Aged Human Thymus Hassall's Corpuscles Are Immunoreactive for IGF‐I and IGF‐I Receptor

Although Hassall's corpuscles have been proposed to act in both maturation of developing thymocytes and removal of apoptotic cells, their function remains an enigma. The involvement of insulin‐like growth factor I (IGF‐I) in the local autocrine and paracrine control of T‐cell development in human thymus is still unclear. In this study, we investigated the structure and distribution of IGF‐I and IGF‐I receptor (IGF‐IR)‐immunopositive Hassall's corpuscles in aged human thymus using bright‐field immunohistochemistry and immunoelectron microscopy. We report new immunocytochemical data for the presence of IGF‐I/IGF‐IR double‐immunopositive Hassall's corpuscles in structurally preserved regions of age‐involuted thymus and discuss the involvement of these unique thymic components in the local regulation of T‐cell development and thymus plasticity during aging by IGF‐I/IGF‐IR‐mediated cell signaling pathway. Anat Rec., 2009. © 2009 Wiley‐Liss, Inc.     

Hassall's Corpuscles—A Site of Thymocyte Death

Cortical thymocytes incorporated tritiated thymidine within ½-4 hours after injection and retained decreasing amounts of the isotope for 5-7 days. In contrast with the remainder of the medulla, Hassall''s corpuscles selectively included tritiated nuclear material one day after injection. Corpuscular labelling reached a maximum by the 4th day, then became fragmented and disappeared by the 7th day.It is deduced that some of the DNA generated in the cortex is transported to the medulla and disintegrates in Hassall''s corpuscles. The biological significance of the apparently wasteful DNA synthesis remains unexplained.     

Ultrastructure of the thymic reticulum in guinea pig cytological aspects of the problem of the thymic secretion

Thymic reticular cells of the guinea pig were studied at different stages of its development and involution: the fetus of the last third of pregnancy, the newborn, the puberal adult and the adult implanted with estradiol. Most of the reticular cells were epithelial with desmosomes and tonofilaments originating from the endodermic primordium. In the medulla, some of these epithelial cells appeared to be transformed into elements of Hassall's corpuscles with an increase of tonofilaments in close association with keratohyalin granules. Moreover, phagocytic reticular cells were occasionally seen. Their origin remains unknown (epithelial or menschymal ?). The problem of the thymic secretion is discussed. There was no convincing evidence of a secretion of protein or polypeptid inside these reticular cells whatever the age of the animal. However, it is not possible to exclude the presence of another form of endocrin secretion, especially a colloid or a steroid secretion, at least in the fetus and newborn thymus.     

Ageing of the somatosensory system at the periphery: age‐related changes in cutaneous mechanoreceptors

Decline of tactile sensation associated with ageing depends on modifications in skin and both central and peripheral nervous systems. At present, age‐related changes in the periphery of the somatosensory system, particularly concerning the effects on mechanoreceptors, remain unknown. Here we used immunohistochemistry to analyse the age‐dependent changes in Meissner's and Pacinian corpuscles as well as in Merkel cell‐neurite complexes. Moreover, variations in the neurotrophic TrkB‐BDNF system and the mechanoprotein Piezo2 (involved in maintenance of cutaneous mechanoreceptors and light touch, respectively) were evaluated. The number of Meissner's corpuscles and Merkel cells decreased progressively with ageing. Meissner's corpuscles were smaller, rounded in morphology and located deeper in the dermis, and signs of corpuscular denervation were found in the oldest subjects. Pacinian corpuscles generally showed no relevant age‐related alterations. Reduced expression of Piezo2 in the axon of Meissner's corpuscles and in Merkel cells was observed in old subjects, as well was a decline in the BDNF‐TrkB neurotrophic system. This study demonstrates that cutaneous Meissner's corpuscles and Merkel cell‐neurite complexes (and less evidently Pacinian corpuscles) undergo morphological and size changes during the ageing process, as well as a reduction in terms of density. Furthermore, the mechanoprotein Piezo2 and the neurotrophic TrkB‐BDNF system are reduced in aged corpuscles. Taken together, these alterations might explain part of the impairment of the somatosensory system associated with ageing.     

