounced fecundity and fertility benefits that females gain from multiple mating, coupled with a lack of longevity costs, apparently explain the extreme polyandry in B. longissima.

Blockage of Akt activation suppresses cadmium-induced renal tubular cellular damages through aggrephagy in HK-2 cells.

We have reported that an environmental pollutant, cadmium, promotes cell death in the human renal tubular cells (RTCs) through hyperactivation of a serine/threonine kinase Akt. However, the molecular mechanisms downstream of Akt in this process have not been elucidated. Cadmium has a potential to accumulate misfolded proteins, and proteotoxicity is involved in cadmium toxicity. To clear the roles of Akt in cadmium exposure-induced RTCs death, we investigated the possibility that Akt could regulate proteotoxicity through autophagy in cadmium chloride (CdCl2)-exposed HK-2 human renal proximal tubular cells. CdCl2 exposure promoted the accumulation of misfolded or damaged proteins, the formation of aggresomes (pericentriolar cytoplasmic inclusions), and aggrephagy (selective autophagy to degrade aggresome). Pharmacological inhibition of Akt using MK2206 or Akti-1/2 enhanced aggrephagy by promoting dephosphorylation and nuclear translocation of transcription factor EB (TFEB)/transcription factor E3 (TFE3), lysosomal transcription factors. TFEB or TFE3 knockdown by siRNAs attenuated the protective effects of MK2206 against cadmium toxicity. These results suggested that aberrant activation of Akt attenuates aggrephagy via TFEB or TFE3 to facilitate CdCl2-induced cell death. Furthermore, these roles of Akt/TFEB/TFE3 were conserved in CdCl2-exposed primary human RTCs. The present study shows the molecular mechanisms underlying Akt activation that promotes cadmium-induced RTCs death.

Cellular localization of interleukin 13 receptor alpha2 in human primary bronchial epithelial cells and fibroblasts.

BACKGROUND: Interleukin (IL) 13 is a key cytokine in asthma, regulating fibrosis, airway remodeling, induction of immunoglobulin E synthesis by B cells, bronchial hyperresponsiveness, and mucus production. IL-13 signals through the type II IL-4 receptor (IL-4R), which is composed of the IL-4Ralpha and the IL-13Ralpha1 chains. Another IL-13 binding chain, IL-13Ralpha2, binds IL-13 with high affinity but has no known signaling capability and is thought to serve as a decoy receptor providing tight regulation of IL-13 responses. METHODS: In this study, we investigated the cellular localization of IL-13Ralpha2 in human primary bronchial epithelial cells and fibroblasts using flow cytometry and confocal microscopy, as well as the in vivo expression of IL-13Ralpha2 in the human bronchial mucosa by means of immunohistochemistry. RESULTS: IL-13Ralpha2 is predominantly an intracellular rather than a membrane-bound molecule in both human primary bronchial epithelial cells and fibroblasts and displays a diffuse granular cytoplasmic distribution in both cell types. IL-13Ralpha2 protein is expressed in vivo in the human bronchial mucosa with its expression being higher in bronchial epithelial cells than bronchial fibroblasts both in vivo and in vitro. CONCLUSIONS: IL-13Ralpha2 is expressed by both human primary bronchial epithelial cells and fibroblasts as an intracellular protein with a diffuse cytoplasmic distribution. In vivo, IL-13Ralpha2 is expressed in the human airway mucosa mainly by bronchial epithelial cells.

[Use of a balloon occlusion catheter for descending aortic aneurysm after total arch replacement using the elephant trunk technique].

A 74-year-old man who had previously undergone prosthetic graft replacement of the total aortic arch using the elephant trunk technique and of the abdominal aorta was admitted to our hospital for surgical treatment of descending aortic aneurysm. Computed tomography (CT) on admission revealed descending aortic aneurysm of 6.5 cm in diameter, and the previously placed prosthetic graft was detected in the aneurysm. Surgery for the descending aorta was performed under femoro-femoral partial bypass. During the operation, a balloon occlusion catheter introduced through the right brachial artery into the 'elephant trunk' graft was inflated before the aneurysm was opened, then the previously placed prosthetic graft was cross-clamped and the descending aorta was replaced with a new prosthetic graft with usual fashion. The postoperative course was uneventful.

