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Background: Koalas, an Australian arboreal marsupial, depend on eucalypt tree leaves for their diet. They selectively consume only a few of the hundreds of available eucalypt species. Since the koala gut microbiome is essential for the digestion and detoxification of eucalypts, their individual differences in the gut microbiome may lead to variations in their eucalypt selection and eucalypt metabolic capacity. However, research focusing on the relationship between the gut microbiome and differences in food preferences is very limited. We aimed to determine whether individual and regional differences exist in the gut microbiome of koalas as well as the mechanism by which these differences influence eucalypt selection., Methods: Foraging data were collected from six koalas and a total of 62 feces were collected from 15 koalas of two zoos in Japan. The mitochondrial phylogenetic analysis was conducted to estimate the mitochondrial maternal origin of each koala. In addition, the 16S-based gut microbiome of 15 koalas was analyzed to determine the composition and diversity of each koala's gut microbiome. We used these data to investigate the relationship among mitochondrial maternal origin, gut microbiome and eucalypt diet selection., Results and Discussion: This research revealed that diversity and composition of the gut microbiome and that eucalypt diet selection of koalas differs among regions. We also revealed that the gut microbiome alpha diversity was correlated with foraging diversity in koalas. These individual and regional differences would result from vertical (maternal) transmission of the gut microbiome and represent an intraspecific variation in koala foraging strategies. Further, we demonstrated that certain gut bacteria were strongly correlated with both mitochondrial maternal origin and eucalypt foraging patterns. Bacteria found to be associated with mitochondrial maternal origin included bacteria involved in fiber digestion and degradation of secondary metabolites, such as the families Rikenellaceae and Synergistaceae. These bacteria may cause differences in metabolic capacity between individual and regional koalas and influence their eucalypt selection., Conclusion: We showed that the characteristics (composition and diversity) of the gut microbiome and eucalypt diet selection of koalas differ by individuals and regional origins as we expected. In addition, some gut bacteria that could influence eucalypt foraging of koalas showed the relationships with both mitochondrial maternal origin and eucalypt foraging pattern. These differences in the gut microbiome between regional origins may make a difference in eucalypt selection. Given the importance of the gut microbiome to koalas foraging on eucalypts and their strong symbiotic relationship, future studies should focus on the symbiotic relationship and coevolution between koalas and the gut microbiome to understand individual and regional differences in eucalypt diet selection by koalas., Competing Interests: The authors declare there are no competing interests., (©2024 Kondo et al.)

Early child maltreatment, such as child abuse and neglect, is well known to affect the development of social skills. However, the mechanisms by which such an adverse environment interrupts the development of social skills remain unelucidated. Identifying the period and brain regions that are susceptible to adverse environments can lead to appropriate developmental care later in life. We recently reported an excitatory/inhibitory imbalance and low activity during social behavior in the medial prefrontal cortex (mPFC) of the maternal separation (MS) animal model of early life neglect after maturation. Based on these results, in the present study, we investigated how MS disturbs factors related to excitatory and inhibitory neurons in the mPFC until the critical period of mPFC development. Additionally, we evaluated whether the effects of MS could be recovered in an enriched environment after MS exposure. Rat pups were separated from their dams on postnatal days (PDs) 2-20 (twice daily, 3 h each) and compared with the mother-reared control (MRC) group. Gene expression analysis revealed that various factors related to excitatory and inhibitory neurons were transiently disturbed in the mPFC during MS. A similar tendency was found in the sensory cortex; however, decreased parvalbumin (PV) expression persisted until PD 35 only in the mPFC. Moreover, the number of PV + interneurons decreased in the ventromedial prefrontal cortex (vmPFC) on PD 35 in the MS group. Additionally, perineural net formation surrounding PV + interneurons, which is an indicator of maturity and critical period closure, was unchanged, indicating that the decreased PV + interneurons were not simply attributable to developmental delay. This reduction of PV + interneurons improved to the level observed in the MRC group by the enriched environment from PD 21 after the MS period. These results suggest that an early adverse environment disturbs the development of the mPFC but that these abnormalities allow room for recovery depending on the subsequent environment. Considering that PV + interneurons in the mPFC play an important role in social skills such as empathy, an early rearing environment is likely a very important factor in the subsequent acquisition of social skills., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Irie, Ohta, Ujihara, Araki, Honda, Suzuki, Warita, Otabi, Kumei, Nakamura, Koyano, Miki and Kusaka.)

Epidemiological studies have indicated that child maltreatment, such as neglect, is a risk factor of escalated aggression, potentially leading to delinquency and violent crime in the future. However, little is known about the mechanisms by which an early adverse environment may later cause violent behavior. In this study, we aimed to thoroughly examine the association between aggression against conspecific animals and the activity of amygdala subnuclei using the maternal separation (MS) model, which is a common model of early life stress. In the MS group, pups of Sprague-Dawley rats were separated from their dam during postnatal days 2-20 (twice a day, 3 h each). We only included 9-week-old male offspring for each analysis and compared the MS group with the mother-reared control group; both groups were raised by the same dam during postnatal days 2-20. The results revealed that the MS group exhibited higher aggression and excessive activity of only the central amygdala (CeA) among the amygdala subnuclei during the aggressive behavior test. Moreover, a significant positive correlation was observed between higher aggression and CeA activation. While CeA activity is known to be involved in hunting behavior for prey, some previous studies have also indicated a relationship between CeA and intraspecific aggression. It remains unclear, however, whether excessive CeA activity directly induces intraspecific aggression. Therefore, we stimulated the CeA using optogenetics with 8-week-old rats to clarify the relationship between intraspecific aggression and CeA activity. Notably, CeA activation resulted in higher aggression, even when the opponent was a conspecific animal. In particular, bilateral CeA activation resulted in more severe displays of aggressive behavior than necessary, such as biting a surrendered opponent. These findings suggest that an adverse environment during early development intensifies aggression through excessive CeA activation, which can increase the risk of escalating to violent behavior in the future., (© 2023 International Society for Neurochemistry.)

