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T. Ortega, M.B.A., M.D.

Vice Chair, Pennsylvania State University College of Medicine

Treatment for vaginal infections usually includes acidified carriers to reestablish a more acidic pH like that usually seen in mid-menstrual cycle. The delay in menstruation coupled with the presence of basophilic cells in a vaginal smear are clues. Ovulation is the midpoint of the cycle and should be more than a few days away (answers a and b). She is relatively young for the onset of menopause and there are no other symptoms (answer e). Exfoliative cytology can be used to diagnose cancer and to determine if the epithelium is under stimulation of estrogen and progesterone. The presence of basophilic cells in the smear with the Pap-staining method would indicate the presence of both estrogen and progesterone (answer c). The corpus luteum forms from the granulosa and theca layers of the follicle following ovulation. The luteal phase is the second half of the menstrual period and follows the follicular phase during which follicles mature. They pass through the basalis layer of the endometrium into the functional zone, and their distal ends are subject to degeneration with each menses. In the proliferative phase, the endometrium is only 382 Anatomy, Histology, and Cell Biology 1- to 3-mm thick, and the glands are straight, with the spiral arteries only slightly coiled. This diagram of the early secretory phase shows an edematous endometrium that is 4-mm thick, with glands that are large, beginning to sacculate in the deeper mucosa, and coiled for their entire length. Those molecules, along with plasmin and prostaglandins, facilitate the rupture of the ovarian follicle, leading to ovulation. Those proteases facilitate ovulation by initiating connective tissue remodeling, including the breakdown of the basement membrane between thecal and granulosa layers. This process occurs throughout life and involves the death of follicular cells as well as oocytes, but there is no basement membrane between the theca interna and externa. In fact, there is an absence of a clear delineation between the theca interna and externa. Development of ovarian follicles begins with a primordial follicle that consists of flattened follicular cells surrounding a primary oocyte. The connective tissue around the follicle differentiates into two layers: theca externa (D) and theca interna (E). The theca externa is closest to the ovarian stroma and consists of a highly vascular connective tissue. Liquor folliculi is produced by the granulosa cells and is secreted between the cells. When cavities are first formed by the development of follicular fluid between the cells, the follicle is called secondary. When the antrum is completely formed, the follicle is called a mature (Graafian) follicle, and the antrum is completely filled with liquor folliculi. The corona radiata (C) represents Reproductive Systems Answers 383 those granulosa cells that remain attached to the zona pellucida. The cumulus oophorus (not labeled) represents those granulosa cells that surround the oocyte (B) and connect it to the wall. It synthesizes milk including antibodies from IgA secreting plasma cells in the connective tissue of the gland. The lactating mammary gland differs histologically from the thyroid gland (answer a) in the presence of lactiferous ducts for exocrine secretion compared to the endocrine secretion of the thyroid. The placenta removes waste products during gestation (answer c); secretions from the seminal vesicle [fructose, prostaglandins and other proteins, (answer d)] facilitate clotting of ejaculated semen; and prostatic secretions (zinc, citric acid, antibiotic-like molecules, and enzymes) enhance sperm function (answer e). Acetazolamide, a member of the sulfonamide family of antibacterial drugs, blocks carbonic anhydrase activity. Which of the following would most likely occur after treatment with acetazolamide? In the accompanying transmission electron micrograph of the renal corpuscle, which of the following is the function of the cell marked with an asterisk? A 15-year-old boy presents with hematuria, hearing loss, lens dislocation, and cataracts.