Heparan sulfate in human cutaneous Meissner's and Pacinian corpuscles

Heparan sulfate proteoglycans are pericellular/cell surface molecules involved in somatosensory axon guidance in the peripheral nervous system. However, the distribution of heparan sulfate proteoglycans in the extracellular matrix of human cutaneous sensory corpuscles is unknown. Immunohistochemistry and immunofluorescence assays were performed to define the localization of heparan sulfate proteoglycans in human cutaneous Meissner's and Pacinian corpuscles using two anti-heparan sulfate antibodies together with anti-S100 protein, anti-PGP9.5, anti-CD34 (to immunolabel basement membranes, Schwann cells, axon and the intermediate endoneurial layer of Pacinian corpuscles, respectively), anti-Type IV collagen, and anti-chondroitin sulfate antibodies. Heparan sulfate proteoglycans were colocalized with Type IV collagen in Meissner's corpuscles and were located in the outer core lamellae and capsule, but not in the inner core or the intermediate layer, in Pacinian corpuscles. Chondroitin sulfate was observed in the intermediate layer of Pacinian corpuscles but was never colocalized with heparan sulfate proteoglycans. The present results strongly suggest that heparan sulfate proteoglycans are associated with the basement membranes of the lamellar cells in Meissner's corpuscles and with the complex outer core capsule in Pacinian corpuscles. The functional significance of these results, if any, remains to be elucidated.     

Electron microscopic study of involuting thymus of “lethargic” mutant mice

The thymus, which undergoes spontaneous involution three weeks after birth in “lethargic” mutant mice, was studied by electron microscopy. Ultrastructural alterations observed in the involuting thymus of “lethargic” mice resemble those of acute thymic involution induced by the administration of adrenal corticosteroids. The responsive cells in thymic involution of “lethargic” mice were cortical thymocytes, macrophages, and epithelial cells. The first indication of the involution was the appearance of a large number of degenerating thymocytes in the cortex. Pyknotic nuclei of degenerating thymocytes were observed within the macrophages. Macrophages of the involuting thymus were characterized by their content of thymocyte pyknotic nuclei as well as a variety of cytoplasmic inclusions. Cytoplasmic inclusions were also found in the epithelial cells. The inclusions were of two different types: (a) tonofibrils in markedly increased numbers in relation to a non-involuted thymus, and (b) large vacuoles with dense bodies and/or myelin figures, as found in a normal cell, but several times the number one would expect to find. A large number of lipid-laden cells were found in the involuted thymus. This type of cell was not seen in the normal thymus. Numerous Hassall's corpuscles were also found in the involuted thymus of “lethargic” mice.     

Primary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue-type in the thymus of a patient with Sjögren's syndrome and rheumatoid arthritis

Primary thymic marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT)-type is a very rare disease with distinct clinicopathologic features. I herein report a rare case of primary thymic MZBL of MALT-type arising in the thymus in a patient with Sjogren''s syndrome and rheumatoid arthritis. A mediastinal mass was detected by computerized tomography in a 43-yr-old Korean woman with a history of Sjögren''s syndrome and rheumatoid arthritis and the thymus was resected through median sternotomy. The solid and nodular tumor (7x6x3 cm) was confined in the thymus. Histologically, the lymphoid infiltrate comprised monotonous centrocyte-like cells with monocytoid cells, small lymphocytes, and plasma cells. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating the Hassall''s corpuscles. Immunohistochemically, the tumor cells were positive for CD20, CD79a, and bcl-2 and negative for CD3, CD5, CD10, CD23, and bcl-6. IgA and kappa light chain restriction were also found in plasma cells in the tumor. Sjögren''s syndrome and rheumatoid arthritis are known to be associated with MALT lymphoma and were considered to play an important role in the development of malignant lymphoma in this patient.     

Reticular network of the human thymus.

