Nuclear texture features for classifying benign vs. dysplastic or malignant squamous epithelium of the larynx.

OBJECTIVE: To search for nuclear features and feature combinations able to assess malignancy and premalignant changes on tissue sections of laryngeal squamous epithelium. STUDY DESIGN: A total of 139 lesions of benign changes (BC) (n = 44), epithelial dysplasias (ED) (n = 50) and invasive laryngeal cancer (LC) (n = 45) were retrieved from archival pathology specimens. The goal of this study was to identify the best features or feature combinations that discriminate BC from LC and also reflect the degree of ED. In order to verify the results on independent data, the groups were split into two separate subgroups, one for training and one for testing. RESULTS: On the test set of slides, the overall correct classification of BC vs. LC cases was 82% using only one feature, fractal2_area. This classification rate could be increased to 91% when a discriminant function based on 10 features was used. However, this gain was not significant. CONCLUSION: Fractal texture features can be used to assess malignancy on tissue sections as an alternative to DNA measurement. In this study feature combinations did not significantly improve classification rates.     

喉癌的流行病学病因学动态分析

目的:调查我省喉癌流行病学特征及影响喉癌预后的相关因素。为我省喉癌防治工作提供理论依据。方法:对1995年-2005年哈尔滨医科大学附属第二医院耳鼻咽喉-头颈外科收治的1172例喉癌患者进行回顾性调查研究。结果:喉癌发病男女比例为2．48:1,女性喉癌发病率较其他地区高。在年龄分布中,50-69岁患者占68．9％。城市居民比农村居民发明率偏高,是农民的1.35倍,在职业方面以工人最多。吸烟量越大、吸烟时间越长,患喉癌的例数越多。正常人与喉癌患者ABO血型构成比之间无显著差异。声门上型喉癌占喉癌总数的54．43%,声门型喉癌占喉癌总数的36．60％,声门下型喉癌占喉癌总数的1．96％。病理分型中鳞状细胞癌占95．6％。声门上型及喉咽癌颈淋巴结转移明显偏高。结论:我省喉癌发病女性患者较其他地区多,且以声门上型最显著、50-69岁年龄段发病最高。吸烟与喉癌的发生有一定关系。城市居民比农村居民发病率高。喉癌发病与ABO血型无明显关系。     

Sexual Dimorphism of the Larynx of the Mongolian Gazelle (Procapra gutturosa Pallas, 1777) (Mammalia, Artiodactyla, Bovidae)

The larynges (except for the epiglottis) of two adult Mongolian gazelles, one male and one female, were dissected. This species is characterized by a pronounced sexual dimorphism of the larynx. Dimorphism with regard to the size of the entire larynx and of the thyroid cartilage is about 2:1 whereas the difference of mean body mass is about 1.3:1 between males and females. Unexpectedly, and in contrast to other bovids, the larynx of the male Mongolian gazelle has a paired lateral laryngeal ventricle. However, in contrast to horse, dog, pig and many primate species also possessing such a paired ventricle, its rostral opening in the Mongolian gazelle is situated lateral to the corniculate process of the arytenoid cartilage. The neck of the laryngeal ventricle is embraced by the bifurcated cuneiform process of the epiglottis. Despite the enlarged laryngeal cartilages, the vocal process of the male arytenoid cartilage is relatively shorter than that of the female. The male thyroarytenoid muscle is clearly separated into a rostral ventricular muscle and a caudal vocal muscle whereas the female's, as in other bovids, is almost uniform. The lateral sac of the two-chambered laryngeal ventricle in the male projects laterally between the ventricular and the vocal muscle. As in the domestic bovids and in many other artiodactyls the larynx of the male Mongolian gazelle is lacking any rostrally directed membraneous portion of the vocal fold. Instead, the thick and tough bow-like vocal fold projects caudally into the infraglottic cavity and is supported by a peculiar pan-like fibroelastic pad. This resilient element, situated medial to the bipartite thyroarytenoid muscle, might be a homologue of the vocal ligament, eventually including lateral portions of the elastic cone. A fibroelastic pad is absent in the female. The resilient floor of the laryngeal vestibulum, ventral to the fibroelastic pad, is rostrally and caudally subducted by tube-like spaces. Evolutionary enlargement of the male larynx, including the vocal folds, and of the caudal portions of the vocal tract may have shifted the fundamental and formant frequencies to a lower register. The paired lateral laryngeal ventricle might produce an amplitude increase of the vocalizations assisted by differential action of the bipartite thyroarytenoid muscle. In addition, the peculiar shape, size and tough consistency of the male vocal folds may, as in roaring felids, assist in producing high amplitude and low frequency vocalizations. Perhaps the biological role of the enlarged male larynx of Procapra gutturosa has evolved in relation to its mating system. In the rutting season, dominant males establish individual territories and maintain harems. During prolonged courtship prior to mating, these males perform an acoustic display uttering loud and guttural bellows. In addition, the bulging ventral neck region of males may serve as an optical attractant for the females. Thus, the evolution of the enlarged larynx of the male Mongolian gazelle may have been favoured by sexual selection.     

