Fabrication of Artificial Nerve Conduits Used in a Long Nerve Gap: Current Reviews and Future Studies.

There are many commercially available artificial nerve conduits, used mostly to repair short gaps in sensory nerves. The stages of nerve regeneration in a nerve conduit are fibrin matrix formation between the nerve stumps joined to the conduit, capillary extension and Schwann cell migration from both nerve stumps, and, finally, axon extension from the proximal nerve stump. Artificial nerves connecting transected nerve stumps with a long interstump gap should be biodegradable, soft and pliable; have the ability to maintain an intrachamber fibrin matrix structure that allows capillary invasion of the tubular lumen, inhibition of scar tissue invasion and leakage of intratubular neurochemical factors from the chamber; and be able to accommodate cells that produce neurochemical factors that promote nerve regeneration. Here, we describe current progress in the development of artificial nerve conduits and the future studies needed to create nerve conduits, the nerve regeneration of which is compatible with that of an autologous nerve graft transplanted over a long nerve gap.

Treatment of Complete Brachial Plexus Injuries Using Double Free Muscle Transfer.

PURPOSE: The purpose of this study was to examine the surgical outcomes of double free muscle transfer (DFMT) performed in patients with complete brachial plexus injury (BPI). METHODS: We retrospectively analyzed the outcomes of DFMT for 12 patients with complete BPI who were followed up for more than 2 years after the final muscle transplantation. Their mean age was 29 years (range, 18-41). Three patients underwent contralateral C7 nerve root transfer before the DFMT. The range of motion (ROM) of the shoulder, elbow, and fingers was measured. Patient-reported outcome measures, including Disability of the Shoulder, Arm, and Hand (DASH) scores and visual analog scale (VAS) scores for pain, were also examined. RESULTS: The mean shoulder ROM against gravity was 22° ± 8° in abduction and 33° ± 5° in flexion. Seven patients underwent phrenic nerve (PhN) transfer to the suprascapular nerves, and five exhibited asymptomatic lung impairment on spirography more than 2 years after PhN transfer. The mean elbow ROM against gravity was 111° ± 9° in flexion and -32° ± 7° in extension. All patients obtained elbow flexion >90° against a 0.5-kg weight. All patients obtained touch sensation and two recognized warm and cold sensations in the affected palm. The mean total active motion of the affected fingers was 44° ± 11°. All patients exhibited hook function of the hands. The mean preoperative and postoperative DASH scores were 70.3 ± 13.4 and 51.8 ± 15.9, respectively. The mean pain VAS score was 28 ± 31 at the final follow-up. CONCLUSIONS: Double free muscle transfer provided patients with complete brachial plexus palsy with good elbow flexion and hand hook functions. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

How proximal femur fracture patients aged 65 and older fare in survival and cause of death 5+ years after surgery: A long-term follow-up.

Although the incidence of proximal femur fractures (PFFs) is increasing, few detailed reports on associated long-term outcomes and causes of death exist. We aimed to evaluate long-term outcomes and causes of death ≥5 years after surgical treatment of PFFs. This retrospective study included 123 patients (18 males, 105 females) with PFFs treated at our hospital between January 2014 and December 2016. Cases (median age: 90 [range, 65-106] years) comprised 38 femoral neck fractures (FNFs) and 85 intertrochanteric fractures (IFs). Surgical procedures included bipolar head arthroplasty (n = 35), screw fixation (n = 3), and internal fixation with nails (n = 85). The mean post-surgical follow-up time was 58.9 (range, 1-106) months. Surveyed items included survival (1 vs 5 years; sex; age, >90 vs <90 years; IF vs FNF), comorbidities, waiting time after the injury (died vs survived), operative time (proximal femoral nail antirotations [PFNA] vs FNF, died vs Survived), blood loss (PFNA vs FNF; died vs survived), and cause of death (IF vs FNF; <1 vs >1 year). Among all patients, 83.7% had comorbidities (IF, 90.5%; FNF, 81.5%). Among patients who died and survived, 89.1% and 80.5% had comorbidities, respectively. The most common comorbidities were cardiac (n = 22), renal (n = 10), brain (n = 8), and pulmonary (n = 4) diseases. Overall survival (OS) rates at 1 and 5 years were 88.9% and 66.7%, respectively. Male/female OS rates were 88.8%/88.3% and 66.6%/66.6% (P = .89) at 1 and 5 years, respectively. OS rates for the <90/≥90 age groups were 90.1%/76.7% and 75.3%/53.4 (P < .01) at 1 and 5 years, respectively. The 1- and 5-year OS (IF/FNF) rates were 85.7%/88.8% and 60%/81.5%, respectively; patients with IFs had significantly lower OS than those with FNFs at both timepoints (P = .015). There was a marked difference in the operative time between died (43.5 ± 24.0: mean ± S.D.) and survived (60 ± 24.4: mean ± S.D.) patients. The main causes of death were senility (n = 10), aspiration pneumonia (n = 9), bronchopneumonia (n = 6), worsening heart failure (n = 5), acute myocardial infarction (n = 4), and abdominal aortic aneurysm (n = 4). Overall, 30.4% of the cases were related to comorbidities and related causes (e.g., hypertension-related ruptured large abdominal aneurysm). Managing comorbidities may improve long-term postoperative outcomes of PFF treatment.