Cellular senescence induces inflammation and is now considered one of the causes of organismal aging. Accumulating evidence indicates that age-related deterioration of mitochondrial function leads to an increase in reactive oxygen species (ROS) and DNA damage, which in turn causes cellular senescence. Thus, it is important to maintain mitochondrial function and suppress oxidative stress in order to inhibit the accumulation of senescent cells. Sesamin and its isomer episesamin are types of lignans found in sesame oil, and after being metabolized in the liver, their metabolites have been reported to exhibit antioxidant properties. However, their effects on cellular senescence remain unknown. In this study, the effects of sesamin, episesamin, and their metabolites SC1 and EC1-2 on replicative senescence were evaluated using human diploid lung fibroblasts, and TIG-3 cells. The results showed that sesamin and episesamin treatment had no effect on proliferative capacity compared to the untreated late passage group, whereas SC1 and EC1-2 treatment improved proliferative capacity and mitigated DNA damage of TIG-3 cells. Furthermore, other cellular senescence markers, such as senescence-associated secretory phenotype (SASP), mitochondria-derived ROS, and mitochondrial function (ROS/ATP ratio) were also reduced by SC1 and EC1-2 treatment. These results suggest that SC1 and EC1-2 can maintain proper mitochondrial function and suppress the induction of cellular senescence.

Cancer cells often respond to chemotherapeutic inhibitors by redirecting carbon flow in the central metabolism. To understand the metabolic redirections of inhibitor treatment on cancer cells, this study established a 13 C-metabolic flux analysis ( 13 C-MFA)-based method to evaluate metabolic redirection in MCF-7 breast cancer cells using mass spectrometry. A metabolic stationary state necessary for accurate 13 C-MFA was confirmed during an 8-24 h window using low-dose treatments of various metabolic inhibitors. Further 13 C-labeling experiments using [1- 13 C]glucose and [U- 13 C]glutamine, combined with gas chromatography-mass spectrometry (GC-MS) analysis of mass isotopomer distributions (MIDs), confirmed that an isotopic stationary state of intracellular metabolites was reached 24 h after treatment with paclitaxel (Taxol), an inhibitor of mitosis used for cancer treatment. Based on these metabolic and isotopic stationary states, metabolic flux distribution in the central metabolism of paclitaxel-treated MCF-7 cells was determined by 13 C-MFA. Finally, estimations of the 95% confidence intervals showed that tricarboxylic acid cycle metabolic flux increased after paclitaxel treatment. Conversely, anaerobic glycolysis metabolic flux decreased, revealing metabolic redirections by paclitaxel inhibition. The gap between total regeneration and consumption of ATP in paclitaxel-treated cells was also found to be 1.2 times greater than controls, suggesting ATP demand was increased by paclitaxel treatment, likely due to increased microtubule polymerization. These data confirm that 13 C-MFA can be used to investigate inhibitor-induced metabolic redirection in cancer cells. This will contribute to future pharmaceutical developments and understanding variable patient response to treatment.

This article indicates that capability building in the local community and accumulation of collaborative practice experiences gained at the local community level prove effective in actual disaster response and recovery. A case study of the Japanese community is introduced to illustrate this point. The article concludes with a discussion of the role and function of social workers in the context of such a community. In terms of disaster response and recovery, one of the essential roles of social workers is to encourage local people to empower other local people, organizations, and community.

In the present study, two alkaloids isolated from Pterogyne nitens, a plant native to Brazil, have been shown to induce apoptosis in human breast cancer cells. These compounds, pterogynine (PGN) and pterogynidine (PGD), were tested for their effect on a human infiltrating ductal carcinoma cell line (ZR-7531). The cell line was treated with each alkaloid at several concentrations. Time-dependence (with or without recuperation time) and concentration-dependence (in the range 0.25-10 mM) were investigated in cytotoxicity and apoptosis assays. The annexin assay indicated an apparently higher percentage of death by necrosis of malignant cells after 24 h exposure to both P. nitens extracts than the Hoechst assay. Thus, our results in the two tests demonstrated that the Hoechst assay can discriminate between late apoptotic cells and necrosis, whereas the flow cytometry-based annexin V assay cannot. We concluded that PGN and PGD have effective antineoplastic activity against human breast cancer cells in vitro, by inducing programmed cell death.

The carboxy-terminal domain (CTD) of the RNA polymerase II (Pol II) largest subunit undergoes reversible phosphorylation during transcription cycle. The phosphorylated CTD plays critical roles in coordinating transcription with chromatin modification and RNA processing by serving as a scaffold to recruit various proteins. Recently, we identified a novel human WW domain-containing protein PCIF1 as a phosphorylated CTD-interacting factor and demonstrated that PCIF1 negatively modulates Pol II activity in vivo. In the present study, to explore cellular functions of PCIF1, we generated PCIF1-deficient chicken DT40 cell lines. We observed significant up-regulation of WW domain-containing prolyl isomerase Pin1 in two independently established PCIF1-deficient mutant clones. As reconstitution of PCIF1 in the mutants did not reduce Pin1 expression, PCIF1 may not be a negative regulator of Pin1 expression. We assume that Pin1 over-expression might suppress defects caused by PCIF1 deficiency in DT40 cells. We furthermore compared PCIF1 and Pin1 for their functional properties and found that these two proteins exhibit most similar target specificity among other CTD-binding WW proteins, overlapping subcellular localization and comparative inhibitory effects on transcriptional activation by Pol II in human cultured cells. These results suggest that Pin1 may have overlapping cellular function with PCIF1 in vertebrate cells.

We evaluated the effects of a substrate in the biosynthesis of nitric oxide (NO)-l-arginine (LARG)-on hepatic lesions caused by ischemia/reperfusion (I/R) injury in rabbit livers. Rabbits were pretreated with LARG (150 mg/kg IV) or saline solution 0.9% (SS) before the hepatic I/R procedure. The effects of LARG on hepatic injury were evaluated before and after I/R. The warm hepatic I/R procedure produced profound acute liver injury, as indicated by elevated values of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH), as well as a high apoptotic cell count. All changes were attenuated by treatment with LARG before the hepatic I/R procedure. These results suggested that LARG produced protective effects on hepatic I/R lesions. This protective effect of LARG was probably associated with blocking generation of superoxide anions during the hepatic I/R procedure.

