Frailty Reduces Vaccine Effectiveness Against SARS-CoV-2 Infection: A Test-Negative Case Control Study Using National VA Data.

OBJECTIVES: To assess the variation of vaccine effectiveness against SARS-CoV-2 infection during the Delta wave according to frailty status among U.S. veterans. DESIGN: Test-negative case-control study of SARS-CoV-2 mRNA vaccine effectiveness. SETTING: Veterans Health Administration (VHA) medical centers. PARTICIPANTS: Veterans 19 years and older who had at least one COVID-19/Flu like symptoms and received a SARS-CoV-2 PCR or antigen test at VHA medical centers between July 25 to September 30, 2021. INTERVENTION: mRNA vaccination. MEASUREMENTS: New SARS-CoV-2 infection. Vaccine effectiveness was defined as 1-odds of vaccination in cases/odds of vaccination in controls, where cases were patients who had a COVID-19 test and tested positive for SARS-CoV-2, and controls were those who tested negative. Frailty was measured using the VA frailty index, categorized as robust (0-<0.1), pre-frail (≥0.1-<0.21) and frail (≥0.21). RESULTS: A total of 58,604 patients (age:58.9±17.0, median:61, IQR:45-72; 87.5%men; 68.1%white; 1.3%African American, 8.3%Hispanic) were included in the study. Of these, 27,733 (47.3%) were robust, 16,276 (27.8%) were prefrail, and 14,595 (24.9%) were frail. mRNA vaccine effectiveness against the Delta variant symptomatic infection was lower in patients with frailty, 62.8 %(95%CI:59.8-65.7), versus prefrail 73.9%(95%CI:72.0-75.7), and robust, 77.0 %(95%CI:75.7-78.3). CONCLUSIONS: This test-negative case control study showed that mRNA vaccine effectiveness against infection declined in veterans with frailty. Frailty status is a factor to consider when designing, developing, and evaluating COVID-19 vaccines.

A new scoring system using multiple immunohistochemical markers for diagnosis of uterine smooth muscle tumors.

The diagnosis of uterine smooth muscle neoplasms by light microscopy is difficult. Multiple classification schemes have been proposed based on mitotic rate, nuclear atypia, and the presence or absence of necrosis. None of these classification systems has been entirely successful. This study was undertaken to evaluate the use of selected immunohistochemical and histochemical markers in differentiating these tumors, in addition to accepted morphologic criteria. Ten cases of each of the following: leiomyosarcomas (LMS), atypical leiomyomas (AL), cellular leiomyomas (CL) and usual leiomyomas (UL), were classically evaluated for histological diagnosis and were stained for Ki-67 (MIB-1), bcl- 2 and p53 using monoclonal antibodies and the avidin-biotin peroxidase method, and argyrophilic nucleolar organizer region (AgNORs). The number of stained cells was counted in the most positively stained region in a 4 mm2 square cover glass mounted on each slide. The mean value was calculated for each group of tumors. The data for Ki-67 (MIB- 1), bcl-2, p53 and AgNOR staining respectively, were significantly higher in LMS by comparison to UL, CL or AL. Because many singular cases had superimposed data being difficult to diagnose, a new scoring system for pathological evaluation was created. The results obtained by this scoring system suggest that immunohistochemical markers Ki-67 (MIB-1), bcl-2, p53 together with the AgNOR staining could be useful, by the scoring system, as an adjunct to the current accepted morphologic criteria in differentiating smooth muscle tumors of the uterus.

Changes in the distribution of anionic constituents in secretory granules of mouse pancreatic acinar cells after pilocarpine-induced degranulation.

