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Follicular-helper T cells (T FH ) are an essential arm of the adaptive immune system. Although T FH were first discovered through their ability to contribute to antibody affinity maturation through co-stimulatory interactions with B cells, new light has been shed on their ability to remain a complex and functionally plastic cell type. Due to a lack sample availability, however, many studies have been limited to characterizing T FH in mice or non-canonical tissue types, such as peripheral blood. Such constraints have resulted in a limited, and sometimes contradictory, understanding of this fundamental cell type. One subset of T FH receiving attention in chronic infection are CXCR3-expressing T FH cells (CXCR3 + T FH ) due to their abnormal accumulation in secondary lymphoid tissues. Their function and clonal relationship with other T FH subsets in lymphoid tissues during infection, however, remains largely unclear. We thus systematically investigated this and other subsets of T FH within untreated HIV-infected human lymph nodes using Mass CyTOF and a combination of RNA and TCR repertoire sequencing. We show an inflation of the CXCR3 + T FH compartment during HIV infection that correlates with a lower HIV burden. Deeper analysis into this population revealed a functional shift of CXCR3 + T FH away from germinal center T FH (GC-T FH ), including the altered expression of several important transcription factors and cytokines. CXCR3 + T FH also upregulated cell migration transcriptional programs and were clonally related to peripheral T FH populations. In combination, these data suggest that CXCR3 + T FH have a greater tendency to enter circulation than their CXCR3 - counterparts, potentially functioning through distinct modalities that may lead to enhanced defense., Competing Interests: NJ is a Scientific Advisor and holds equity interest in ImmuDX, LLC, and Immune Arch, Inc. In the interest of full disclosure, DBW reports that he serves on Advisories for AstraZeneca, Geneos, Advaccinepharma, he participates in BOD service for Inovio. Remuneration received by DBW for these services includes SRA funding, direct payments, stock or stock options disclosed here. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Malone, Wendel, Ma, Del Alcazar, Weiner, De Jager, Del Río-Estrada, Ablanedo-Terrazas, Reyes-Terán, Su and Jiang.)

CXCR5 is a key marker of follicular helper T (T FH ) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified a population of CXCR5 - CD4 + T cells with T FH -cell-like features. This CXCR5 - subset becomes expanded in severe HIV infection and is characterized by the upregulation of activation markers and high PD-1 and ICOS surface expression. Integrated analyses on the phenotypic heterogeneity, functional capacity, T cell receptor (TCR) repertoire, transcriptional profile, and epigenetic state of CXCR5 - PD-1 + ICOS + T cells revealed a shared clonal relationship with T FH cells. CXCR5 - PD-1 + ICOS + T cells retained a poised state for CXCR5 expression and exhibited a migratory transcriptional program. TCR sequence overlap revealed a contribution of LN-derived CXCR5 - PD-1 + ICOS + T cells to circulating CXCR5 - CD4 + T cells with B cell help function. These data link LN pathology to circulating T cells and expand the current understanding on the diversity of T cells that regulate B cell responses during chronic inflammation., (Published by Elsevier Inc.)

Recent studies strongly suggest that surfactant protein D (SP-D) plays important roles in pulmonary host defense and the regulation of immune and inflammatory reactions in the lung. Although SP-D can bind to alveolar macrophages and can elicit their chemotaxis, relatively little is known about the direct cellular consequences of SP-D on the function of these cells. Because matrix metalloproteinases (MMPs) are synthesized in increased amounts in response to various proinflammatory stimuli, we investigated the capacity of SP-D to modulate the production of MMPs by freshly isolated human alveolar macrophages. Unexpectedly we found that recombinant rat SP-D dodecamers selectively induce the biosynthesis of collagenase-1 (MMP-1), stromelysin (MMP-3), and macrophage elastase (MMP-12) without significantly increasing the production of tumor necrosis factor alpha and interleukin-1beta. SP-D did not alter the production of these MMPs by fibroblasts. Phosphatidylinositol, a surfactant-associated ligand that interacts with the carboxyl-terminal neck and carbohydrate recognition domains of SP-D, inhibited the SP-D-dependent increase in MMP biosynthesis. A trimeric, recombinant protein consisting of only the neck and carbohydrate recognition domain did not augment metalloproteinase production, suggesting that the stimulatory effect on MMP production depends on an appropriate spatial presentation of trimeric lectin domains. Although SP-D dodecamers can selectively augment metalloproteinase activity in vitro, this effect may be competitively inhibited by tissue inhibitors of metalloproteinases or surfactant-associated ligands in vivo.

