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Article ; Online: Sex differences in quadrupedal walking gaits of Uner Tan syndrome cases, healthy humans and nonhuman primates.

Tan, Uner

2017 Volume 39, Issue 3, Page(s) 212–216

Abstract: Background: Uner Tan syndrome (UTS) cases with habitual quadrupedal locomotion (QL), impaired ...

Abstract	Background: Uner Tan syndrome (UTS) cases with habitual quadrupedal locomotion (QL), impaired intelligence, and dysarthric or no speech predominantly use lateral sequence (LS) gait like nonprimates rather than the predominantly diagonal sequence (DS) gait of nonhuman primates. However, these studies neglected possible sex-related differences in these gait types. Objectives: (1) To assess the possible sex-related gait types in UTS cases, healthy infants and adults with requested QL, and the nonhuman primates. (2) To test the hypothesis that sex differences may exist in quadrupedal walking gaits in UTS cases, healthy humans, and nonhuman primates. Methods: The UTS cases were filmed, the other study groups were taken from public open 'youtube' videos, which were used to assess the walking gait types as DS and LS. The right and left hind-limb phase values were calculated separately for males and females to allow a possible sex difference in walking gaits to be determined. Results: Females predominantly used DS gait, contrary to males with predominantly LS gait. Conclusions: Consistent with the working hypothesis, the results suggested a biological sex-related trend in preferred walking gaits exists in all of the human and nonhuman primates using QL.
MeSH term(s)	Adult ; Animals ; Biomechanical Phenomena ; Dysarthria/physiopathology ; Female ; Gait Ataxia/physiopathology ; Gait Disorders, Neurologic/physiopathology ; Humans ; Infant ; Intellectual Disability/physiopathology ; Male ; Movement Disorders/physiopathology ; Primates ; Sex Factors ; Syndrome
Language	English
Publishing date	2017-03
Publishing country	England
Document type	Journal Article
ZDB-ID	424428-x
ISSN	1743-1328 ; 0161-6412
ISSN (online)	1743-1328
ISSN	0161-6412
DOI	10.1080/01616412.2016.1275457
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Article ; Online: Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability.

Breuss, Martin W / Nguyen, Thai / Srivatsan, Anjana / Leca, Ines / Tian, Guoling / Fritz, Tanja / Hansen, Andi H / Musaev, Damir / McEvoy-Venneri, Jennifer / James, Kiely N / Rosti, Rasim O / Scott, Eric / Tan, Uner / Kolodner, Richard D / Cowan, Nicholas J / Keays, David A / Gleeson, Joseph G

Human molecular genetics

2016 Volume 26, Issue 2, Page(s) 258–269

Abstract: ... known as Uner Tan syndrome (UTS), to the growing list of diseases caused by tubulin variants. Analysis ...

Abstract	The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly referred to as the tubulinopathies. Here we report the addition of recessive quadrupedalism, also known as Uner Tan syndrome (UTS), to the growing list of diseases caused by tubulin variants. Analysis of a consanguineous UTS family identified a biallelic TUBB2B mutation, resulting in a p.R390Q amino acid substitution. In addition to the identifying quadrupedal locomotion, all three patients showed severe cerebellar hypoplasia. None, however, displayed the basal ganglia malformations typically associated with TUBB2B mutations. Functional analysis of the R390Q substitution revealed that it did not affect the ability of β-tubulin to fold or become assembled into the α/β-heterodimer, nor did it influence the incorporation of mutant-containing heterodimers into microtubule polymers. The 390Q mutation in S. cerevisiae TUB2 did not affect growth under basal conditions, but did result in increased sensitivity to microtubule-depolymerizing drugs, indicative of a mild impact of this mutation on microtubule function. The TUBB2B mutation described here represents an unusual recessive mode of inheritance for missense-mediated tubulinopathies and reinforces the sensitivity of the developing cerebellum to microtubule defects.
MeSH term(s)	Adult ; Amino Acid Substitution/genetics ; Basal Ganglia/pathology ; Brain/growth & development ; Brain/pathology ; Cerebellum/abnormalities ; Cerebellum/physiopathology ; Developmental Disabilities/genetics ; Developmental Disabilities/physiopathology ; Female ; Homozygote ; Humans ; Male ; Malformations of Cortical Development/genetics ; Malformations of Cortical Development/physiopathology ; Microtubules/genetics ; Microtubules/pathology ; Mutation ; Nervous System Malformations/genetics ; Nervous System Malformations/physiopathology ; Phenotype ; Saccharomyces cerevisiae/genetics ; Tubulin/genetics
Chemical Substances	TUBB2B protein, human ; Tubulin
Language	English
Publishing date	2016-11-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddw383
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Article ; Online: Siblings in Kars, Turkey, with Uner Tan syndrome (quadrupedal locomotion, severe mental retardation, and no speech): a novel theory for the evolution of human bipedalism.