We used cationized colloidal gold (CCG) to investigate the distribution of anionic sites in different secretory granules of mouse pancreatic acinar cell regranulation. Localization of anionic sites with CCG was carried out on ultrathin sections of a mouse pancreas, fixed in Karnovsky's fixative and OsO4 and embedded in Araldite. After pilocarpine-stimulated degranulation, there was a marked diminution in the anionic charge density of immature and mature granules of the 4-hr group (approximately 43.0 gold particles/microm2) compared to the 8-hr mature granules group (approximately 64.6 gold particles/microm2). Scattergram analysis to investigate the correlation between section profile size and cationized gold labeling density revealed a reverse correlation, the small granule profiles demonstrated a higher density compared to the larger profiles of the same group. On the basis of these observations, it appears that a post-translational processing of secretory content influences the granule anionic charge and thus may affect the intragranular buffer capacity.

Evaluation of atrial natriuretic peptide and brain natriuretic peptide in atrial granules of rats with experimental congestive heart failure.

The natriuretic peptides are believed to play an important role in the pathophysiology of congestive heart failure (CHF). We utilized a quantitative cytomorphometric method, using double immunocytochemical labeling, to assess the characteristics of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in atrial granules in an experimental model of rats with CHF induced by aortocaval fistula. Rats with CHF were further divided into decompensated (sodium-retaining) and compensated (sodium-excreting) subgroups and compared with a sham-operated control group. A total of 947 granules in myocytes in the right atrium were analyzed, using electron microscopy and a computerized analysis system. Decompensated CHF was associated with alterations in the modal nature of granule content packing, as depicted by moving bin analysis, and in the granule density of both peptides. In control rats, the mean density of gold particles attached to both peptides was 347.0 +/- 103.6 and 306.3 +/- 89.9 gold particles/microm2 for ANP and BNP, respectively. Similar mean density was revealed in the compensated rats (390.6 +/- 81.0 and 351.3 +/- 62.1 gold particles/microm2 for ANP and BNP, respectively). However, in rats with decompensated CHF, a significant decrease in the mean density of gold particles was observed (141.6 +/- 67.3 and 158.0 +/- 71.2 gold particles/microm2 for ANP and BNP, respectively; p<0.05 compared with compensated rats, for both ANP and BNP). The ANP:BNP ratio did not differ between groups. These findings indicate that the development of decompensated CHF in rats with aortocaval fistula is associated with a marked decrease in the density of both peptides in atrial granules, as well as in alterations in the quantal nature of granule formation. The data further suggest that both peptides, ANP and BNP, may be regulated in the atrium by a common secretory mechanism in CHF.

Decelerated rate of dendrite outgrowth from dopaminergic neurons in primary cultures from brains of hypoxanthine phosphoribosyltransferase-deficient knockout mice.

Lesch-Nyhan syndrome (LNS), caused by the complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT), is characterized by a neurological deficit, the etiology of which is still unclear. Evidence has accumulated indicating that it reflects dopamine deficiency associated with defective arborization of dopaminergic dendrites. We monitored the differentiation in vitro of dopaminergic neurons, cultured from HPRT-deficient knockout mice. The HPRT-deficient dopaminergic neurons exhibited a decelerated rate of outgrowth of dendrites in comparison to that of control neurons resulting, after 8 days in culture, in 32% smaller average total length of dendrites per neuron (P<0.025). The results suggest that the abnormal dendrite outgrowth in LNS reflects a defective developmental process.

The structure of mast cell secretory granules in the blind mole rat (Spalax ehrenbergi).

Eosinophils, basophils, and mast cells produce and secrete active substances whose role is to attack invading parasites and protect the host. In this study we use morphometric methods to study mast cells in the blind mole rat (Spalax ehrenbergi). The subterranean and solitary way of life of this species has led to the evolutionary development of special anatomical, morphological, behavioral, and physiological adaptations. Because of its particular lifestyle, the mole rat is less exposed to parasites than other rodents. This could provide a unique model for research into the pathobiology of mast cells. The paracrystalline structure of the mast cell granule content is composed of parallel plates. Diffraction analysis of electron micrographs of thin sections of araldite-embedded tissues indicated that each crystal line plate is a periodic array of parallelograms. The crystal unit cell volume is approximately 930 nm(3), suggesting that each unit cell is composed of one heparin molecule and one to three additional adsorbed proteins. Morphometric data show that characteristics of the secretory granules of mast cells of the blind mole rat resemble those of other rodents. The mast cell unit granule volume in the present study was calculated to be 0.055 microm(3), similar to that of rat peritoneal mast cells.