125I-[Tyr0,D-Trp8]somatostatin-14 binding sites in the locus coeruleus of the rat are located on both ascending and descending projecting noradrenergic cells

Radioautographic determinations of 125I-[Tyr0,D-Trp8]somatostatin-14 (125I-SRIF) binding sites were performed on frozen serial sections of the locus coeruleus (LC) of control rats and of rats subjected to either bilateral microinjections of 6 hydroxydopamine (6-OHDA) into the LC or unilateral microinjection into the ascending noradrenergic bundles. These experiments were performed in order to determine whether 125I-SRIF binding was localized to noradrenergic-containing cells and in which regions the cells which contain the binding sites are projecting. The extent of the lesions was assessed by measuring norepinephrine (NE) levels in the hippocampus (88% decrease as compared to sham-operated animals) for bilateral LC lesions and in the frontal cortex (87% reduction vs. contralateral side) for unilateral bundle lesions. In control rats, 125I-SRIF binding sites were restricted to the boundaries of the LC and followed closely the distribution of tyrosine hydroxylase-labeled cells. Three weeks after bilateral injections of 6-OHDA, 125I-SRIF binding decreased by 79% in all regions of the LC. In contrast, unilateral destruction of the ascending noradrenergic bundles resulted in a moderate decrease only in the middle part of the LC with a more important effect in the dorsal (55%) than in the ventral (24%) portion of the nucleus. These data demonstrate that: 1) most SRIF receptors in the LC are located in the vicinity of NE-containing cell bodies and 2) NE-containing cells bearing SRIF receptors project to the forebrain as well as to other terminal areas located more caudally in the brain. These data suggest a general role for SRIF in the control of the multiple functions of the LC.     

Capsaicin administration inhibits the abducent branch but excites the thyroarytenoid branch of the recurrent laryngeal nerves in the rat.

Our recent study showed that both inspiratory and expiratory activities of the recurrent laryngeal nerve (RLN) were enhanced by capsaicin administration in the rat (Lu IJ, Ku LC, Lin JT, Lee KZ, and Hwang JC. Chin J Physiol 45: 143-154, 2002). There are two intralaryngeal branches of the RLN: one innervates the thyroarytenoid (TA) muscle and the other innervates the abductor (Abd) muscles. To examine whether these two intralaryngeal branches respond similarly to capsaicin administration, their discharges as well as activities of the phrenic nerve (PNA) and the superior laryngeal nerve (SLNA) were monitored in anesthetized and ventilated rats at normocapnia in hyperoxia. The low dose of capsaicin (0.625 microg/kg) produced a cardiopulmonary chemoreflex, showing apnea, a decrease in PNA, hypotension, and bradycardia, and significant decreases in SLNA and the activity of the Abd branch. Concurrently, there was an increase in the intralaryngeal TA activity during both apnea and the recovery from apnea. The high dose of capsaicin (1.25 microg/kg) evoked larger chemoreflexive responses and laryngeal nerve activities. In addition, both doses of capsaicin initiated a similar delay in the onset of Abd activity and SLNA but an earlier onset for the TA branch to commence during inspiration. A bilateral vagotomy abolished the laryngeal responses to capsaicin administration. However, PNA and blood pressure were enhanced with capsaicin administration after the vagotomy. These results suggest that laryngeal adduction in response to capsaicin administration is vagal afferent dependent and that it may also represent reflexive protection for the airway and lungs.     