The asynchrony within a particular chromosome appears coordinated (Singh N et al 2003 Nature Genet 33:339). Actually some lower organisms (Plasmodium, Trypanosoma) also express only one allele of some genes of the diploid. Monobrachial chromosome Monocentric Chromosome: A monocentric chromosome has a single centromere, as is most common. The individuals in the trial developed serious organ failures and one fell into a coma for three weeks. The "magic bullet" approach of combining specific monoclonal antibodies (prepared from individual cancer patients) against a specific cancer tissue with Yttrium90 isotope (emitting rays of 2. More recently, several monoclonal antibody drugs targeting tyrosine kinase (Gleevec, Trastuzumab) and antiangiogenesis Avastin have been approved for therapeutic use alone or in combination with other treatments. These antibodies can then be transformed into bacteria by using phage or filamentous phage such as M13. The advantage of using filamentous phages is that they display the antibodies on their surface and permit screening in a liquid medium that enhances the efficiency by orders of magnitude. Monoclonal antibodies cannot be produced against self-antigens or against less than about 1-kDa antigens. In the latter case, high molecular weight carrier proteins such bovine serum albumin or limpet hemocyanin are used. Currently, mammalian cells are used mainly to produce IgG and obtain post-translational modifications. Monoclonal Antibody Therapies: Monoclonal antibody therapies open a variety of applications in medicine. Although at the moment they do not offer perfect solutions, they do have a lot of potential. Reocclusion of blood vessels after angioplasty-caused by unwanted aggregation of the platelets-may be alleviated by the 7E3 antibody fragments of the chimeric mouse-human Fab. Monoclonal antibody-mediated cytotoxicity responses are activated or inhibited through the Fc receptors of the antibody. Monocotyledones: Plants that form only one cotyledon such as the grasses (cereals). Monocytes: Mononuclear leukocytes that become macrophages when transported by the blood stream to the lung and the liver. This fruit may, however, be genetically modified to contain a single seed or mechanically fragmented to become monogerm. The agronomic advantage of the monogerm seed is that the emerging seedlings are not crowded and the laborconsuming thinning may be avoided or is at least facilitated. Monomer: One unit of a molecule (which frequently has several in a complex); a subunit of a polymer protein Monomorphic Locus: In the population, a monomorphic locus is represented by one type of allele. Monomorphic Trait: A monomorphic trait is represented by one phenotype in the population. Mononucleosis: Caused by cytomegalovirus; infectious mononucleosis is the result of activation of the Epstein-Barr virus. Monoecious plant Monofactorial Inheritance: A single (dominant or recessive) gene (factor) determines the inheritance of a particular trait. Although this term has some value for classification of inheritance, in most of the case the phenotype is the function of a number of genes with different alleles that respond to a variety of internal and external factors at the same time. Sequencing of the human disease genes and encoded proteins often reveals more than a single alteration even within the single gene. Also, environmental factors and the genetic background may modify the phenotypes substantially. Monofunctional Alkylating Agent:: A monofunctional alkylating agent has only a single reactive group. Monosomic Analysis 1253 Monoparous: Species, which generally produce a single offspring at a time. Chinese restaurant syndrome Monosomic: In a monosmic, the homologous chromosome(s) is represented only once in a cell or all cells of an individual. About 80% of the human 45 + X monosomics involve the loss of a paternal sex chromosome.

Yamauchi Y, Abe K, Mantani A, Hitoshi Y, Suzuki M, Osuzu F, Kuratani S, Yamamura K: A novel transgenic technique that allows specific marking of the neural crest cell lineage in mice. Karger C, Kurtz F, Steppan D, Schwarzensteiner I, Machura K, Angel P, Banas B, Risteli J, Kurtz A: Procollagen I-expressing renin cell precursors. Analysis of correlations in endocapillary (acute) glomerulonephritis and in moderately severe mesangioproliferative glomerulonephritis. Renal Physiology Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters Sanjay K. The analysis of murine knockouts has revealed a key role for these transporters in the renal handling not only of drugs and toxins but also of gut microbiome products, as well as liverderived phase 1 and phase 2 metabolites, including putative uremic toxins (among other molecules of metabolic and clinical importance). Functional activity of these transporters (and polymorphisms affecting it) plays a key role in drug handling and nephrotoxicity. Apart from excreting unmodified small molecule drugs, the kidney handles many conjugated metabolites, most of which are produced by phase 1 and phase 2 metabolism in the liver. Genes for phase 1 and 2 reactions are also expressed in the kidney and are likely to be very important in metabolic functions of the proximal tubule cells of kidney as well (9), although this area of research is underexplored. This scenario thus includes a host of drugs, metabolites, and molecules that are handled by proximal tubule transporters, which orchestrate their clearance from the blood and their elimination into the urine. The variables that affect serum, tissue, and body fluid levels of a single drug, toxin, or metabolite excreted by the transporters that handle small molecules is quite complicated; much more so if one simultaneously considers several small molecules. Nevertheless, a great deal of progress has been made in the past few decades on the basic biology of drug, toxin, and metabolite handling, including those functioning in the kidney proximal tubule. With these details at hand, integration of this information and application to clinical settings, such as the scenario presented in the preceding paragraph, should eventually be feasible. Many of the small molecules of clinical interest are charged: organic anions, organic cations, or molecules that have a zwitterionic character (both positive and negative charges). Molecules that are too large or albumin bound have limited glomerular filtration, and excretion instead depends largely on tubular secretion. For the most part, these molecules are secreted unchanged into the tubular lumen by a set of transporters at the apical (luminal or urine) surface of the proximal tubule cell. There appear to be more than two dozen types of transporters involved in the net transport of organic anion, organic cation, or organic zwitterions by the proximal tubule. Classification of Organic Ion Transporters Organic ion transporters in the proximal tubule are frequently collectively called multispecific drug transporters because of their multispecific nature and their crucial role in drug handling. But depending on the discipline (physiology, biochemistry, or pharmacology), or for historical reasons, a single transporter can sometimes be described by multiple different names in the literature (Table 1) (1). Furthermore, while much of the data from in vitro transport assays and mouse knockout studies seems relevant to humans, caution must be exercised in extrapolating to human physiology. By convention, transporters are displayed as all uppercase letters when referring to proteins or human genes. Basic Organic Ion Transporter Physiology Excretion of organic cations begins with transport on the basolateral surface of the proximal tubular cell (Figure 1A). Several carriers on the apical surface subsequently transport organic cations across the apical membrane through electroneutral transport by exchange with proton (H1), which capitalizes on the electrochemical gradient that favors movement of H1 into the cells. These transporters are organic anion/ dicarboxylate exchangers, which use a tertiary active transport system on the basolateral side of the proximal tubule cell. Organic anion secretion has been recognized as an important function of the kidney for more than half a century.