Histopathology of the inferior turbinate with compensatory hypertrophy in patients with deviated nasal septum.

OBJECTIVE: To measure the dimensions, composition, and possible structural and/or histopathological changes of the compensatory hypertrophic inferior turbinate in patients with deviated nasal septum. STUDY DESIGN: A prospective, nonrandomized, and morphometric study. METHODS: Nineteen patients with deviated nasal septum and compensatory hypertrophy of the inferior turbinate in the contralateral nasal cavity underwent surgery for correction of nasal obstruction. Patients' specimens were compared with those of a control group consisting of 10 inferior turbinates removed at autopsy. Quantitative measurements of the inferior turbinate histological sections were carried out and included the width of the layers and morphometric calculations of the relative proportions of the soft tissue constituents. Also, qualitative study was performed to detect pathological changes. RESULTS: Of all layers, the inferior turbinate bone underwent a twofold increase in thickness and manifested the most significant expansion (P < or =.001), whereas the contribution of the mucosal layers to the inferior turbinate hypertrophy was modest. The morphometric analysis revealed a larger proportion of venous sinusoids in hypertrophic turbinates, but the difference was small and statistically insignificant. Qualitative assessment disclosed normal mucosal architecture in all inferior turbinates with compensatory hypertrophy. Eleven remained intact, while eight disclosed mild to moderate pathological changes. CONCLUSIONS: The data gathered in the present study are of importance to the decision-making process regarding turbinate surgery. The significant bone expansion and the relative minor role played by the mucosal hypertrophy would support the decision to excise the inferior turbinate bone at the time of septoplasty.

Effect of photoperiod variation on testes and accessory sex organs in the male blind mole rat Spalax ehrenbergi.

The blind mole rat is a seasonally breeding fossorial rodent that is perceptionally blind. This study examines the effect of photoperiod on the morphology and histology of the male mole rat reproductive system, three groups of male mole rats were maintained in the laboratory under short day (SD) conditions (9L: 15D); long day (LD) conditions (15L:9D); and constant darkness (CD), and compared to animals trapped in the field (FL). It was found that the field animals revealed higher testes and prostate gland weights, higher prostate tubuli volume (v*) and lower testes tubuli volume (v*) compared to the other three groups. Distribution of the tubuli in the testes (Vv) was low in the FL group compared to the SD and LD groups but still higher than in the CD group. Distribution of lumen in the testes (Vv) was higher in the CD group in comparison to the other three groups. Distribution of interstitial tissue in the testes (Vv) was higher in the FL group than in the other three groups. Electrolytes and elements secreted from the prostate gland did not differ among the four groups. In the FL group distribution of the tubuli (Vv) in the prostate gland was low and lumen ratio (Vv) was high compared to the other three groups. Distribution of connective tissue in the prostate gland did not differ among all four groups. Testosterone levels and total sperm count was highest in the FL group. Sperm production was noted in all groups; however spermatid and spermatozoa cell production was higher in the FL group. This study shows that photoperiod could be important in initiating timing in the breeding season but that certain other conditions which are absent in the laboratory appear to be responsible for successful breeding in the field.

Maturation phenotype of Sertoli cells in testicular biopsies of azoospermic men.