The distribution of luteinizing hormone-releasing hormone (LHRH) neurons and fibers in the Formosan rock-monkey

The anatomical distribution of neurons and fibers containing Luteinizing Hormone Releasing Hormone-Immunoreactivity (LHRH-IR) in the brain of the Formosan Rock-Monkey was investigated employing immunohistochemical techniques. LHRH-IR neurons were observed in an area demarcated rostrally by the diagonal band of Broca and caudally by the mammillary area. The majority of these neurons were principally localized in the preoptic area, periventricular zone, and the arcuate nucleus. The supraoptic nucleus, septal area, triangular septal nucleus, nucleus of the diagonal band of Broca, suprachiasmatic nucleus, retrochiasmatic area, mammillary area, and the amygdala also exhibited neuronal LHRH immunoreactivity. LHRH-IR fibers appeared to originate in all of the above areas of the hypothalamus, project caudally, and subsequently terminate in the median eminence (ME). In addition to the above, LHRH-IR fibers were also detected in the organum vasculosum of the lamina terminalis (OVLT). A scattering of LHRH-IR fibers were also observed in several extrahypothalamic regions, notably the subfornical organ, indusium griseum, habenular complex, septohypothalamic nucleus, and amygdala.     

Laryngeal papillomas: local cellular immune response, keratinization and viral antigen

Various parameters of the local cellular response have been studied in 16 laryngeal papillomas from ten patients with recurrent papillomas as well as normal control laryngeal and tracheal tissue by indirect immunofluorescence on frozen sections using monoclonal antibodies specific for T-cell subsets, Langerhans cells (LC) and HLA-DR antigens. Keratinization was investigated with a monoclonal antibody KL1 recognizing an acidic 56.5 Kd keratin, which is a marker of suprabasal cells in stratified squamous epithelium and is absent from the basal layer. The presence of viral antigen was detected with a rabbit antiserum raised against SDS-dissociated purified virus. A mild inflammatory response was observed in most biopsies. Cytotoxic/suppressor T-cells were the predominant cells found in the lesions. Compared with normal epithelium, the number of LC was dramatically reduced in the papillomatous epithelium. High densities of HLA-DR-positive cells were found mainly in the corium. The keratinization process was disturbed in most specimens in that both basal and suprabasal compartments reacted positively with the KL1 monoclonal antibody. Viral antigen was present in the nucleus of very occasional epithelial cells in some samples.     

喉癌术后复发的分析

目的:探讨喉癌手术后复发的相关因素。方法:回顾性分析1996年1月至2005年12月哈尔滨医科大学附属第二医院耳鼻喉科住院手术治疗病历1139例,患者随访3年以上,确诊复发128例。128例中男102人,女26人。按肿瘤TNM分型:声门上型72例,声门型37例,声门下型4例,喉咽癌15例;T分期:T1期14例,T2期57例,T3期57例。术前有颈淋巴结转移62例,无淋巴结转移66例。术后局部复发20例,颈淋巴结转移95例,局部复发合并颈淋巴结转移11例,远处转移2例。对复发128例的相关性因素包括肿瘤分期,肿瘤原发部位,淋巴结转移,术式,病理分级,年龄,性别,病史,吸烟,职业等进行分析。结果:经统计学分析显示肿瘤分期T(p<0．01),手术方式(p<0．01),淋巴结转移(p<0．01),病理类型(p<0．01),肿瘤类型(p<0．01),吸烟(p<0．05),职业(p<0．05)与喉癌术后复发有显著意义。结论:肿瘤分期,肿瘤原发部位,术式,淋巴结转移,病理类型,吸烟,职业是引起喉癌术后复发的重要因素。     

Human drowning: Phylogenetic origin

Because most animals are able to survive much longer when in water than most humans and apes, it is likely that at some time during human phylogeny the-innate-ability to swim like animals has been lost. Paleontology and comparative zoology provide indications for selective pressures and adaptations explaining this phenomenon. Among these are (a) buoyancy having become reduced slightly due to a smaller lung air/body weight ratio, less air trapped in the body covering hairs and reduction in gastrointestinal gas, (b) the caudally directed nasal entrance cranially to which there is the heavy neurocranium, (c) the low position of the laryngeal entrance, (d) the ineffective propulsion by the human innate crawling and walking movements, and (e) the well developed cerebrum being present cranially to the airway entrance, being sensitive for anoxia and hypothermia, and causing behaviour adding to drowning risks.     