The Sexuality Study Group (chairperson: Chineko Araki) has researched the sexuality of middle-aged to elderly men and women who were having problems with their spouse, and suggestions for an improved sexual life. According to the result of the survey, the problem seemed to lie in the gap between men and women; men want sexual intercourse with women, while many women are satisfied with emotional affection. Discontinuance of intercourse is mainly caused by the loss of women's interest in sex. The responses to 'What kind of sexual relationship do you want to have with your spouse?' and other questions showed that whether women want to have sexual intercourse or not is not simply caused by a physical problem such as decrease of sexual desire or pain during intercourse, but is affected by various factors such as the affection to the spouse, physical and mental satisfaction by intercourse and a different way of thinking about sex. Also the survey showed even though both men and women wanted to have a 'casual conversation' or 'showing affection daily', in actual life they lacked having conversations and had little physical contact except for sex. For aging couples to keep matured sexual relations, it is more desirable to build the couples' relationship with casual conversation and physical contact, and also enjoy slow sex, such as pillow talk or caressing one another and not focusing on sex only.

Rheumatoid factor (RF) has been commonly used as a marker of rheumatoid arthritis (RA). RF can be detected in 60-80% of RA patients, but the specificity is low against other rheumatic diseases patients. We evaluated the diagnostic accuracy of anti-cyclic citrullinated peptide antibody (anti-CCP), a new diagnostic test for RA. Anti-CCP demonstrated higher sensitivity (81.0%) and specificity (92.4%). By the receiver operating characteristic (ROC) curve analysis, anti-CCP was superior to other markers (ie. RF, CARF, IgG-RF, and MMP-3). In early RA patients (RA patients who had had disease symptoms for < 2 years), sensitivity was 68.8%. Positivities of anti-CCP in RA patients became higher as the advance of stage defined by the Steinbrocker classification. We concluded that anti-CCP is a very valuable tool for the diagnosis of RA. Moreover, anti-CCP is a useful for finding RA of recent onset.

Immunohistochemistry was used to verify whether choline-acetiltransferase colocalizes with calcium-binding proteins and NMDA receptor subunit NR1 in the rat retina. Whereas calbindin and parvalbumin were not observed in cholinergic amacrine cells, calretinin and NR1 were very frequently colocalized with ChAT. Calretinin/NR1-positive cells were also shown, suggesting that calretinin in cholinergic cells of the rat may be related to the buffering of excess intracellular calcium generated by activation of NMDA receptors.

Immunohistochemical techniques reveal that the dopamine- and cAMP-regulated phosphoprotein DARPP-32 is detectable in neurons of the chick optic tectum starting on embryonic day 13. The expression levels then increase steadily from embryonic day 15 through the first posthatching day. After 15 days posthatching, expression of DARPP-32 reaches the adult pattern, with many labeled cells in tectal layers 11 and 12. These cells exhibit a bipolar shape, with long processes directed both to the deep and superficial layers. These results suggest that DARPP-32 is present in specific neuronal populations of the chick tectum and that this protein may not have a function in early ontogenetic processes.

Fos immunohistochemistry was used to characterize neurons in the chick retina activated by optokinetic and stationary stimuli. Higher percentages of co-localization of Fos and the alpha5 subunit of the nicotinic acetylcholine receptor, and Fos and GABA were observed in retinal neurons after optokinetic compared to the stationary stimulation. These results indicate an involvement of the cholinergic and GABAergic circuitries in the motion detection by chick retinal cells., (Copyright 1998 Elsevier Science B.V. All rights reserved.)

Purpose: We studied the efficacy of preoperative noninvasive assessment of the upper extremity to identify arteries and veins suitable for hemodialysis access to increase our use of autogenous fistulas (AF)., Methods: From Sep. 1, 1994, to Apr. 1, 1997, 172 patients who required chronic hemodialysis underwent segmental upper extremity Doppler pressures and duplex ultrasound with mapping of arteries and veins. The following criteria were necessary for satisfactory arterial inflow: absence of a pressure gradient between arms, patent palmar arch, and arterial lumen diameter 2.0 mm or more. The criteria necessary for satisfactory venous outflow were venous luminal diameter greater than or equal to 2.5 mm for AF and greater than or equal to 4.0 mm for synthetic bridging grafts (BG) and continuity with distal superficial veins in the arm. Intraoperative and duplex ultrasound measurements were compared. Contemporary experience was compared with the 2-year period (1992 to 1994) before implementation of the protocol., Results: During the period from Sep. 1, 1994, to Apr. 1, 1997, 108 patients (63%) had AF, 52 (30%) had prosthetic BG, and 12 (7%) had permanent catheters (PC) placed. Early failure was seen in 8.3% of AFs. Primary cumulative patency rates were 83% for AF and 74% for BG at 1 year (p < 0.05), with a mean clinical follow-up of 15.2 months. No postoperative infections were observed with AF, whereas six infections (12%) were observed with BG and two (17%) with PC insertion. During the period from June 1, 1992, to Aug. 31, 1994, 183 procedures were performed with a distribution of 14% AF, 62% BG, and 24% PC. In this earlier period the AF early failure rate was 36%, and the patency rates were 48%, 63%, and 48% for AF, BG, and PC, respectively (mean follow-up, 13.8 months)., Conclusion: A protocol of noninvasive assessment increased use of AFs. The cumulative patency rate of AFs was improved, and early failure rates were reduced when compared with the preceding institutional experience. Routine noninvasive assessment is recommended to document adequacy of arterial inflow and delineate venous outflow to maximize opportunities for AF.

Purpose: We describe a technique of superficial venous transposition in the forearm used for the formation of an arteriovenous fistula for hemodialysis access. These modifications of the single-incision radiocephalic fistula are designed to increase options for arteriovenous fistulas by using veins and arteries that are suitable for use but are not in immediate proximity., Methods: Arteries and veins suitable for a primary arteriovenous fistula were identified and mapped using duplex ultrasound in 89 patients. Separate incisions were used in the majority of cases, and the selected forearm vein was mobilized, angiodilated, and transposed into a subcutaneous tunnel on the volar aspect of the forearm. Before initiation of hemodialysis, duplex ultrasound scanning was performed, and the location that was most suitable for cannulation was identified. Repeat scans were performed at 3-month intervals for analysis of patency., Results: Superficial venous transpositions were performed using a single incision in 13 instances in which the vein was in immediate proximity to the radial artery (type A). Dorsal-to-volar forearm transposition (type B) was performed in 30 veins with anastomoses to the radial (n = 26), ulnar (n = 2), or brachial (n = 2) arteries. Volar-to-volar forearm transposition (type C) was performed in the remaining 46 veins, with anastomoses to the radial (n = 42), ulnar (n = 2), or brachial arteries (n = 2). Successful hemodialysis was accomplished in 81 of 89 patients (91%). The primary cumulative patency rate was 84% at 1 year and 69% at 2 years. The mean duration of follow-up was 14.3 months., Conclusions: The use of superficial venous transposition for the formation of autogenous hemoaccess was associated with ease of cannulation by dialysis personnel, high maturation rates, reduced early failure rates, and enhanced patency rates. We recommended the use of these technical modifications to increase the use of autogenous fistulas in the forearm.