The involvement of Sertoli cells in different spermatogenic impairments has been studied by an immunohistomorphometric technique using cytokeratin-18 (CK-18) as a marker for immature Sertoli cells. CK-18 is known to be expressed in Sertoli cells during prenatal and prepubertal differentiation and is normally lost at puberty. Forty-nine azoospermic men were included in the current study. Quantitative measurements on testicular biopsies revealed the highest CK-18 expression in the mixed atrophy biopsies (22 men), a lower expression in the Sertoli cell-only (SCO) biopsies (12 men), and minimal residual staining in the group considered as representing normal spermatogenesis (six obstructive azoospermia patients). The cytokeratin immunopositive-stained tubules were associated either with arrest in spermatogenesis or with SCO. Examination of sections from nine men with microdeletions in the AZF region of the Y chromosome revealed that these men were either negative for CK-18 expression or showed only weak residual staining. This may suggest that the spermatogenic defect in the AZF-deleted men originates in the germ cell and has no impact on Sertoli cell maturation. The cause that determined the spermatogenic defect in the other cases of male infertility with high CK-18 expression may have damaged both the Sertoli and the germ cells.

Morphometric studies of secretory granule formation in mouse pancreatic acinar cells. Dissecting the early structural changes following pilocarpine injection.

Secretory granule formation in pancreatic acinar cells is known to involve massive membrane flow. In previous studies we have undertaken morphometry of the regranulation mechanism in these cells and in mast cells as a model for cellular membrane movement. In our current work, electron micrographs of pancreatic acinar cells from ICR mice were taken at several time points after extensive degranulation induced by pilocarpine injection in order to investigate the volume changes of rough endoplasmic reticulum (RER), nucleus, mitochondria and autophagosomes. At 2-4 h after stimulation, when the pancreatic cells demonstrated a complete loss of granules, this was accompanied by an increased proportion of autophagosomal activity. This change primarily reflected a greatly increased proportion of profiles retaining autophagic vacuoles containing recognisable cytoplasmic structures such as mitochondria, granule profiles and fragments of RER. The mitochondrial structures reached a significant maximal size 4 h following injection (before degranulation 0.178 +/- 0.028 microm3; at 4 h peak value, 0.535 +/- 0.109 microm3). Nucleus size showed an early volume increase approaching a maximum value 2 h following degranulation. The regranulation span was thus divided into 3 stages. The first was the membrane remodelling stage (0-2 h). During this period the volume of the RER and secretory granules was greatly decreased. At the intermediate stage (2-4 h) a significant increase of the synthesis zone was observed within the nucleus. The volume of the mitochondria was increasing. At the last step, the major finding was a significant granule accumulation in parallel with an active Golgi zone.

Differential expression of p53 and Ki-67 proteins in classic and iatrogenic Kaposi's sarcoma.

In many neoplasms, the finding p53 immunoreactivity correlates with striking cytologic atypia, a high tumor cell proliferation rate, and poor prognosis. The literature regarding p53 and Ki-67 (a nuclear proliferation-associated antigen) immunoreactivity in Kaposi's sarcoma is limited. We aimed to: (1) evaluate the role of p53 in the development of Kaposi's sarcoma; (2) determine whether there is a correlation between p53 and Ki-67 protein expression; and (3) determine possible differences between classical Kaposi's sarcoma, known usually to have a benign course, and iatrogenic Kaposi's sarcoma, the course of which is unpredictable, by studying the differential expression of p53 and Ki-67. Among 26 cases of classic KS and 19 of iatrogenic KS, 12 were classified histopathologically as early type and 33 as mixed or spindle-cell type. P53 and Ki-67 immunoreactivity correlated significantly with the histopathologic stage of KS (r=0.63, p=0.0001; r=0.42, p=0.0084, respectively). P53 was not detected in any of the cases in an early histopathologic stage but was present in 55% of the cases in a more advanced stage. The spindle cells increased in proportion with the histopathologic progression and were more often positive (p=0.019) and displayed more extensive staining than the endothelial cells (p=0.0001). There was a strong positive correlation between p53 and Ki-67 protein expression (r=0.43, p=0.0087). There was no correlation between the expression of either p53 or Ki-67 and the extent of the eruption. The expression of p53 and Ki-67 was significantly lower in iatrogenic cases than in the classic cases (p=0.009, p=0.0014, respectively), although no statistical difference was found between the histopathologic stages in the two clinical forms of KS. P53 immunoreactivity was detected in 79% of the cases of classic Kaposi's sarcoma in the mixed or spindle cell stage but in only 21.5% of the iatrogenic cases showing the same histopathologic stage (p=0.001), and the percentage of spindle cells as well as the endothelial cells expressing p53 was higher in the classic cases than in the iatrogenic cases (p=0.0032, p=0.0142, respectively). We conclude that p53 immunoexpression is a marker of tumor progression in classic Kaposi's sarcoma but not in most cases of iatrogenic Kaposi's sarcoma. The proliferative activity of the tumor cells in classic Kaposi's sarcoma is much higher than in iatrogenic Kaposi's sarcoma. Our work implies that the molecular steps involved in classic and iatrogenic Kaposi's sarcoma differ.