Radiosensitizing effects of curcumin alone or combined with GLUT1 siRNA on laryngeal carcinoma cells through AMPK pathway-induced autophagy

In this study, we investigated the ability of curcumin alone or in combination with GLUT1 siRNA to radiosensitize laryngeal carcinoma (LC) through the induction of autophagy. Protein levels in tumour tissues and LC cells were measured by immunohistochemistry and Western blotting. In vitro, cell proliferation, colony formation assays, cell death and autophagy were detected. A nude mouse xenograft model was established through the injection of Tu212 cells. We found that GLUT1 was highly expressed and negatively associated with autophagy-related proteins in LC and that curcumin suppressed radiation-mediated GLUT1 overexpression in Tu212 cells. Treatment with curcumin, GLUT1 siRNA, or the combination of the two promoted autophagy. Inhibition of autophagy using 6-amino-3-methypourine (3-MA) promoted apoptosis after irradiation or treatment of cells with curcumin and GLUT1 siRNA. 3-MA inhibited curcumin and GLUT1 siRNA-mediated non-apoptotic programmed cell death. The combination of curcumin, GLUT1 siRNA and 3-MA provided the strongest sensitization in vivo. We also found that autophagy induction after curcumin or GLUT1 siRNA treatment implicated in the AMP-activated protein kinase-mTOR-serine/threonine-protein kinase-Beclin1 signalling pathway. Irradiation primarily caused apoptosis, and when combined with curcumin and GLUT1 siRNA treatment, the increased radiosensitivity of LC occurred through the concurrent induction of apoptosis and autophagy.     

白花蛇舌草多糖提取物对喉癌Hep-2细胞内质网自噬的影响*

目的:探讨白花蛇舌草多糖提取物(HDPE)对喉癌Hep-2细胞内质网自噬的影响。方法:实验分为对照组、HDPE 100、200、400 mg/L组和3-MA(自噬抑制剂)组,噻唑盐比色法(MTT)检测各组细胞培养24 h、48 h、72 h后增殖抑制率;原位末端转移酶标记法(TUNEL)法检测各组培养48 h细胞凋亡情况;单丹黄酰尸胺(MDC)染色观察各组培养48 h细胞自噬体及自噬溶酶体的变化;透射电镜观察培养48 h细胞内质网周围自噬囊泡的产生情况;蛋白印迹法(Western blot)检测各组培养48 h细胞Beclin-1蛋白(Beclin-1)、微管相关轻链蛋白3Ⅰ(LC3Ⅰ)、微管相关轻链蛋白3Ⅱ(LC3Ⅱ)、葡萄糖调节蛋白 78(GRP78)、活化转录因子6(ATF6)及CCAAT 增强子结合蛋白同源蛋白(CHOP)表达。结果:与对照组比较,HDPE 100、200、400 mg/L组和3-MA组细胞增殖抑制率、凋亡指数AI升高,MDC阳性细胞率量降低,内质网周围自噬囊泡减少,GRP78、ATF6及CHOP表达及LC3Ⅰ/LC3Ⅱ比值升高,Beclin-1表达降低(P＜0.05);与3-MA组比较,HDPE 400 mg/L组细胞增殖抑制率、凋亡指数AI升高,MDC阳性细胞率、GRP78、ATF6及CHOP表达及LC3Ⅰ/LC3Ⅱ比值升高,Beclin-1表达降低(P＜0.05)。结论:HDPE可能通过抑制喉癌Hep-2细胞内质网自噬,促进细胞内质网应激凋亡,进而抑制Hep-2细胞增殖能力。     

Afferent projections of the trigeminal nerve in the goldfish,Carassius auratus

The horseradish peroxidase (HRP) histochemical technique was used to examine the peripheral distribution and afferent projections of the trigeminal nerve in the goldfish, Carassius auratus. Sensory fibers of the trigeminal nerve distribute over the head via four branches. The ophthalmic branch distributes fibers to the region above the eye and naris. The maxillary and mandibular branches innervate the regions of the upper and lower lip, respectively. A fourth branch of the trigeminal nerve was demonstrated to be present in the hyomandibular trunk. Upon entering the medulla the trigeminal afferent fibers divide into a rostromedially directed bundle and a caudally directed bundle. The rostromedially directed bundle terminates in the sensory trigeminal nucleus (STN) located within the rostral medulla. The majority of fibers turn caudally, forming the descending trigeminal tract. Fibers of the descending trigeminal tract terminate within three medullary nuclei: the nucleus of the descending trigeminal tract (NDTV), the spinal trigeminal nucleus (Spv), and the medial funicular nucleus (MFn). All projections, except for those to the MFn, are ipsilateral. Contralateral projections were observed at the level of the MFn following the labeling of the ophthalmic and maxillomandibular branches. All branches of the trigeminal nerve project to all four of the trigeminal medullary nuclei. Projections to the STN and MFn were found to be topographically organized such that the afferents of the ophthalmic branch project onto the ventral portion of these nuclei, while the afferents of the maxillo- and hyomandibular branches project to the dorsal portion of these nuclei. Cells of the mesencephalic trigeminal nucleus were retrogradely labeled following HRP application to the ophthalmic, maxillary, and mandibular branches of the trigeminal nerve. In addition to demonstrating the ascending mesencephalic trigeminal root fibers, HRP application to the above-mentioned branches also revealed descending mesencephalic trigeminal fibers. The descending mesencephalic trigeminal fibers course caudally medial to the branchiomeric motor column and terminate in the ventromedial portion of the MFn.     

