"Hypotyrosinemia" in phenylketonuria

It has been postulated that the significant incidence of learning disabilities in well-treated patients with phenylketonuria (PKU) may be due, in part, to reduced production of neurotransmitters as a result of deficient tyrosine transport across the neuronal cell membrane. Hypotyrosinemia has been reported in treated and untreated PKU but virtually no data are available. We decided to examine this in our patient population and to compare it with the published norms, patient data from our hospital clinical biochemical laboratory database, and a group of normal children and adolescents in a private pediatric practice. We found that the mean nonfasting plasma tyrosine in 99 classical PKU patients was 41.1 micromol/L, in 26 mild (atypical) PKU patients 53.3 micromol/L, and in 35 non-PKU mild hyperphenylalaninemia patients 66.6 micromol/L. This compared to nonfasting plasma tyrosine levels in 102 non-PKU subjects of 64.0 micromol/L in our hospital biochemistry database, 69.1 micromol/L in 58 volunteers in the private office practice, and 64-78.8 micromol/L in infants, children, and adolescents in the literature review. Our data support the previously undocumented statements in the literature that plasma tyrosine levels are low in PKU.     

Sleep and body temperature in "morning" and "evening" people

Three groups of young, normal sleepers were selected as morning types (MTs), evening types (ETs), and neither types (NTs) as determined by the Horne and Ostberg questionnaire. Sleep and rectal temperatures were recorded under three conditions: baseline nights (Cond. 1), sleep on the recovery day after 1 night of sleep deprivation (Cond. 2), and sleep on the recovery night after 1 night and 1 day of sleep deprivation (Cond. 3). During Conds. 1 and 3, when sleep schedules were self-determined, sleep structure and body temperature were similar in MTs, and ETs, and NTs. During Cond. 2, however, MTs had poorer sleep, i.e., a smaller percentage of REM sleep and more awakenings, than ETs. This difference can be related to the evolution of temperature during Cond. 2; i.e., a temperature increase in the MT and NT and a decrease in the ET.     

Hypercalcaemia in "non-secretory" myeloma

A patient is described with hypercalcaemia due to myelomatosis without paraproteinaemia or Bence-Jones proteinuria. Immunological investigations yielded some evidence of intra-cellular immunoglobulin production. Histological features suggested the secretion of osteoclast activating factor. Relevant experimental work in support of this interpretation is reviewed.     

"Tissue" transglutaminase in AIDS

Apoptosis or programmed cell death (PCD) is an active process of cellular self-destruction, essential for embryonic development and maintenance of homeostasis of multicellular organisms. Programmed cell death induction can serve as a defence mechanism of the host against intracellular microbes. Virus infections trigger host cell apoptosis, which can either limit virus production or contribute directly to viral pathogenesis.Several independent laboratories have identified "tissue" transglutaminase (tTG) as a potentially important player of the cell death program(s). This gene is specifically expressed in cells dying during mammalian development as well as in those undergoing apoptosis in various patho-physiological and experimental settings [Eur. J. Cell Biol. 56 (1991) 170; Piacentini, M., Davies, P.J.A., Fesus, L., 1994. Tissue transglutaminase in cells undergoing apoptosis. In: Tomei, L.D., Cope, F.O. (Eds.), Apoptosis II: The molecular basis of apoptosis in disease. Cold Spring Harbor Lab. Press, pp. 143-165.]. This chapter reviews recent studies concerning the expression and the possible role of "tissue" transglutaminase (tTG) in apoptotic cells; particular emphasis is given to its expression in the cell death pathways associated with HIV infection in the immune system.We propose here that the induction of the tTG gene in cells of the immune system, as well as the detection of the isodipeptide epsilon(gamma-glutamyl)lysine in plasma, are useful markers of apoptosis and might make it possible to monitor disease progression in HIV-infected individuals.     

HLA-D "BG" in Israel

An homozygous typing cell for a local HLA-D determinant"BG", defined by family study, is described. HLA-D "BG" recognizes a specificity identical to the Japanese HLA-DHO (Dw12). Two families and 102 randomly selected healthy Israeli individuals were typed for the HLA-D "BG" determinant. HLA-D "BG" showed segregation as a single determinant within families. The gene frequency for this allele was 0.045, compared to the frequency of 0.148 for DHO in Japanese. In the Israeli population "BG" is in strong association with HLA-Bw52 (joint occurrence = 7.80%) and DR2 (joint occurrence = 8.80%), resembling the data reported foar DHO (Dw12) in Japan. The frequency of this allele may partially account for the low frequency of HLA-Dw2 in the Israeli population.     

Nature of "basal" and "reserve" cells in oviductal and cervical epithelium in man

The epithelium of the human fallopian tube (oviduct) and cervix were studied by histological, immunohistological, and ultrastructural methods with a view to establishing the nature of the so called "basal" and "reserve" cells. The results indicated that the "basal" cells of the oviductal epithelia were T lymphocytes, with a predominance of T cytotoxic and suppressor cells. A more heterogeneous inflammatory cell population was present in cervical epithelium, although once again T cytotoxic and suppressor cells were the most numerous subtype. The intraepithelial inflammatory cells were quite distinct from the cells commonly referred to as "reserve" cells (reserve cell hyperplasia), which have epithelial characteristics. The origin of the "reserve" cells is unclear, but they seem to arise within the epithelium. They probably represent an early sign of squamous metaplasia. The lymphoid tissue of fallopian tube and endocervix shows similarities with that of the endometrium and mucosal associated lymphoid tissue in general.     