This article provides a complete review of current renal reconstructive techniques. The techniques described include partial nephrectomy, intrasinusal surgery, anatrophic nephrolithotomy, nonvascular bench procedures with autotransplantation, and allograft partial nephrectomy in renal transplantation. A detailed discussion on renovascular and collecting system anatomy and current indications for these procedures is presented.

Purpose: We determined the clinical applicability, safety and efficacy of endoscopically injected glutaraldehyde cross-linked collagen for the treatment of efferent limb incompetence in the incontinent Indiana urinary reservoir., Materials and Methods: Six patients were diagnosed with incompetence of the efferent limb of the Indiana reservoir by video urodynamics. Glutaraldehyde cross-linked collagen was injected through the efferent limb at the level of the ileocecal valve. Outcome was assessed by evaluation of dryness and pouchograms., Results: With a mean followup time of 26 months (range 6 to 36) after the last injection 5 of the 6 patients were cured. The remaining patient, although improved, had a small capacity and subsequently underwent ileal patch augmentation. No patient failed to improve. The mean volume of collagen was 16 ml. (range, 5 to 26). Reservoir volume increased from 150 to 400 ml., Conclusions: The use of glutaraldehyde cross-linked collagen in the treatment of the incontinent Indiana reservoir is safe and effective.

The continued success of renal transplantation has provided a higher quality of life for properly selected patients with ESRD. It is also a much more cost-effective and efficient treatment of ESRD compared with chronic dialysis. Innovative urologic reconstructive surgery using enteric segments for both continent and incontinent urinary diversions has permitted this therapeutic modality to be offered to the recipient with lower urinary tract disease not previously amenable to renal transplantation. These same reconstructive techniques using ileal segments have also permitted preservation of renal allografts with previously nonreconstructable renal pelvic or ureteral disease.

The actual mechanism for risk of developing cancer in intestinal segments used for urinary diversion remains uncertain. The clinical and laboratory experiences are reviewed in this article. The pathogenesis is multifaceted, involving initiators and promoters of carcinogenesis. Molecular genetic technology may provide the key to decoding the mechanisms involved.

This article reviews stomal complications and their management. To accomplish this goal, the authors review techniques used for planning and creating the stomas for both continent reservoirs and incontinent conduits.

This study evaluated the hypothesis that the behavior problems that place children at risk for victimization by peers are associated with victimization primarily when children are also at social risk for victimization. Social risk was defined as lacking supportive friends or as being rejected by the peer group. Participants were 229 boys and girls in the 3rd through 7th grades (M age = 11 years 2 months). As predicted, behavior problems (internalizing problems, externalizing problems, and physical weakness) were more strongly related to victimization when children had few friends, had friends who were incapable of fulfilling a protective function (e.g., were physically weak), or were rejected by peers than when children had more friends, had friends capable of defending them, or were better liked by peers. Results illustrate the principle that individual risk variables depend on social context for expression.

Bony metastasis is common in patients with germ cell tumor of the testicle; however, it is usually seen late in the disease process and is associated with lymph node or other visceral involvement. We present a case of isolated bony metastasis in a patient with a nonseminomatous germ cell tumor of the testis and normal retroperitoneal lymph nodes as determined by surgical resection.