The peritoneal membrane in peritoneal dialysis patients: estimation of its functional surface area by applying stereologic methods to computerized tomography scans.

The surface area of the peritoneal membrane in contact with dialysate is an important determinant of solute transport across the peritoneum. Yet there is no method for its estimation in peritoneal dialysis patients. In this study, stereologic methods were applied to computerized tomography (CT) imaging of the peritoneal membrane to estimate the peritoneal membrane surface area. The method was first validated by implementing stereologic methods on a phantom of known surface area. The phantom was a distorted bottle filled with contrast media. Series of thin helical CT sections were performed, and random sections were obtained after reconstruction. A transparent counting grid was placed over the random sections. The surface area was estimated using 9, 18, and 36 random sections. To calculate the coefficient of variation (CV) of the method, 20 different combinations of 9, 18, and 36 random sections were used. With 36 random sections, the error in estimation of the bottle's surface area was -9.4% to +8.8%. The CV was 5.0%. Decreasing the number of sections used to 18 and 9 yielded a CV of 7.8 and 12.3%, respectively. This method was then applied to the peritoneal membrane, which was visualized by instilling dialysate containing contrast media into the peritoneal cavity of peritoneal dialysis patients. The estimated peritoneal membrane surface area of six patients was 0.55 +/- 0.04 m2. This novel method permits the measurement of the peritoneal membrane surface area with a high degree of accuracy.

Pathways of macromolecular extravasation across microvascular endothelium in response to VPF/VEGF and other vasoactive mediators.

OBJECTIVE: The goal of these studies was to define the anatomic pathways by which circulating macromolecules extravasate from the hyperpermeable microvessels that supply tumors and from normal venules that have been rendered hyperpermeable by vasoactive mediators. METHODS: Extravasation pathways of circulating macromolecular tracers were followed by several morphological techniques: light and fluorescence microscopy, transmission electron microscopy of routine as well as ultrathin and serial sections, computer-assisted three-dimensional reconstructions, and morphometry. RESULTS AND DISCUSSION: Macromolecules extravasated across tumor microvessels or across normal venules rendered hyperpermeable by VPF/VEGF, histamine, or serotonin by three primary pathways: 1) Vesiculo-vacuolar organelles (VVOs), clusters of cytoplasmic vesicles and vacuoles that span endothelial cytoplasm from lumen to ablumen; 2) trans-endothelial cell (EC), pores, and 3) fenestrae. We also present data concerning the structure and function of VVOs as well as evidence that VVOs form as the result of linking together and fusion of caveolae-sized unit vesicles. Under suitable conditions VVOs also afforded a pathway for macromolecular transport in the reverse direction, i.e., from vascular ablumen to lumen. Finally, in addition to opening VVOs to the passage of macromolecules, mediators such as VPF/VEGF may also induce structural rearrangements of VVOs, transforming them into trans-EC pores or fenestrae.

Mechanisms leading to cortical reaction in the mammalian egg.