To investigate the development of the reticular network of the thymus with aging and under pathologic conditions, we performed reticulin stains on the following samples; 5 fetal thymi (22 to 33 weeks of gestational age) and 35 postnatal thymi (less than 1 month to 33 years of age). The latter included 1 hyperplastic thymus, 4 pathologically involuted thymi and 1 physiologically involuted thymus as well as 29 normal thymi. Reticulin fibers were invariably seen along the capsule and interlobular septae of all the thymi. In fetal thymi, reticulin fibers circumscribed only cortical blood vessels and Hassall''s corpuscles. Postnatal thymi from the children aged less than 1 month showed discontinuous reticulin fibers along the blood vessels of the corticomedullary junction. With aging, the amount of reticulin fibers increased and formed a "fibroreticular network(FRN)" from the branching point of the interlobular septae along the corticomedullary junction. It completely circumscribed the outer medulla in fully developed thymi. In the hyperplastic thymus, the reticular network retained its original structure. Both pathologically and physiologically involuted thymi revealed irregularly collapsed reticulin fibers. These findings suggest that the reticular network of the thymus consists of FRNs as well as capsule and interlobular septae and matures with aging before involution.     

Nerve growth factor receptor immunoreactivity in Meissner and Pacinian corpuscles of the human digital skin

The presence of nerve growth factor receptors (NGFr) in sensory nerve corpuscles of human digital skin, primarily Meissner and Pacinian corpuscles, was investigated immunohistochemically using two monoclonal antibodies directed against human-NGFr. To ensure the localization of NGFr immunoreactivity (IR) alternative sections to that processed for NGFr detection were assayed for neurofilament protein (NFP) and S-100 protein which selectively label the axon and the periaxonic specialized cells (lamellar cells of Meissner's corpuscles; inner-core cells of Pacinian corpuscles), respectively. Occurrence of NGFr IR was observed in both types of sensory corpuscles. In Meissner's corpuscles NGFr-IR was found in the lamellar cells, whereas in the Pacinian corpuscles the lamellae of the inner core, outer core, and capsule displayed NGFr IR. Moreover, a positive IR was observed in the central axon of some Pacinian corpuscles. However, remarkable differences were encountered among Pacinian corpuscles in the pattern of NGFr IR distribution. Present results demonstrate puscles in the pattern of NGFr IR distribution. Present results demonstrate the presence of NGFr IR in sensory nerve corpuscles of the human digital skin, suggesting that NGFr could be involved in the concentration of NGF and in the conveying of this molecule from the cutaneous sources to the cell body of NGF-dependent primary sensory neurons. However, the mechanisms involved in this process remain to be clarified. © 1993 Wiley-Liss, Inc.     

The thymus and skin wound healing in Xenopus laevis adults

The capacity to heal wounds without scars is generally lost during the development in vertebrates. To explore the involvement of cells of the adaptive immune system in a scar-like tissue based repair, we studied the thymus in 15-month-old Xenopus after skin incisional wounding. After injury, the organ size significantly increased and marked changes in structure and TNF-α immunoreactivity were detected in the medullary microenvironment when the granulation tissue was present in the repair area. Most of the lymphocytes present in this wound connective tissue were found to be immunoreactive to specific T cell markers. Thymic mucocyte-like cells and epithelial cysts increased in number, the myoid cells acquired a faster turnover and associated in large clusters, blood vessels were dilated and corpuscles similar to mammalian Hassall's bodies were formed in medulla. A higher number of stronger medullary TNF-α immunoreactive cells, i.e., dendritic, epithelial, granular basophilic and myoid cells were also induced after wounding. With progression of healing the thymus gradually returned to histochemical patterns of controls. Our results suggest that during the scar-based skin repair of Xenopus adults the activity of the thymus may be stimulated and associated with the T lymphocyte infiltration observed into injured granulation tissue.     