Longitudinal Association between Maternal Autonomy Support and Controlling Parenting and Adolescents' Depressive Symptoms.

Most studies on autonomy support and controlling parenting rely on children's perceptions, despite the limitations of this approach. This study investigated congruency between autonomy support and controlling parenting reported by mothers and adolescents and their association with adolescents' depressive symptoms via basic psychological needs satisfaction. Participants included 408 Japanese mother-adolescent (Mage = 13.73, SD = 0.90, 52% female) pairs who completed a questionnaire at two time points four months apart. Results demonstrated low to moderate levels of mother-adolescent agreement. Cross-lagged regression models revealed that mothers' reported autonomy support positively predicted adolescents' basic psychological needs satisfactions, which was negatively associated with depressive symptoms. The independent roles of parenting reported by mothers and adolescents for adolescents' well-being were discussed.

Parental perception matters: Reciprocal relations between adolescents' depressive symptoms and parental perceptions.

A large body of research has shown that parents play a vital role in the development of adolescents' depression. However, previous research has overlooked the effects of a potentially critical factor, namely, parental perceptions, and beliefs about adolescents' depression. The present study examined whether parental perceptions of an adolescent's depressive symptoms predict longitudinal changes in adolescents' symptoms (i.e., the parental perception effect). The longitudinal relationship between adolescents' depressive symptoms and parental perceptions of the adolescents' symptoms was analyzed in three independent groups of parent-adolescent pairs (in total N = 1,228). Parental perception and monitoring effects were found in Studies 1B and 2 only in the depressive mood subscale. While a decreased enjoyment subscale showed a perception effect in Study 1A, we obtained null results from other studies. We synthesized the results by applying meta-analytic structural equation modeling to obtain a more robust estimate. The analysis qualified both perception and monitoring effects in both subscales. Our results suggest that when parents believe that their adolescent child is depressed, adolescents are cognitively biased by their parental perceptions over time, resulting in more severe depressive symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PD-1, PD-L1, NY-ESO-1, and MAGE-A4 expression in cutaneous angiosarcoma: A case report.

RATIONALE: The genomic alteration of cutaneous angiosarcoma (cAS) is complex. Treatment efficacy of immunotherapy for cAS remains controversial and prognosis remains poor. Herein, we report a case of cAS with programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4. PATIENT CONCERNS: A 69-year-old man presented with a chief complaint of left thumb pain, with a soft tissue mass in the palmar side of the thumb. He had no past medical history. Three months prior, the man experienced the pain while scuba diving. He visited a nearby clinic, and magnetic resonance imaging revealed a soft tissue tumor on the palmar side of the thumb. He was referred to our hospital and a marginal excisional biopsy was performed. DIAGNOSIS: Pathological findings revealed an angiosarcoma with high-flow serpentine vessels. INTERVENTIONS: An excision was performed from the base of the thumb to achieve a wide margin. OUTCOMES: One year after the treatment, the patient has not experienced recurrence, metastasis, or complications. LESSONS: Histopathology of the excised specimen was positive for programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4; their expression may be a therapeutic target for cAS. Combining immunotherapy with surgical treatment may be effective for cAS.