Immunohistochemistry was used to examine the co-occurrence of nicotinic acetylcholine receptor subunits with calcium-binding proteins in ganglion cells of the chick retina. The alpha3 subunit was rarely observed in ganglion cells containing calbindin, calretinin, or parvalbumin. On the other hand, the alpha8 subunit was more often co-localized with all calcium-binding proteins studied. These results may be related to the high calcium permeability of nicotinic receptors that contain the alpha8 subunit.

Purpose: Vascular surgeons are ideally suited to select and perform endovascular interventions either as primary therapy or as an adjunct to bypass surgery. Attaining proficiency in endovascular techniques is an important goal in the training of vascular surgeons. We report our initial experience with a program of endovascular intervention performed in the operating room by vascular surgeons., Methods: During the previous three years, we performed 109 angioplasty procedures, 60 aortoiliac (55%), 32 femoropopliteal (29%), and 17 popliteal/tibial (16%), using guidewires and angioplasty balloons directed by intraoperative digital subtraction C-arm arteriography with road-mapping capabilities. Indications for angioplasty included disabling claudication in 59 patients (54%), rest pain in 18 (17%), and tissue loss in 32 (29%). Angioplasty was accompanied by stent placement in 39 of 60 aortoiliac procedures (65%) and in two of 32 femoral procedures (6%). In 16 cases (15%), the endovascular procedure was performed in conjunction with a bypass procedure. In selected cases (15, 14%), duplex scanning was the sole diagnostic method used before surgery to identify the lesion, eliminating the need for preoperative arteriographic scans. Segmental pressure measurements, duplex ultrasound scans, and treadmill exercise testing as indicated were performed before and after surgery. The efficacy of the endovascular intervention was assessed at 3-month intervals during the first year and at 6-month intervals thereafter., Results: A successful results was defined using criteria recommended by the Ad Hoc Subcommittee on Reporting Standards for Endovascular Procedures from the Society for Vascular Surgery/International Society for Cardiovascular Surgery. This included the combination of symptomatic improvement, obtaining an anatomically successful result with < 30% residual lumen stenosis, and elimination of the translesion gradient with an improvement in high thigh-brachial index or ankle-brachial index greater than 0.15. Initial success was achieved in 55 of 60 aortoiliac (92%), 28 of 32 femoropopliteal (88%), and 16 of 17 popliteal/tibial (94%) angioplasty procedures. Clinical follow-up has been achieved in all cases, with continued clinical success rates of 80%, 75%, and 82% for aortoiliac, femoropopliteal, and popliteal/tibial angioplasty procedures, respectively, with a mean follow-up of 15.7 months., Conclusion: These results confirm the value of a program in which C-arm technology was used by vascular surgeons in the performance of angioplasty and stenting procedures in the operating room. This experience in therapeutic endovascular intervention will facilitate the credentialing process for future vascular surgeons.

Purpose: This study was undertaken to determine the degree of clinical and hemodynamic improvement after surgical ablation of incompetent superficial and perforator veins in limbs with combined deep and superficial venous incompetence manifested by chronic dermal ulceration., Methods: Eleven limbs in 10 patients with class 5 or 6 venous insufficiency (ulceration) were assessed by CEAP (clinical, etiologic, anatomic, pathophysiologic) clinical scores, air plethysmography, color duplex ultrasonography, and phlebography (both ascending and descending). Surgical ablation of superficial and perforating veins was performed, followed by repeat clinical, air plethysmographic, and color duplex ultrasonographic examinations., Results: All 11 limbs had combined deep and superficial vein reflux on the preoperative color duplex ultrasound scan. Clinical symptom scores decreased from 10 to 1.4 after operation. Postoperative air plethysmography demonstrated significant reduction in reflux as measured by the mean venous filling index, which decreased from 12 +/- 5 ml/sec to 2.7 +/- 1 ml/sec after surgery. Calf pump function was also significantly improved, with a mean ejection fraction that increased from 43% +/- 11 to 59% +/- 13 and mean residual volume fraction that decreased from 56% +/- 15 to 33% +/- 16. Each of these measures was significantly different from the preoperative value (p < 0.05). Similar improvement characterized subgroups of limbs with three or more incompetent deep segments (n = 6) or popliteal segment incompetence (n = 6)., Conclusions: Superficial and perforating vein incompetence accounts for a substantial and correctable component of venous insufficiency in limbs with combined deep and superficial vein reflux and venous ulceration. These data indicate that surgical correction of this component significantly improves clinical symptoms and venous hemodynamics. Superficial and perforator ablation is an appropriate initial step in the management of combined deep and superficial venous incompetence.

The Fos protein was immunocytochemically detected in the chick ventral lateral geniculate nucleus after novel stationary and optokinetic stimulation. Fos-positive nuclei were mainly detected in the internal part of the ventral geniculate when the animals were submitted to stationary visual stimulation. On the other hand, Fos-positive nuclei were mainly seen in the external part of the nucleus when optokinetic stimuli were used. These data reveal functional subdivisions of the avian ventral geniculate, and support the hypothesis that this nucleus is involved in several aspects of the visual function.

Purpose: Calf muscle pump dysfunction is a recognized factor in chronic venous insufficiency (CVI). We investigated the hypothesis that limbs with CVI have a reduced ankle range of motion (ROM) that may be responsible for the poor calf pump function associated with venous ulceration., Methods: Ankle ROM and calf pump function were assessed in 32 limbs of 26 adult men. Limbs were selected on the basis of clinical presentation: normal (n = 6 limbs), class 1 or 2 CVI with no history of ulceration (n = 9 limbs), class 3 CVI with healed ulceration (n = 9 limbs), and class 3 CVI with active ulceration (n = 8 limbs). ROM was determined by goniometry during maximal plantar flexion and dorsiflexion of the ankle. Calf pump function was determined by air plethysmographic measurement of ejection fraction (EF) and residual volume fraction (RVF)., Results: Ankle ROM was significantly (p < 0.05) reduced in each CVI group compared with age-matched control subjects, because of decreases in both plantar flexion and dorsiflexion. Calf pump function was significantly impaired (decreased EF and increased RVF) in ulcerated limbs. ROM was significantly correlated to EF and RVF. Impairment of ROM and calf pump function was associated with deterioration in the clinical classification of venous disease., Conclusions: Limbs with CVI have a limited ankle ROM that decreases with increasing severity of clinical symptoms. This decreased ROM is associated with, and may contribute to, poor calf pump function.