Herniation of the bladder is not uncommon and it can occur with any type of hernia in the groin. Most bladder hernias are discovered unexpectedly during herniorrhaphy, and serious complications can result from intraoperative injury to the bladder. The appearance of hernias on excretory urography and cystography has been described extensively but experience with computerized tomography (CT) has been limited. We describe the appearance of 8 bladder hernias on CT: 2 incisional, 2 femoral, 3 small direct inguinal, and 1 massive direct inguinal hernia with bladder necrosis and perforation. Appearance on CT is characteristic, and this modality may be useful for preoperative evaluation.

They're slow, they're hard-of-hearing, they don't get better--elderly patients can be a pain in the practice. Here's how to keep them away.

A case of metastatic mesothelioma of the tunica vaginalis testis in a 57-year-old man is reported. Clinicopathological findings and treatment options are reviewed.

Ureteroscopy with the rigid instrument is now an integral part of the endourologic armamentarium for the management of patients with ureteral calculi. Our experience demonstrates that ureteroscopy can be a safe, efficacious, and less invasive modality. Morbidity will be lowered with proper patient selection, meticulous attention to technique, and use of the proper equipment. Prevention is the best way to avoid serious complications of ureteroscopy. The following guidelines are recommended: Ureteroscopy should be used primarily for patients with distal ureteral calculi. A guidewire should be in place at all times during ureteroscopy. Fragmentation devices should be available. No forceful manipulations should be undertaken during either introduction of the instrument or manipulation of the calculus. When access or manipulation is difficult, a stent should be placed in the ureter for ureteroscopy at a later date. When perforation occurs, a stent should be placed in the ureter and the injured dry unstented ureter complex avoided. Alternative endourologic modalities should be used when appropriate. When practicing urologists are aware of the indications, potentials, and limitations, ureteroscopy and other endourologic methods will permit safe successful treatment of most patients with ureteral calculi.

The disorders presented consist of those clinical entities in which a reasonably well defined lipid storage material accumulated within nervous tissue. Many other progressive, degenerative disorders are suspected of being storage disorders, but their chemical pathology remains unclear. Collectively this group could be designated the sphingolipidoses. In each case, the disease is a genetic disturbance and transmitted as an autosomal recessive. Sphingolipid storage in each disorder is associated with deficient activity of a specific degradative enzyme or enzyme system, and these deficient enzymes are all lysosomal hydrolases. Lysosomal hydrolases catalyze the breakdown of complex molecules in digestive vacuoles (phagocytic or autophagic) within the cells. Lysosomes show structural latency (requiring osmotic shock or freeze thawing in vitro); their enzymes show maximal activity at acidic pH ranges, and on electron microscopic examination they appear as small, electron-dense intracellular bodies. These hydrolytic enzymes seem to have some form of biological vulnerability in terms of their genetic expression, and this vulnerability underlies the sphingolipidoses. Diagnosis in each case is primarily a clinical problem. The presentation of these disorders, especially in intermediate or advanced forms, is sufficiently distinctive to permit a reasonably accurate diagnosis on the basis of history, physical examination, and routine laboratory data. Patients seen in early stages may be more difficult to recognize but follow-up evaluations usually clarify the problem. Specific enzyme assays are now available for confirmation of the diagnosis in these disorders. A frequent finding in this connection is an increase in the activities of noninvolved lysosomal hydrolases in the storage disorders. Once a case is clinically diagnosed, the clinician has the responsibility of ensuring that proper genetic counseling is made available to the affected families. Considerable supportive care is needed in each case. These patients can survive for prolonged periods, and great stress is placed on their families by these prolonged, hopeless illnesses. Since the disorders affect infants or young children, their parents are usually young adults in their early reproductive years. It is essential that they receive information concerning the risk of subsequent pregnancies. Specific diagnosis of the fetus in early pregnancy can be made now by amniocentesis and enzyme assays on cultured fibroblasts. If the fetus is a homozygote on the basis of enzyme assays, the option of therapeutic abortion should be discussed with the family. For many parents there will be considerable sensitivity to the ethical implications of this course and, if any doubt arises, ethical or pastoral consultation should be sought. Although there are no specific therapeutic approaches, a considerable degree of supportive care can and should be given. In the gangliosidoses and late in the course of the leukodystrophies, seizures will present management problems...