Tan, Uner

Neurological research

2015 Volume 37, Issue 2, Page(s) 139–146

Abstract: ... locomotion (QL), severe mental retardation, and no speech (Uner Tan syndrome, UTS), in relation ...

Abstract	Objective: To investigate siblings from Kars (n = 2), Turkey, with diagonal-sequence quadrupedal locomotion (QL), severe mental retardation, and no speech (Uner Tan syndrome, UTS), in relation to the evolutionary emergence of human bipedal locomotion (BL). Methods: Video recordings were made to assess gaits. Brain MRI scanning was performed to visualize the cerebro-cerebellar malformations. Genome-wide association analyses were performed in venous blood samples. Results: One of the two men with UTS showed early-onset QL and late-onset BL without infantile hypotonia, the other consistent QL with infantile hypotonia. No homozygosity was found in the genetic analysis. The family lived under extremely poor socioeconomic conditions. Conclusions: Low socioeconomic status may be a triggering factor for the epigenetic emergence of UTS. The neural networks responsible for the ancestral diagonal-sequence QL, evolutionarily preserved since about 400 MYA, may be selected during locomotor development, under the influence of self-organizing processes during pre- and postnatal periods. The diagonal-sequence QL induced ipsilateral limb interference in UTS cases as in nonhuman primates. To overcome this condition, our ancestors would prefer the attractor BL. This novel theory for the evolution of human bipedalism was evaluated in light of dynamical systems theory.
MeSH term(s)	Biological Evolution ; Brain/abnormalities ; Gait/genetics ; Genome-Wide Association Study ; Humans ; Intellectual Disability/genetics ; Locomotion/genetics ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Siblings/psychology ; Social Class ; Speech Disorders/genetics ; Syndrome ; Systems Theory ; Turkey ; Video Recording
Language	English
Publishing date	2015-02
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424428-x
ISSN	1743-1328 ; 0161-6412
ISSN (online)	1743-1328
ISSN	0161-6412
DOI	10.1179/1743132814Y.0000000433
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Article ; Online: A new case of Uner Tan syndrome--with late childhood quadrupedalism.

Tan, Meliha / Karaca, Sibel / Tan, Uner

Movement disorders : official journal of the Movement Disorder Society

2010 Volume 25, Issue 5, Page(s) 652–653

MeSH term(s)	Brain Diseases/complications ; Brain Diseases/pathology ; Cerebellum/pathology ; Child ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Movement Disorders/complications ; Movement Disorders/pathology ; Positron-Emission Tomography/methods ; Posture ; Quadriplegia/complications ; Quadriplegia/pathology
Language	English
Publishing date	2010-04-15
Publishing country	United States
Document type	Case Reports ; Letter
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.22951
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Zs.A 2555: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Two families with quadrupedalism, mental retardation, no speech, and infantile hypotonia (Uner Tan Syndrome Type-II); a novel theory for the evolutionary emergence of human bipedalism.

Tan, Uner

Frontiers in neuroscience

2014 Volume 8, Page(s) 84

Abstract: Two consanguineous families with Uner Tan Syndrome (UTS) were analyzed in relation to self ...