What's new in "in situ hybridization"

In situ hybridization (ISH) represents a technique which allows the visualization of cellular DNA or RNA in tissue sections, single cell or chromosome preparations. In addition to the originally used nick-translated DNA probes, synthetic oligodeoxyribonucleotides and single stranded cDNA probes are applied to ISH. With the more recent introduction of single stranded antisense RNA probes a highly specific and more sensitive technique became available. Besides the labeling of probes by the incorporation of radionucleotides non-radioactive labeling, particularly with biotin, is gaining increasing importance. Today, the most significant application for ISH in diagnostic pathology is the morphological analysis of viral infections because of the restricted availability of specific antibodies for immunohistochemistry. Furthermore, the visualization of mRNAs by ISH has proved to be useful for the visualization of specific gene expression of tumor cells, particularly, for the localization of mRNAs encoded by oncogenes and neuroendocrine genes. ISH was shown to be a more reliable tool to characterize the expression of a specific gene than conventional immunocytochemical procedures, because ISH demonstrates the actual amount of specific mRNA, whereas immunocytochemistry reflects the actual amount of immunoreactive peptide and is, therefore, dependent on peptide secretion, intracellular peptide degradation, peptide transport, and post-translational peptide processing. With the steadily increasing number of cloned nucleotide sequences the number of potentially useful probes and, consequently, the field of applications for ISH and its impact in research and diagnostic pathology is growing rapidly.     

Synthesis and separation in the history of "nature" and "nurture"

For much of the 20th century scientific psychology treated the relative contributions of nature and nurture to the development of phenotypes as the result of two quite separate sources of influence. One, nature, was linked to biological perspectives, often manifest as "instinct", while the other, nurture, was taken to reflect psychological influences. We argue that this separation was contingent on historical circumstance. Prior to about 1920, several perspectives in biology and psychology promoted the synthesis of nature and nurture. But between 1930 and 1980 that synthetic consensus was lost in America as numerous influences converged to promote a view that identified psychological and biological aspects of mind and behavior as inherently separate. Around 1960, during the hegemony of behaviorism, Daniel Lehrman, Gilbert Gottlieb, and other pioneers of developmental psychobiology developed probabilistic epigenesis to reject predeterminist notions of instinct and restore a synthesis. We describe the earlier and later periods of synthesis and discuss several influences that led to the separation of nature and nurture in the middle of the 20th century.     

Ultrastructural comparison of "alveolar" and "solid" areas in bronchioloalveolar carcinoma

The purpose of this study was to compare the ultrastructural features of bronchioloalveolar carcinomas, contrasting the well-differentiated alveolar component and the poorly-differentiated solid component in the same tumor. We studied 7 cases of non-mucinous bronchioloalveolar carcinomas by electron microscopy. Two of these cases showed lamellar bodies in both the alveolar and solid components and the remaining 5 cases revealed Clara cell granules in both components. We conclude that the neoplastic cells in bronchioloalveolar carcinoma retain their ultrastructural phenotypes after becoming invasive carcinoma with loss of alveolar differentiation.     

"Small-for-size graft" and "small-for-size syndrome" in living donor liver transplantation

The indications for living donor liver transplantation (LDLT) were successfully expanded from pediatric to adult cases last 15 years. During this process, graft type has been shifted from left side liver to right side liver. Although the introduction of right lobe graft can successfully increase the actual graft size in LDLT, problem related to "small-for-size grafts" have gradually come to light. "Small-for-size syndrome", such as poor bile production, delayed synthetic function, prolonged cholestasis, and intractable ascites, leading to septic complications and higher mortality, are neither specific nor inevitable in low-weight liver grafts. Many factors other than actual graft weight contribute to the occurrence of "small- for-size syndrome". In the clinical setting, surgical modification targeting portal hemodynamics and tissue congestion is a key to overcome "small-for-size syndrome". Until now, several therapeutic options were reported, but further elucidation of the pathogenesis in "small-for-size syndrome" will be a solution for improving the outcomes in adult-to-adult LDLT.     

Opioid peptides in the dynamics of "physiological" and "pathological" stress

Clinical studies showed that short-term "physiological" stress (bicycle ergometry) did not cause increase of the blood plasma enkephalin content. Moderate-term (60-minute) stress, according to O. Desiderato, causes a rise of the blood enkephalin level in rats. It is supposed that such a reaction of the opioid system is characteristic of borderline conditions between normal and pathological states in stress. Severe "pathological" stress (myocardial infarction, experimental coronary occlusion, 6-hour stress after O. Desiderato) in rats led to a decrease of the concentration of enkephalins in the blood and disorders of their secretion and storage in the adrenals. It is suggested that changes of the activity of the opioid system are a predictor of the transition of a "physiological" stress to a "pathological" stress.     

The interrelation of the "local" and the "general" in inflammation

The relationships between the local and the general in inflammation are analysed basing on the literature and original data. Local chemoattraction is postulated to be an underlying factor initiating primary local cooperation of cells relevant to inflammation. Being essential in this cooperation, macrophage seems to warrant both the local developments and triggering of general mechanisms of regulation which are relevant to control over subsequent secondary cell cooperation. The latter is biologically aimed at localization of the inflammation focus and separation of its pathogenic factors from intact internal medium. General mechanisms of inflammation control are provided by neuroendocrine, immune, vascular, coagulative, fibrinolytic and other systems, and operate through the products of the acute phase, by immune defence factors and rearrangement of nervous regulation of homeostasis in intact organs and tissues. The result of the regulation manifests with sequential presentation of the inflammation stages in time, correlation of local and general responses intensity. Eventually, local inflammation and lesion involve stress and intoxication which are not considered direct attributes of inflammation, nevertheless can influence general regulatory systems concerned with the course of local inflammation. It is concluded that inflammation implies dialectic unity of local and systemic responses of the body outlined to resolve inflammation and restore homeostasis.