The evolution of genomic imprinting.

In some mammalian genes, the paternally and maternally derived alleles are expressed differently: this phenomenon is called genomic imprinting. Here we study the evolution of imprinting using multivariate quantitative genetic models to examine the feasibility of the genetic conflict hypothesis. This hypothesis explains the observed imprinting patterns as an evolutionary outcome of the conflict between the paternal and maternal alleles. We consider the expression of a zygotic gene, which codes for an embryonic growth factor affecting the amount of maternal resources obtained through the placenta. We assume that the gene produces the growth factor in two different amounts depending on its parental origin. We show that genomic imprinting evolves easily if females have some probability of multiple partners. This is in conflict with the observation that not all genes controlling placental development are imprinted and that imprinting in some genes is not conserved between mice and humans. We show however that deleterious mutations in the coding region of the gene create selection against imprinting.

Four novel mutations of the connexin 32 gene in four Japanese families with Charcot-Marie-Tooth disease type 1.

DNA-based mutation analysis on the connexin 32 gene was performed in 49 families with Charcot-Marie-Tooth disease (CMT) type 1 but without duplication involving the chromosomal region, 17p12-p11.2. Mutations were identified in five of the 49 families, and four of the five mutations were hitherto undescribed: Va137Met, Glu57His, Arg142Glu, Val177Ala. X-linked CMT sometimes lacks evidence for X-linked transmission and cannot be differentiated from CMT type 2, especially in females with mildly decreased nerve conduction velocity. Therefore, molecular analysis is useful for molecular pathology of their disease.

Blood compatible aspects of poly(2-methoxyethylacrylate) (PMEA)--relationship between protein adsorption and platelet adhesion on PMEA surface.

Platelet adhesion and spreading is suppressed when a poly(2-methoxyethylacrylate) (PMEA) surface is used, compared with other polymer surfaces. To clarify the reason for this suppression, the relationship among the amount of the plasma protein adsorbed onto PMEA, its secondary structure and platelet adhesion was investigated. Poly(2-hydroxyethylmethacrylate) (PHEMA) and polyacrylate analogous were used as references. The amount of protein adsorbed onto PMEA was very low and similar to that absorbed onto PHEMA. Circular dichroism (CD) spectroscopy was applied to examine changes in the secondary structure of the proteins after adsorption onto the polymer surface. The conformation of the proteins adsorbed onto PHEMA changed considerably, but that of proteins adsorbed onto PMEA differed only a little from the native one. These results suggest that low platelet adhesion and spreading are closely related to the low degree of the denaturation of the protein adsorbed onto PMEA. PMEA could be developed as a promising material to produce a useful blood-contacting surface for medical devices.

Argentophilic intracytoplasmic inclusions in multiple system atrophy.

Argentophilic intracytoplasmic glial inclusions were recently reported in olivo-ponto-cerebellar atrophy (OPCA). We examined the brains of 3 cases of OPCA [2 with striato-nigral degeneration (SND) and 1 without SND], 1 case of pure autonomic failure (PAF) without pathology of OPCA or SND, as well as 36 controls including 2 cases of Holmes' type cerebellar cortical atrophy and 2 cases of Joseph's disease. Although the inclusions were tubulin-positive, the immunoreactivity was different from that of the dendrites. Electron microscopically, the microtubular structures composing the inclusion were fuzzy with granular material. These findings may indicate that the microtubules composing the inclusions are modified. Inclusion-bearing cells appeared to be oligodendrocytes while many of them had larger and lighter nuclei than those of normal-looking oligodendrocytes without the inclusions. The inclusions were widely distributed in a characteristic fashion beyond the typical lesions of OPCA, SND and PAF. The distribution pattern was essentially the same in the case of PAF and 3 cases of OPCA irrespective of the presence or absence of OPCA or SND lesions. In contrast, argentophilic inclusions were not observed in other types of spinocerebellar degeneration, in Holmes' type cerebellar cortical atrophy or in Joseph's disease. It is suggested, in line with other studies, that the inclusion may be specific to OPCA and related disorders which include PAF and a useful marker to distinguish OPCA from other neurodegenerative diseases.

