A broader perspective: Functional symptoms beyond Neurology.

•Functional (psychogenic) symptoms exist in all specialties.•They are by definition not under voluntary control, unlike factitious disorders and malingering.•The diagnostic approach to functional symptoms varies among specialties.

Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis.

The serine proteinase granzyme B is crucial for the rapid induction of target cell apoptosis by cytotoxic T cells. Granzyme B was recently demonstrated to enter cells in a perforin-independent manner, thus predicting the existence of a cell surface receptor(s). We now present evidence that this receptor is the cation-independent mannose 6-phosphate/insulin-like growth factor receptor (CI-MPR). Inhibition of the granzyme B-CI-MPR interaction prevented granzyme B cell surface binding, uptake, and the induction of apoptosis. Significantly, expression of the CI-MPR was essential for cytotoxic T cell-mediated apoptosis of target cells in vitro and for the rejection of allogeneic cells in vivo. These results suggest a novel target for immunotherapy and a potential mechanism used by tumors for immune evasion.

Assessment of protein synthesis and secretion by rat seminiferous and epididymal tubules in vivo.

In vivo microperifusion and micropuncture were used to study tubule protein synthesis and proluminal secretion by the male reproductive tract in vivo. Seminiferous and caput and cauda epididymal tubules were perifused for 3 h. with [35S]-methionine. Perifused interstitial fluid (IF), lumen fluid (LF), and tubule extract (TE) were collected. Proteins were separated by SDS-PAGE, and autoradiograms were developed. Trichloroacetic acid precipitable proteins in each fluid were determined and a protein synthesis index (PSI) was calculated. PSI values demonstrated that the cauda epididymis synthesized less protein in vivo than did either seminiferous or caput tubules. Seminiferous tubules synthesized and secreted into the tubule lumen a relatively constant panel of proteins. Epididymal tubules synthesized and secreted proteins in a region-specific manner. In the caput epididymis the most prominent secreted bands were consistent with the heavy and light chains of epididymal clusterin. In the cauda epididymis, the most prominent synthesized and secreted protein was a 25 kDa protein consistent with the protein D. The above approach to studying protein synthesis and secretion will allow direct study of the physiological and pathophysiological effects on this important epithelial function in vivo.

Restoration of spermatogenesis and subsequent fertility by direct intratesticular hormonal therapy.

Testosterone-laden microspheres (TLM) were used in an attempt to restore spermatogenesis and sustain fertility in rats with previously suppressed gonadal function. Adult rats received 62.5 micrograms. gonadotropin-releasing hormone antagonist (GnRH-antagonist) per day for 15 days prior to being divided into three groups: 1) animals to be examined immediately, 2) animals to continue receiving 62.5 micrograms. GnRH-antagonist per day alone, and 3) animals to continue receiving GnRH-antagonist + a single intratesticular injection of 20 mg. TLM per testis. Unoperated control and sham-operated animals were also studied. Testicular interstitial fluid (TIF) testosterone concentrations, testicular sperm production and fertility were assessed 105 days after initiation of the experiment. Testicular interstitial fluid testosterone concentrations and sperm production were significantly reduced from control values after the initial 15-day GnRH-antagonist treatment (p < .05). After 105 days of GnRH-antagonist treatment, these values were further reduced (p < .05), but the TIF testosterone and sperm production values of GnRH-antagonist treated animals receiving TLM supplementation were not different from those of controls (p < .05). Fertility trials were also performed. Animals which had received GnRH-antagonist alone for 90 days were completely infertile, but animals receiving GnRH-antagonist + TLM for 90 days had fertility values not different from those of control animals (p < .05). Thus, spermatogenesis reduced because of testicular insufficiency was restored to normal, as was fertility, by intratesticular administration of TLM. This technique has possible clinical applications in selected groups of infertile men.

Spermatic cord torsion in an infant receiving human chorionic gonadotropin.

Human chorionic gonadotropin and gonadotropin-releasing hormone administration has been advocated for the nonoperative management of undescended testes. Proponents of hormonal manipulation cite the low morbidity of endocrine treatment as its major advantage over conventional surgical repair. We report a serious potential complication of human chorionic gonadotropin administration, intravaginal spermatic cord torsion and testicular infarction, in an infant with bilateral cryptorchidism.