Kinome: the system of cellular protein kinases; the human kinome includes > 5000 kinases. Kiss (1q32): A 145/154 amino acid polypeptide (called metastin) suppresses metastasis of melanoma and breast cancer but it does not affect tumorigenesis. These interactions stabilize the structures and may facilitate recognition by various ligands or metal ions. After titration of the distilled ammonia in the presence of phenolphthalein, 1 mL 0. Underdeveloped testes (hypogonadism) and seminiferous ducts characterize the Klinefelter syndrome (see. Klinefelter syndrome the afflicted individuals are generally sterile, although effeminate yet heterosexual in behavior. About half of them show increased breast size and they are about as likely to develop breast cancer as women. They are more likely to develop insulin-dependent diabetes and heart failure (mitral valve prolapse) than normal males. Their intelligence is generally low, particularly in those having a higher number of sex chromosomes. Klinefelter individuals are frequently slow in development and have learning disabilities. Although they tend to be shy and immature in behavior, they were considered 1064 Klippel-Feil Syndrome to be prone to violence but this latter classification turned out to be based on false statistics. It is also true that there is higher incidence of Klinefelter syndrome in prison populations but this is due to their mental deficiency. Klippel-Feil Syndrome: In the autosomal dominant form, it is associated with fusion of cervical (neck) vertebrae and malformation of head bones conducive to conductive and/or sensorineural hearing loss. It involves venous and lymphatic capillaries and hypertrophy of bony or soft tissues. Klotho: aging Klotz Test: Estimates the statistical variance of two populations, which display identical median values. Kluyveromyces lacti: A yeast species in which the first time linear plasmids were found. The defect involves a deficiency of the C propeptide that is required for normal fibril formation. Specifically, the afflicted individuals cannot tightly close their fist, their palm is purplish, suffer from severe myopia (nearsightedness), the retina is detached and various types of bone defects, including dwarfism, may be evident. The first seven abdominal segments are abnormal (fused/deleted) but the head, thorax, the eighth abdominal segments and tail are normal. Knobs have been used to identify the fate of particular chromosomes during meiosis and evolution. Knobs were implicated in preferential segregation in maize and as affecting the frequency of recombination of syntenic markers (see. These are composed of tandem arrays of about 180-bp elements and may function as neocentromeres. Molecular evidence suggests that through inversion centromeric heterochromatin moved to the arm of the chromosome where it is composed largely of tandem repeats and retrotransposons. Knob: the terminal part of the viral fiber on the capsid, an essential means of infection by recognizing host receptor (see. Generally low levels of phosphophorothioate are used to avoid toxicity and still protect against nucleases. Knock-In (Ki): Insertion of a functional copy or a domain into an inactive/active gene. Removal of genes by site-specific recombination is expected to specifically knock out a discrete genic sequence. The cells are then electroporated with a gene construct carrying a selectable marker. The disrupted gene is flanked by sequences homologous to the target to facilitate homologous double crossing over. These recombinants will not be able to carry out the normal function of the target gene because of the insert in the coding sequence.