Suppressive effects of F-1322 on the antigen-induced late asthmatic response and pulmonary eosinophilia in guinea pigs.

We investigated the effects of F-1322 (N-[2-[4-(benzhydryloxy)piperidino]ethyl]-3-hydroxy-5-(3-pyridylmethoxy)-2-naphthamide), a new compound that inhibits both thromboxane A2 synthetase and 5-lipoxygenase and that functions as a histamine antagonist, on the Ascaris antigen-induced late asthmatic response and pulmonary eosinophilia in guinea pigs. Oral administration of F-1322 (10-100 mg/kg) inhibited the antigen-induced late asthmatic response in a dose-dependent manner. Histological analysis revealed that F-1322 prevented the accumulation of eosinophils in the airways and this was paralleled by a decrease in the number of eosinophils and lymphocytes recovered in bronchoalveolar lavage fluid. F-1322 (0.1-10 microM) inhibited eotaxin-induced chemotaxis and actin polymerization of eosinophils in vitro in a concentration-dependent manner, while oral administration of F-1322 dose-dependently suppressed the migration of eosinophils into the airways in vivo in response to infusion of interleukin 5 and eotaxin in combination. F-1322 may, thus, improve the late asthmatic response in this model, in part, by preventing the accumulation of eosinophils in the airways. The pharmacological profile of F-1322 indicates that this drug is likely to be useful in the treatment of allergic diseases such as asthma.

Inhibitory effect of F-1322 on allergic eosinophil infiltration in airways.

The effects of F-1322 (N-[2-[4-(benzhydryloxy)piperidino]ethyl]-3-hydroxy-5-(3-pyridy lmethoxy)-2-naphthamide) on antigen-induced eosinophil infiltration and interleukin-5 production in the airways and on in vitro eosinophil migration were investigated. F-1322 (10-30 mg/kg, p.o.) inhibited antigen-induced eosinophil infiltration and interleukin-5 production in the airways of sensitized mice in a dose-dependent manner. Furthermore, F-1322 (0.1-10 microM) prevented the in vitro migration of eosinophils from guinea-pigs and humans induced by recombinant human interleukin-5, platelet-activating factor, and leukotriene B4 in a concentration-dependent manner. These results indicate that F-1322 has an inhibitory effect on allergic eosinophil infiltration of the airways by preventing both eosinophil migration and interleukin-5 production. These pharmacological profiles suggest that F-1322 will be a useful therapeutic for allergic diseases, especially asthma.

Single fiber EMG and repetitive nerve stimulation of the same extensor digitorum communis muscle in myasthenia gravis.

OBJECTIVE: To compare voluntary single fiber electromyography (v-SFEMG) and repetitive nerve stimulation (RNS) at the same extensor digitorum communis (EDC) muscle in myasthenia gravis (MG). METHODS: We examined v-SFEMG and RNS successively on the same day in the same EDC muscle. We studied 45 examinations of both v-SFEMG and RNS in 29 patients suffering from MG, together with examinations of RNS in 30 control subjects. RESULTS: Forty-one of 45 (91%) v-SFEMGs showed abnormal results, whereas only 18/45 (40%) RNSs showed an abnormal decrement. The percentage of decrement showed similar correlations with 3 v-SFEMG parameters: percentage of abnormal pairs, percentage of blocking pairs, and the mean MCD value. Examinations showing a significant decrement in RNS had at least 60%, and usually no less than 90%, abnormal pairs, and 10-80% blocking pairs. Some muscles without a decrement had up to 50% blocking pairs. CONCLUSIONS: These results suggest that the blocking phenomenon observed in v-SFEMG is not a direct counterpart of the decrement in RNS. This must be partly because fibers contributing to the decrement are continuously blocked during voluntary contraction, and partly, because smaller motor units explored by v-SFEMG are probably more abnormal in MG than larger motor units mainly contributing to a decrement. Both factors make v-SFEMG much more sensitive than RNS.

