Regulated CPEB phosphorylation during meiotic progression suggests a mechanism for temporal control of maternal mRNA translation

CPEB is an mRNA-binding protein that stimulates polyadenylation-induced translation of maternal mRNA once it is phosphorylated on Ser 174 or Thr 171 (species-dependent). Disruption of the CPEB gene in mice causes an arrest of oogenesis at embryonic day 16.5 (E16.5), when most oocytes are in pachytene of prophase I. Here, we show that CPEB undergoes Thr 171 phosphorylation at E16.5, but dephosphorylation at the E18.5, when most oocytes are entering diplotene. Although phosphorylation is mediated by the kinase aurora, the dephosphorylation is due to the phosphatase PP1. The temporal control of CPEB phosphorylation suggests a mechanism in which CPE-containing mRNA translation is stimulated at pachytene and metaphase I.     

The epidemiology of atopic dermatitis at a tertiary referral skin center in Singapore

Atopic dermatitis is a common chronic, relapsing, pruritic ecematous skin condition with a predilection for the flexural areas and occurs in patients with a personal or family history of atopy. The aim of this study is to describe the profile of atopic dermatitis seen at the National Skin Centre in Singapore. A retrospective chart review was conducted of all the patients with atopic dermatitis seen during the first six months of 1994. There were 492 patients whose ages ranged from one month to 74 years with an equal sex ratio. The prevalence was 2%. The onset of the disease occurred before the age of 10 years in 61.2% of patients. In 13.6% of the patients, the onset was after the age of 21 years. Two hundred and fifty-four patients (52%) had "pure" atopic dermatitis without concomitant respiratory allergies. Two hundred and thirty-eight patients (48%) suffered from a "mixed" type, with 23% having allergic rhinitis, 12% having asthma and 13% having both asthma and allergic rhinitis. Two hundred and thirty-one patients (47%) had at least one first-degree family member with atropy: atopic dermatitis (17%), asthma (15%) and allergic rhinitis (15%). Most of the patients, 416 (84.5%), had subacute eczema at presentation. Ichthyosis vulgaris was present in 38 patients (8%) and pityriasis alba in 13 patients (3%). The most common infective complication was bacterial infection (impetiginized eczema, folliculitis, cellullitis) present in 95 patients (19%) followed by viral infections (eczema herpeticum, viral warts and molluscum contagiosum) in 17 patients (3%). Allergies were noted in 43 patients (9%) based on the history given. The most common was drug allergies (penicillin and co-trimoxazole) in 28 patients followed by food allergies in 11 patients. Common aggravating factors reported include heat, sweating, stress, thick clothing and grass intolerance. Most patients could be controlled with a fairly simple regimen of moisturizers, topical steroids and antibiotics for acute flares. Short courses of systemic steroids were used in 78 patients (16%). Three patients were treated with phototherapy, Two on UVAB and one on PUVA. The pattern of atopic dermatitis in Singapore is similar to that reported in the Western literature except for a lower prevalence and a significant proportion of adult onset atopic dermatitis.     

Ultrastructural study of the effects of 6-hydroxydopamine on the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis)

The present study examined the ultrastructural changes in the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis) after 6-hydroxydopamine (6-OHDA) at survival times of 1, 3, 5, 7 and 14 days. Changes ranged from dissolution of the cytoplasm to amorphous appearance and darkening of the nodal cells. Initially, the ultrastructural changes were quite similar in both sinuatrial (SA) and atrioventricular (AV) nodal cells but in the later stage, especially at fourteen days, affected SA nodal cells showed empty-looking appearance while affected AV nodal cells displayed a darkened appearance. The cardiac neurons also showed ultrastructural changes such as diffuse accumulation of glycogen particles, distended cisternae of the rough endoplasmic reticulum and increased lipofuscin granules. Some of the vacuolated axonal profiles containing large dense-cored vesicles were in close association with the somata of the cardiac neurons. There were also changes in the non-neuronal cells such as darkening and vacuolation of the cells capping the neurons. Macrophages and Schwann cells were activated to engulf the degenerating nodal cells and axonal profiles. The ultrastructural changes in the nodal cells and the cardiac neurons reflect a disturbance in the cell metabolism presumably brought about by the impairment of the sympathetic nervous system.     

Ultrastructural changes in the atrioventricular valves of streptozotocin-induced diabetic rats

The present study describes ultrastructural changes in the atrioventricular (AV) valves of diabetic rats at 3, 6, 9 and 12 months. At 3 and 6 months of diabetes, the interstitial cells were characterized by an accumulation of vacuoles, lysosomes, electron-dense vesicles, mitochondria and cisternae of rough endoplasmic reticulum in the cytoplasm. There were numerous collagen fibres in the interstitial space. Unmyelinated axons were ensheathed by Schwann cells. Infiltration of macrophages was observed near the interstitial cells. Each macrophage showed a large round or oval nucleus containing heterochromatin masses at the periphery of the cell nucleus. At 9 and 12 months of diabetes, the interstitial cells contained numerous vacuoles, dilated mitochondria, agranular vesicles and a prominent multivesicular body in the cytoplasm. Degenerating unmyelinated nerve fibres were encountered near the interstitial cells. Phagocytic macrophages contained numerous vacuoles of various sizes, which occupied most of the cytoplasmic area. Several vacuoles and degenerated electron-dense granules (some of them appeared to be fragmented) were present in the cytoplasm of interstitial cells and macrophages. It is concluded that interstitial cells in the AV valves contribute to valvular dysfunction in the streptozotocin-induced diabetic rats.     