Salmonella Osteomyelitis of the Rib Mimicking a Mammary Tumor: A Case Report.

Salmonella infection predominantly causes four clinical syndromes: enteric fever, gastroenteritis, bacteremia, and asymptomatic carrier state. Salmonella osteomyelitis is an extremely rare manifestation of salmonella infection except in children with hemoglobinopathies. Salmonella osteomyelitis has been reported to mostly affect the diaphysis of long bones and lumbar spine. Here, we describe a case of salmonella osteomyelitis of the right 6th rib in a 74-year-old woman who presented with breast pain, swelling, high fever and local heat. Her medical history showed myocardial infarction; namely, at the age of 71, the patient had undergone the drug-eluting stent placement in the left anterior descending artery. A computed tomography (CT) scan at the first visit to another hospital showed a mass in the chest that invaded the ribs. 18F-fluorodeoxyglucose-positron emission tomography-computed tomography imaging showed a lesion suspected to be a mammary malignant tumor. A needle biopsy revealed mesenchymal cells and suspected mammary sarcoma. However, the osteomyelitis of the rib was diagnosed when pyogenic tissue was observed during an open biopsy. The bacterial culture examination identified Salmonella enterica. Surgical drainage and antibiotic treatment were performed. Importantly, there was no evidence for any underlying disease that could lead to an immunocompromised status of the patient. To our knowledge, this is the first report of salmonella osteomyelitis of the rib presenting in an older female that required differentiation from a mammary tumor. Clinicians should consider rib osteomyelitis when they find swelling and local heat in the female's breast tissue and detect no cancerous tissue.

Parental Motivational Perseverance Predicts Adolescents' Depressive Symptoms: An Intergenerational Analysis with Actor-Partner Interdependence Model.

Adolescents' depressive symptoms are affected by a number of factors including life stress, gender, socio-economic status, and parental depression symptoms. However, little is known about whether adolescent depressive symptoms are also affected by parental motivational characteristics. The current study explores the relationship between parental motivational perseverance (i.e., parents' persistency in the face of setbacks and difficulties) and children's depressive symptoms during the adolescence, given the critical role of perseverance in psychological well-being. The predictive utility of two motivational characteristics relevant to perseverance: parents' growth mindset (i.e., one's belief about the malleability of human competence) and grit (i.e., perseverance for long term goals) were examined. Four hundred pairs of Japanese parents (82% mothers) and their adolescent children (50% females; average age at the time of the first assessment = 14.05 years; SD = 0.84) independently completed surveys measuring their growth mindset, grit, and depressive symptoms at two time points (approximately one year apart; attrition rate = 25%). The Actor-Partner Independence Model, a statistical model that accounts for inter-dependence between dyads (e.g., parents and children), was used to examine how parental motivational perseverance predicts the long-term change in their offspring's depressive symptoms. The results showed that parental grit led to the decrease in adolescents' depressive symptoms through the changes in adolescents' grit. On the other hand, parental growth mindset directly predicted the adolescents' depressive symptoms, and this was not mediated by the adolescents' growth mindset. These findings underscore the importance of parental motivational characteristics in regards to adolescents' depressive symptoms.

Treatment of a patient suffering from posttraumatic painful neuromas formed at the bilateral digital nerves of the left middle finger using two neurovascular island flaps.

Hand surgeons often encounter painful posttraumatic neuromas in daily practice and the treatment of these neuromas is still challenging for them, because of the tendency of recurrence.1,2 The patient injured his left middle finger and was treated by amputation in a previous hospital. After this operation, the patient started to feel pain at the fingertip and complained of severe electric radiating pain when the radial and ulnar ends of the finger were touched. We treated painful neuromas formed on both palmar digital nerve stumps using a reverse pedicle island flap containing subcutaneous nerves, which were connected to the nerve stumps after removal of the neuromas of the finger. This maneuver relieved the finger pain completely. Removal of finger digital nerve neuromas, connecting the nerve stumps to the subcutaneous nerves included in a skin island flap and, covering the neurorrhaphy sites with the flap may have reduced the chance of the recurrence of neuromas and resulted in restoration of considerable function of the hand.