Purpose: With clinical progression of chronic venous insufficiency (CVI), dermal infiltration of mononuclear cells increases. Because these cells regulate chronic inflammatory responses and modulate wound healing, cellular dysfunction could explain alterations in wound healing with CVI. The purpose of this study was to determine whether monocytes in patients with CVI are dysfunctional., Methods: Mononuclear cell function was measured as the degree of proliferation in response to a mitogenic challenge. Fifty patients were separated into four groups: group 1, 14 patients with normal limbs; group 2, 10 patients with class 2 CVI; group 3, 15 patients with active venous ulcers; group 4, 11 patients with healed venous ulcers and current evidence of lipodermatosclerosis. Duplex scanning and air plethysmography correlated with the clinical classification of CVI. Systemically circulating monocytes and lymphocytes were obtained by antecubital venipuncture from groups 1 to 4. Cells were cultured in the presence of staphylococcal enterotoxins A, B, C1, D, and E (mitogens) at 1, 8, 31, and 125 micrograms/well on the basis of previous dose-response experiments. Phytohemagglutinin (PHA), 5 micrograms/well, served as a control mitogen. The dose-response curves indicated that 8 micrograms/well elicited the greatest degree of cell proliferation. Proliferative responses at 8 micrograms/well were analyzed for statistical significance among groups 1 to 4. Comparisons among groups were performed by use of the nonparametric Mann Whitney U post tests and a one-tailed unpaired t test. Results were considered significant at p < or = 0.05., Results: Proliferative responses to PHA indicate that lymphocytes and monocytes from patients with CVI are not globally depressed. However, patients in group 2 did not exhibit the same degree of proliferation to PHA as did groups 1, 3 and 4. Proliferative responses between groups 2 and 1 (44.38 +/- 43.9 vs 118.87 +/- 27.1, p < or = 0.05) and groups 2 and 3 (44.38 +/- 43.9 vs 105.95 +/- 60.99, p < or = 0.05) were significant. Challenges with staphylococcal enterotoxin A and B reveal significant diminution of proliferative responses in groups 2 (42.73 +/- 11.55, p < or = 0.05) and 3 (45.57 +/- 9.1, p < or = 0.05) and groups 3 (36.81 +/- 6.9, p < or = 0.05) and 4 (35.04 +/- 7.5, p < or = 0.05), compared with staphylococcal enterotoxin A controls (68.68 +/- 9.9) and staphylococcal enterotoxin B controls (66.25 +/- 13.56), respectively. A trend of diminished mononuclear cell function with progression of CVI was observed with staphylococcal enterotoxins B, C1, D, and E, strongly suggesting biologic significance. Furthermore, patients with lipodermatosclerosis uniformly exhibited the poorest proliferative responses., Conclusions: Deterioration of mononuclear cell function is associated with CVI. A trend of diminishing proliferative responses with clinical disease progression is observed and suggests biologic significance. The decreased capacity for mononuclear cell proliferation in response to various challenges may manifest itself clinically as poor and prolonged wound healing.

Alteration in leukocyte activation has been implicated as an etiological factor in the development of chronic venous stasis ulcers (CVSU). The purpose of this study was to determine differences in expression of cell surface activation markers on circulating leukocytes and systemic, soluble, serum cytokine levels between healthy controls and patients with CVSU. Twenty-three patients were separated into two groups. Group I consisted of 12 healthy, adult, age-matched male patients with no venous disease. Group II consisted of 11 adult male patients with CVSU who underwent air plethysmography (APG) and duplex scanning to determine the severity of venous insufficiency. All patients had measurements of systemic, serum-based, soluble IL-1 beta, IL-2, IL-6, TNF-alpha, and beta 2 microglobulin levels. Using fluorescence flow cytometry, we measured the percentage of lymphocytes (CD3), monocytes (CD14), and granulocytes (CD15) expressing various cell surface activation markers. By APG and duplex scan, all group II patients exhibited venous insufficiency, with a mean venous filling index of 6.9 +/- 3.9 sec. Relative to group I, group II patients demonstrated a decreased expression of the CD3+/DR+ (13.3 +/- 1.5, P < or = 0.01) and CD3+/CD38+ (31.1 +/- 2.1, P < or = 0.04) markers on T-lymphocytes and an increased expression of CD14+/CD38+ (99.6 +/- 0.2, P < or = 0.008) markers on monocytes. Circulating neutrophils showed no evidence of activation. In addition, a significant elevation in the T-helper to T-suppressor ratio (2.9 +/- 0.6, P < or = 0.0001) between groups I and II was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: Patients with clinically evident chronic venous insufficiency were evaluated to relate the degree of insufficiency and calf muscle pump dysfunction to venous ulceration., Methods: Sixty-nine limbs in 55 patients with chronic venous insufficiency by Society for Vascular Surgery/International Society for Cardiovascular Surgery Classification were compared in three groups: classes 1 and 2 with no history of ulceration (19 limbs); class 3 with healed ulceration (20 limbs); and class 3 with active ulcers (30 limbs). Air plethysmography measurements of outflow fraction, venous volume, venous filling time, venous filling index, ejection fraction, ejection volume, residual volume fraction, and residual volume were made. In 62 of the 69 limbs, color-flow duplex ultrasonography was used to determine the pattern of reflux., Results: The outflow fraction was normal in 84%, 75%, and 77% of nonulcerated, healed, and ulcerated limbs. The venous filling index was abnormal in most limbs (nonulcerated 95%, healed 90%, ulcerated 98%) but not significantly different among groups. Differences in calf muscle pump function were significant. Ulcerated limbs had significantly poorer ejection fractions (p = 0.0002) and greater residual volume fractions (p = 0.0006) than nonulcerated or healed limbs. By ultrasonography, deep and superficial vein incompetence was present in most limbs and was not statistically different among groups. Although venous insufficiency was not measurably different among groups, limbs with active venous ulcers had significantly poorer calf muscle pump function than those with healed ulcers or with no history of ulceration., Conclusion: Venous insufficiency is necessary but not sufficient to cause ulceration, and a deficiency of the calf muscle pump is significant to the severity of venous ulceration.