Activation of the mammalian egg results in cortical reaction (CR), which is correlated with an increase in intracellular Ca2+ concentration and PKC activation. The CR is a gradual rather then an "all or none" response, and can be regulated by different concentrations of parthenogenetic activators. To evaluate the biological significance of parthenogenetic induced CR, rat eggs were fertilized or activated by different concentrations of ionomycin and TPA. Cortical granules (CG) were monitored by electron microscopy, while the CG exudate was visualized by Lens culinaris lectin and Texas Red, using light and confocal microscopy. The ability of the CR to trigger a full block to polyspermy was examined in an IVF system. Our study demonstrates the existence of light and dark CG, which differ by number, distribution in the egg cortex, and sensitivity to parthenogenetic activators. Sperm penetration or high concentration of activators, trigger depletion of both light and dark CG, leading to a full CR. Low concentration of activators altered the CG density, the ratio of dark/light CG, and induced partial CR that was sufficient to cause a block to polyspermy. The results imply that Ca2+ rise or PKC activation have different effects on light and dark CG. In recently fertilized or parthenogenetically activated eggs, CG exudate appeared as evenly distributed spots, whereas in more advanced stages of fertilization the exudate was scattered as patchy aggregates. This observation suggests a difference in the dispersion of CG exudate after fertilization as compared to parthenogenetic activation.

Defective cytoplasmic granule formation.II. Differences in patterns of radiolabeling of secretory granules in beige versus normal mouse pancreatic acinar cells after [3H]glycine administration in vivo.

We investigated the development of secretory granules in the pancreatic acinar cells of normal (C57BL/6J +/+) and beige (C57BL/6J Lystbg/Lystbg) mice by analyzing the distribution of 3H label in pancreatic acinar cells after a pulse of [3H]glycine administered in vivo. The results provide quantitative confirmation of the hypothesis that the maturation of condensing vacuoles/immature granules to mature granules in pancreatic acinar cells is associated with a significant volume reduction. Beige mice differ from control mice by exhibiting a more rapid distribution of 3H label from the rough endoplasmic reticulum-rich cytoplasm to the secretory granules and a slightly faster rate of maturation of 3H-labeled granules. Beige mouse pancreatic acinar cells also exhibited, as early as 1 h after pulsing with [3H]glycine, a much higher proportion of 3H-labeled secretory granules than did the cells of control mice. These findings identify additional abnormalities in secretory granule formation in pancreatic acinar cells which are related to the beige (Lystbg) mutation and provide support for the hypothesis that beige mice exhibit an abnormal pattern of granule-granule fusion.

Determination of mean particle volume, a Monte Carlo simulation.

Either length measurements or area measurements may be made on a sample of profiles for the purpose of estimating the mean volume of a population of convex particles. Diameters of spheres, caliper diameters of ellipsoids and intercept lengths are available length measurements. Profile areas can be evaluated by planimetry or point counting. Either all the available profiles in random sections or point sampled profiles can be utilized. We have applied a Monte Carlo simulation to compare several of the stereologic methods for the estimation of the mean volumes of spheres and ellipsoids. Populations of spherical, prolate ellipsoidal and oblate ellipsoidal particles were subjected to random sectioning and measurement. Diameter, point sampled intercept length, area and point sampled area were measured in the case of the spherical particles. With the ellipsoids, the same measurement excepting diameters were performed. The measurements were converted to volumes by the appropriate equations, and the means, the standard deviations of the means and the 95% confidence intervals were determined for increasing sample sizes. All the methods provide estimates that converge on their theoretical mean volumes. The area measurements and particularly the point sampled area measurement show some advantage over the length measurements, but differences among the methods are small, not entirely consistent over the different cases and unlikely to be significant in most real applications.

Evidence for endogenous ADP-ribosylation of GTP-binding proteins in neuronal cell nucleus. Possible induction by membrane depolarization.

GTP-binding protein(s) recognized by antibodies against the alpha-subunits of Gi- and Go-proteins were detected in crude nuclei isolated from rat brain stem and cortex. Immunohistochemical staining indicated that in the cortex these proteins are perinuclear, or are embedded in the nuclear membrane. Evidence is presented for an endogenous ADP-ribosylation of these proteins, which competes with their PTX-catalyzed ADP-ribosylation. The endogenous reaction has the characteristics of nonenzymatic ADP-ribosylation of cysteine residues, known to involve NAD-glycohydrolase activity. In vitro experiments showed that the alpha-subunit of Go-proteins in the cell membrane also acts as a substrate of this endogenous ADP-ribosylation. The in situ effect of membrane depolarization on the nuclear GTP-binding proteins may be attributable to their depolarization-induced endogenous ADP-ribosylation, suggesting a novel signaling mechanism in neuronal cells in the central nervous system.