Sensory innervation of the human male prepuce: Meissner's corpuscles predominate

Meissner's corpuscles are the most abundant sensory corpuscles in the glabrous skin of the male prepuce. They are type I, rapidly adapting, low-threshold mechanoreceptors, and their function is linked to the expression of the mechanoprotein piezo-type mechanosensitive ion channel component 2 (PIEZO2). Stimulation of genital Meissner's corpuscles gives rise to sexual sensations. It has been recently demonstrated that digital Meissner's corpuscles, Meissner-like corpuscles, and genital end bulbs have an endoneurium-like capsule surrounding their neuronal elements; that is, the axon and glial lamellar cells, and their axons, display PIEZO2 immunoreactivity. It is unknown whether this is also the case for preputial Meissner's corpuscles. Furthermore, the expression of certain proteins that have been found in Meissner's corpuscles at other anatomical locations, especially in the digits, has not been investigated in preputial Meissner's corpuscles. Here, we used immunohistochemistry to investigate the expression of axonal (neurofilament, neuron-specific enolase), glial (S100 protein, glial fibrillary acidic protein, vimentin), endoneurial (CD34), and perineurial (glucose transporter 1) markers in the preputial and digital Meissner's corpuscles of male participants aged between 5 and 23 years. Furthermore, we investigated the occurrence of the mechanoprotein PIEZO2 in male preputial Meissner's corpuscles. Human male prepuce contains numerous Meissner's corpuscles, which may be grouped or isolated and are regularly distributed in the dermal papillae. Lamellar glial cells display strong expression of S100 protein and vimentin but lack expression of glial fibrillary acidic protein. In addition, they show axonal PIEZO2 expression and have an endoneurial capsule, but no perineurial. Our results indicate that human male preputial Meissner's corpuscles share the immunohistochemical profile of digital Meissner's corpuscles, which is considered to be necessary for mechanotransduction. These data strongly suggest that the structure and function of Meissner's corpuscles are independent of their anatomical location.     

Proximal-tubule-like epithelium in Bowman's capsule in spontaneously hypertensive rats. Changes with age.

Kidneys were samples from male spontaneously hypertensive rats (SHR) and normotensive rats (WKY) in four groups. Renal tissues were examined in 64 rats: 6 SHR and 6 WKY rats 8 and 16 weeks of age and 10 SHR and 10 WKY rats 32 and 64 weeks of age. Tissue samples were fixed, processed, and stained by routine histologic procedures. The parietal layer of Bowman''s capsule in 100-115 renal corpuscles from right to left kidney sections was classified as squamous or cuboidal epithelium. The cuboidal epithelium was similar in structure to that of the proximal tubule. Quantitative information from right and left kidneys was pooled, because the data did not differ significantly. The percentages of renal corpuscles with proximal tubule-like epithelium present at the parietal layer of Bowman''s capsule in the SHR was 13%, 35%, 44%, and 81% at 8, 16, 32, and 64 weeks, respectively. In WKY rats the values were 4%, 0.5%, 5%, and 13% at 8, 16, 32, and 64 weeks, respectively. The increase in the percentage of renal corpuscles with proximal tubule-like epithelium in SHR Bowman''s capsules suggest an association between this tissue and hypertension. The modified layer of Bowman''s capsule may be a response to an increase in blood pressure, may have some role in the etiology of hypertension, or may be irrelevant to hypertension.     

A histopathological variant of mixed thymoma presenting with prominent calcification and desmoplasia in an aged Japanese Brown cow

Herein an unusual variant of mixed thymoma with extensive fibrosis and calcification is described in a Japanese Brown cow, aged 18 years and 8 months, that was culled from old age. At necropsy, a solitary tumor mass (approximately10 cm in diameter) was found in the cranial mediastinal region. Microscopically, the tumor consisted of two distinct cell types, namely tightly packed sheets of immunohistochemically cytokeratin-positive neoplastic epithelial cells intermingled with CD3-positive T lymphocyte populations of varying density. Immature Hassall's corpuscles, cystoid cavities, and small mineralized bodies (calcispherites) were observed. A particularly characteristic feature that highlighted this tumor was the presence of extensive and multifocal areas of sclerotic and fibroconnective stroma. These areas were frequently associated with calcification undergoing granulomatous reaction. Histopathological and immunohistochemical findings were similar, to some degree, to those described in only a few reports of sclerosing thymoma, a rare variant of thymoma in human beings.     

Verification and characterisation of human digital Ruffini’s sensory corpuscles

Ruffini's corpuscles are present as long fusiform encapsulated sensory structures in different tissues including the skin. Although physiological analyses strongly suggest their existence in glabrous digital skin, such localisation remains unconfirmed. Here, we have investigated the occurrence of typical Ruffini's corpuscles in 372 sections of human digital skin obtained from 186 subjects of both sexes and different ages (19–92 years). S100 protein, neuron-specific enolase and neurofilament proteins were detected, and the basic immunohistochemical profile of these corpuscles was analysed. Fewer than 0.3 Ruffini's corpuscles/mm² were detected, with density distribution across the fingers being F4 > F3 > F2 > F1 > F5 and absolute values being F2 > F1 > F3 > F4 > F5. Axons displayed neuron-specific enolase immunoreactivity, glial cells forming the core contained S100 protein, and the capsule was positive for CD34 but not Glut1, demonstrating an endoneurial origin. Present results demonstrate the existence of Ruffini's corpuscles in human glabrous digital skin at very low densities. Moreover, the identified Ruffini's corpuscles share the basic immunohistochemical characteristics of other dermal sensory corpuscles.     