Effects of microinjection of a cholinergic agonist into the locus coeruleus on the gain of vestibulospinal reflexes in decerebrate cats

1. Experiments were performed in precollicular decerebrate cats to determine whether activation of locus coeruleus (LC) neurons elicited by local injection of the cholinergic agonist carbachol modifies the dynamic characteristics of responses of forelimb extensors to selective stimulation of labyrinth receptors resulting from roll tilt of the animal. 2. Injection of 0.1-0.4 microliter (usually 0.25 microliter) of carbachol at a concentration of 0.02-0.1 micrograms/microliter of sterile saline into the LC of one side, which slightly increased the tonic contraction of limb extensors ipsilateral to the side of the injection, greatly decreased the amplitude of the multiunit EMG response of the ipsilateral triceps brachii to animal tilt at 0.15 Hz, +/- 10 degrees. Correspondingly, the response gain of this forelimb extensor decreased. Moreover, a significant increase in phase lag of the responses was observed. These findings did not result from the increased postural activity, since they were still observed when the limb position was adjusted so that the spontaneous EMG activity remained constant throughout the experiments. 3. The changes in posture as well as in response characteristics of the forelimb extensor to labyrinth stimulation produced by carbachol injection appeared a few min after the injection and soon reached a plateau level which persisted for several hours before returning to the control levels. 4. The effects described above involved mainly, if not exclusively, the limbs ipsilateral to the side of the injection. However, the effects of local injection into the LC of one side could be reproduced on the contralateral side following injection into the LC of that side. 5. The increase in phase lag of the multiunit EMG responses of the triceps brachii to labyrinth stimulation appeared at a threshold lower than that required to decrease the response gain of this extensor muscle. These findings suggest that different neuronal populations within the LC complex, one projecting directly to the spinal cord, the other projecting indirectly through the pontine reticular formation, are involved in the control of phase angle and gain of the vestibulospinal reflexes, respectively. However, as soon as the threshold was reached the effects described above were dose-dependent. 6. Histological controls indicated that the structure responsible for the postural and reflex changes described above corresponded to the LC. In fact, postural and reflex changes opposite in sign to those described above were obtained when the same amount of carbachol was injected into the dorsal aspect of the pontine reticular formation (pRF) located immediately ventral to the LC.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of laryngeal nerve transection on squirrel monkey calls

Summary Six squirrel monkeys (Saimiri sciureus) were implanted with intracerebral electrodes yielding specific call types when electrically stimulated. Two animals then received bilateral transection of the recurrent nerve; in another two animals the external branch of the superior laryngeal nerve was cut bilaterally; two further animals received unilateral transection of either the recurrent or the external laryngeal nerve. In one animal with both recurrent nerves cut, the external laryngeal nerves were cut in addition 3 months later. The vocal changes caused by these transections were observed and can be summarized as follows:Unilateral interruption of the recurrent nerve causes only minor disturbances which are limited to low-pitched sounds. Bilateral interruption of the same nerve leads to a reduction of maximal intensities and durations in general. Whereas the frequency-time structure is severely disorganized in all harmonic calls with a fundamental below 1 kHz and all non-harmonic, noise-like calls, it remains unaffected in harmonic calls with a fundamental above 1 kHz. Unilateral transection of the external laryngeal nerve causes a drop of fundamental frequency in high-pitched calls to almost half. Bilateral transection of the same nerve abolishes all calls with a fundamental above 1 kHz. In wide-band frequency calls it is followed by a shift of main energy towards lower frequencies. Low-pitched harmonic as well as noise-like calls remain normal. Cutting both external laryngeal nerves in addition to recurrent nerves is followed by loss of all sounds except one coughing-like, abnormal call. All animals with transection of the external laryngeal nerve show recovery of the high-pitched calls which seems to be due to new innervation of the cricothyroid muscle from the pharyngeal plexus.     