Abstract	Two consanguineous families with Uner Tan Syndrome (UTS) were analyzed in relation to self-organizing processes in complex systems, and the evolutionary emergence of human bipedalism. The cases had the key symptoms of previously reported cases of UTS, such as quadrupedalism, mental retardation, and dysarthric or no speech, but the new cases also exhibited infantile hypotonia and are designated UTS Type-II. There were 10 siblings in Branch I and 12 siblings in Branch II. Of these, there were seven cases exhibiting habitual quadrupedal locomotion (QL): four deceased and three living. The infantile hypotonia in the surviving cases gradually disappeared over a period of years, so that they could sit by about 10 years, crawl on hands and knees by about 12 years. They began walking on all fours around 14 years, habitually using QL. Neurological examinations showed normal tonus in their arms and legs, no Babinski sign, brisk tendon reflexes especially in the legs, and mild tremor. The patients could not walk in a straight line, but (except in one case) could stand up and maintain upright posture with truncal ataxia. Cerebello-vermial hypoplasia and mild gyral simplification were noted in their MRIs. The results of the genetic analysis were inconclusive: no genetic code could be identified as the triggering factor for the syndrome in these families. Instead, the extremely low socio-economic status of the patients was thought to play a role in the emergence of UTS, possibly by epigenetically changing the brain structure and function, with a consequent selection of ancestral neural networks for QL during locomotor development. It was suggested that UTS may be regarded as one of the unpredictable outcomes of self-organization within a complex system. It was also noted that the prominent feature of this syndrome, the diagonal-sequence habitual QL, generated an interference between ipsilateral hands and feet, as in non-human primates. It was suggested that this may have been the triggering factor for the attractor state "bipedal locomotion" (BL), which had visual and manual benefits for our ape-like ancestors, and therefore enhancing their chances for survival, with consequent developments in the psychomotor domain of humans. This was put forward as a novel theory of the evolution of BL in human beings.
Language	English
Publishing date	2014-04-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2014.00084
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Article ; Online: Uner tan syndrome: history, clinical evaluations, genetics, and the dynamics of human quadrupedalism.

Tan, Uner

The open neurology journal

2010 Volume 4, Page(s) 78–89

Abstract: ... in Uner Tan syndrome, which is characterized by habitual quadrupedalism, impaired intelligence, and ... may not be a single factor that predetermines human quadrupedalism in Uner Tan syndrome ...

Abstract	This review includes for the first time a dynamical systems analysis of human quadrupedalism in Uner Tan syndrome, which is characterized by habitual quadrupedalism, impaired intelligence, and rudimentary speech. The first family was discovered in a small village near Iskenderun, and families were later found in Adana and two other small villages near Gaziantep and Canakkale. In all the affected individuals dynamic balance was impaired during upright walking, and they habitually preferred walking on all four extremities. MRI scans showed inferior cerebellovermian hypoplasia with slightly simplified cerebral gyri in three of the families, but appeared normal in the fourth. PET scans showed a decreased glucose metabolic activity in the cerebellum, vermis and, to a lesser extent the cerebral cortex, except for one patient, whose MRI scan also appeared to be normal. All four families had consanguineous marriages in their pedigrees, suggesting autosomal recessive transmission. The syndrome was genetically heterogeneous. Since the initial discoveries more cases have been found, and these exhibit facultative quadrupedal locomotion, and in one case, late childhood onset. It has been suggested that the human quadrupedalism may, at least, be a phenotypic example of reverse evolution. From the viewpoint of dynamic systems theory, it was concluded there may not be a single factor that predetermines human quadrupedalism in Uner Tan syndrome, but that it may involve self-organization, brain plasticity, and rewiring, from the many decentralized and local interactions among neuronal, genetic, and environmental subsystems.
Language	English
Publishing date	2010-07-16
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2395982-4
ISSN	1874-205X ; 1874-205X
ISSN (online)	1874-205X
ISSN	1874-205X
DOI	10.2174/1874205X01004010078
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Article: Evidence for "Uner Tan Syndrome" as a human model for reverse evolution.