Use of Dorsal Skin Islands as Firebreak Grafts to the Palm to Reduce the Recurrence Rate of Dupuytren's Contracture.

Dupuytren's pathologic tissue usually involves the palmar skin and rarely infiltrates into the dorsal skin. In this study, we hypothesized that transplantation of a vascularized cutaneous flap harvested from the dorsum of the hand to the palmar skin, under which the pathologic cord existed might be useful for blocking reformation of the pathologic cords and for decreasing the recurrence rate. After removal of the pathologic tissue under the palmar skin, we harvested 2 types of skin islands nourished by the dorsal digital arterial network including the dorsal perforating arteries arising from the palmar digital arteries. The skin islands were transplanted into skin defects in the palm of the fingers and hand that had been created after correction of flexion contracture of the fingers. We performed this surgical maneuver on 24 fingers in 24 patients who exhibited severe flexion contracture because of Dupuytren disease. During the mean 40-month follow-up, only 1 patient experienced metacarpophalangeal joint flexion contracture ≥20 degrees in the operated finger. The recurrence rate was 4.2%, which was almost similar to that for a dermofasciectomy followed by a large full-thickness skin graft.

Activation of the renin-angiotensin system in mice aggravates mechanical loading-induced knee osteoarthritis.

Epidemiological studies have shown an association between hypertension and knee osteoarthritis (OA). The purpose of this study was to investigate whether activation of the renin-angiotensin system (RAS) can aggravate mechanical loading-induced knee OA in mice. Eight-week-old male Tsukuba hypertensive mice (THM) and C57BL/6 mice were divided into running and non-running groups. Mice in the running group were forced to run (25 m/min, 30 min/day, 5 days/week) on a treadmill. All mice in the four groups (n=10 in each group) were euthanized after 0, 2, 4, 6, or 8 weeks of running or natural breeding. Cartilage degeneration in the left knees was histologically evaluated using the modified Mankin score. Expression of Col X, MMP-13, angiotensin type 1 receptor (AT1R), and AT2R was examined immunohistochemically. To study the effects of stimulation of the AT1R in chondrocytes by mechanical loading and/or Angiotensin II (AngII) on transduction of intracellular signals, phosphorylation levels of JNK and Src were measured in bovine articular chondrocytes cultured in three-dimensional agarose scaffolds. After 4 weeks, the mean Mankin score for the lateral femoral condylar cartilage was significantly higher in the THM running group than in the C57BL/6 running group and non-running groups. AT1R and AT2R expression was not detected at 0 weeks in any group but was noted after 4 weeks in the THM running group. AT1R expression was also noted at 8 weeks in the C57BL/6 running group. The expression levels of AT1R, COL X, and MMP-13 in chondrocytes were significantly higher in the THM running group than in the control groups. Positive significant correlations were noted between the Mankin score and the rate of AT1R-immunopositive cells, between the rates of AT1R- and Col X-positive cells, and between the rates of AT1R- and AT2R-positive cells. The phosphorylation level of JNK was increased by cyclic compression loading or addition of AngII to the cultured chondrocytes and was reversed by pretreatment with an AT1R blocker. A synergistic effect on JNK phosphorylation was observed between compression loading and AngII addition. Transgene activation of renin and angiotensinogen aggravated mechanical load-induced knee OA in mice. These findings suggest that AT1R expression in chondrocytes is associated with early knee OA and plays a role in the progression of cartilage degeneration. The RAS may be a common molecular mechanism involved in the pathogenesis of hypertension and knee OA.

LOX-1 deficient mice show resistance to zymosan-induced arthritis.