Nitric oxide, microglial activities and neuronal cell death in the lateral geniculate nucleus of glaucomatous rats

The present study was initiated to investigate neuronal degeneration, microglial reactivity and possible roles of NO in the lateral geniculate nucleus (LGN) of glaucomatous rats. An experimental one-eye glaucoma model was created by cauterization of the limbal-derived veins. Neuronal cell viability was studied by immunostaining with antibody against neuronal nuclei. Changes of expressions of nitric oxide synthase I (NOS I), NOS II, ED 1, OX6 and OX42 in the LGN were studied by immunohistochemistry. NADPH-d histochemistry was also employed. In the experimental glaucomatous rats, the number of NeuN labelled neurons was significantly decreased in both the ipsi- and contra-lateral sides of the ventral LGN (vLGN) but not the dorsal LGN (dLGN) at 1 month post-operation and beyond. Expressions of NOS I and NADPH-d were notably increased from 1 week post-operation in the ipsilateral vLGN. In the contralateral side of the vLGN, however, this change was only observed from 1 month post-operation. No NOS II immunoreaction was observed in LGN of both the normal control and glaucomatous rats. Increased microglial reactivity as indicated by OX-42 immunoreactivity was first observed in both sides of the LGN at 1 week post-operation, and this was most significant especially at 1 and 2 months post-operation. The present results suggest that NO and microglial cells may play some important roles in the pathologic processes of neuronal degeneration in the LGN of glaucomatous rats.     

Quantitative computer‐assisted digital‐imaging upper airway analysis for obstructive sleep apnoea*

This was a prospective study of a new objective method which quantitatively analyses the upper airways in patients with obstructive sleep apnoea (OSA). Video‐nasopharyngoscopic examinations of the upper airways of 45 patients were carried out with an endoscopic calibrator. Images of the upper airway during quiet respiration and Mueller's manoeuvre in erect and supine positions were digitized by computer to generate the actual dimensions of obstructive sites. Measurements by the new method were validated by comparing 90 pairs of videoendoscopic images with upper airway magnetic resonance imaging (MRI) measurements at two identical levels. Quantitative precision is 100% for the retropalatal level and 95.6% for the retrolingual level with a tolerance of 0.5 cm² between the two methods. The absolute mean of the difference between the two methods of measurement is 0.08 cm² at the retropalatal level and 0.18 cm² at the retrolingual level. The agreement between the digital‐imaging videoendoscopic and MRI measurements was 93.3% for the retropalatal level and 95.6% for the retrolingual level. Quantitative computer‐assisted digital imaging is a reliable, cost‐effective clinical method of upper airway evaluation in OSA patients. This method allows us to examine the dynamic and static morphology objectively, measure surgical outcomes of upper airway, opening up new avenues for OSA management.     

Attempted suicide and polymorphism of the serotonin transporter gene in Chinese patients with schizophrenia

Abnormalities of serotonin synthesis and metabolism may be associated with suicidality. The serotonin transporter gene (5-HTT) is one of the important genes involved in the regulation of serotonin neurotransmission. We examined the association of suicidal behavior in Chinese schizophrenic patients with a functional polymorphism of the promoter region of the 5-HTT gene (5-HTTLPR). The 5-HTTLPR genotype was determined by polymerase chain reaction for 76 suicidal and 262 non-suicidal patients with a diagnosis of schizophrenia (DSM-IV criteria). All subjects were unrelated to each other, and all were Chinese. There was no significant genotypic or allelic association of the 5-HTTLPR polymorphism with history of attempted suicide. From our results, this 5-HTTLPR polymorphism is unlikely to have a major effect on suicidal behavior in Chinese patients with schizophrenia.     

Sexual dysfunction damages: A legal database review

IntroductionProcedural specialties are at higher risk for malpractice claims than non-procedural specialties. Previous studies have examined common damages and malpractice lawsuits resulting from specific procedures. Our goal was to analyze urological interventions that led to sexual dysfunction (SD) claims.MethodsThe Casetext legal research platform was queried using search terms for medical malpractice and common men’s health procedures between 1993 and 2020. In total, 236 cases were found, and 21 cases met the inclusion criteria: malpractice cases against a urologist or urology group, clearly stated legal outcome, and allegation of sexual dysfunction from an intervention that directly caused damages.ResultsA total of 42 damages were cited in 21 lawsuits. The top three damages claimed were erectile dysfunction (ED) (14/42, 33.3%), genital pain syndrome (7/42, 16.7%), and urinary incontinence (5/42, 11.9%). The most commonly cited treatments were urinary catheter placement or removal (3/21, 14.3%), robotic-assisted laparoscopic radical prostatectomy (RALP) (3/21, 14.3%), circumcision (3/21, 14.3%), and penile implant (3/21, 14.3%). In 19 of 21 suits (90.4%), the outcome favored the defendant. Two cases favored the plaintiff: penile implant (failure to prove the patient was permanently, organically impotent prior to the procedure; missed urethral injury at time of surgery, $300 000) and vasectomy (damage to vasculature resulting in loss of testicle, $300 000).ConclusionsMost suspected malpractice cases resulting in SD favored the defendant urologist. Interestingly, urinary catheter placement is as likely to result in litigation as other operative interventions, such as RALP, inflatable penile prosthesis, and circumcision. It is possible that thorough preoperative counselling and increased responsiveness to patients’ postoperative concerns may have avoided litigation in several cases.