Exacerbation of myasthenia gravis in a patient after interferon-beta treatment for chronic active hepatitis C.

We report the case of a 53-year-old female patient, who developed bilateral blepharoptosis, limb weakness, dysphagia, and dyspnea several days after human natural interferon-beta (IFN-beta) treatment for chronic active hepatitis C. A positive edrophonium test, an elevated anti-acetylcholine receptor antibody titer, and decrements in the amplitude of muscle action potentials evoked by repetitive stimulation confirmed the diagnosis of myasthenia gravis (MG). Since she had been suffering from drooping of her right eyelid, fluctuating diplopia and easy fatiguability of limbs before receiving IFN-beta, her symptoms of MG were considered to be exacerbated by IFN-beta. It is recommended that IFN-beta should be used with particular care in patients with known MG or its compatible symptoms.

Horner's syndrome associated with mononeuritis multiplex due to cytomegalovirus as the initial manifestation in a patient with AIDS.

We report on a 60-year-old male with AIDS who presented Horner's syndrome that was associated with mononeuritis multiplex due to cytomegalovirus (CMV) infection. This is the first case who presented Homer's syndrome in the course of AIDS. Horner's syndrome associated with mononeuritis multiplex in this patient was the initial manifestation without any opportunistic infections. Since Horner's syndrome and mononeuritis multiplex in the present case were both improved by ganciclovir, it is important to consider CMV infection when Horner's syndrome or mononeuritis multiplex is observed in immunocompromised patients, such as those with HIV-1 infection or AIDS, even if they do not show any other opportunistic infections.

Lower cervical origin of the P13-like potential in median SSEPS.

The authors studied the origin of the scalp P13-like potential in median somatosensory evoked potentials, which have been reported to be preserved in patients with cervicomedullary lesions or in brain death. There were five patients with high to middle cervical lesions (C2/3 or C3/4 level). Small P13-like potentials after P11 were identified for all patients with a noncephalic reference but not with an ear reference. Their onset latencies were slightly earlier than the expected latency of the true P13/14 onset. In two patients, delayed true P13/14s followed by N18s were identified with both noncephalic and ear references. The authors argue that the P13-like potential observed in these patients is a different entity from scalp P13 in normal subjects. Because the C3/4 vertebral level corresponds to the C5 cord level, the origin of the P13-like potential must be below C5, contradicting the previous opinion that it is generated at the cervicomedullary junction or at the high cervical dorsal column. The authors named this potential lower cervical P13 (or lcP13), and present an opinion that it is generated by the beginning of the second spinal ascending volley, which has been described by direct-recording studies in humans.

Characterization of platelet activity in neuroblastoma.

A study was conducted to characterize the platelet aggregation induced by neuroblastoma tissue to investigate the mechanism of hypercoagulability in patients with neuroblastoma. The patients whose tumor tissues were examined had been shown clinically to have enhanced platelet activity. Platelet aggregation induced by neuroblastoma tissue extract was compared with that of other pediatric tumors. The effects of pretreatment with an antithrombin agent and prostacyclin (PGI2) on the platelet aggregation induced by tumor tissue extracts were also evaluated. Tissue extracts of 12 of 15 neuroblastomas, 3 of 3 Wilms' tumors, and 1 pheochromocytoma were demonstrated to have an activity that potentiated platelet aggregation in vitro. The platelet aggregation induced by tissue extracts of neuroblastomas and other tumor tissues was suppressed almost completely by pretreatment with a PGI2 analogue. The aggregation induced by neuroblastomas and the pheochromocytoma was also suppressed by pretreatment with an antithrombin agent, argatroban, whereas the aggregation induced by Wilms' tumors was not suppressed by this agent. These results suggest that (1) malignant tumors in children also have some chemical substances that sensitize platelet activity, such as those in adult cancers, and (2) thrombin is one of the mediators stimulating platelet aggregation in cases of neuroblastoma, although it is unlikely to be a contributing factor in other pediatric malignancies such as Wilms' tumor.