Tan, Uner

The International journal of neuroscience

2006 Volume 116, Issue 12, Page(s) 1539–1547

Abstract: Uner Tan Syndrome" was further studied in a second family. There was no cerebellar atrophy, except ... of the "Uner Tan Syndrome", since in the first and second families there were bipedal men exhibiting very ...

Abstract	"Uner Tan Syndrome" was further studied in a second family. There was no cerebellar atrophy, except a mild vermial atrophy in MRI scans of the affected individuals. This is not, however, the pathogenesis of the "Uner Tan Syndrome", since in the first and second families there were bipedal men exhibiting very similar MRI scans. The second family may also be considered a live model for reverse evolution in human beings. The present work provided evidence for a reverse evolution: (i) quadrupedality; (ii) primitive mental abilities including language; (iii) curved fingers during wrist-walking of the quadrupedal woman; (iv) arm to leg ratios being close to those of the human-like apes. The quadrupedal individuals were raised in separate places, so that they could not imitate each other, excluding the socio-cultural factors contributing to the habitual quadrupedal gait. The results are consistent with the single gene theory, suggesting a single gene controlling multiple behavioral traits, and the psychomotor theory, and a co-evolution of the human mind, an emergent property of the motor system expressed by human language.
MeSH term(s)	Adult ; Anthropometry ; Ataxia/genetics ; Ataxia/pathology ; Ataxia/physiopathology ; Biological Evolution ; Cerebellum/pathology ; Cerebellum/physiopathology ; Family Health ; Female ; Gait ; Genes, Recessive ; Hand ; Humans ; Intellectual Disability/genetics ; Intellectual Disability/pathology ; Intellectual Disability/physiopathology ; Intelligence ; Magnetic Resonance Imaging ; Male ; Posture ; Speech Disorders/genetics ; Speech Disorders/pathology ; Speech Disorders/physiopathology ; Syndrome ; Turkey ; Walking
Language	English
Publishing date	2006-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3061-2
ISSN	1543-5245 ; 0020-7454
ISSN (online)	1543-5245
ISSN	0020-7454
DOI	10.1080/10623320600934325
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Zs.A 657: Show issues

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Article ; Online: Two families with quadrupedalism, mental retardation, no speech, and infantile hypotonia (Uner Tan Syndrome Type-II); a novel theory for the evolutionary emergence of human bipedalism

UnerTan

Frontiers in Neuroscience, Vol

2014 Volume 8

Abstract: Two consanguineous families with Uner Tan Syndrome (UTS) were analyzed in relation to self ...

Abstract	Two consanguineous families with Uner Tan Syndrome (UTS) were analyzed in relation to self-organizing processes in complex systems, and the evolutionary emergence of human bipedalism. The cases had the key symptoms of previously reported cases of UTS, such as quadrupedalism, mental retardation, and dysarthric or no speech, but the new cases also exhibited infantile hypotonia and are designated UTS Type-II. There were 10 siblings in Branch I and 12 siblings in Branch II. Of these, there were seven cases exhibiting habitual quadrupedal locomotion (QL): four deceased and three living. The infantile hypotonia in the surviving cases gradually disappeared over a period of years, so that they could sit by about 10 years, crawl on hands and knees by about 12 years. They began walking on all fours around 14 years, habitually using QL. Neurological examinations showed normal tonus in their arms and legs, no Babinski sign, brisk tendon reflexes especially in the legs, and mild tremor. The patients could not walk in a straight line, but (except in one case) could stand up and maintain upright posture with truncal ataxia. Cerebello-vermial hypoplasia and mild gyral simplification were noted in their MRIs. The results of the genetic analysis were inconclusive: no genetic code could be identified as the triggering factor for the syndrome in these families. Instead, the extremely low socio-economic status of the patients was thought to play a role in the emergence of UTS, possibly by epigenetically changing the brain structure and function, with a consequent selection of ancestral neural networks for QL during locomotor development. It was suggested that UTS may be regarded as one of the unpredictable outcomes of self-organization within a complex system. It was also noted that the prominent feature of this syndrome, the diagonal-sequence habitual QL, generated an interference between ipsilateral hands and feet, as in non-human primates. It was suggested that this may have been
Keywords	Ataxia ; complex systems ; evolution ; quadrupedalism ; self-organization ; Uner Tan syndrome ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	120
Language	English
Publishing date	2014-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A wrist-walker exhibiting no "Uner Tan Syndrome": a theory for possible mechanisms of human devolution toward the atavistic walking patterns.