National Library of Medicine research, resource project, and resource improvement grant-related communication activity was measured and examined as an initial task in exploring information exchanges in health sciences librarianship. Grantees were generally found to be reporting results extensively in a variety of written formats and oral presentations. Ways to improve the transfer and utilization of research and development activity results are presented.

A chemical-pathoologic study of globoid leukodystrophy (GLD) was made that compared myelin isolated from maximally involved central white matter with myelin from noninvolved U fiber areas. The results were compared to analyses of myelin from normal, age-matched control human brains. Myelin from U fiber areas contained relatively greater amounts of a lighter myelin fraction and this lighter myelin differed in protein and lipid composition from the heavier myelin fraction. The data have been interpreted to suggest that the metabolic error in GLD results in the formation of an unstable compact or heavier myelin and that a subsequent process of disintegration selectively affects this component.

Myelin was isolated post mortem from brains of patients with metachromatic and globoid forms of leukodystrophy. In the leukodystrophies, isolates were obtained from central white matter and subcortical "U" fiber areas. Myelin also was obtained from age-matched human controls, and the method yielded light and heavy myelin fractions. In both disorders, the pathologic process affected the heavy isolates to a relatively greater degree. Comparative chemical analyses were made of the myelin isolates, and we concluded that a similar pathogenesis--the production of an unstable membrane in later stages of myelin formation--affects both disorders.

In a complementary clinical and biochemical study of patients with globoid leukodystrophy (GLD), cases differed from the classic phenotype of Krabbe disease and suggested a broader spectrum of clinical presentations. In terms of pathogenesis, the advanced development achieved before symptom onset suggested normal early maturation and myelination. Enzyme studies were carried out on white blood cells from the patients, their siblings, parents, and normal agematched controls. These studies utilized galactosyl ceramide of brain origin and a new assay technique. We found a specific deficit in cerebrosidase activity in leukocyte preparations from patients with GLD and intermediate levels of activity in their parents. These findings confirm prior reports and indicate an autosomal recessive mode of genetic expression.

The post-mortem changes in membrane-associated sialidase (N-acetylneuraminosyl glycohydrolase, EC 3.2.1.18) were examined in rat brain obtained and stored in a manner which paralleled neuropathological handling of human brains. When whole brains were held at 4 degrees C in covered containers for varying periods of time (0.67 h), sialidase activity toward endogenous membrane substrate was elevated. This elevated activity was maximal at 8 h of storage and decreased thereafter. The apparent decrease in enzyme activation from 8 to 67 h of storage was not due to a reduction of activity, but was the result of depletion of endogenous membrane substrate, since activity toward exogenous ganglioside remained elevated. The changes were due to whole brain storage at 4 degrees C, and not a result of being stored at -80 degrees C. The post-mortem activation of sialidase was not due to the expression of a new form of the enzyme, since it displayed characteristics similar to those reported previously: (a) membrane gangliosides being the preferred native substrate, and (b) ganglioside GM1 and lactosylceramide being the major hydrolytic products. The results underscore the importance of post-mortem storage conditions when analyzing complex carbohydrates of brain.

We report 6 cases of renal angiomyolipomas and review the pertinent literature concerning this disease. One case involved the rare association of tuberous sclerosis and pregnancy. Another patient without tuberous sclerosis had renal cell carcinoma and later suffered a contralateral angiomyolipoma. The pathological conditions of renal angiomyolipomas with and without tuberous sclerosis are discussed. Since angiomyolipomas present with multiple clinical similarities to renal cell carcinoma, the primary task for the clinician is to differentiate this hamartoma from carcinoma. The distinguishing characteristics and the clinical management of renal angiomyolipomas are discussed.