Histological and immunohistological investigation of lymphoid tissue in the platypus (Ornithorhynchus anatinus)

The gross and histological appearance and the distribution of T and B lymphocytes and plasma cells are described for lymphoid tissues obtained from 15 platypuses. The spleen was bilobed and surrounded by a thick capsule of collagen, elastic fibres and little smooth muscle. White pulp was prominent and included germinal centres and periarterial lymphoid sheaths. Red pulp contained haematopoietic tissue. A thin lobulated thymus was located within the mediastinum overlying the heart. The cortex of lobules consisted of dense aggregates of small and medium lymphocytes, scattered macrophages and few reticular epithelial cells. In the medulla, Hassall's corpuscles were numerous, lymphocytes were small and less abundant, and reticular cells were more abundant than in the cortex. Lymphoid nodules scattered throughout loose connective tissue in cervical, pharyngeal, thoracic, mesenteric and pelvic sites measured 790±370 μm (mean±S.D. , n = 39) in diameter, the larger of which could be observed macroscopically. These consisted of single primary or secondary follicles supported by a framework of reticular fibres. Macrophages were common in the germinal centres. The platypus had a full range of gut-associated lymphoid tissue. No tonsils were observed macroscopically but histologically they consisted of submucosal follicles and intraepithelial lymphocytes. Peyer's patches were not observed macroscopically but histologically they consisted of several prominent submucosal secondary follicles in the antimesenteric wall of the intestine. Caecal lymphoid tissue consisted of numerous secondary follicles in the submucosa and densely packed lymphocytes in the lamina propria. Bronchus-associated lymphoid tissue was not observed macroscopically but was identified in 7 of 11 platypus lungs assessed histologically. Lymphoid cells were present as primary follicles associated with bronchi, as aggregates adjacent to blood vessels and as intraepithelial lymphocytes. The distribution of T lymphocytes, identified with antihuman CD3 and CD5, and B lymphocytes and plasma cells, identified with antihuman CD79a and CD79b and antiplatypus immunoglobulin, within lymphoid tissues in the platypus was similar to that described in therian mammals except for an apparent relative paucity of B lymphocytes. This study establishes that the platypus has a well-developed lymphoid system which is comparable in histological structure to that in therian mammals. It also confirms the distinctiveness of its peripheral lymphoid tissue, namely lymphoid nodules. Platypus lymphoid tissue has all the essential cell types, namely T and B lymphocytes and plasma cells, to mount an effective immune response against foreign antigens.     

Parathyroids and ultimobranchial bodies in monotremes

Only scant information is available in the scientific literature on the parathyroids and ultimobranchial bodies in the primitive mammals, the echidna (Tachyglossus aculeatus) and platypus (Ornithorhynchus anatinus). The major aim of this paper is to describe the morphology of the monotreme parathyroid gland and to compare it with parathyroids in mammals and reptiles. The gross anatomy and light microscopic structure of the ultimobranchial body, thymus, and thyroid are also given. Animals were dissected and routine light and electron microscopic techniques used to examine the microscopic morphology. The locations of parathyroid hormone, calcitonin and calcitonin gene‐related peptide in tissue sections were identified by immunostaining. Monotremes have one pair of parathyroid glands located in the thorax and they are often associated with thymic tissue but never with the thyroid which is also present in the mediastinum. Ultimobranchial bodies are ventrolateral to the commencement of the trachea. Thymic lobules with Hassall's corpuscles are scattered in the fibrofatty tissue of the mediastinum and the ventral surface of the pericardium. Histologically, principal cells, water‐clear cells, and non‐secretory cells were identified in the parathyroid glands. Principal cells showed polarity and had microlamellar projections that formed intercellular canaliculi. Non‐secretory cells had features similar to those of thymic epithelial reticular cells. Immunostaining of parathyroid hormone showed a diffuse distribution in parathyroid principal cells and none in ultimobranchial bodies. Identification of the ultimobranchial bodies was confirmed by immunostaining. The monotreme parathyroid gland, ultimobranchial bodies and thyroid show reptilian as well as mammalian features. Anat Rec 254:269–280, 1999. © 1999 Wiley‐Liss, Inc.     