Recent data suggest that the lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system may be involved in the pathogenesis of arthritis. We aimed to demonstrate the roles of the LOX-1/ox-LDL system in arthritis development by using LOX-1 knockout (KO) mice. Arthritis was induced in the right knees of C57Bl/6 wild-type (WT) and LOX-1 KO mice via zymosan injection. Saline was injected in the left knees. Arthritis development was evaluated using inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration scores at 1, 3, and 7 days after administration. LOX-1, ox-LDL, and matrix metalloproteinase-3 (MMP-3) expression in the synovial cells and chondrocytes was evaluated by immunohistochemistry. The LOX-1, ox-LDL, and MMP-3 expression levels in synovial cells were scored on a grading scale. The positive cell rate of LOX-1, ox-LDL, and MMP-3 in chondrocytes was measured. The correlation between the positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score was also examined. Inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration were significantly reduced in the LOX-1 KOmice with zymosan-induced arthritis (ZIA) compared to WT mice with ZIA. In the saline-injected knees, no apparent arthritic changes were observed. LOX-1 and ox-LDL expression in synovial cells and chondrocytes were detected in the knees of WT mice with ZIA. No LOX-1 and ox-LDL expression was detected in the knees of LOX-1 KOmice with ZIA or the saline-injected knees of both mice. MMP-3 expression in the synovial cells and chondrocytes was also detected in knees of both mice with ZIA, and was significantly less in the LOX-1 KO mice than in WT mice. The positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score showed a positive correlation. Our data show the involvement of the LOX-1/ox-LDL system in murine ZIA development. LOX-1-positive synovial cells and chondrocytes are potential therapeutic targets for arthritis prevention.

Activating types 1 and 2 angiotensin II receptors modulate the hypertrophic differentiation of chondrocytes.

A local tissue-specific renin-angiotensin system (local RAS) has been identified in many organs. However, no report has described the role of a local RAS in the hypertrophic differentiation of chondrocytes. To examine the role of a local RAS in the hypertrophic differentiation, we activated angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) separately in the cell line ATDC5, which involves differentiation from mesenchymal stem cells to hypertrophic chondrocytes. Activation of AT1R suppressed and activation of AT2R enhanced the expression of markers of hypertrophic differentiation, including type X collagen, matrix metalloproteinase 13 and runt-related transcription factor 2.

An ethnobotanical study of medicinal plants and traditional therapies on Batan Island, the Philippines.

ETHNOPHARMACOLOGICAL RELEVANCE: We studied the local knowledge and uses of medicinal plants among the Ivatan people of Batan Island by documenting their traditional practices. AIM OF THE STUDY: To identify the types of medicinal plants used in self-care by the indigenous people of Batan Island, the Philippines and to investigate the extent to which the plants are used. Conservation of medicinal plants and natural resources is becoming increasingly important; thus, this research aims to collect information from local people concerning the use of medicinal plants on Batan Island. MATERIALS AND METHODS: A total of 116 informants were interviewed, allowing for calculated informant consensus factors (ICF), use value (UV), and fidelity levels (FL) for each medicinal plant species used to cure various ailments. This helped to establish a consensus on which species are effective for particular ailments, as well as the species' relative importance, and enabled us to understand the extent of the potential utilization of each species. RESULTS: We describe the therapeutic effects of 112 plant species used medicinally against 13 categories of ailments. The highest ICF value (1.00) was cited for diseases of the ear and respiratory system and for use during pregnancy, childbirth and the postnatal period. The maximum FL of 100% was found for Carica papaya, Stachytarpheta jamaicensis, Musa sapientum, and Pedilanthus tithymaloides, used for the treatment of constipation, cuts and wounds, diarrhea, and dislocations and fractures, respectively. The highest UV was for Hibiscus rosa-sinensis (0.67). All plants with high UV were used for exogenous diseases, certain infectious and parasitic diseases, injuries, poisonings and other consequences of external factors, and diseases of the skin and subcutaneous tissues. In addition to its use for endogenous disease and lifestyle-related diseases and illnesses, Moringa oleifera is also used for diseases of the circulatory system, with a UV of 0.57 and Cocos nucifera is used for diseases of the genitourinary system, with a UV of 0.56. CONCLUSIONS: This study demonstrates that many plant species play an important role in local healing practices and that knowledge of traditional medicine is still utilized and plays a significant role on Batan Island. The documentation of this rich traditional ethno-medicinal knowledge has furnished us with novel information that not only will provide recognition of this undocumented knowledge but also could provide new avenues for pharmacological investigations to improve healthcare for a range of ailments.