Retinoic acid signaling reduction recapitulates the effects of alcohol on embryo size

Intrauterine growth restriction (IUGR) is commonly observed in human pregnancies and can result in severe clinical outcomes. IUGR is observed in Fetal Alcohol Syndrome (FAS) fetuses as a result of alcohol (ethanol) exposure during pregnancy. To further understand FAS, the severe form of Fetal Alcohol Spectrum Disorder, we performed an extensive quantitative analysis of the effects of ethanol on embryo size utilizing our Xenopus model. Ethanol‐treated embryos exhibited size reduction along the anterior–posterior axis. This effect was evident primarily from the hindbrain caudally, while rostral regions appeared refractive to ethanol‐induced size changes, also known as asymmetric IUGR. Interestingly, some embryo batches in addition to shortening from the hindbrain caudally also exhibited an alcohol‐dependent reduction of the anterior head domain, known as symmetric IUGR. To study the connection between ethanol exposure and reduced retinoic acid levels we treated embryos with the retinaldehyde dehydrogenase inhibitors, DEAB and citral. Inhibition of retinoic acid biosynthesis recapitulated the growth defects induced by ethanol affecting mainly axial elongation from the hindbrain caudally. To study the competition between ethanol clearance and retinoic acid biosynthesis we demonstrated that, co‐exposure to alcohol reduces the teratogenic effects of treatment with retinol (vitamin A), the retinoic acid precursor. These results further support the role of retinoic acid in the regulation of axial elongation.     

Anatomical and scanning electron microscopic characteristics of the oropharyngeal cavity (tongue,palate and laryngeal entrance) in the southern lapwing (Charadriidae: Vanellus chilensis,Molina 1782)

This investigation aimed to determine the morphological characteristics of the tongue, palate and laryngeal entrance of southern lapwing by gross anatomy and scanning electron microscopy. For this purpose, the organs of three birds were used as material. Numerous densely distributed acicular projections were found on the lingual apex. Papillary crest consisting of sharp conical papillae were observed between the body and root of the tongue. Conical papillae of the lateral border of the papillary crest were triangular in form, and other conical papillae of the papillary crest were shorter in form. There were no papillary projections or papillae on the smooth surfaces of the lingual body and radix. On the median part of the palate, larger conical papillae, which were directed caudally, also surrounded entrance of the choanal cleft. The transversal papillary rows of conical papillae were observed between the rostral and caudal parts of the choanal cleft and on the caudal border of the infundibular cleft. The laryngeal entrance was surrounded by smooth mucosa without conical papillae. However, in the caudal border of the glottic fissure, there was a conical papillary row formed by numerous conical papillae. There were no anatomical differences between female and male birds.     

Protection against laryngeal and pharyngeal carcinoma: Heterozygous vs. homozygous deletions of GSTM1 and GSTT1

Deletions in GSTM1 and GSTT1 genes are considered to be a risk factor for cancer development but the exact location of these deletions in the genome was unknown. Three main objectives of the current study were to: (a) identify the boundaries of these deletions in the human genome, (b) screen homozygous (−/−) and heterozygous (+/−) deleted, as well as homozygous present (+/+) individuals using PCR assays, (c) detect associations of pharyngeal (PC) and laryngeal cancer (LC) with the respective genotypes. In total, 102 PC and 92 LC patients were screened and compared with 150 controls. PCR mapping and sequencing revealed a 6 kbp deletion for GSTM1 and a 9 kbp deletion for the GSTT1 gene. The mean age of PC cases was 48.1 (±16.7) years; for LC cases it was 48.5 (±17.4) years and for controls 46 (±17.7) years. The OR (odds ratio) for the GSTM1 null genotype in PC and LC cases was 10.2 and 1.0 (95% CI 5.04–20.7 and 1.1–1.7) respectively. Similarly, for GSTT1 the OR was 4.02 with a 95% CI of 2.3–7.1 in PC cases. For LC cases the OR was 0.8 with 95% CI of 0.4–1.7. A non-significant number of LC and PC patients had heterozygous deletions of GSTM1 compared to controls (OD 0.5, 95% CI 0.2– 1.6 and OR 0.5, 95% CI 0.2– 1.5 respectively). The GSTT1 gene also showed a non-significant association in PC (OD 0.9, 95% CI 0.4–1.9), as well as in LC patients (OD 0.7, 95% CI 0.3–1.7). The homozygous genotype was significantly associated with PC and LC, whereas the heterozygous was not so. The GSTM1 (−/−) and GSTT1 (−/−) genotypes are a risk factor for LC and PC, whereas the (+/−) genotypes are not.     