Neonatal hypothyroidism has been shown to induce delayed myelinogenesis in the developing rat brain. This delay in myelin formation is most prominent during the critical 3 - 4 week postnatal period and the heavy myelin fraction is more selectively affected. The experimental animals, however, continue active myelin formation and by 6 weeks post natum, they do not differ significantly from littermate controls. Myelin protein analysis by SDS acrylamide gels and densitometer methods revealed a decreasing proportion of high molecular weight protein and no significant change in either proteolipid or basic protein in developing myelin. The data suggest that neonatal hypothyroidism induces a reversible delay without qualitative change in myelinogenesis.

Myelin development has been studied in the neonatally hypothyroid rat brain by isolation and characterization of purified myelin preparations. The hormone deficiency results in a suppression of compact myelin formation and the persistence of a lighter possibly pro-myelin fraction. The appearance of myelin basic protein was markedly delayed in the hormone-deficient animals and this effect on the basic protein moiety may be responsible for the delayed myelinogenesis.

The clinical awareness of the various presentations of pheochromocytoma, along with newer monitoring and anesthetic techniques, has enabled early diagnosis and less fluctuation of blood pressure during operation. The use of meticulous surgical technique through the various incisions outlined in this article has made the excision of pheochromocytoma an expeditious operation and the accompanying hypertension surgically curable. Thus, pheochromocytoma is less likely to be a fatal lesion.

We studied a patient with a very small somatostatinoma that arose from the prominence of the orifice of the duct of Santorini. The patient presented clinically with epigastric discomfort, marked loss of weight, diarrhea, exertional dyspnea, and chest pain. He flushed intermittently and had occasional tachycardia and hypertension. Levels of serum serotonin and urinary 5-hydroxyindoleacetic acid were normal. A small ampullary tumor was resected and identified by immunohistochemical staining to be a somatostatinoma. The patient had gained 6.75 kg and was essentially free of symptoms 16 months after surgery.

We report a reduction in isolatable myelin in white matter from regional areas of aged human brain. This decrease was most prominent in association subcortex of Alzheimer's material. We also found structural changes in myelin lipids. These changes involved an increase in unsaturated acyl chains and suggest an age-related instability of subcortical white matter. This specific chemical change in myelin glycosphingolipids has been found in all regional areas of normal aged and Alzheimer's brain material. This remains an age-related molecular change that seems unrelated to the pathophysiology of senile dementia of the Alzheimer's type.

Age-related changes in the lipid chemical composition and structure of myelin and myelin subfractions have been studied in the rat brain. Myelin subfractions with a content ranging from the more mature and compact lamellae to fractions containing earlier membrane fractions were isolated from mature, old, and aged animal groups. We found changes in cholesterol-phospholipid ratios and an increasing degree of unsaturation in the longest acyl chains of major myelin glycosphingolipids. These changes suggest that increased fluidity and decreased stability occurs with age in myelin.

Pyrithiamine was administered to newborn rats throughout the vulnerable period for myelinogenesis. A major metabolic defect was produced in the cerebral activities of the thiamine-dependent enzymes, transketolase and pyruvate decarboxylase. In spite of a defect in carbohydrate metabolism which is lethal in adult rats, overall development, and myelination as indicated by biochemical and morphological criteria, proceeded at an essentially normal rate. These findings indicate alternative metabolic pathways may be operational in newborn rat brain enabling it to circumvent major blockage in thiamine-dependent reactions.

The activity of the pH 7.5 NADH-linked nitrate reductase isoform from soybean seedlings is termed inducible. Activity is present only in the leaves of seedlings which have been supplied nitrate. A cDNA clone that encoded part of the mRNA for squash nitrate reductase hybridized specifically with mRNA for this inducible nitrate reductase isoform. Nitrate induction resulted in an increase in the steady-state levels of mRNA for this isoform after 24 hours, while the addition of glutamine to the nitrate diminished steady-steady state levels of this mRNA.