Cytotoxic 16-beta-[(D-xylopyranosyl)oxy]oxohexadecanyl triterpene glycosides from a Malagasy plant, Physena sessiliflora.

Brine shrimp lethality assay-guided separation of the MeOH extract of leaves of Physena sessiliflora, which is endemic to Madagascar, afforded eight triterpene glycosides, Physenoside S1-4 and 16-beta-[(d-xylopyranosyl)oxy]oxohexadecanyl homologues, Physenoside S5-8. Structural elucidation of these compounds was based on both spectroscopic analyses and chemical properties. Physenoside S7 and S8 have significant cytotoxic activities in the brine shrimp lethality assay.

Pregnane and pregnane glycosides from the Malagasy plant, Cynanchum aphyllum.

A new 8,14-seco-pregnane type of steroid called cynaphyllogenin and its eight glycosides, cynaphyllosides A-H, were isolated from the aerial parts of Cynanchum aphyllum. The structures of these compounds were elucidated based on chemical and spectroscopic evidence.

Cholangiocellular carcinoma depending on the kind of intrahepatic calculi in patients with hepatolithiasis.

BACKGROUND/AIMS: Association of cholangiocellular carcinoma in patients with hepatolithiasis has been reported. However, its incidence depending on the kind of stones is obscure. The aim was to examine the association rate of cholangiocellular carcinoma in patients with hepatolithiasis with a special reference to the kind of intrahepatic stones. METHODOLOGY: One hundred and thirty-nine patients with hepatolithiasis who have been treated from 1973 to 1997 were retrospectively reviewed to examine the characteristics of cholangiocellular carcinoma. The type and location of intrahepatic calculi were analyzed. RESULTS: Cholangiocellular carcinoma was found in 8 of 139 patients, the incidence being 5.8%. The incidence of carcinoma was more than twice in patients whose stones were located in intrahepatic bile duct only (9.3%; 5/54) than in those located in both intrahepatic and extrahepatic bile duct (3.5%; 3/85). Of 121 patients excluding 18 whose calculi were not available for classification, the kind of intrahepatic calculi was brown pigment in 106 patients (87.6%), cholesterol in 10 (8.3%), black pigment in 4, and fatty acid calcium in one. Cholangiocellular carcinoma was associated in 3 (2.8%) of 106 patients with brown pigment stones, 3 (30%) of 10 with cholesterol stones, in one with fatty acid calcium stones, and one patient whose stone was not available for analysis. The association rate of cancer was significantly (P < 0.01) higher in patients with cholesterol stones than those with brown pigment stones. One patient survived for 24 months after left lobectomy but the others died within six months. CONCLUSIONS: An early and attentive evaluation for the possible presence of cholangiocellular carcinoma is mandatory not only in patients with brown pigment stones but also in those with intrahepatic cholesterol stones.

A novel prokaryotic phospholipase A2. Characterization, gene cloning, and solution structure.

Until now, phospholipase A(2) (PLA(2); EC 3.1.14) has been found only from eukaryotic sources. In the present study, we found a secreted PLA(2), which is produced by a soil bacterium, Streptomyces violaceoruber A-2688, demonstrating that the enzyme is the first phospholipase A(2) identified in prokaryote. After characterization of the novel PLA(2), a gene encoding the enzyme was cloned, sequenced, and overexpressed using a Streptomyces host-vector system. The amino acid sequence showed that the prokaryotic PLA(2) has only four cysteines and less homology to the eukaryotic ones, which have 12-16 cysteines. The solution structures of the prokaryotic PLA(2), bound and unbound with calcium(II) ion, were determined by using the NMR technique and structure calculation. The overall structure of the S. violaceoruber PLA(2), which is composed of only five alpha-helices, is completely different from those of eukaryotic PLA(2)s, which consist of beta-sheets and alpha-helices. The structure of the calcium-binding domain is obviously distinct from that without the ion; the ligands for the calcium(II) ion are the two carboxylates of Asp(43) (monodentate) and Asp(65) (bidentate), the carbonyl oxygen of Leu(44), and three water molecules. A calcium-binding experiment showed that the calcium dissociation constant ( approximately 5 mm) for the prokaryotic PLA(2) is much larger than those of eukaryotic ones.