Quantitative microscopic changes in the mole rat's accessory sex organs during an annual cycle.

BACKGROUND: The mole rat, Spalax ehrenbergi, is a solitary, aggressive subterranean rodent. The present study summarizes a year-round investigation of morphological changes in the mole rat's accessory sex organs. METHODS: Mole rats maintained in the laboratory were killed after 3 months of acclimation; additional animals trapped in the wild were killed immediately. The accessory sex organs were processed for routine histological examination. Tissues were fixed in Bouin's solution, embedded in paraffin blocks, and stained by hematoxylin-eosin. A systemic sampling approach was used to photomicrograph the tissues for histomorphometric assessment. RESULTS: The volume fraction (Vv, mean +/- SEM) of prostate connective tissue from animals kept in captivity increased significantly in January (0.49 +/- 0.05 mm3/mm3) and April (0.43 +/- 0.04 mm3/mm3) but only 0.26 +/- 0.03 mm3/mm3 in November. In the field group, the Vv of prostate connective tissue was significantly higher in January (0.58 +/- 0.08 mm3/mm3) and April (0.62 +/- 0.08 mm3/mm3) and lower in November (0.44 +/- 0.03 mm3/mm3) and February (0.43 +/- 0.03 mm3/mm3), with a concomitant decrease in prostate tubuli and lumen. The prostate tubuli star volume (v*) in laboratory animals increased in November (0.009 +/- 0.002 mm3) and May (0.09 +/- 0.02 mm3). The same pattern was shown in the field group, with a significant increase in December (0.012 +/- 0.002 mm3) and March (0.007 +/- 0.001 mm3). The Cowper tubuli Vv in the captive animals increased during February (0.24 +/- 0.02 mm3/mm3), with a concomitant reduction in the connective tissue (0.05 +/- 0.02 mm3/mm3). The Cowper tubuli v* in same animals increased in December, April, and July (1.37 +/- 0.18 x 10(-4) mm3, 0.94 +/- 0.10 x 10(-4) mm3, 1.52 +/- 0.20 x 10(-4) mm3, respectively). In field group, a slight decrease in star volume took place from November to May (1.25 +/- 0.16 mm3 to 0.39 +/- 0.05 mm3, respectively). Testosterone levels appeared to be higher in the field group than in the laboratory group. In December the values were 1.62 +/- 0.15 ng/ml in the field group and 0.55 +/- 0.12 ng/ml in the laboratory group, and in May the laboratory group values were 1.66 +/- 0.12 ng/ml. CONCLUSIONS: In captivity and in the field, male mole rats probably undergo an annual cycle of accessory gland tissue structural changes that are correlated with testosterone secretion.

Quantitative histomorphology of the blind mole rat harderian gland.

Anatomical, histological and morphometric studies have been performed on the harderian gland and its surroundings in the blind mole rat (Spalax ehrenbergi). The gland is tubuloalveolar with no true duct system. All ducts within the gland are formed by a single epithelial cell type and drain into a wide secretory duct. This opens into the conjunctival sac which serves as a reservoir for harderian secretions. Drainage from the conjunctival sac follows 2 possible routes: one through the nasolacrimal duct to the external nasal cavity, the other through a unique excretory duct that emerges from the anteromedial part of the conjunctival sac and runs through the dermis to the skin, opening at the base of a hair follicle. The function of this newly described duct is discussed. Morphometric studies revealed that the lumen volume fraction in the female, slightly smaller than that of the male during the summer, becomes significantly greater during the winter breeding season. The dimorphism and seasonal variations found in the gland acini suggests that the gland may be implicated in pheromone production.