Heart inflow tract of the African lungfish Protopterus dolloi

We report a morphologic study of the heart inflow tract of the African lungfish Protopterus dolloi. Attention was paid to the atrium, the sinus venosus, the pulmonary vein, and the atrioventricular (AV) plug, and to the relationships between all these structures. The atrium is divided caudally into two lobes, has a common part above the sinus venosus, and appears attached to the dorsal wall of the ventricle and outflow tract through connective tissue covered by the visceral pericardium. The pulmonary vein enters the sinus venosus and runs longitudinally toward the AV plug. Then it fuses with the pulmonalis fold and disappears as an anatomic entity. However, the oxygenated blood is directly conveyed into the left atrium by the formation of a pulmonary channel. This channel is formed cranially by the pulmonalis fold, ventrally by the AV plug, and caudally and dorsally by the atrial wall. The pulmonalis fold appears as a wide membranous fold which arises from the left side of the AV plug and extends dorsally to form the roof of the pulmonary channel. The pulmonalis fold also forms the right side of the pulmonary channel and sequesters the upper left corner of the sinus venosus from the main circulatory return. The AV plug is a large structure, firmly attached to the ventricular septum, which contains a hyaline cartilaginous core surrounded by connective tissue. The atrium is partially divided into two chambers by the presence of numerous pectinate muscles extended between the dorsal wall of the atrium and the roof of the pulmonary channel. Thus, partial atrial division is both internal and external, precluding the more complete division seen in amphibians. The present report, our own unpublished observations on other Protopterus, and a survey of the literature indicate that not only the Protopterus, but also other lungfish share many morphologic traits.     

Mechanism of systemic immune suppression by UV irradiation in vivo. II. The UV effects on number and morphology of epidermal Langerhans cells and the UV-induced suppression of contact hypersensitivity have different wavelength dependencies

We previously reported that broad band UV radiation or narrow bands of UV (Hbw 3 nm) of wavelengths 250 to 320 nm cause a systemic suppression of contact hypersensitivity (CHS) in mice, observed when the contact sensitizer is applied to a nonirradiated site. To determine if this effect is associated with UV-induced alterations in epidermal Langerhans cell (LC) numbers and morphology, we performed the following study. LC were identified by ATPase staining of EDTA-separated epidermal sheets. Electron microscope studies confirmed that this method was a satisfactory indicator of the presence of LC; we found no evidence for LC which did not stain for ATPase in either irradiated or unirradiated epidermis. Mice were irradiated on the back with narrow band UV of peak wavelength 270, 290, or 320 nm. The irradiated skin was excised 24 hr later and was stained as described. The number of LC with ATPase staining dendrites and the number of nondendritic LC were enumerated. We found that UV radiation of 270 or 290 nm caused 1) an alteration in LC morphology (loss of dendrites) and 2) a decrease in the total number of epidermal LC. Both effects occurred in a dose-dependent fashion. Previously, these same wavelengths of narrow band UV, but at higher doses, had been shown to cause systemic suppression of CHS. In this study, the doses of 270 or 290 nm UV that resulted in the decreased LC numbers and alterations in LC morphology described above were insufficient to cause systemic suppression of CHS. The converse was found if the irradiating waveband of UV had a peak at 320 nm. A dose of 320 nm UV that caused 50% systemic suppression of CHS had no effect on either the number or the morphology of LC at the site of irradiation. In addition, the number and morphology of LC were unaffected in the ventral epidermis (site of contact sensitization) of mice that had been previously irradiated on the back with a systemically suppressive dose of UV. We conclude: (a) UV-induced alterations in the number and morphology of LC at the site of irradiation are not necessary for the generation of systemic suppression of CHS by UV radiation; this indicates that the initial UV-absorbing event triggering systemic suppression is neither a loss of, nor morphologic alterations to, LC at the irradiation site. (b) A systemic effect of UV radiation on the number and morphology of LC at the unirradiated site of contact sensitization does not occur, and thus is not responsible for the UV-induced systemic suppression of CHS by UV radiation.