Sarcoidosis presenting as bilateral hydronephrosis.

We report an unusual case of sarcoidosis associated with bilateral hydronephrosis. The patient was a 53-year-old Japanese woman who presented with dysuria and urinary incontinence. Computed tomography of the abdomen showed bilateral hydronephrosis caused by a retroperitoneal mass, surrounded by enlarged retroperitoneal lymph nodes. Histological examination of the mass demonstrated noncaseating epithelioid cell granulomas involving the retroperitoneal lymph nodes. Corticosteroid therapy led to complete resolution of the retroperitoneal mass and hydronephrosis. This case emphasizes that sarcoidosis should be included in the differential diagnosis of a retroperitoneal mass.

A new blood compatible and permselective hollow fiber membrane for hemodialysis.

The authors have prepared a blood compatible and highly permselective hemodialysis membrane composed of polyether segmented nylon. This block copolymer was synthesized by polycondensation of bis-3-aminopropyl-poly(tetramethylene oxide) (PTMO) and poly(imino-1,3-bismethyl-cyclohexyl-iminoisophtharoyl) (NyBl) prepolymer obtained by polycondensation of 1,3-bis(aminomethyl)cyclohexane (B) and isophthalic acid (I). The molecular weight (MW) calculated from the number of end-groups was 16,000-21,000. In vitro blood compatibility was evaluated in terms of platelet adhesion onto the surface. PTMO-NyBl surfaces showed excellent platelet adhesion preventing properties. The PTMO-NyBl hollow fiber membrane was obtained by a dry-wet spinning process. The membranes had higher permeability coefficients for macromolecules ranging from MW 10,000 to 20,000 than polysulfone hollow fiber membrane (PS membrane), and had acceptably low albumin permeability for use as a dialysis membrane. The ex vivo blood compatibilities of PTMO-NyBl membrane and PS membrane were investigated by extracorporeal circulation in a pig model. The PTMO-NyBl membrane gave excellent results when assessing hemodialysis leukopenia, oxidative burst, and free platelet count decrease.

Hair growth on nude mice due to cyclosporin A.

One of the most common dermatological side effects of cyclosporin A (CsA) is dose-dependent hypertrichosis. Similar hair growth was noted in nude mice in an attempt to increase the acceptance of human xenografts with CsA in the T-cell-deficient congenitally athymic nude (nu/nu) mice. The aim of the present study was to further investigate the stimulation of hair growth on nude mice not only by oral administration of CsA but also by topical and subcutaneous administration of CsA. Young BALB/c female nude mice were treated for 3 or 4 weeks with topical, oral, or subcutaneous applications of CsA dissolved in olive oil at various doses. The hair of CsA-treated mice appeared to grow from 7 days after the treatment, even at low doses. Induced hair growth was dose-dependent and became clearly obvious 3 weeks after the treatment. The stimulation of hair growth was not restricted to the site of topical application. The distribution of the new hair depended on the natural pattern of hair growth in the mice. However, there was no hair growth in the control mice which were given only olive oil. Histological examination revealed that there were no differences in the structures of skin and hair between the control and the CsA-treated mice. Furthermore, the number of hair follicles did not remarkably increase after CsA treatment. The hair growth in the CsA-treated mice stopped after cessation of the treatment and returned to the level of the control mice on day 14 after the end of the treatment. Subsequent retreatment with CsA resulted in further regrowth of the hair.(ABSTRACT TRUNCATED AT 250 WORDS)

Reoperative surgery in calves with a total artificial heart.

Two surgical techniques have been developed in our laboratory to deal with identifiable problems in long-term artificial heart experiments. A right throacotomy is used to deal with problems such as extensive bleeding, which occur in the immediate postoperative stage of the experiment, while a left thoracotomy is used in cases in which the original implantation is preceded by more than one week, since extensive adhesions complicate the right thoracotomy at that stage. Pulmonary problems have been eliminated as primary cause of difficulties after reoperation, but infection remains a serious problem.