Color-flow and duplex ultrasonography were used to determine the optimal method for documenting venous valvular reflux. Popliteal veins were examined in 10 normal limbs and 11 limbs with clinical evidence of chronic venous insufficiency (CVI). Peak reflux velocity (spectral) and duration of reflux (spectral and color) were measured with the patient in supine and standing positions, with manual and pneumatic compression applied sequentially to thigh and calf. Manual and pneumatic compression produced equivalent reflux velocity and duration. In normal limbs peak reflux velocity was always less than 22 cm/sec, with a mean reverse flow duration of 0.3 sec +/- 0.03 (SEM). In limbs with CVI, reflux velocity varied widely among protocols. Reflux duration and velocity were greater in the supine position than in the standing position for both normal limbs and limbs with CVI (p < 0.04). Duration was significantly increased for thigh versus calf compression in normal limbs (p < 0.001) but decreased in limbs with CVI (p < 0.003). Methods that used thigh compression or supine position were less capable of discriminating normal limbs from limbs with CVI. Standing calf compression provided the greatest rates of sensitivity (91%), specificity (100%), and accuracy (95%). Compared with spectral Doppler scanning, color-flow ultrasonography produced a consistently shorter reflux duration (p < 0.001). In limbs with CVI with a mean spectral duration of 2.5 sec +/- 0.2 (SEM), mean color Doppler duration was 0.7 sec shorter. Our results demonstrate that popliteal vein incompetence is identified optimally by reflux duration after standing calf compression; adequate manual compression is sufficient to identify reflux; color-flow Doppler ultrasonography may underestimate reflux duration.

Purple urine bag syndrome is a rare phenomenon in which bags turns purple or blue following catheterization. This phenomenon was reported to occur by Providencia stuartii in the presence of indicanuria. We reported herein three females above 75 years of age having a similar phenomenon. All were bedridden chronically and constipated. In these cases, no growth of P. stuartii was found on repeated urine culture, but Escherichia coli and Morganella morganii were concomitantly isolated during the blue bags. It is suggested that purple urine bag syndrome develops in a combination of E. coli and M. morganii besides P. stuartii.

We report a case of diarrhea associated with Giardia lambria and Salmonella. A 28-year-old male who had no chance to go abroad visited our hospital with complaints of abdominal pain, watery diarrhea and fever, but his symptoms persisted in spite of medication. He was admitted to our hospital on the next day for definite diagnosis and treatment. Many trophozoites of Giardia lambria were recognized in the feces. The symptoms were improved using metronidazole, so he was discharged on the 8-th day. The cause of this double infection was not determined. The domestic infection like this case is rare in Japan.

The nature and distribution of venous disease surrounding the development of varicose veins and its treatment is controversial. Using duplex ultrasonography, we evaluated 54 lower extremities in 32 patients with varicose veins who were symptomatic and had obvious varicose veins by clinical examination. Twenty-eight percent had greater saphenous trunk incompetence, 2% had lesser saphenous trunk incompetence, and 96% had branch disease. Deep valvular incompetence was seen in 41%, saphenofemoral junction incompetence in 46%, and incompetence of one or more perforators in 46% of the extremities. Thirty-three percent demonstrated no evidence of associated saphenofemoral junction, deep vein, or perforating vein incompetence, while 20% had concurrent saphenofemoral junction, deep vein, and perforating vein incompetence. These data support the heterogeneity of venous disease seen in patients with varicose veins and suggest that surgical therapy be directed to a patient's specific pattern of incompetence rather than routine saphenofemoral junction ligation or stripping of the greater saphenous trunk.

To evaluate the effect of carotid surgery on the cerebral circulation, transcranial Doppler sonography and ocular pneumoplethysmography were performed on 36 patients who underwent unilateral carotid endarterectomy. Ocular pneumoplethysmography and transcranial Doppler sonography tests were performed within a week before and after operation, and transcranial Doppler sonography was repeated greater than or equal to 30 days after operation. Middle and anterior cerebral arteries were insonated bilaterally, and flow velocities ipsilateral (iMCAFV or iACAFV) and contralateral (cMCAFV or cACAFV) to the side of surgery were recorded. The iMCAFV and iACAFV increased significantly in the immediate postoperative period, and the iMCAFV remained elevated on the second follow-up study. Patients with greater than or equal to 75% ipsilateral carotid stenosis (N = 23) had increased iMCAFV, iACAFV, and decreased cACAFV after operation, whereas those with less than 75% stenosis (N = 13) had no significant transcranial Doppler sonography changes. Those with greater than or equal to 75% contralateral carotid stenosis (N = 17) had significant increases in iMCAFV, cMCAFV, and iACAFV after operation, whereas those with less than 75% contralateral carotid stenosis had no significant transcranial Doppler sonography changes. A subset of patients (N = 13) did not increase iMCAFV after surgery. The ocular pneumoplethysmography changes were significantly different in both groups when preoperative and postoperative values were compared. We conclude that carotid endarterectomy can cause lasting cerebral hemodynamic changes, but that its effects are not uniform among all patients.

Valvular incompetence associated with venous ulceration can occur in the superficial, deep, or perforating systems. Duplex imaging was used to evaluate 95 extremities (78 patients) with current venous ulceration to determine the location of incompetence in each extremity. In addition, in 91 of the 95 extremities the area of the venous ulcer was evaluated for the presence of perforating veins or any other superficial veins or both conditions. Sixty-three (66.3%) of the 95 extremities had multisystem incompetence (superficial and perforating plus superficial and deep plus perforating and deep plus superficial and perforating and deep), whereas single system incompetence (superficial plus perforating plus deep) was seen in only 26 (27.3%). Isolated deep incompetence was identified in only two extremities (2.1%). Furthermore, 45% (41/91) of the ulcers had no duplex evidence of any venous abnormality in the ulcer bed. These data show that the site of valvular incompetence occurred in multiple locations, that isolated valvular incompetence of the deep venous system was uncommon, and that perforating veins were not always in the ulcer bed itself. Because standard venous surgery has traditionally been directed toward only one system, this may provide one explanation for ulcer recurrence. Therefore complete venous evaluation with duplex imaging allowing for surgical intervention directed specifically to the sites of involvement in each system is recommended.