胸腺小体在胸腺发育中的形态发生及其功能探讨

用组织化学与免疫组织化学技术对8例人胎(胎龄16～32周)的胸腺进行研究,观察在其发育过程中胸腺小体的形态变化及增殖细胞核抗原(Proliferating Cell Nuclear Antigen,PCNA)、花生凝集素(Peanut Aggulutinin,PNA)和细胞角蛋白(Cytokeratin,CK)等的表达特征.结果显示:胸腺小体是在胸腺发育阶段由胸腺上皮细胞呈同心圆状排列而成,且胎儿胸腺中单个和融合状的胸腺小体都较成体胸腺中明显增多.围成胸腺小体的上皮细胞从周边向中央,角蛋白含量明显减少,增殖能力逐渐减弱,表现为逐渐退化的过程.证实胸腺小体是处理退变的上皮细胞的场所.另外,在胸腺小体的上皮细胞膜有PNA受体的表达,这提示在胸腺的发育成熟过程中,胸腺小体上皮细胞与胸腺细胞之间可能存在着相互识别相互诱导的作用.     

3～20周人胚和胎儿肾小体的组织发生

应用光、电镜对3～20周22例人胚和胎儿肾小体的组织发生进行了观察.受精后第25天胚肾已有肾小体发生.随着胚龄的增长,肾小体的发生数目增多,肾小体的形成方式是:胚肾内先形成许多厚壁小管,在一部分厚壁小管的诱导下,另一部分厚壁小管的一侧壁呈帽状增厚,分化形成造血干细胞、毛细血管内皮及肾小囊脏层,对侧壁形成肾小囊壁层.即厚壁小管的双侧壁形成肾小体.     

Primary thymic neuroblastomas in adults: A clinicopathological and immunohistochemical study of three cases

Three cases of primary neuroblastomas presenting as anterior mediastinal tumors are presented. The patients are two women and one man between the ages of 57 and 63 year. Clinically, the patients presented with symptoms of chest pain, cough, and shortness of breath. Diagnostic imaging revealed the presence of an anterior mediastina mass. Initial biopsy was non-diagnostic in two patients, while in one patient no biopsy was obtained. Surgical resection via thoracotomy was performed in all three patients. Grossly, the tumors vary in size from 3 to 4.5 cm in greatest dimension, and they were described as well circumscribed but not encapsulated, light brown in color. Areas of hemorrhage and/or necrosis were not described. Histologically, at low power the tumors were surrounded by a rim of adipose tissue containing remnants of thymic tissue with Hassall's corpuscles. At higher magnification, the tumors show the characteristic small round cell proliferation with varying amounts of neurophil. Mitotic activity was present but not in large number. Areas of necrosis and/or hemorrhage were not identified. Immunohistochemically, the tumors show positive staining for NSE, while synaptophysin highlighted neurophil. Other markers epithelial and neuroendocrine were negative. Clinical follow-up information shows that two patients have remained alive 8 and 12 months after initial surgical resection. One patient was lost to follow-up.     

Tumour of Wagner-Meissner touch corpuscles*

Summary Two benign tumours composed mainly or exclusively of Wagner-Meissner corpuscles are described. In the first case the touch corpuscles are composed of closely piled laminar cells and surrounded by argyrophilic fibres. In the second case some Schwann cells are observed in between the tactile corpuscles. The light microscopic, electron-microscopic and immunohistochemical results demonstrate that these corpuscles are comparable with the tactile end organs of the skin. Immunohistochemically, neuron-specific enolase, vimentin and protein S-100 could be demonstrated in the tactile corpuscles. Neural processes present in normal Meissner corpuscles are absent and immunohistochemically no nerve fibres or nerve endings can be demonstrated using antibodies to neurofilaments as they are observed in normal touch corpuscles of the skin.Tumours which consist mainly of multiple touch corpuscles have not been described in the literature. It is suggested to call these tumours Wagner-Meissner neurilemmoma.Dedicated to Professor Dr. Dr. h.c. K. Lennert in honor of his 65th birthday