Tan, Uner

The International journal of neuroscience

2007 Volume 117, Issue 1, Page(s) 147–156

Abstract: After discovering two families with handicapped children exhibiting the "Uner Tan syndrome ... that there may be sporadic wrist-walkers exhibiting no "Uner Tan Syndrome." The results suggest ...

Abstract	After discovering two families with handicapped children exhibiting the "Uner Tan syndrome," the author discovered a man exhibiting only wrist-walking with no primitive mental abilities including language. According to his mother, he had an infectious disease with high fever as a three months old baby; as a result, the left leg had been paralyzed after a penicilline injection. This paralysis most probably resulted from a viral disease, possibly poliomyelitis. He is now (2006) 36 years old; the left leg is flaccid and atrophic, with no tendon reflexes; however, sensation is normal. The boy never stood up on his feet while maturing. The father forced him to walk upright using physical devices and making due exercises, but the child always rejected standing upright and walking in erect posture; he always preferred wrist-walking; he expresses that wrist-walking is much more comfortable for him than upright-walking. He is very strong now, making daily body building exercises, and walking quite fast using a "three legs," although he cannot stand upright. Mental status, including the language and conscious experience, is quite normal. There was no intra-familiar marriage as in the two families mentioned earlier, and there is no wrist-walking in his family and relatives. There were no cerebellar signs and symptoms upon neurological examination. The brain-MRI was normal; there was no atrophy in cerebellum and vermis. It was concluded that there may be sporadic wrist-walkers exhibiting no "Uner Tan Syndrome." The results suggest that the cerebellum has nothing to do with human wrist-walking, which may rather be an atavistic trait appearing from time to time in normal individuals, indicating a live model for human reverse evolution. It was concluded that pure quadrupeds may sporadically appear due to random fluctuations in genotypes and/or environmental factors (hormonal or nutritional); the human development following the human evolution may be stopped in the stage of transition from quadrupedality to bipedality. That is, the activity of the philogenetically youngest supraspinal centers for bipedal walking responsible for suppression of the older supraspinal centers for quadrupedal gait may be interrupted at the atavistic level due to genetic and/or environmental factors. Consequently, it is assumed that these individuals prefer their natural wrist-walking to move around more quickly and efficiently.
MeSH term(s)	Adult ; Biological Evolution ; Cerebellum/pathology ; Cerebral Cortex/pathology ; Gait ; Gait Disorders, Neurologic/complications ; Gait Disorders, Neurologic/physiopathology ; Humans ; Intelligence ; Magnetic Resonance Imaging ; Male ; Paralysis/complications ; Paralysis/physiopathology ; Pedigree ; Posture ; Syndrome ; Walking ; Wrist
Language	English
Publishing date	2007-01
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	3061-2
ISSN	1543-5245 ; 0020-7454
ISSN (online)	1543-5245
ISSN	0020-7454
DOI	10.1080/00207450600936866
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Book ; Online: Physical Disabilities

Tan, Uner

Therapeutic Implications

2017

Keywords	Neurosciences ; rehabilitation, stroke, cerebral palsy, environment, autism, stem cell therapy
Language	English
Size	1 electronic resource (178 pages)
Publisher	IntechOpen
Document type	Book ; Online
Note	English
HBZ-ID	HT030646404
ISBN	9789535147923 ; 9535147927
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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