The purpose of this study was to evaluate duplex imaging as a means of assessing perforating veins in patients with longstanding venous stasis ulceration. Thirty patients with nonhealing venous stasis ulcers and twenty normal volunteers serving as controls were evaluated with a standard 8-MHz imaging probe and integrated pulsed Doppler. The internal diameter of perforating veins was measured and perforators were grouped into one of four categories based on functional criteria: competent perforator with venous flow (C); incompetent perforator with venous flow (IC); competent perforator with arteriovenous flow (C-AVC); incompetent perforator with arteriovenous flow (IC-AVC). Sixteen of the patients with ulcers were subsequently studied by ascending venography and in 11 patients, intraoperative identification of perforating veins was made during the Rob procedure. In this subset of patients the vessel was categorized as competent or incompetent regardless of flow signal. There were significant differences in mean perforator diameter between ulcer patients and normal volunteers. Duplex imaging identified 93 perforators and venography a total of 70. In all 16 extremities, duplex imaging made the diagnosis of significant perforating vein incompetence, verified by venography. Intraoperative findings demonstrated an excellent correlation with duplex imaging. We believe duplex imaging to be a promising new modality for evaluation of the perforating veins of the lower extremity.

Genetic polymorphism of the second component of human complement (C2) was investigated in 521 unrelated healthy adult Japanese using isoelectric focusing in polyacrylamide gel followed by a specific hemolytic overlay method. Besides the phenotypes reported previously (C, AC and BC), a relatively infrequent double-banded phenotype (tentatively named A'C) was observed. Moreover, a homozygous variant (A) and a heterozygous "double" variant (AB) were observed. The estimated frequencies for the common allele, C2c(= C2(1)), and the variant alleles, C2A, C2B(= C2(2)) and C2A' were 0.939, 0.034, 0.022, and 0.006, respectively. The results of further typing for HLA-A, -B, -C specificities indicated the presence of significant associations of C2A with HLA-B15 and with A26, and of C2B with HLA-Bw61. These findings support our previous observation that in Japanese there are allelic combinations showing linkage disequilibrium between C2 and HLA loci which are different from those in Caucasians, and that the C2 structural locus is more closely linked to HLA-B than to HLA-A. C2 hemolytic activities of each phenotypes were assayed. The mean activity of type AC sera was significantly higher than that of type C or type BC, while there were no differences in the activities among the types C, BC or A'C. Also presented are two pedigrees demonstrating the segregation of C2 with HLA alleles in which a homozygous C2 A or C2 B individual was observed.

Numerous blebs were observed in contact with smooth muscle cells (SMC) by light microscopy in the myometrium of the rat uterus after parturition. Electron-microscopically the cell surface of SMC showed bulbous protrusions, which often lacked a basement membrane and were less electron-dense than the surrounding cytoplasm or sometimes nearly electron-lucent. Many bulbous protrusions were separated from SMC and became the isolated structures which we called cytoplasmic blebs. These bulbous protrusions and cytoplasmic blebs were often found to be phagocytosed by fibroblast-like cells and macrophages. A series of these tissue changes in the uterine myometrium after delivery, possibly due to hypoxic conditions, contribute to a rapid involution of SMC which have enlarged during pregnancy.

Polymorphism of the properdin factor B (BF) was investigated using an agarose gel immunofixation electrophoresis in 487 unrelated healthy adult Japanese who were already typed for HLA-A, -B, -C and C2. Besides the previously reported phenotypes in Japanese (S, FS, and F), a rare heterozygous phenotype (tentatively maned FTS) was observed once. The estimated allele frequencies for BS*S, BF*F, and FB*FT (F Tokyo) were 0.801, 0.198, and 0,001 respectively. The relative electrophoretic mobility of the variant band of type FTS was measured by Dr. G Mauff to be F 0.75. The conversion fragment Bb of the type showed a double-banded pattern. BF hemolytic activity of the FTS individual was at the same level as other phenotypes. Statistical tests for the phenotypic data of BF with HLA-A, -B, -C, and C2 indicated the presence of the following significant associations in Japanese: Aw33-BF*F, A11-BF*S, Aw24-BF*S, B15-BF*F, B17-BF*F, Bw44-BF*F, B7-BF*S, Bw52;-BF*S, BW54-BF*S, BW59-BF*S, Cw3-BF*F, C2*AT-BF*F, and C2*A'-BF*F.

We used an in vitro pulsatile flow model to examine the velocity profile distal to a variable nonaxisymmetric stenosis. Using a continuous-wave Doppler velocimeter, the peak systolic frequency was determined distal to the stenosis and in planes parallel and perpendicular to the long axis of the stenosis. In both planes, an exponential regression best describes the relationship between peak systolic frequency and reduction in cross-sectional area. Regressions at each point of insonation diverged as a direct function of reduction in cross-sectional area and as an indirect function of distance from the stenosis. At each point of insonation, regressions representing the relationship in the mutually perpendicular planes diverged in direct proportion to reduction in cross-sectional area. Slopes were greater in parallel planes of insonation. These data demonstrate that two variables, distance and geometry, may influence the results of spectral analytic studies.

Peak systolic frequency (PSF) and percentage systolic window (%SW) are spectral parameters used to characterize poststenotic flow velocity patterns. The PSF, obtained using a continuous-wave (CW) Doppler velocimeter, has been used more frequently, however, in the quantitation of carotid occlusive disease. The authors have employed a microprocessor-driven pulsatile flow model to evaluate more completely the relationship between stenosis and the %SW. Using an 8 MHz CW Doppler probe, the Doppler-shifted frequencies were recorded at 1, 2, 3, 4, and 5 diameters distal to a variable, nonaxisymmetric stenosis, which reduced the cross-sectional area (CSA) 25, 40, 50, 60, 70, 85, and 97 per cent. Four sets of observations were made and the %SW derived using a spectrum analyzer. At one diameter from the stenosis, the relationship between the %SW (Y) and the reduction in CSA (X) is best described by two first-order regressions (Y = MX + B). The slope of the relationship from 0 to 60 per cent reduction in CSA is nearly flat, -0.052, while there is a significant (P less than 0.05) decrease in the slope, -1.538, when the CSA is further reduced from 60 to 97 per cent. Beyond 1 diameter, the relationship is best described by a single linear regression, the gradual slope of which does not permit clinically useful comparisons. These data explain the lack of strong correlation between CSA and %SW when the data are evaluated over the entire range of stenoses. However, they do indicate that the %SW may be a useful correlate if it is obtained within one diameter of the stenosis.

The mechanisms of ischemia-reperfusion injury in skeletal muscle remain controversial. We investigated the ability of postischemic hypothermia to diminish reperfusion edema and improve skeletal muscle pH in a bilateral, in vivo isolated canine gracilis muscle model. In five anesthetized animals, both gracilis muscles were subjected to 6 hr of ischemia followed by 1 hr of reperfusion. After 5 hr of warm ischemia, one gracilis muscle was cooled to 21 degrees C (cold reperfusion, CR) while the contralateral gracilis muscle was maintained at ambient temperature (warm reperfusion, WR). Reperfusion muscle edema was quantitated by measurement of gracilis muscle weight gain. Interstitial muscle pH was monitored by glass microelectrodes. Vascular permeability was measured by analysis of albumin (125I-Alb) leak. Results are presented as the means +/- SEM. (table; see text) Postischemic hypothermia significantly increased the interstitial muscle pH and significantly reduced postreperfusion muscle edema, without changing the vascular permeability to albumin. These data suggest that hypothermia may provide a clinical method for salvaging ischemic skeletal muscle from the postreperfusion edema that can lead to compartment syndromes, reperfusion injury, and subsequent limb loss.

Ten cows in early stages of lactation (less than 100 days postpartum) were used to test the effect of sprinkler/fan cooling on vaginal temperature patterns. Cows were assigned to two groups matched according to milk production. The trial was divided into three periods: period 1, when one group was treated and the other group was not, period 2, when neither group was treated, and period 3, when treatment was switched from period 1 between groups. Treatment consisted of forced air misting in a premilking holding pen, fan cooling during milking, and forced air-sprinkling in a postmilking holding area. Weather conditions were measured by dry bulb, wet bulb, and black globe temperatures. Black globe temperatures in pre- and postmilking holding areas were used to estimate treatment magnitude. All measures were obtained through radiotelemetry at 15-min intervals for 31 days. Animals were milked twice a day. Animals spent an average of 140 min in treatment at each milking. In both morning and afternoon milking, treatment caused a transient increase of body temperature. However, this was followed in the afternoon by low vaginal temperatures for 1 to 2 h beyond treatment with lower temperatures throughout the day.

A study of a small patient sample sought to assess the effects of head angulation on the vertical dimension of occlusion. In some patients, increasing the head angulations showed a positive tendency of displacement, whereas in others the displacements were negative. Most displacements were mixed and irregular. A mathematical analysis revealed no correlation and no significance in the relationship of displacement versus the progressive changes in head angulation. The tested hypothesis was that the vertical dimension of occlusion would increase (or progressively alter) as the angulation of the head was progressively increased. Twelve attempts failed to produce a recognizable and mathematically acceptable pattern of distortion. This experiment failed to support the widely held hypothesis that the patient should be seated in an upright position to prevent distortion of the recording of VDO. It appears that the best recommendation for patient posture during the establishment of the maxillomandibular relationship is one that is comfortable for the patient and is easy for the dentist to obtain the recording.

This study reports the phenotype frequencies (PF) and gene frequencies (GF) of a homogeneous Sichuan Han Chinese population by typing of unrelated 229 individuals and 16 families for HLA-A, B, C, DR and DQ antigens. The frequencies of Bw67, Bw71, DRw12, DRw13 and DRw14 are the first to be reported in Chinese. Two two-locus haplotypes with significant linkage disequilibrium among the Sichuan have also been listed.

Vaginal temperature patterns were obtained from 15 Holstein cows through radiotelemetry. Animals were divided into three groups with five animals per group: 1) cows in early lactation, less than 100 days postpartum, 2) cows in late lactation, greater than 240 days postpartum, and 3) dry cows. Animal temperatures, dry bulb, wet bulb, and black globe temperatures were monitored every 15 min for 17 days. Analysis of variance showed no significant difference for daily mean vaginal temperature between lactation groups. However, on hotter days, lactating cows had higher temperatures than dry cows. Daily mean vaginal temperatures of cows in early lactation were correlated with daily mean dry bulb temperature, black globe temperature, and relative humidity. Comparison of group temperature patterns isolated differences to specific times of day. In groups with early and late lactations, temperatures were lower in either group after milking. Vaginal temperatures were higher in lactating cows than in dry cows through most of the day. Results were 1) diurnal temperature patterns differ among groups; 2) lactating cows are sensitive to environmental changes; and 3) animal management can affect patterns of animal temperature.

Latent and active forms of collagenase were detected in culture media of the normal rabbit colon. During culture, the collagenase appeared to be produced by surviving and growing mucosas on the degenerated or necrotic colon wall. Type III collagen was most readily degraded by the collagenase, followed by type I and II collagens. The collagenase did not attack type IV or V collagens. The latent collagenase was activated by trypsin and chaotropic agents such as 3 M NaSCN or NaI, and autoactivated gradually during storage. Activated latent collagenase showed the properties of metalloproteinase as in the active collagenase. The apparent molecular weights, determined by calibrated Sephadex G-75, were 39,000 and 31,000 for the latent and active enzymes, respectively. After 12 h of tissue culture, the latent collagenase appeared in the culture media 10-20 h earlier than the active collagenase. The collagenase in the culture media of the early period was mainly the latent form, while the media of the late period contained a large amount of the active form.

Twelve edentulous patients were evaluated for changes in facial contour and lip support when the head was progressively tilted backward. The mandibular facial contour changes did not occur in a progressive cause and effect type of relationship. A trend pattern could not be discerned. The maxillary facial contour did have a significant progressive cause and effect relationship in two of the 12 patients and was a positive relationship. As the angles were increased, the displacement of the maxillary facial contour increased anteriorly. The question as to why the maxillary facial contour had a significant progressive cause-and-effect relationship in two of the 12 patients and the mandibular facial contour did not remain unresolved. In a practical sense, it seems reasonable to establish the maxillomandibular relationship with the patient in a comfortable position. This and the ease of recording by the dentist are the primary considerations.